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Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults

May 2016
Progress in Lipid Research 63(Suppl. 1)

May 2016
63(Suppl. 1)

DOI:10.1016/j.plipres.2016.05.001

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Authors:

Ken D Stark

University of Waterloo

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Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33.0%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA + DHA in erythrocyte equivalents. Regions with high EPA + DHA blood levels (> 8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤ 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA + DHA and the very low to low range of blood EPA + DHA for most of the world may increase global risk for chronic disease.

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Global survey of the omega-3 fatty acids, docosahexaenoic acid and

eicosapentaenoic acid in the blood stream of healthy adults

Ken D. Stark

⁎, Mary E. Van Elswyk

, M. Roberta Higgins

,CharliA.Weatherford

, Norman Salem Jr.

University ofWaterloo, Department of Kinesiology, 200 University Avenue, Waterloo, ON, N2L 3G1, Canada

Scientiﬁc Affairs, Van Elswyk Consulting, Inc., 10350 Macedonia St., Longmont, CO 80503, USA

MEDetect Clinical Information Associates, Inc., PO Box 152, Skippack, PA 19474, USA

Weatherford Consulting Services, Poteet, TX, USA

DSM Nutritional Products Ltd., 6480 Dobbin Road, Columbia, MD 21045, USA

abstractarticle info

Article history:

Received 18 December 2015

Received in revised form 14 May 2016

Accepted 18 May 2016

Available online 20 May 2016

Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA), were systematically identiﬁed in order to create a global map identifying countries

and regions with different blood levels. Included studies were those of healthyadults, published in 1980 or later.

A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including

plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid

data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one

of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equiva-

lents. Regions with high EPA+ DHA blood levels (N8%) included the Sea of Japan, Scandinavia, and areas with in-

digenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%)

were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa.

The presentreview reveals considerable variability inblood levels of EPA+ DHAand the very low to low rangeof

blood EPA+DHA for most of the world may increase global risk for chronic disease.

(http://creativecommons.org/licenses/by/4.0/).

Contents

1. Introduction.............................................................. 133

2. Systematicreviewmethodology..................................................... 133

2.1. Searchstrategy.......................................................... 133

2.2. Inclusionexclusioncriteria .................................................... 133

2.3. Searchresultsscreeninganddataextraction ............................................ 133

2.4. Searchresults .......................................................... 133

3. Convertingfattycompositiondatatosimilarunitsforcomparison...................................... 134

3.1. Convertingfattyaciddatatorelativeweightpercentages....................................... 134

3.2. ConvertingbloodlevelsofEPA+DHAtoerythrocytebasedranking.................................. 134

4. Results................................................................. 135

4.1. Includedstudycharacteristics................................................... 135

4.2. GlobaldistributionofEPA+DHAinhumanblood.......................................... 135

4.3. Globaldistributionofindividualn-3LCPUFA ............................................ 137

5. Discussion............................................................... 137

5.1. Countrieswithlimited,excludedornodata............................................. 139

5.2. Unitsforexpressingfattyacidcompositionaldata.......................................... 139

5.3. Dietandblood.......................................................... 142

5.4. PotentialconsequencesoflowbloodlevelsofEPA+DHA....................................... 143

5.5. ThechallengeofincreasingbloodEPA+DHAlevelsthroughdietaryintakes.............................. 144

Progress in Lipid Research 63 (2016) 132–152

⁎Corresponding author at: Department of Kinesiology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.

E-mail addresses: kstark@uwaterloo.ca (K.D. Stark), mveconsulting@q.com (M.E. Van Elswyk),medetect@aol.com (M.R. Higgins), charliaweatherford@gmail.com (C.A. Weatherford),

Norman.Salem@dsm.com (N. Salem).

http://dx.doi.org/10.1016/j.plipres.2016.05.001

Contents lists available at ScienceDirect

Progress in Lipid Research

journal homepage: www.elsevier.com/locate/plipres

6. Concludingremarks........................................................... 145

Conﬂictsofinterest............................................................. 145

Acknowledgments.............................................................. 145

References................................................................. 145

1. Introduction

Noncommunicable disease or “chronic disease”mortality is estimat-

ed to be the cause of death for 38 million people worldwide each year,

disproportionately effecting those in low and middle-income countries

and unhealthy diets are considered a main contributor [1]. Determining

global variation in nutrient status informs the process of creating na-

tional and worldwide dietary guidance. Dietary omega-3 long-chain

polyunsaturated fatty acids (LCPUFA), eicosapentaenoic acid (EPA,

20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), have been associ-

ated with a decreased risk of chronic disease, in particular cardiovascu-

lar mortality [2] and cognitive decline [3]. Global dietary intakes of

omega-3 LCPUFA has been examined and it has been estimated that

less than 20% of the world population consumes ≥250 mg/day of sea-

food omega-3 polyunsaturated fatty acids (PUFA) [4].However,there-

liability of EPA + DHA intake estimates is limited by various factors

including the availability of accurate and timely food composition data

in nutrient databases that can differ across countries [4,5] but also the

challenge of reporting errors in the collection of dietary data [6,7].The

fatty acid composition of blood does not have these limitations and

blood EPA+DHA also reﬂects other metabolic factors and behavioral

choices that can inﬂuence EPA + DHA status [8–12]. Blood levels of

omega-3 PUFA, particularly EPA and DHA have been linked to a reduced

risk of primary cardiac arrest [13], sudden cardiac death [14] and all-

cause dementia [15]. Therefore, our objective was to systematically re-

view the available literature and identify studies reporting blood

EPA+DHA levels to create a visualization of global EPA+DHA status

useful for identifying countries and regions potentially at an increased

risk of chronic disease due, at least in part, to their omega-3 LCPUFA sta-

tus. The results of the global mapof blood levels of EPA+ DHA and blood

level recommendations are contrasted against reports of dietary intakes

and dietary intake recommendations. In addition, the possible conse-

quences of global blood levels on chronic diseaserisk and the challenges

of achieving blood levels recommended to reduce chronic disease risk

are discussed.

2. Systematic review methodology

2.1. Search strategy

To identify relevant studies, a comprehensive literature search was

conducted using two scientiﬁc literature databases (PubMed and

Embase) through April 2014. Supplementary literature searches includ-

ed examining the reference lists of all relevant studies, pertinent review

articles, and meta-analyses. Included studies published after the date of

literature search were identiﬁed via publication alerts. Relevant terms

representing EPA and DHA and blood fatty acid measurement were

used for each database searched. When appropriate, subject headings

were exploded and terms truncated (see PubMed search strategy in

Supplementary Table S1).

2.2. Inclusion exclusion criteria

Included studies were those of healthy adults (≥16 years) reporting,

at a minimum, red blood cell, plasma, or whole blood of both EPA and

DHA fatty acid data, published in 1980 or later, and using a capillary col-

umn to separate fatty acids. Studies of pregnant and nursingwomen, in-

fants and children or subjects with existing disease were excluded.

Studies of individuals with disease risk factors were included. All

study designs were eligible with the exception of individual case stud-

ies. Preference was given to studies published in English, however, stud-

ies in other languages were considered if data was otherwise

unavailable for a particular country. When data from randomized, con-

trolled trials was used only baseline data from subjects in the placebo

group was included.

2.3. Search results screening and data extraction

Level I screening of search results included a review of all titles and/

or abstracts compared to eligibility criteria. Full-text publications of any

studies not eliminated at Level I were retrieved for complete review at

Level II screening. All search results were screened by two individuals

with approximately 95% agreement regarding included and excluded

studies. Differences were resolved by discussion and consultation with

a third researcher as needed. Two researchers completed data extrac-

tion for all studies, one review author checked text entries, and one in-

dependent quality control person checked numeric outcome data.

Included studies were further examined to identify related or “kin”

studies. When kin studies were identiﬁed, the study reporting the

most detailed fatty acid data for the largest sample size was selected

for further data extraction and the other kin publications were exclud-

ed. All included studies provided at minimum, individual data for EPA

and DHA and, if available, data for 14:0, 16:0, 18:0, 20:0, 22:0, 24:0,

16:1n-7, 18:1n-7, 18:1n-9, 20:1n-9, 22:1n-9, 24:1n-9, 18:2n-6, 18:3n-

6, 20:2n-6, 20:3n-6, 20:4n-6, 22:4n-6, 22:5n-6, 18:3n-3, 20:5n-3,

22:5n-3, and 22:6n-3 was also collected for further evaluation.

Age range was an extracted variable of interest that was not consis-

tently reported in all studies. Some studies, for example, reported age

only as N18 or as a population mean age. If an age range of the studypar-

ticipants was not presented, the upper and lower limits of the age range

were calculated from the standard deviation by adding and subtracting

2 times the standard deviation from the mean age (2SD method). Stan-

dard deviations were calculated as needed. In some instances, generally

in studies with samples sizes lessthan 100 subjects (n = 15), the range

generated from 2SD method was inconsistent with recruited (e.g. age

consistent with young children in study of adults)or was an implausible

range –i.e. a negative age for the lower bound. In these instances, the

standard error of the mean was multiplied by the appropriate critical z

value and added and subtracted from the mean to determine 99.99%

conﬁdence intervals that were used to establish the age range.

To ensure data integrity the spreadsheet containing all extracted

data was quality checked, assigned a version code and maintained

apart from the live/working spreadsheet to prevent any further chang-

es. If the live/working spreadsheet required modiﬁcation in a manner

that would impact analytical outcomes the previously “locked”spread-

sheet was modiﬁed accordingly, assigned a new version code, and then

maintained as the “locked”dataset. The ﬁnal locked dataset, used for

outcome summaries, was the third dataset in a series.

2.4. Search results

The original search yielded 877 references, supplemental searching

resulted in identiﬁcation of an additional 47 references, of these 585

were excluded based on initial (Level I) screening of abstracts and/or ti-

tles (Fig. 1). The most commonreasons for exclusionof studies at Level I

screening were participants with existing disease (38% of excludes)

133K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

followed by studies that had no outcomes of interest or a lack a data on

individual fatty acids (29%). In addition, there were several studies ex-

cluded as the participants were pregnant/lactating (16%), children

(2.2%) or “other”(institutionalized, selected for low ﬁsh intakes, etc.)

populations (2.3%). Other exclusions included relationship to an

existing kin study already in the database (4.5%), inappropriate publica-

tion type (e.g. abstract) (4.3%), or irrelevant/unrelated studies (3.7%).

Full-text publications of 339 studies were retrieved for complete review

at Level II. At Level II, most studies were excluded for providing only

graphical data or not providing results for a blood fraction of interest

(Fig. 1). Although some studies had multiple reasons for exclusion,

each study was classiﬁed into only one exclusion category. A total of

298 studies were included [5,6,14,16–310] and a total of 626 studies

were excluded (Supplementary Table S2).

3. Converting fatty composition data to similar units for comparison

3.1. Converting fatty acid data to relative weight percentages

Extracted data was sorted into categories of blood fraction analyzed

and included plasma totallipids, plasma phospholipid, erythrocytes and

whole blood. Serum data was included in the appropriate plasma cate-

gories and erythrocyte phospholipid data was included in the erythro-

cyte category based on previous ﬁndings that the fatty acid

composition of plasma and serum [311] and of erythrocyte total lipid

and erythrocyte phospholipids [312] are similar, respectively. Within a

blood fraction, studies were also sorted according to the units used to

express the data. The units used fell into categories of relative quantiﬁ-

cation (theweight or mole percentage of anindividual fatty acid relative

to the total fattyacids) and absolute concentration (the concentration of

a fatty acid in a volume or mass of the blood fraction). The most com-

mon method of data expression was as the weight percentage of total

fatty acids (78% of theextracteddata) while expression as mole percent

accounted for only 5% of the extracted data. Fatty acid weights

expressed in a blood fraction volume was the most common method

of expressing concentrations and accounted for 12% of the extracted

data with the units, μg of fatty acid/mL of blood being used most

commonly. Mole based concentrations accounted for only 5% of the

data extracted. Within blood fractions, the fatty acid composition of

plasma phospholipids, erythrocytes and whole blood were presented

mainly as relative percentages (92, 98 and 92%, respectively) while for

plasma total lipids the use of relative percentages was slightly lower

(62%) as the use of concentration units (mole and weight based) was

slightly more common (38% of data from this blood pool).

In order to facilitate comparisons, data was converted to relative

weight percentages within each blood fraction. This approach was

employed based on the fact that most of the data was already expressed

in this format and could not be converted to concentration data due to

the lack of quantitative information on fatty acid and blood fraction vol-

ume reported in the original publications. Concentration data that indi-

cated either the concentration of the sum of total fatty acids; the sums of

saturates, monounsaturates and polyunsaturates; or a comprehensive

list of the concentration of individual fatty acids were readily converted

to relative percentage data. Data expressed as mole concentrations was

converted to mass units using the molecular weight of individual fatty

acids and then converted into relative weight percentages. Fatty acid

compositions presented as mole percentages were converted by divid-

ing the mole percentage of an individual fatty acid by 100 and then mul-

tiplying by the respective fatty acid molecular weight to express the

data as g of individual fatty acids over the total sum of fatty acids in

moles. The individual fatty acids were summed to determine the total

sum of fatty acids in g over the total sum of fatty acids in moles. The

mass of each individual fatty acid over total sum of fatty acids in

moles was then divided by the mass of the total sum of fatty acids

over the moles of the total sum of fatty acid and multiplied by 100 to

convert the fatty acid composition to weight percentages. This conver-

sion method required comprehensive fatty acid proﬁles to complete.

Approximately 12% of the data extracted was converted (47/398 lines

of extracted data within our spreadsheet) to relative weight percent-

ages and 6.5% of the data could not be converted (26/398 lines of ex-

tracted data) due to the inability to determine the sum of total fatty

acids (usually no saturated and monounsaturated fatty acids reported).

Data not converted to relative weight percentages was not included in

the development of the global map of the sum of the percentages of

EPA+ DHA, but this data is included in the summary tables.

3.2. Converting blood levels of EPA+ DHA to erythrocyte based ranking

In order to compare the omega-3 PUFA status across the globe,

EPA+ DHA in erythrocytes was selected over other omega-3 PUFA

blood biomarkers [311],a

sithasbeenwelldeﬁned in the literature pre-

viously [313]. Therefore, it was necessary to convert the fatty acid com-

positiondata from different blood fractionsto EPA +DHA equivalents to

generate a single, comprehensive global map. If EPA+ DHA as a speciﬁc

sum was not presented in the original publication, it was calculated by

summing reports of 20:5n-3 and 22:6n-3 and added to the database.

The amount of data extracted from the literature was relatively equal

from plasmatotal lipid (33%), plasma phospholipids (32%) and erythro-

cytes (32%) while data from whole blood (3%) was relatively limited.

Within each blood fraction, data from each study was weighted by

study sample size, summed with studies from the same country and di-

viding by the sum of study sample sizes for that country. In order to

combine data from different blood fractionsfor each country, previously

published modelingand translation methods were applied [314]. These

methods indicate that converting continuous EPA+DHA in one blood

fraction to continuous data in another blood fraction is possible, but

that the degree of concordance is greater when discrete categories are

used for translation. Therefore, the categories used in this translation

study were derived from levels of EPA+ DHA inerythrocytes associated

with high to low risk of death from coronary heart disease that were

presented when the “omega-3 index”was introduced [313]. The contin-

uous data was assigned to one of four discrete blood level groupings

that corresponded to EPA + DHA weight percentage values in

Fig. 1. Flow diagram of inclusion exclusion process.

134 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

erythrocytes of ≤4(verylow),N4–6(low),N6–8 (moderate), N8 (high).

Equivalent groupings for plasma total lipids [≤2.9 (very low), N2.9–4.0

(low), N4.0–5.2 (moderate), N5.2 (high)], plasma phospholipids [≤3.8

(very low), N3.8–5.7 (low), N5.7–7.6 (moderate), N7.6 (high)] and

whole blood [≤3.0 (very low), N3.0–4.4 (low), N4.4–5.9 (moderate),

N5.9 (high)] were determined according to equations as described pre-

viously [314]. Each grouping was assigned a categorical score (1 —very

low through 4 —high). The categorical scores for different blood frac-

tions were weighted by total number of participants for each blood frac-

tion and summed with the weighted values of other blood fractions for

each country. The sum of the weighted score values were then divided

by the sum of the samples sizes and rounded to the nearest whole num-

ber (1 —very low, 2 —low, 3 —moderate, 4 —high) to determine the

discrete category to represent the country. Data for individual studies

within a country were also ranked and compared to the blood level cat-

egory of their representative country as a check for potential regional

differences within a country. Large differences were observed between

the overall country rank with studies examining indigenous popula-

tions in Alaska (versus United States of America), Northern Canada

(versus Canada), a ﬁshing region of South Africa (versus Cape Town)

and Northern Russia (versus Central Russia), as well as the Primorsky

Krai region of Russia (located on the Sea of Japan). These regions were

removed from country data and categorized to their own distinct re-

gion. The country blood level categories were assigned colors (very

low —red, low —orange, moderate —yellow, high —green, no data —

gray) that were used to generate a global heat map for blood levels of

EPA+ DHA using a royalty-free vector map of the world image pur-

chased from Adobe Stock (Adobe Systems Incorporated, San Jose, CA

USA) that was modiﬁed using Adobe Illustrator CS6 ver. 16.03 (Adobe

Systems Incorporated).

4. Results

4.1. Included study characteristics

The main characteristics of the included studies are summarized in

Table 1. Epidemiologic observational studies provided the majority of

data points. The majority of studies enrolled subjects 20 years or older

with slightly more males than females. Plasma total lipid fatty acid com-

position totaled 131 lines of extracted data, representing 36, countries/

distinct regions with the USA having the most data reported with 27

lines followed by Japan with 20 data lines (Table 2). Plasma

phospholipid based data lines totaled 127 lines of data overall, with 31

countries/regions represented (Table 3). The USA had the most lines

of data reported at 18 followed by Canada with 14 lines of data. For

erythrocyte data, there were 128 lines of data, representing 33 coun-

tries/distinct regions (Table 4). China had 29 data lines, but 24 of

these data lines came from a single study [126] that examined the var-

ious provinces and municipalities across China. The USA had 17 lines of

data for erythrocytes. Whole blood data was limited to 12 lines of data

that represented 4 countries with 5 lines of data from the USA and 4

from Canada (Table 5).

Overall, data from 54 countries/distinct regions were identiﬁed but

the amount of data for a speciﬁc country varied widely. Studies conduct-

ed in North America contributed the most data points (n = 114 lines of

extracted data) followed by Asia (n = 96), Scandinavia (n = 73) and

countries within Europe (n = 71). In contrast, data from Central and

South America and Africa was limited. The USA had 67 lines of data in

total, which was by far the most data for a single country. Japan, China

and Canada had 32–35 lines of data, while Italy, France, the UK, Austra-

lia, Norway, the Netherlands, Finland and Sweden had 10–20 lines of

data. It is concerning that for almost half of the countries/regions

(n = 26), there were only 2 (10 countries/regions) or 1 (16 countries/

regions) lines of data. When the data was examined according to sam-

ples size of the studies, Japan had the largest amount of individuals ex-

amined (n = 26,877) followed by the USA (n = 22,700). China, the UK,

Finland, France, Italy and Australia were countries with data collected

from more than 5000 individuals. Again, data from almost half of the

countries was based on limited data as 27 of the countries had data

that represented less than 300 individuals with 14 countries having

data from less than 100 individuals. There was an interesting pattern

where “normative”data for some countries was exceeded by data for

distinct populations. Sampling from Russia was particularly uneven

with a large study sample from the Primorsrky Krai region on the Sea

of Japan (n = 1174) and study samples on indigenous people living in

the north (n = 131 in total), while we could only recover limited data

for central Russia (n = 113). In South Africa, a ﬁshing population in St.

Helena Bay (n = 25 subjects) was compared to urban Cape Town inhab-

itants (n = 25 subjects) [250]. The focus on distinct populations was

also observed in data from Canada as the number of individuals exam-

ined in a distinct Cree/Inuit region (n = 5087) was greater than the

number of individuals examined for the country as a whole (n =

4104). The only other example was studies examining the Alaskan

Yupik (n = 1573 subjects), but the number of total subjects

representing the general population of the USA was much larger

(n = 22,700).

4.2. Global distribution of EPA+ DHA in human blood

Detailed fatty acid composition data for plasma total lipids, plasma

phospholipids, erythrocytes and wholeblood extracted from the includ-

ed studies is presented by country within continentalregions (Tables 2–

5). The data are presented as relative weight percentages whenever

possible with data that could not be converted included at the end of

each country list. The number of individual fatty acids reported in addi-

tion to EPA and DHA was variable across the studies. Values for 20:0,

22:0, 24:0, 18:1n-7, 20:1n-9, 22:1n-9, 24:1n-9, and 20:2n-6 were pre-

sented forless than 20% of the included data which is somewhat under-

standable given that they make up a relatively small percentage of the

total fatty acid composition. However, fatty acids that make up a consid-

erable percentage were also reported inconsistently, with 16:0, 18:0

and 18:1n-9 being reported for only 55% of the included data while

18:2n-6 and 20:4n-6 values were reported for 74% and 79% of the stud-

ies, respectively. The other n-6 polyunsaturated fatty acids were also

poorly reported, with 18:3n-6 at 25%, 22:4n-6 at 31%, and 22:5n-6 at

23% of the total included data lines.

By rank assigning blood levels of EPA+ DHA for each country and

assigning colors for very low (red), low (orange), moderate (yellow)

Table 1

Demographics of included studies.

Characteristic Percentage of studies

Age inclusion criteria (years of age)

≥18 17.0

≥19 3.0

≥20 31.0

≥30 17.5

≥40 17.0

≥50 3.4

≥60 7.7

“Adult”⁎3.4

Sex

Female 47

Male 53

Study type

Prospective cohorts and case–control studies 70

Randomized trials 30

Blood fraction

Plasma total lipid 33.0

Plasma phospholipid 32.0

Erythrocyte 32.0

Whole blood 3.0

⁎The authors deﬁned study age range as “adult”but included teenaged subjects b18

years.

135K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

and high (green) blood levels, distinctive global patterns can be ob-

served (Fig. 2). Regions with high blood levels of EPA+DHA were

found in distinct regions with countries on the Sea of Japan (Japan,

South Korea, and Primorsrky Krai region of Russia), Scandinavia (Den-

mark, Norway, and Greenland) and regions with indigenous popula-

tions or populations that are not fully adapted to industrial based or

Table 2

Global fatty acid compositions of plasma total lipids expressed as relative percentages.

Author (Year) Ref Country n

14:0

16:0

18:0

20:0

22:0

24:0

EPA+DHA

Asia

Chien (2011) [49] China 986 0.54 2.78 3.32

Zhang (2010)2[302] China 92 703 1567 54 245 30 59 25 152 210

Kibayashi (2000)2[135] China 75 21 40 61

Lee (2000) [155] Hong Kong 133 0.50 17.80 13.00 1.00 18.80 29.50 0.50 0.20 1.10 6.30 0.40 0.20 0.80 1.30 3.40 4.70

Abraham (2013) [16] India 50 1.76 32.19 11.90 2.17 21.03 19.93 0.54 5.27 0.37 0.45 0.68 1.13

Mehendale (2009) [186] India 26 0.74 20.28 7.85 15.58 0.42 36.00 0.50 1.30 7.76 0.63 0.53 0.41 0.96 1.37

Hirai (2000)3[108] Japan 62 1.55 22.34 5.56 3.75 19.11 37.70 5.05 1.57 1.38 2.21 3.60

Itakura (2011)3[119] Japan 16397 1.08 23.76 7.24 2.95 21.89 26.49 0.48 1.11 5.15 0.64 3.02 0.79 5.37 8.39

Ito (1999)3[120] Japan 108 26.38 8.79 21.10 1.30 24.60 1.20 5.83 0.89 4.31 5.61 9.92

Kuriki (2003) [144] Japan 94 0.83 23.08 7.71 2.23 18.94 31.61 6.17 0.79 2.32 0.59 4.51 6.83

Kuroki (1997) [147] Japan 18 0.72 19.48 6.69 0.17 0.44 0.28 2.22 21.05 0.15 0.77 32.63 0.25 1.06 6.62 0.68 2.17 4.06 6.23

Motoyama (2009) [194] Japan 285 26.40 6.60 2.60 0.90 6.00 8.60

Nakamura (1995) [201] Japan 110 0.70 25.10 8.90 3.70 21.60 21.20 1.00 5.70 0.80 3.40 0.90 7.50 10.90

Nogi (2007)4[206] Japan 411 22.75 7.91 18.92 32.08 6.51 0.60 3.28 1.06 6.91 10.18

Oda (2005) [210] Japan 42 0.89 23.22 7.24 0.24 0.59 2.96 2.11 18.98 0.07 1.20 27.47 0.21 0.19 0.99 2.99 0.11 0.88 3.45 0.78 0.52 3.97

Sekikawa (2008) [251] Japan 281 26.80 6.60 0.20 2.50 5.90 8.40

Takita (1996) [273] Japan 394 24.30 7.30 3.40 21.60 29.50 4.50 1.90 3.40 5.30

Umemura (2005) [281] Japan 421 0.88 19.70 6.70 2.80 20.70 34.80 0.30 0.98 1.06 1.62 0.44 3.28 4.90

Wakai (2005) [290] Japan 1257 2.64 0.82 5.00 7.64

Yamada (2000) [296] Japan 261 2.70 29.90 5.90 0.63 3.80 1.34 8.40 12.20

Yamada (2000) [296] Japan 202 2.50 21.10 5.30 0.71 3.20 1.20 7.70 10.90

Ikeya (2013)2[117] Japan 65 167 99 155 253

Kibayashi (2000)2[135] Japan 25 48 114 162

Kitayama (2011)2[137] Japan 1656 138

Konagai (2013)2[140] Japan 42 25 143 110 191 301

Kondo (2010)2[141] Japan 17 750 7 150 19 65 116 182

Tomiyama (2011)2[278] Japan 2206 33 172 52 122 174

Nogi (2007)4[206] Mongolia 252 22.41 8.36 22.16 33.55 6.54 0.70 1.10 1.30 3.88 4.98

Rezvukhin (1996) [234] Russia 28 2.24 21.56 9.49 0.71 2.23 2.98 29.56 0.53 1.18 23.76 0.94 1.61 3.73 1.04 0.00 0.47 1.97 1.97

Rezvukhin (1996) [234] Russia–IN 18 4.39 29.69 13.27 0.62 1.33 3.06 21.70 0.32 0.22 17.25 0.42 0.79 4.31 0.18 0.94 0.38 3.39 4.33

Rode (1995) [239] Russia–IN 41 27.74 0.90 7.43 0.55 2.73 1.79 4.13 6.86

Manav (2004) [178] Singapore 145 4.83 0.47 0.33 3.07 3.40

Manav (2004) [178] Singapore 147 4.50 0.57 0.30 3.53 3.83

Nogi (2007)4[206] S. Korea 418 21.82 6.82 19.60 36.11 6.75 0.60 2.19 0.71 5.40 7.60

Sekikawa (2012) [252] S. Korea 301 24.70 6.02 1.97 0.81 4.83 6.80

Oceania

Munro (2012) [198] Australia 28 0.95 2.06 3.01

Sullivan (2006) [267] Australia 53 0.84 0.48 2.02 2.86

van der Pols (2011)2[286] Australia 147 242 124 2 11 39 49

Rao (1996) [230] PNG 14 1.77 22.96 8.50 0.30 0.66 2.53 21.17 18.40 1.56 5.24 0.54 0.69 0.53 2.30 4.14 6.45

Middle East

Alshatwi (2007)2[19] S. Arabia 57 363 68 34 42 98 140

Yerlikaya (2011)3[299] Turkey 45 0.74 15.74 5.04 0.71 0.48 0.27 0.87 6.77 0.71 0.40 0.35 32.34 5.34 7.32 1.23 1.01 1.79 2.80

Europe

Astorg (2008) [26] France 533 34.28 0.52 0.22 1.52 7.97 0.20 0.51 1.32 0.54 2.57 3.89

Féart (2008) [77] France 1273 1.24 28.14 11.51 2.34 20.43 24.89 0.40 6.77 0.41 1.01 0.46 2.38 3.39

Merle (2013) [187] France 605 0.41 1.00 0.48 2.50 3.50

Samieri (2008) [246] France 1149 1.24 28.14 11.58 2.32 20.34 24.90 0.41 6.75 0.41 1.03 0.47 2.41 3.44

Samieri (2011) [247] France 1228 1.01 2.39 3.40

Samieri (2012) [248] France 281 1.10 2.40 3.50

Dawczynski (2010) [61] Germany 40 23.59 4.94 0.29 0.81 0.36 1.40 2.21

Geppert (2008) [84] Germany 39 0.36 1.88 6.87 1.96

Kalogeropoulos (2010) [128] Greece 374 20.40 6.70 19.00 26.40 5.18 0.25 0.36 0.32 1.56 1.92

Panagiotakos (2010) [213] Greece 640 28.00 5.90 0.29 0.47 0.38 1.80 2.27

McAfee (2011) [183] Ireland 38 1.13 25.66 6.79 27.42 7.57 1.33 0.82 1.01 1.05 1.87

Cherubini (2007) [48] Italy 725 22.50 6.50 26.20 24.50 8.00 0.40 0.59 2.28 2.87

Ferrucci (2006) [79] Italy 1123 24.92 8.08 0.46 0.64 2.30 2.94

Lauretani (2007)3[152] Italy 1241 25.26 8.19 0.47 0.47 2.35 2.83

Palozza (1996) [212] Italy 40 21.50 1.60 6.60 0.80 0.90 0.70 2.20 3.10

Tremoli (1995) [280] Italy 16 32.50 6.60 0.60 1.40 2.00

Visioli (2003)3[288] Italy 16 0.55 1.68 2.23

Emanuele (2009)2[76] Italy 60 387 71 33 37 84 120

Torres (2000)2[279] Portugal 50 688 236 627 44 110 76 35 102 138

Torres (2000)2[279] Portugal 37 717 247 666 53 145 60 20 61 82

Amiano (2001) [21] Spain 102 0.55 4.03 4.58

Carrero (2004) [43] Spain 30 20.05 7.32 1.00 1.34 20.66 26.41 8.25 0.32 0.56 0.81 1.83 2.39

Fernandez–Real (2003) [78] Spain 232 0.40 19.47 7.71 0.30 0.86 1.08 21.21 1.22 31.86 0.44 7.05 0.30 0.54 2.00 2.54

Mayneris–Perxachs (2010) [182] Spain 516 20.38 6.55 23.73 32.28 6.70 0.48 1.99 2.47

Rusca (2009)2[242] Switzerland 48 10 56 66

Hirai (2000)3[108] NLD 39 1.51 23.29 5.06 4.17 17.75 38.62 6.93 1.04 0.27 1.31 1.58

Dangour (2010)3[60] UK 119 23.92 7.42 2.72 23.49 27.30 1.69 6.81 0.53 1.07 0.74 1.31 0.65 2.37 3.68

Leeson (2002) [156] UK 326 0.70 1.86 2.56

Rosell (2005) [241] UK 659 1.04 21.71 6.67 0.24 1.38 22.45 33.71 1.11 5.74 1.37 0.53 0.76 1.18 1.71

Sanders (2006)3[249] UK 79 23.06 7.58 0.80 20.82 32.41 1.71 6.98 0.18 0.55 0.80 1.24 1.08 2.79 4.03

Scandinavia

Reinders (2012) [233] Finland 1395 0.75 1.65 0.56 2.46 4.11

Rissanen (2003) [236] Finland 242 1.43 25.69 8.35 3.51 24.39 24.60 0.18 1.00 2.57 0.37 0.47 0.25 0.95 1.42

Ruusunen (2011) [243] Finland 2031 1.68 0.55 2.50 4.18

Solakivi (2011) [258] Finland 59 1.03 21.30 6.53 2.79 23.40 28.10 0.33 5.12 0.92 1.07 0.50 1.86 2.93

Suominen–Taipal (2010) [269] Finland 1128 4.40 1.20 0.50 2.20 3.40

Suominen–Taipal (2010) [269] Finland 260 5.95 2.04 0.65 4.15 6.19

Virtanen (2012) [287] Finland 1766 1.66 0.55 2.46 4.12

Sekikawa (2012) [252] Iceland 97 28.00 6.32 1.66 0.72 3.04 4.70

Brox (2001)3[40] Norway 36 2.08 24.88 8.66 0.24 0.80 0.19 2.58 21.90 0.32 34.73 0.07 0.20 0.76 0.11 1.38 0.36 0.09 0.65 1.01

Grønn (1991) [90] Norway 15 25.00 10.00 19.40 28.00 1.60 5.60 1.70 1.50 7.30 9.00

Nenseter (2000) [202] Norway 70 1.00 21.30 6.70 0.10 0.30 0.20 2.10 1.60 18.80 31.40 0.30 0.20 1.10 4.80 0.50 1.90 0.50 3.80 5.70

Ottestad (2012) [211] Norway 54 29.90 6.20 0.60 0.60 0.50 2.10 2.70

Vognild (1998) [289] Norway 266 1.20 23.70 7.50 2.00 1.90 18.20 0.10 31.60 0.40 1.30 4.80 0.60 1.70 0.40 2.70 4.40

Cederholm (1994)3[47] Sweden 20 1.83 23.85 8.53 0.33 0.53 2.94 24.13 0.86 28.35 0.19 0.94 3.75 0.75 0.92 2.05 2.97

Karlsson (1996)2[129] Sweden 27 812 11 47 145 8 20 10 76 96

22:6n–3

22:5n–3

20:5n–3

18:3n–3

22:5n–6

22:4n–6

20:4n–6

20:3n–6

18:3n–6

20:2 n–6

18:2n–6

24:1n–9

22:1n–9

20:1n–9

18:1 n–9

18:1 n–7

16:1 n–7

(continued on next page)

136 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

“Western pattern”diets (Northern Russia, Alaska, Greenland, Papua

New Guinea, Fiji, Nigeria, and the St. Helena Bay region of South Africa).

Moderate blood levels of EPA + DHA (yellow) were observed in North-

ern Canada (Cree/Inuit populations), Chile, Iceland, Finland, Sweden,

Tunisia, Hong Kong, Mongolia and French Polynesia. Europe had eight

countries with low EPA+DHA blood levels (Belgium, Czech Republic,

France, Germany, Scotland, Spain, and The Netherlands) while countries

from the middle East (Israel), Asia (China, Russia, and Singapore), Oce-

ania (Australia and New Zealand) and Africa (South Africa and Tanza-

nia) were observed to have low levels as well. Very low blood levels

were observed in North America (Canada and USA), Central and South

America (Guatemala and Brazil), Europe (Ireland, UK, Italy, Greece, Ser-

bia, and Turkey), the Middle East (Iran and Bahrain), Southeast Asia

(India) and Africa (Kenya). The map also clearly indicates there are sev-

eral regions with little to no blood fatty acid data for adult populations

meeting our inclusion criteria (shaded in gray). This included most of

Africa and the Middle East, Mexico and Central America, a considerable

amount of South America, and most of Eastern Europe and Central and

Southeast Asia.

4.3. Global distribution of individual n-3 LCPUFA

The levels of the individual n-3 LCPUFA were also examined against

the EPA+ DHA categories in the various blood fractions (Table 6). Each

data line was assigned a blood level group based on the methodology

used to determine groupings for the global map. Blood fractions were

kept separate in order to examine and compare the responses of the in-

dividual n-3 LCPUFA within blood fractions. The mean values of the per-

centagesof EPA, DHA and docosapentaenoic acid n-3(DPAn-3, 22:5n-3)

within a blood level category for each blood fraction were calculated.

DPAn-3 values were not reported as frequently as EPA or DHA (see de-

tails in Table 6 footnotes).In order to assist incomparing the response of

EPA and DHA, the ratio of DHA to EPA, and the percentage of DHA in

EPA+ DHA was calculated. In general, DHA was the dominantcontribu-

tor to EPA+ DHA, but the relative amount of EPA tended to increase

more as EPA+DHA status reached the highest category. The amount

of DHA relative to EPA also tended to be higher in the blood fractions

that were dominated by glycerophospholipids (plasma phospholipids

and erythrocytes), while blood fractions with triacylglycerols and

cholesteryl ester components (plasma total lipids and whole blood)

had slightly lower percentages of DHA. These latter blood fractions,

tended to show shifts towards an increasing relative amount of EPA as

EPA+ DHA status increased as one ascended the categories, while the

relative amount of EPA did not increase in glycerophospholipid based

blood fractions until the high EPA + DHA blood level (green) was

reached. While DPAn-3 also appeared to increase with EPA+DHA sta-

tus, the increases tended to be relatively small in scale and absolute

amount.

5. Discussion

This is the ﬁrst systematic review to examine blood levels of omega-

3 LCPUFA (speciﬁcally EPA+ DHA) for different countries/distinct re-

gions on a global scale. While the present review reveals considerable

variability in blood levels of EPA +DHA, it also suggests that EPA +DHA

blood levels are in the very low to low range for most of the globe espe-

cially when the population size of the countries [315] with very low and

low blood levels of EPA+DHA are considered. There were several limi-

tations and challenges in generating a global map of blood levels of

EPA+ DHA. This included numerous countries without data, data that

1Data in italics and highlighted in grey is not expressed as weight % as not enough data was published in original manuscript to allow conversion

2Data is ug/mL

3Weight % data calculated from concentration data in original manuscript

4Weight % data calculated from mole % data in original manuscript

CAN–CI, Canada –Cree/Inuit; NLD, The Netherlands; PNG, Papua New Guinea; Russia–IN, Russia Indigenous; S. Arabia, Saudi Arabia; SHB–SA, St. Helena Bay South Africa; S. Africa, South Africa; S. Korea, South Korea; UK,

United Kingdom; USA, United States of America; USA–AY, United States of America –Alaskan Yupik.

Africa

Yeh (1996)3[298] Nigeria 397 0.99 29.37 7.32 2.11 23.51 24.87 0.26 1.17 4.74 0.25 1.80 3.62 5.42

Schloss (1997) [250] SHB–SA 25 0.44 22.12 8.03 1.61 20.50 29.72 0.85 5.78 0.31 0.41 3.93 0.50 5.56 9.49

Schloss (1997) [250] S. Africa 25 0.72 22.24 7.85 1.91 20.80 33.50 1.52 6.10 0.71 0.35 0.66 0.29 2.97 3.63

Pauletto (1996) [219] Tanzania 53 27.10 8.30 22.60 15.00 1.15 9.70 0.60 0.30 2.30 1.10 5.70 8.00

Pauletto (1996) [219] Tanzania 53 25.60 7.70 23.40 23.90 1.74 8.30 0.30 0.60 0.70 0.60 1.50 2.20

Barkia (2011)3[32] Tunisia 25 0.65 22.95 6.85 0.15 0.89 0.89 1.29 1.46 19.41 0.25 32.54 0.13 0.07 5.41 0.67 6.30

Sfar (2010) [253] Tunisia 200 18.87 5.17 17.88 39.23 6.94 0.79 0.95 3.10 4.05

North America

Rode (1995) [239] CAN–CI 145 21.62 0.90 4.17 0.44 5.24 1.44 3.65 8.89

Dodin (2008) [71] Canada 175 1.07 23.41 6.58 2.66 2.09 23.39 30.18 5.02 0.60 0.79 0.36 1.10 1.89

Fortier (2010) [81] Canada 51 1.00 23.60 7.60 2.30 1.80 22.30 29.80 1.50 6.40 0.80 0.70 0.40 1.50 2.20

Metherel (2009) [190] Canada 16 1.03 22.69 6.32 0.12 0.31 0.26 2.58 2.02 20.80 0.18 0.43 28.17 0.31 1.47 5.83 0.20 0.18 0.56 0.34 0.36 1.20 1.54

Metherel (2012) [191] Canada 8 1.00 20.95 7.29 0.17 0.46 0.46 1.88 1.81 18.63 0.16 0.10 0.64 29.75 0.44 0.25 1.62 7.47 0.24 0.19 0.80 0.67 0.58 1.75 2.42

Patenaude (2009)3[218] Canada 37 1.00 22.57 6.84 0.51 2.05 22.24 0.75 30.17 0.18 1.47 7.44 0.78 0.73 1.62 2.34

Philibert (2006)3[223] Canada 243 24.19 0.57 1.33 1.90

Austria (2008)2[28] Canada 25 11 16 23 39

Parkinson (1994) [217] USA–AY 20 16.61 7.51 2.54 18.22 30.57 0.16 0.55 5.27 0.41 6.41 5.22 11.63

Parkinson (1994) [217] USA–AY 20 16.38 7.56 2.00 17.88 36.25 0.20 0.72 4.12 0.51 3.03 3.98 7.01

Bagdade (1992) [29] USA 12 1.25 1.94 3.19

CDC (2012)3[226] USA 1808 1.28 32.83 9.30 0.35 1.11 0.94 2.61 1.95 28.02 0.20 0.06 1.30 0.99 0.62 0.31 2.19 11.16 0.39 0.31 0.83 0.61 0.65 1.94 2.55

Conklin (2007)3[51] USA 105 30.12 7.91 0.60 0.56 1.44 2.00

Gong (1992) [88] USA 91 21.48 9.93 17.24 28.15 0.32 1.41 6.35 1.27 0.49 0.36 1.34 1.83

Harris (2004) [98] USA 106 30.60 0.50 0.20 1.60 8.00 0.30 0.20 0.60 0.60 0.50 1.50 2.10

Hibbeln (1998)3[106] USA 49 32.30 7.26 0.21 0.56 0.56 1.62 2.19

Hoffman (1993) [113] USA 20 28.86 0.43 0.41 2.28 8.98 0.50 0.28 0.44 0.56 0.63 1.99 2.55

Ito (1999)3[120] USA 124 24.96 8.17 22.46 0.81 30.85 1.60 7.56 0.75 0.97 1.88 2.85

Keenan (2012)4[131] USA 30 0.58 20.62 9.78 1.12 16.52 0.27 30.76 0.44 0.44 2.69 11.13 0.55 0.42 0.68 0.59 0.88 2.52 3.12

Kelley (2008) [132] USA 24 1.30 22.30 6.20 1.52 21.85 26.94 1.50 5.90 0.25 0.32 0.77 0.92 0.69 1.18 2.10

Lewis (2011) [162] USA 800 0.41 18.29 7.01 0.33 1.05 0.87 1.51 2.41 22.53 0.71 1.15 31.39 0.41 0.26 1.68 7.29 0.32 0.24 0.55 0.45 0.48 1.19 1.64

Meydani (1991) [192] USA 23 0.67 1.77 2.44

Motoyama (2009) [194] USA 261 30.10 8.90 0.80 0.70 2.40 3.20

Motoyama (2009) [194] USA 212 30.70 8.90 1.10 0.70 3.30 4.40

Parkinson (1994) [217] USA 13 20.80 6.42 2.25 21.25 32.92 0.36 1.34 5.97 0.57 0.46 1.49 1.95

Sekikawa (2008) [251] USA 281 30.80 8.90 0.40 1.00 3.20 4.20

Sekikawa (2008) [251] USA 306 29.90 9.00 0.30 0.80 2.40 3.20

Sun (2007) [268] USA 132 0.58 19.31 7.29 1.94 18.60 30.58 7.80 0.50 0.49 0.44 1.56 2.05

Surette (2004)3[271] USA 11 1.38 27.39 10.08 1.96 24.23 0.14 25.68 0.41 1.51 4.57 0.24 0.79 0.30 0.32 1.00 1.30

Zhao (2012)3[303] USA 23 25.59 12.06 1.53 17.70 32.13 0.52 7.47 0.72 0.50 1.78 2.28

Johnson (2008)2[125] USA 49 20

Sublette (2011)2[266] USA 27 22 21 62 84

Bloomer (2009)2[35] USA 14 82735

Harper (2006)2[97] USA 49 25 401 192 5 7 6 26 34

High (2003)2[107] USA 16 427 12 28 164 9 37 46

Maki (2009)2[177] USA 76 51 111 161

Sublette (2007)2[265] USA 10 352 25 68 94

Central and South America

Brignardello (2011) [38] Chile 12 1.31 22.20 8.82 2.01 20.40 30.40 1.59 6.20 0.57 0.88 2.30 3.18

Table 2(continued)

137K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

was limited to small sample sizes or data that was excluded because it

did not meet criteria, but also the challenge of considerable variability

in how fatty acid “levels”are reported. In addition, implications of the

present ﬁndings in terms of dietary intake and health outcomes as

well as the challenge of increasing EPA+ DHA blood levels must be con-

sidered. These topics will be taken up in the following sections.

Table 3

Global fatty acid compositions of plasma phospholipids expressed as relative percentages.

Author (Year) Ref Country n

14:0

16:0

18:0

20:0

22:0

24:0

EPA+DHA

Asia

Huang (2012) [116] China 940 23.58 11.05 0.32 1.36 1.08 5.49 6.85

Zheng (2012) [304] China 100 0.36 28.26 14.51 0.37 0.49 1.25 8.69 0.93 0.45 0.73 21.01 0.61 0.39 2.10 9.15 0.22 0.23 0.15 1.48 0.79 5.79 7.27

Hamazaki–Fujita (2011) [96] Japan 54 29.00 16.10 8.30 20.40 8.60 0.17 1.60 5.80 7.40

Hojo (1998) [114] Japan 60 27.30 14.50 10.80 14.70 7.30 4.50 10.00 14.50

Kawabata (2011) [130] Japan 104 19.70 1.70 7.60 0.20 2.30 0.90 5.60 7.90

Kobayashi (2001) [139] Japan 87 28.70 15.10 8.80 17.30 6.40 0.20 3.70 1.20 7.30 11.00

Kurotani (2012) [148] Japan 437 28.40 15.80 0.70 10.00 21.40 2.20 9.90 2.30 1.07 7.50 9.80

Kusumoto (2007) [149] Japan 24 27.80 13.70 8.05 2.03 17.70 9.52 3.07 1.35 8.63 11.70

Moriguchi (2004) [193] Japan 234 2.86 3.08 5.94

Watanabe (2009) [292] Japan 17 24.50 12.30 9.60 18.80 9.40 3.60 8.60 12.20

Gerasimova (1991) [86] Russia 34 26.70 13.50 1.10 12.40 21.70 10.90 1.90 1.40 5.20 7.10

Gerasimova (1991) [86] Russia–IN 11 28.50 11.20 4.40 16.80 12.30 4.60 5.40 1.50 5.50 10.90

Kim (2012) [136] S. Korea 215 27.30 14.80 1.05 0.78 7.80 13.90 0.25 1.36 2.72 6.60 0.57 2.90 8.80 11.70

Oceania

Hodge (1993)2[112] Australia 7 28.83 11.97 1.27 13.33 26.84 3.45 9.34 0.27 0.36 0.63 0.73 2.99 3.63

Hodge (2007) [111] Australia 4439 25.30 0.43 9.70 20.20 10.40 0.17 1.10 4.10 5.20

James (2003) [124] Australia 44 1.16 1.39 3.60 4.76

Mantzioris (2000) [179] Australia 15 21.00 9.54 0.19 0.98 1.14 3.16 4.14

McNaughton (2007)2[185] Australia 43 26.53 14.71 9.83 20.94 10.59 0.12 0.84 1.11 3.70 4.54

Metcalf (2003) [189] Australia 16 9.80 20.90 0.23 1.13 1.39 3.76 4.89

Stough (2012) [264] Australia 39 3.45

Dewailly (2008) [68] PYF 116 1.10 5.01 6.11

Crowe (2007)3[56] N. Zealand 2416 0.52 35.38 17.82 2.08 23.14 3.51 9.48 0.68 0.69 0.30 1.36 1.29 3.76 5.12

Middle East

Khanaki (2012) [134] Iran 74 0.26 48.53 13.35 0.39 6.28 19.66 7.23 0.35 0.36 0.70 1.06

Europe

Crispim (2011) [55] Belgium 123 5.30

Maes (1999) [174] Belgium 14 22.11 0.21 0.30 2.24 9.25 0.46 0.24 0.22 1.08 0.94 3.81 4.89

Rodriguez (2004) [240] Belgium 26 0.36 28.38 12.40 0.62 1.19 0.50 1.66 8.71 2.28 20.20 0.33 9.20 0.26 0.22 1.08 0.75 3.61 4.68

Crispim (2011) [55] CZE 118 4.20

Hlavaty (2008)3[110] CZE 39 0.34 27.53 13.04 0.03 0.74 1.60 12.31 0.14 21.89 0.08 0.48 3.21 11.64 0.30 0.20 0.22 1.08 0.85 4.32 5.40

Astorg (2009) [25] France 222 0.51 27.11 12.74 0.22 0.35 0.30 0.78 1.79 9.94 0.18 0.45 22.19 0.11 0.34 2.62 10.02 0.28 0.27 0.25 1.10 0.91 4.31 5.41

Crispim (2011) [55] France 111 5.50

Delyfer (2012) [66] France 107 18.70 3.00 0.30 12.00 0.20 1.20 0.90 4.50 5.70

Saadatian–Elahi (2009) [244] France 96 0.26 24.80 14.30 0.03 0.70 1.50 9.40 0.19 22.30 0.08 0.36 3.30 12.50 0.37 0.25 0.16 1.40 1.14 6.30 7.70

Geppert (2005) [85] Germany 108 28.10 12.00 0.66 10.30 22.00 0.11 3.40 8.90 0.41 0.35 0.21 0.57 0.87 2.70 3.27

Geppert (2008) [84] Germany 39 0.10 3.27 9.38 3.21

Saadatian–Elahi (2009) [244] Germany 386 0.28 25.90 14.20 0.02 0.70 1.50 10.20 0.21 22.70 0.10 0.36 3.40 11.80 0.37 0.26 0.21 1.20 1.12 4.60 5.80

Saadatian–Elahi (2009) [244] Greece 191 0.21 24.50 14.30 0.04 0.45 1.55 11.75 23.20 0.09 0.33 3.70 11.00 0.33 0.24 0.13 1.05 5.45 6.50

Saadatian–Elahi (2009) [244] Italy 578 0.24 25.20 14.10 0.03 0.50 1.60 11.90 0.17 21.00 0.10 0.34 4.00 12.40 0.41 0.34 0.14 0.90 0.93 4.60 5.50

Di Stasi (2004)4[70] Italy 36 0.65 3.30 3.95

Masson (2013)4[181] Italy 1203 0.11 0.85 0.78 3.37 4.22

Leng (1994) [160] Scotland 122 28.00 10.30 13.06 25.86 0.01 2.81 9.14 0.18 0.17 0.31 1.45 0.91 3.89 5.34

Leng (1999) [161] Scotland 770 12.63 24.37 2.96 9.27 0.31 1.42 3.81 5.23

Surai (2000) [270] Scotland 40 26.80 13.90 2.00 12.00 22.20 3.50 9.50 1.50 1.20 3.90 5.40

Saadatian–Elahi (2009) [244] Spain 193 0.19 23.80 15.10 0.03 0.40 1.60 11.90 0.16 21.90 0.09 0.36 3.60 11.90 0.34 0.24 0.11 1.10 0.77 6.00 7.10

Saadatian–Elahi (2009) [244] Spain 196 0.18 23.90 15.10 0.03 0.40 1.60 10.90 0.15 22.30 0.09 0.36 3.40 11.80 0.31 0.21 0.13 1.50 0.85 6.40 7.90

Saadatian–Elahi (2009) [244] Spain 194 0.19 24.20 14.70 0.03 0.50 1.50 10.80 0.16 23.00 0.09 0.35 3.30 12.00 0.33 0.22 0.11 1.30 0.80 6.10 7.40

Saadatian–Elahi (2009) [244] Sweden 388 0.28 25.90 13.80 0.02 0.60 1.70 11.20 0.23 22.00 0.07 0.34 3.10 10.00 0.28 0.17 0.28 1.80 1.24 5.80 7.60

Crispim (2011) [55] NLD 120 4.60

De Groote (2008) [64] NLD 46 0.84 3.09 3.93

deGroot (2007) [62] NLD 54 9.63 0.33 0.21 0.75 0.75 3.22 3.97

deGroot (2009) [63] NLD 234 21.83 0.08 3.18 9.61 0.29 0.23 0.18 0.99 0.92 3.45 4.43

Saadatian–Elahi (2009) [244] NLD 195 0.28 25.35 14.20 0.03 0.60 1.50 9.40 0.21 24.40 0.09 0.36 3.50 11.50 0.37 0.25 0.21 1.20 1.15 4.40 5.60

Sobczak (2004) [257] NLD 15 19.80 0.31 2.65 8.53 0.58 0.21 0.31 0.99 0.78 3.61 4.60

Tiemeier (2003) [276] NLD 461 21.80 3.30 9.00 0.90 0.90 3.70 4.60

van den Ham (2001) [285] NLD 88 23.48 8.97 0.32 0.18 0.55 2.94 3.49

Zuijdgeest–Van Leeuwen (2002) [308] NLD 45 29.00 14.84 24.69 3.16 11.16 1.24 1.11 4.10 5.34

Kew (2004) [133] UK 39 27.90 11.70 9.10 21.90 3.50 13.10 1.50 0.90 7.10 8.60

Rees (2006) [232] UK 155 21.20 2.95 9.00 1.20 1.00 4.00 5.20

Saadatian–Elahi (2009) [244] UK 195 0.27 25.40 14.10 0.03 0.70 1.60 10.50 0.28 23.10 0.09 0.37 3.40 10.60 0.33 0.20 0.23 1.70 1.30 5.40 7.10

Saadatian–Elahi (2009) [244] UK 195 0.19 23.10 14.90 0.06 0.40 1.70 10.20 0.21 27.50 0.08 0.48 3.00 12.30 0.54 0.28 0.24 0.70 1.17 2.40 3.10

Yaqoob (2000) [297] UK 40 1.80 7.40 0.60 3.10 3.70

Welch (2006)4[293] UK 4949 0.23 1.27 1.42 5.21 6.48

Scandinavia

Madsen (2011) [173] Denmark 40 9.03 2.11 5.32 7.43

Madsen (2011) [173] Denmark 50 9.03 2.22 4.92 7.14

Saadatian–Elahi (2009) [244] Denmark 196 0.25 26.00 14.00 0.03 0.70 1.70 10.40 0.20 21.60 0.07 0.32 2.90 10.70 0.29 0.15 0.24 2.20 1.27 6.20 8.40

Laasonen (2009)3[150] Finland 36 0.60 30.16 13.07 0.30 0.83 0.59 0.73 12.57 0.30 0.06 1.55 21.26 0.06 2.52 7.40 0.10 0.35 2.18 0.82 4.57 6.75

Nikkari (1995) [204] Finland 84 28.33 13.24 0.93 12.31 21.18 0.07 2.74 9.25 2.03 5.84 7.87

Valsta (1996) [284] Finland 39 0.60 31.20 14.10 0.80 1.95 11.75 22.40 2.25 7.25 1.45 0.90 5.25 6.70

Skuladottir (1995) [256] Iceland 119 0.66 30.43 14.38 0.53 12.14 19.26 1.83 5.53 2.28 1.13 4.31 6.59

Almendingen (2007) [18] Norway 160 34.39 15.38 0.42 9.00 25.64 7.26 0.07 1.85 5.98 7.83

Bonaa (1992) [36] Norway 146 23.10 13.40 0.50 10.50 3.50 2.00 20.10 2.60 8.00 1.00 0.20 3.30 1.50 8.30 11.60

Brude (1997)2[41] Norway 42 26.10 15.86 10.00 23.36 3.36 9.22 0.13 1.56 1.09 6.25 7.81

Crispim (2011) [55] Norway 121 7.10

Grønn (1991) [90] Norway 15 10.90 24.60 6.40 1.70 6.70 8.40

Grundt (1995) [91] Norway 57 21.30 8.50 2.60 8.05 10.65

Harvei (1997) [103] Norway 282 0.40 26.10 14.70 0.80 3.40 1.40 0.30 9.80 0.30 2.80 23.10 0.50 2.10 5.90 0.10 1.70 1.10 4.70 6.40

Haug (2012) [104] Norway 46 0.37 29.40 13.40 0.62 9.75 20.60 8.78 0.26 1.06 0.91 4.78 5.84

Hjartåker (1997) [109] Norway 234 0.35 25.61 13.71 0.30 0.89 0.50 0.39 9.30 0.30 1.04 24.67 0.38 2.96 8.75 0.23 0.09 0.19 1.98 1.33 6.92 8.90

Lindberg (2013) [163] Norway 214 0.33 24.10 13.30 0.66 2.43 0.99 20.20 0.47 3.07 8.85 0.58 0.13 0.23 2.17 1.29 7.10 9.27

Toft (1995)5[277] Norway 78 21 39 60

Ambring (2006)3[20] Sweden 22 28.81 12.95 0.60 1.85 1.39 0.42 9.18 3.58 21.60 0.05 0.27 3.42 7.84 0.21 1.68 6.16 7.83

Cederholm (1994) [47] Sweden 20 1.10 36.10 18.60 0.48 0.89 0.70 11.10 1.40 14.70 0.30 1.85 6.50 0.13 1.07 4.47 5.54

Gustafsson (1994) [93] Sweden 95 30.39 14.70 0.73 12.44 21.86 3.21 8.75 0.31 1.49 1.14 4.94 6.43

Lindqvist (2009) [164] Sweden 254 2.50 5.50 8.00

Wennberg (2011) [294] Sweden 434 1.37 4.63 6.00

Wennberg (2011) [294] Sweden 122 1.40 4.37 5.77

22:6n–3

22:5n–3

20:5n–3

18:3n–3

22:5n–6

22:4n–6

20:4n–6

20:3n–6

20:2 n–6

18:3n–6

18:2n–6

24:1n–9

22:1n–9

20:1n–9

18:1 n–9

18:1 n–7

16:1 n–7

(continued on next page)

138 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

5.1. Countries with limited, excluded or no data

Data was not found for most of Africa, Eastern Europe, the Middle

East and Central Asia, Southeast Asia, and Central and South America.

Based on the data in neighboring countries, it is most likely that blood

levels of EPA + DHA in Eastern Europe and Central Asia would fall in

the low to very low categories. Similarly, most of the countries in Central

and South America would most likely fall into the lower blood level cat-

egories, although some of the countries with large coastal populations

could fall into the higher categories. Africa might follow a similar pat-

tern as South America but the limited blood fatty acid data and the

small samples sizes reported for this continent make it difﬁcult to pre-

dict. For countries of Southeast Asia for which we found no data, it is

possible that many of them would have blood EPA+ DHA levels in the

higher categories. While these speculations are based on blood level

patterns in and surrounding these geographical regions, recently pub-

lished data on omega-3 PUFA intakes across theglobe (see detailed dis-

cussion below in Section 5.3) appear to support these assumptions [4].

In addition to countries without blood level data, there are several

countries with blood levels that are based on limited numbers of studies

and small sample sizes. While this can be expected for small or develop-

ing countries, it is a concern when large countries, with large popula-

tions such as Russia and India have limited data. For some of the

countries with limited or no data in this review, fatty acid compositional

data of human blood exists, but not for the general adult population.

While some data was excluded due to the study of blood fatty acids in

morbidity or disease, several studies were excluded because the partic-

ipants were pregnant women or children. For example, data on erythro-

cyte levels of pregnant women in Mexico is available [316], but we were

unable to ﬁnd data for the general adult population in Mexico. Also with

any systematic review, new studies meeting inclusion criteria may be

published after analysis is complete. However, new studies may not

change theglobal map assignments. For example, the EPA+DHA levels

recently presented in a large study (n = 826) examining the plasma

fatty acids of healthy students at the University of Toronto (Canada)

[317] conﬁrm the global map assignment for Canada based on prior

data.

Finally, there was evidence ofsigniﬁcant regional and cultural varia-

tion in blood levels of EPA+ DHA within certain countries. In particular,

populations living on coastal regions of countries, and populations that

traditionally rely on hunting, ﬁshing and gathering for sustenance

tended to have moderate to high blood levels of EPA+ DHA. This latter

observation tends to be supported by assessments of changes in the

consumption of omega-3 PUFA in North America with the expansion

of and dependency on industrial scale agricultural practices [318].It

was also interesting that there was a tendency of these populations to

be oversampled relative to the rest of the country, particularly in Russia,

but also in Canada. This could reﬂect a bias against funding towards the

collection of “normative”data that should be reconsidered, as standard

ranges are necessary as a reference for proper comparisons and estab-

lishing normal values.

5.2. Units for expressing fatty acid compositional data

The lack of a “gold standard”for measurement of fatty acid status in

human blood makes it very difﬁcultto compare studies across the globe.

The lack of a standardized method for measurement was ﬁrst highlight-

ed in 2004 by Harris and von Schacky when the omega-3 index wasﬁrst

proposed [313]. At the time, erythrocytes were identiﬁed as the poten-

tial standard of the future, but a widespread shift to erythrocyte fatty

acid analysis has not occurred. This is partly based on logistical chal-

lenges with erythrocyte sample preparation and storage [319–321].

The diversity in the choice of units for reporting fatty acid data also re-

mains a challenge. Based on studies included in this systematic review,

Table 3(continued)

Africa

Glew (2010) [87] Nigeria 51 0.22 30.20 12.90 0.18 0.41 1.09 10.00 0.43 19.90 0.14 0.38 3.51 14.10 0.79 0.63 0.18 0.42 0.92 3.14 3.56

Njelekela (2005) [205] Tanzania 36 0.70 28.20 14.90 13.80 13.60 5.80 0.70 1.10 1.40 2.50

Njelekela (2005) [205] Tanzania 37 0.30 27.80 15.50 13.80 14.10 7.00 0.90 1.10 1.20 2.30

Njelekela (2005) [205] Tanzania 32 0.50 27.20 15.30 15.50 15.10 4.80 1.00 0.80 0.50 1.30

North America

Allard (1997) [17] Canada 72 11.25 25.31 13.64 1.11 3.99 5.10

Conquer (1996) [53] Canada 24 26.60 13.00 22.40 3.00 9.30 0.28 0.25 0.26 0.60 0.92 2.30 2.90

Conquer (1999) [52] Canada 19 28.20 14.20 18.90 2.70 10.80 0.77 0.17 0.99 1.02 2.90 3.89

Conquer (2002) [54] Canada 10 26.30 14.20 9.30 20.80 4.10 11.80 0.33 0.01 0.20 0.95 0.92 3.30 4.25

Cunnane (1995) [57] Canada 10 0.40 0.80 1.10 3.60 4.40

Dewailly (2001) [69] Canada 1460 6.40 0.52 1.28 1.79

Garneau (2012) [83] Canada 198 0.17 1.08 0.95 3.21 4.29

Laurin (2003) [153] Canada 79 0.58 2.13 2.71

Liou (2007) [165] Canada 22 26.30 13.90 12.60 23.60 10.20 0.27 1.35 4.59 5.94

Metherel (2012) [191] Canada 8 0.55 28.44 16.14 0.40 1.10 1.06 0.46 1.69 8.05 0.16 0.10 1.39 19.33 0.08 0.32 2.73 9.89 0.37 0.40 0.20 0.73 0.84 2.75 3.48

Skuladottir (1995) [256] Canada 119 0.55 32.22 15.36 0.91 14.13 18.89 2.16 6.73 0.76 0.55 1.39 2.15

Stark (2000) [262] Canada 35 27.30 13.80 12.20 17.50 2.90 10.00 1.10 0.84 3.70 4.80

Stark (2002) [261] Canada 16 25.49 13.19 0.59 1.89 12.55 0.14 18.40 0.58 2.57 10.03 0.99 0.33 0.17 1.30 1.03 4.23 5.53

Stark (2004) [260] Canada 32 27.75 13.11 1.25 0.94 0.64 12.51 1.92 18.96 3.29 10.65 0.41 0.27 0.25 1.03 0.95 3.89 4.92

Dewailly (2002) [67] CAN–CI 917 0.86 9.16 3.02 12.18

Lucas (2009) [171] CAN–CI 698 18.50 9.30 0.21 0.93 0.74 3.10 4.03

Lucas (2009) [170] CAN–CI 297 18.30 6.30 0.20 3.50 1.40 5.30 8.80

Stark (2002) [261] Greenland 15 26.60 13.89 0.50 1.35 13.20 0.61 13.97 0.49 1.15 5.24 0.49 0.05 0.14 4.90 1.62 7.89 12.79

Antalis (2006) [23] USA 12 1.36 26.57 13.71 0.01 0.22 0.16 0.47 2.06 8.75 0.02 0.20 25.95 0.36 2.98 11.40 0.44 0.27 0.10 0.68 0.90 2.96 3.64

Arterburn (2007) [24] USA 12 21.65 0.11 0.38 3.36 13.40 0.60 0.33 0.22 0.72 0.94 3.22 3.94

Brasky (2011) [37] USA 1803 19.56 11.18 0.14 0.57 2.84 3.41

Cao (2006) [42] USA 19 4.23

Cunnane (2012)2[58] USA 10 27.14 16.43 0.57 9.79 16.50 11.43 0.07 0.64 0.79 3.36 4.00

de Oliveira Otto (2013) [65] USA 2837 21.40 12.00 0.18 1.00 1.00 4.20 5.20

Harris (2007) [100] USA 23 12.60 0.55 3.03 3.58

Lopez (2011) [168] USA 267 1.54

Mozaffarian (2011) [196] USA 2735 0.59 0.83 3.03 3.62

Mozaffarian (2013) [195] USA 2692 0.51 0.82 2.87 3.38

Muldoon (2010) [197] USA 280 0.16 0.49 1.52 2.01

Phinney (1990) [224] USA 100 12.53 0.33 1.11 8.87 23.90 0.47 3.41 12.81 0.21 0.59 3.59 4.18

Raatz (2009) [227] USA 10 0.37 26.38 12.32 8.87 25.47 0.14 11.06 0.28 0.53 0.77 2.37 2.90

Wang (2003) [291] USA 3309 25.40 13.30 0.64 8.60 22.00 0.11 3.32 11.50 0.15 0.56 2.80 3.36

Young (2011) [300] USA 17 21.53 9.25 0.29 0.81 2.22 3.03

Liu (2011)4[166] USA 265 0.50 1.53 2.03

Raatz (2013)4[228] USA 19 17.12 0.76 4.96 18.20 0.87 1.55 3.22 4.09

Young (2013)5[301] USA 17 286 123 4 11103041

Central and South America

Fillion (2011) [80] Brazil 243 0.44 1.98 2.42

Moriguchi (2004) [193] Brazil 160 1.47 1.06 2.53

1Data in italics and highlighted in grey is not expressed as weight % as not enough data was published in original manuscript to allow conversion

2Weight % data calculated from concentration data in original manuscript

3Weight % data calculated from mole % data in original manuscript

4Data is mole %

5Data is µg/ml

CAN–CI, Canada –Cree/Inuit; CZE, Czech Republic; NLD, The Netherlands; N. Zealand, New Zealand; PYF, French Polynesia; Russia–IN, Russia Indigenous;S. Korea, South Korea; UK, United Kingdom; USA, United States of

America.

139K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

Table 4

Global fatty acid compositions of erythrocytes expressed as relative percentages.

Author (Year) Ref Country n

14:0

16:0

18:0

20:0

22:0

24:0

EPA+DHA

Asia

Huan (2004) [115] China 100 23.30 13.70 1.40 1.70 3.90 0.20 11.50 0.79 3.60 12.10 1.40 11.30 2.10 0.51 1.80 1.06 1.70 5.30 6.36

Junshi (1990) [126] China 124 24.20 14.60 13.80 8.61 1.95 14.30 1.13 0.96 0.61 1.96 4.52 5.13

Junshi (1990) [126] China 124 24.00 15.50 12.30 8.85 3.01 13.50 4.08 0.44 0.29 2.68 2.78 3.07

Junshi (1990) [126] China 124 26.60 18.00 12.30 7.83 2.49 11.90 3.59 0.44 0.22 2.01 1.86 2.08

Junshi (1990) [126] China 124 26.00 15.80 13.00 7.93 2.76 14.20 2.93 0.37 0.26 1.95 2.46 2.72

Junshi (1990) [126] China 124 25.30 17.70 13.90 7.88 2.86 10.40 4.68 0.42 0.26 1.95 2.49 2.75

Junshi (1990) [126] China 124 23.00 15.50 12.80 10.04 2.86 13.90 3.81 0.31 0.26 1.98 2.84 3.10

Junshi (1990) [126] China 124 23.20 17.60 11.70 11.69 2.89 12.40 4.89 0.40 0.42 2.62 3.00 3.42

Junshi (1990) [126] China 124 26.20 15.40 14.40 9.04 2.73 11.30 4.49 0.35 0.33 1.44 3.65 3.98

Junshi (1990) [126] China 124 25.40 15.70 14.30 8.94 2.06 12.20 1.80 0.92 0.38 1.70 2.51 2.89

Junshi (1990) [126] China 124 23.00 14.50 13.90 7.16 2.14 13.20 1.67 0.92 0.55 2.12 3.25 3.80

Junshi (1990) [126] China 124 24.10 14.90 14.40 7.80 1.98 12.50 1.63 0.94 1.30 2.37 4.53 5.83

Junshi (1990) [126] China 124 23.90 16.00 14.70 8.44 2.60 11.90 3.62 0.38 1.02 2.04 5.85 6.87

Junshi (1990) [126] China 124 25.60 16.00 15.30 7.76 2.42 12.90 2.46 0.60 0.41 2.00 2.88 3.29

Junshi (1990) [126] China 124 24.30 16.50 15.20 7.59 2.45 13.00 2.65 0.72 0.40 1.92 2.70 3.10

Junshi (1990) [126] China 124 24.10 15.60 13.30 9.77 2.14 13.60 1.75 0.76 0.28 1.66 2.45 2.73

Junshi (1990) [126] China 124 23.90 15.20 15.20 9.15 3.14 13.40 3.77 0.53 0.29 1.95 2.65 2.94

Junshi (1990) [126] China 124 24.70 15.70 14.90 7.79 2.49 12.60 2.22 0.99 0.44 2.27 2.43 2.87

Junshi (1990) [126] China 124 31.30 17.20 15.70 9.27 2.68 13.20 2.69 0.55 0.47 2.62 2.65 3.12

Junshi (1990) [126] China 124 26.60 14.40 14.50 7.93 2.23 13.00 1.46 0.96 0.51 2.23 2.59 3.10

Junshi (1990) [126] China 124 26.00 15.20 13.40 9.65 2.43 13.80 2.02 0.65 0.40 2.27 2.31 2.71

Junshi (1990) [126] China 124 24.90 16.50 14.30 7.95 2.94 12.10 4.18 0.46 0.57 1.88 3.67 4.24

Junshi (1990) [126] China 124 23.70 16.00 13.60 9.04 2.42 14.00 2.44 0.80 0.53 2.64 2.49 3.02

Junshi (1990) [126] China 124 23.50 17.00 16.60 8.11 2.87 10.80 4.06 0.70 1.20 3.07 2.12 3.32

Junshi (1990) [126] China 124 22.70 17.30 15.90 7.97 3.24 11.10 5.16 0.67 1.06 3.01 2.11 3.17

Liu (2003) [167] China 37 25.97 21.36 13.07 13.94 2.31 17.18 6.12

Shannon (2007) [254] China 1030 18.73 13.93 0.20 0.93 10.50 0.35 12.17 0.08 12.08 0.27 0.60 1.86 4.92 5.52

Zhu (2013) [306] China 1574 14.60 0.12 0.40 1.40 13.80 3.04 1.71 0.21 0.34 1.67 3.97 4.31

Zhu (2013) [306] China 1636 13.60 0.11 0.38 1.27 12.00 2.24 1.33 0.29 0.57 1.80 4.85 5.42

Kale (2008) [127] India 46 20.08 16.54 9.68 3.53 10.86 1.40 14.68 0.19 0.17 2.98 2.79 2.96

Mehendale (2009) [186] India 30 0.30 20.43 15.70 10.25 3.42 11.51 0.14 1.53 14.96 3.53 0.15 0.25 2.74 2.99

Hamazaki (2006) [95] Japan 351 9.70 10.80 1.70 6.90 8.60

Itomura (2008) [121] Japan 456 1.60 6.80 8.50

Kawabata (2011) [130] Japan 104 9.25 1.10 11.25 0.15 1.60 2.03 6.30 7.90

Kuriki (2006)2[145] Japan 221 0.57 27.71 21.48 1.00 17.48 10.34 0.09 0.82 10.35 0.40 1.64 1.66 6.47 8.11

Watanabe (2009) [292] Japan 17 21.30 14.60 14.65 10.40 13.15 3.40 11.00 14.40

Kuriki (2007)3[146] Japan 357 31.70 8.70 1.30 1.10 4.60 5.90

Gerasimova (1991) [86] Russia 41 21.70 11.20 3.70 13.20 11.20 13.30 1.20 2.90 4.40 5.60

Iusupova (1995) [122] Russia 10 15.15 10.24 1.03 11.32 2.64 0.40 0.53 1.00 2.84 3.37

Gerasimova (1991) [86] Russia–IN 61 25.90 13.70 1.90 15.60 6.70 7.20 6.30 3.20 5.30 11.60

Novgorodtseva (2011) [208] Russia–PK 11 0.65 23.37 17.23 0.18 0.80 1.38 13.25 13.74 0.28 1.16 11.13 2.15 0.20 1.08 2.42 5.80 6.88

Novgorodtseva (2013) [207] Russia–PK 10 0.39 23.98 13.40 0.15 0.39 1.53 14.84 15.75 0.25 1.59 12.95 2.37 0.37 0.15 1.23 1.99 4.67 5.90

Zhukova (2009) [307] Russia–PK 1153 0.68 19.26 15.16 14.19 11.01 0.67 1.05 10.81 1.98 0.28 0.11 1.55 2.45 8.32 9.87

An (2009) [22] S. Korea 10 0.51 21.76 16.40 0.20 6.91 10.88 0.14 0.36 8.50 0.51 0.59 1.26 11.97 0.43 0.43 2.52 3.00 9.75 12.27

Lee (2008) [310] S. Korea 88 0.34 21.50 15.30 5.09 11.25 9.10 0.07 11.84 0.20 2.78 3.09 9.61 12.39

Park (2009) [215] S. Korea 50 11.81

Park (2009) [216] S. Korea 40 0.48 22.93 17.76 13.17 0.44 1.72 2.82 8.83 10.55

Park (2012) [214] S. Korea 88 0.42 22.20 17.82 0.29 13.41 12.13 0.16 14.82 0.29 1.49 2.72 7.98 9.47

Oceania

Brown (1991) [39] Australia 23 20.10 16.60 0.39 1.96 1.04 4.20 9.80 1.80 14.70 3.10 0.88 2.90 5.40 6.28

Coates (2009) [50] Australia 29 12.50 0.61 2.30 2.91

James (2003) [124] Australia 44 0.88 3.02 4.49 5.37

Murphy (2007) [199] Australia 86 6.90 11.10 0.58 2.00 3.61 4.19

Sullivan (2006) [267] Australia 53 0.43 2.08 4.06 4.49

Vaddadi (1996) [282] Australia 39 11.46 0.13 1.48 12.06 2.56 0.14 1.03 2.44 4.62 5.65

Sutherland (1995) [272] Fiji 154 0.90 27.90 15.00 13.80 3.30 9.90 0.60 1.20 10.60 3.40 1.40 2.30 2.20 5.80 8.10

Stonehouse (2011) [263] N. Zealand 41 0.57 19.60 14.90 11.20 7.72 11.10 0.13 0.83 1.62 5.19 6.02

Middle East

Freije (2009) [82] Bahrain 26 19.24 15.59 16.48 11.20 10.14 14.25 0.06 0.33 2.81 3.14

Green (2006) [89] Israel 22 11.25 0.38 1.48 14.85 3.67 0.58 0.19 0.59 2.48 5.62 6.21

Lemaitre (2008) [158] Israel 417 23.30 17.60 2.70 16.70 15.70 1.80 14.70 0.90 0.30 4.10 4.40

Europe

Berr (2009) [33] France 200 9.11 13.60 1.14 6.25 7.39

Caspar–Bauguil (2010) [44] France 20 22.82 17.23 0.30 14.72 11.71 0.05 1.77 16.53 3.11 0.65 0.13 1.04 2.44 6.10 7.14

Caspar–Bauguil (2012)2[45] France 25 23.71 17.50 0.36 14.60 11.83 1.76 16.92 3.10 0.16 1.03 2.67 6.35 7.39

Heude (2003) [105] France 219 19.16 13.06 11.07 9.14 13.57 1.15 6.34 7.49

Legrand (2010) [157] France 160 20.10 10.50 23.10 21.50 8.90 0.42 0.67 2.60 3.27

Sirot (2012) [255] France 382 20.80 24.80 14.60 11.60 11.40 0.20 0.74 1.70 4.03 4.77

Baghai (2011) [30] Germany 80 1.31 1.90 3.84 5.14

Dawczynski (2010) [61] Germany 40 6.57 14.40 0.07 0.68 1.52 2.71 3.39

Geppert (2005) [85] Germany 103 21.40 13.90 0.36 12.20 10.30 0.05 1.90 13.90 3.30 0.75 0.13 0.41 2.30 4.30 4.71

Kroger (2011) [143] Germany 2114 0.38 22.30 13.90 0.39 1.60 4.20 0.45 1.03 12.80 0.29 0.29 4.10 10.70 0.05 0.25 1.50 13.10 2.70 0.15 0.75 2.30 4.70 5.45

Imre (1994) [118] Hungary 5 27.50 19.40 17.20 11.20 18.90 5.70

Cazzola (2004)2[46] Italy 100 26.56 16.30 0.53 5.49 2.61 12.71 7.52 9.95 1.03 11.40 0.23 0.63 1.52 3.51 4.14

Guarini (1998) [92] Italy 40 0.41 22.62 17.61 0.49 1.74 5.06 14.64 0.26 10.52 0.28 19.47 0.18 0.75 5.78 6.53

Marangoni (2007) [180] Italy 10 21.22 11.05 18.39 19.17 1.64 9.54 0.24 0.33 0.95 3.18 3.51

Messa (2000) [188] Italy 40 28.40 17.40 17.10 12.50 11.30 0.57 1.54 3.40 3.97

Paloza (1996) [212] Italy 40 8.68 1.65 13.58 3.43 0.70 2.28 4.98 5.68

Rizzo (2012) [237] Italy 76 0.52 2.83 3.35

Leng (1999) [161] Scotland 770 19.58 10.20 1.04 7.59 0.25 0.68 2.37 3.05

Whalley (2004) [295] Scotland 60 10.90 0.80 2.10 4.60 5.40

Duricic (2007) [72] Serbia 15 0.70 26.70 13.40 0.10 0.55 21.60 0.10 1.80 15.60 0.30 0.50 0.80 9.30 0.40 0.20 0.80 0.80 2.70 3.50

Sala–Vila (2011) [245] Spain 198 0.77 22.47 14.25 0.21 0.20 0.53 17.64 0.30 0.56 13.42 0.12 1.93 16.52 0.17 0.94 1.81 6.09 7.03

Rusca (2009)4[242] Switzerland 48 12 71 83

Assies (2001) [309] NLD 14 0.47 25.75 17.78 0.44 12.31 0.03 3.55 11.61 0.03 0.24 1.87 14.13 2.56 0.47 0.11 0.47 1.99 3.77 4.24

De Groote (2008)5[64] NLD 46 0.53 3.04 3.57

van den Ham (2001) [285] NLD 83 12.07 11.10 2.83 0.42 0.55 3.13 3.68

Leeson (2002) [156] UK 326 0.47 3.06 3.53

Peet (1995) [221] UK 16 0.30 22.30 11.80 0.80 15.70 14.20 1.80 17.30 2.10 0.50 0.20 1.60 2.90 7.20 8.80

Peet (1998) [222] UK 15 0.32 19.50 18,1 0.70 15.75 10.54 1.80 14.20 3.90 1.64 0.24 0.86 2.50 5.43 6.29

Richardson (2003) [235] UK 25 12.17 0.03 1.42 11.69 1.72 0.21 0.12 0.86 1.83 4.28 5.14

Sanders (2006) [249] UK 79 19.80 16.50 0.30 14.10 11.30 1.80 16.35 3.00 0.45 1.20 2.86 6.30 7.50

Scandinavia

Lauritzen (2011) [154] Denmark 109 10.50 0.25 1.95 15.60 3.18 0.65 0.18 0.76 2.52 5.40 6.16

Paunescu (2013) [220] Greenland 118 14.89 0.11 0.50 1.71 5.41 0.06 0.11 0.27 4.81 1.48 7.32 12.13

Magnusardottir (2009) [175] Iceland 25 19.87 15.22 1.35 3.52 1.13 12.32 3.12 9.55 1.78 13.53 2.59 0.88 2.85 6.11 6.99

Thorlaksdottir (2006) [274] Iceland 99 20.17 15.25 1.21 3.21 12.08 2.95 10.90 1.63 13.02 2.25 1.45 3.16 7.31 8.76

Dahl (2011)6[59] Norway 53 43 56 145 188

16:1 n–7

18:1 n–7

18:1 n–9

20:1n–9

22:1n–9

24:1n–9

18:2n–6

18:3n–6

20:2 n–6

20:3n–6

20:4n–6

22:4n–6

22:5n–6

18:3n–3

20:5n–3

22:5n–3

22:6n–3

(continued on next page)

140 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

the apparent preferred manner for presenting fatty acid data is as rela-

tive weight % of the total fatty acids. The advantage of relative percent-

age data is that it simpliﬁes the comparisons of the complex interactions

between fatty acids competing for positions in the blood lipidome and

allows for an assessment of the “quality”of the fat. However, as a “rela-

tive”unit, percentage fatty acid data should be presented as full fatty

acid proﬁles to allow proper interpretation of the changes in the proﬁle.

A limitation of relative percentage data is that it can obscure and poten-

tially mask changes in the size of lipid pools. In the blood of normal,

healthy adults, the changes in lipid pools in blood should be minimal

in erythrocytes and plasma phospholipids. However, the plasma total

lipid pool is subject to considerable biological variation even in healthy

populations based largely on lipoprotein status, particularly in the triac-

ylglycerol content even when fastingand feeding is controlled [191,314,

322]. The use of relative percentage units also presents a challenge for

performance elements and validation methods for standardized clinical

testing as limits of detection and repeatability are measures based on

absolute concentrations of individual analytes [323]. While the

omega-3 index increased awareness and the clinical use of omega-3

biomarkers [324], it has likely contributedto the practice of not present-

ing relative percentage data as full fatty acid proﬁles particularly in large

intervention trials focused on clinical outcomes [325,326]. The omega-3

index was initially described as the sum of the relative weight percent-

age of EPA+DHA with respect to the total fatty acids in erythrocytes

[313], but total fatty acids is a vague term and the sum total of fatty

acids can differ depending on the expertise of the chromatographer

and the little discussed practice of reporting data as total fatty acids

“identiﬁed”vs. total fatty acids that include peaks that were not identi-

ﬁed (the sum of the total peak area). Also, total fatty acids available for

analyses can also be inﬂuenced by sample preparation techniques, par-

ticularly extraction and derivitization protocols [311], but also analytical

practices with gas chromatography and data handling such as the appli-

cation of response factors [327]. The increasing use of whole blood as

dried blood spots has further complicated the ability to standardize

“the omega-3 index”as whole blood measures are mathematically

translated based on calculations based on the relationship to the

omega-3 index in erythrocytes [328]. Unfortunately, detailedmethodol-

ogies employed are not consistently reported in the literature. Therefore

a standardized measure of omega-3 status across laboratoriescapable of

fatty acid determinations does not currently exist and authors must be

encouraged to provide more details on how relative percentage data

were calculated. In addition, authors should be encouraged to include

an internal standard in their analyses so as to allow the report of the

concentration of total fatty acids in addition to the weight % data as it al-

lows for the conversion of fatty acid data between different units of

measure and therefore enables literature comparisons.

In this review, studies using the fatty acid composition of plasma

total lipid, plasma phospholipid, erythrocytes and whole blood were in-

cluded. Fatty acid data from serumfractions were considered equivalent

to data from plasma fractions, and data from erythrocyte phospholipids

and erythrocyte membrane preparations were considered equivalent to

data fromerythrocytes. There are several other blood fractions that have

been examined in the literature, but they were not included in the pres-

ent review due to limited prevalence and an increased challenge to

translate the data to erythrocyte EPA+ DHA equivalents. These include

mononuclear cells and platelets but also phosphatidylcholine,

cholesteryl ester, nonesteriﬁed fatty acid, and triacylglycerol fractions

in plasma [321,329].The relationship between EPA + DHA levels in

cholesteryl ester, nonesteriﬁed fatty acid, and triacylglycerol fractions

in plasma and levels in erythrocytes has been shown to be weaker

than those between the pools examined presently [314]. Although, the

number of studies reporting whole blood EPA+DHA data were much

smaller, whole blood data was included as this type of analysis is in-

creasing and will likely become a very common method in the future

as dried blood spot blood collections enable economical high through-

put fatty acid proﬁling [311]. The ease of collection and processing for

dried blood spot sampling has great potential for ﬁeld studies [191,

311,330,331] particularly in developing countries where scientiﬁc re-

sources are limited [332]. Dried blood spotting also has the potential

to solve challenges around the storage of blood samples [191,319,320].

Table 4(continued)

Africa

Knoll (2011) [138] Kenya 18 0.42 28.22 11.78 0.50 17.06 12.93 0.07 13.66 0.16 0.84 2.84 2.23 3.07

North America

Edwards (1998) [74] Canada 14 0.12 0.73 2.03 4.72 5.45

Kröger (2009) [142] Canada 514 0.64 3.58 4.22

Lucas (2009) [169] Canada 65 9.99 12.80 0.18 0.86 2.33 3.73 4.50

Metherel (2009) [190] Canada 16 0.69 22.89 13.21 0.26 1.04 2.80 0.36 1.47 12.76 0.27 2.74 9.83 0.01 1.48 12.16 3.06 0.32 0.12 0.35 1.77 2.98 3.33

Metherel (2012) [191] Canada 8 1.40 21.84 12.48 0.32 1.37 4.31 0.25 1.31 11.82 0.24 0.08 3.74 10.18 0.04 0.26 1.46 13.70 3.34 0.57 0.16 0.65 2.39 4.03 4.68

Nagasaka (2014)2,7 [200] Canada 649 0.39 26.00 21.51 0.26 0.43 1.09 13.75 2.07 19.30 3.51 0.56 0.24 1.29 3.35 6.25 6.23

Barcelo–Coblijn (2008)3[31] Canada 62 13.68 18.01 2.60 0.36 0.74 2.18 3.09 3.83

Lucas (2010) [172] CAN–CI 649 10.50 1.77 11.50 0.44 0.03 1.67 2.17 5.39 7.06

Valera (2011) [283] CAN–CI 181 2.10 6.70 8.80

Zhou (2011) [305] CAN–CI 2200 1.10 1.40 2.60 3.70

Thorseng (2009) [275] Greenland 452 0.18 2.70 2.10 6.40 9.10

Ebbesson (2010) [73] USA–AY 707 20.90 0.80 0.20 1.70 2.20 6.70 8.90

Makhoul (2011) [176] USA–AY 330 2.80 6.80 9.60

O'Brien (2009) [209] USA–AY 496 2.40 6.40 8.80

Antalis (2006) [23] USA 12 0.27 21.11 15.10 0.34 0.30 2.06 14.32 0.19 0.20 12.90 0.30 1.60 15.75 4.31 0.71 0.56 2.71 4.65 5.21

Arterburn (2007) [24] USA 12 13.70 0.08 0.32 1.73 14.29 3.94 0.51 0.18 0.57 2.00 3.53 4.10

Aupperle (2008) [27] USA 33 0.23 20.01 16.19 0.20 0.23 1.68 0.21 11.96 1.20 1.62 11.40 0.04 0.24 1.05 17.15 4.14 0.76 0.09 0.41 2.13 3.76 4.17

Block (2008) [34] USA 768 0.72 3.53 4.25

Cao (2006) [42] USA 9 0.60 1.80 3.80 4.40

Harris (2007) [100] USA 23 15.75 0.90 3.28 4.18

Harris (2008) [99] USA 33 0.47 3.67 4.14

Harris (2012) [101] USA 291 0.34 21.50 17.70 0.44 0.38 13.80 0.23 0.43 11.00 0.06 0.29 1.65 16.80 3.83 0.70 0.20 0.60 2.59 4.76 5.36

Hoffman (1993) [113] USA 20 12.60 0.04 0.41 1.99 16.24 4.73 0.87 0.11 0.43 2.27 3.91 4.34

Keenan (2012)2[131] USA 30 0.24 19.25 18.31 0.21 13.13 0.30 13.04 0.10 0.35 1.97 19.60 4.99 1.02 0.14 0.41 2.72 4.23 4.63

Kelley (2008) [132] USA 20 0.33 26.64 11.91 2.11 17.09 13.53 1.82 13.56 3.61 0.48 0.18 0.47 1.77 2.69 3.16

Ladesich (2011) [151] USA 228 0.35 21.00 18.00 0.38 0.32 14.00 0.16 0.38 12.00 0.11 0.24 1.60 17.00 4.00 0.74 0.20 0.53 2.60 4.10 4.63

Lemke (2010) [159] USA 252 16.95 0.45 2.55 3.85 4.31

McNamara (2010) [184] USA 20 16.90 16.40 1.20 11.90 10.90 1.50 16.90 4.00 0.80 0.40 2.30 4.40 4.80

Newcomer (2001) [203] USA 156 9.53 14.04 0.19 0.61 4.17 4.78

Sun (2007) [268] USA 132 0.19 18.65 13.14 0.49 13.26 13.66 14.63 0.18 1.15 1.85 3.71 4.86

Reddy (2004)8[231] USA 31 317 339 60 40 69 61

Central and South America

Elizondo (2007) [75] Chile 8 0.88 16.80 19.50 1.24 1.32 2.27 7.81 0.85 17.20 1.75 0.58 2.61 7.12 15.20 17.81

Solomons (2015) [259] Guatemala 158 0.71 27.09 9.66 0.36 0.87 1.57 15.80 0.22 0.30 16.37 0.11 2.58 12.88 3.79 0.84 0.27 0.35 1.78 3.09 3.43

1Data in italics and highlighted in grey is not expressed as weight % as not enough data was published in original manuscript to allow conversion

2Weight % data calculated from mole % data in original manuscript

3Data ismole %

4Data is µg/mL

5Weight % data calculated from concentration data in original manuscript

6Data is µg/mg

7EPA+DHA was presented as weight % in original manuscript

8Data is nmol/mL

CAN–CI, Canada –Cree/Inuit; NLD, The Netherlands; N. Zealand, New Zealand; Russia–IN, Russia Indigenous; Russia–PK, Russia Primorsky Krai;S. Korea, South Korea; UK, United Kingdom; USA, United States of America;

USA–AY, United States of America–Alaskan Yupik.

141K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

5.3. Diet and blood

Blood levels of EPA+DHA have long been known to correspond to

dietary intakes of EPA+ DHA [139,190,333,334]. Recent studies exam-

ining the determinants of blood levels of EPA and DHA consistently in-

dicate that diet is the main predictor although other factors such as

age, smoking, sex, and physical activity are commonly identiﬁed as pre-

dictors as well [8–12]. In addition, genotyping studies have linked single

nucleotide polymorphisms of FADS1, FADS2, FADS3 and ELOVL2 [335–

337] to slightly increased levels of EPA+ DHA. Recently a unique FADS

haplotype more efﬁcient at biosynthesizing DHA has been identiﬁed

in humans as compared with hominid ancestors [335], and supports

the hypothesis that DHA was important for the evolution of the

human brain [338]. The complex relationship between dietary fatty

acid intake and blood levels of long chain PUFA including EPA and

DHA were ﬁrst empirically deﬁned by Lands et al. in rats [339], adapted

to humans [340] and then further revised as data from other

populations became available [341]. Despite these robust equations,

this previously deﬁned relationship between dietary intake and blood

levels is often forgotten when examining increases in EPA + DHA in

blood relative to prescribed dose in dietary intervention studies [342].

Recently, the simple relationship between dietary EPA + DHA and

blood levels of EPA+ DHAhave been examined and it appears thatsim-

ple linearequations can be used to deﬁne the blood-diet EPA+ DHA for

intakes typical of Western populations and possibly higher intakes

[343].

Global intakes of dietary fats and oils derived from nutrition surveys

have been examined at thenational level for adults recently that includ-

ed a map of seafood omega-3 fat intake [4]. As suspected, the seafood

omega-3 map shares several similarities with the map of blood levels

presented herein (Fig. 2), but there are also distinctive differences. The

seafood omega-3 fat intake is more comprehensive as intake data was

available for Africa, Eastern Europe, the Middle East and Central Asia,

Southeast Asia, and Central and South America, where we were unable

Table 5

Global fatty acid compositions of whole blood total lipids expressed as relative percentages.

Author (Year) Ref Country n

14:0

16:0

18:0

20:0

22:0

24:0

EPA+DHA

Europe

Rizzo (2010) [238] Italy 300 22.63 11.28 1.50 23.97 21.61 1.95 11.19 0.45 1.05 1.26 3.11 4.16

Rizzo (2012) [237] Italy 76 1.04 2.89 3.93

Scandinavia

Jabbar (2006) [123] Sweden 18 1.12 25.65 11.11 0.38 2.79 1.96 1.88 19.84 21.09 1.35 6.93 0.55 0.70 1.19 2.62 3.81

North America

Fratesi (2009) [6] Canada 15 2.50 28.70 11.40 0.40 0.70 1.00 2.20 1.80 15.10 1.00 16.20 0.40 0.70 1.10 6.40 0.60 0.50 0.80 0.70 1.90 2.70

Metherel (2009) [190] Canada 16 0.85 22.45 9.68 0.17 0.47 0.90 1.71 1.86 18.12 0.28 1.00 21.90 0.19 1.50 8.79 1.29 0.32 0.41 0.34 0.93 1.87 2.21

Metherel (2012) [191] Canada 8 0.98 22.63 12.29 0.34 0.88 1.40 1.31 1.62 16.18 0.19 0.29 1.42 22.05 0.33 0.24 1.48 9.35 1.10 0.29 0.60 0.61 1.00 2.04 2.65

Patterson (2012) [5] Canada 78 0.61 1.95 2.56

Albert (2002) [14] USA 184 18.80 10.60 17.00 24.20 10.60 0.37 1.84 1.01 2.38 4.22

Hall (2007) [94] USA 282 24.36 9.93 0.36 1.87 0.96 2.27 4.14

Harris (2007) [102] USA 94 0.57 1.84 2.41

Pottala (2010) [225] USA 956 3.80

Ramsden (2010) [229] USA 15 23.20 0.20 1.59 7.17 0.33 0.46 0.46 0.97 2.71 3.17

USA, United States of America.

22:6n–3

22:5n–3

20:5n–3

18:3n–3

22:5n–6

22:4n–6

20:4n–6

20:3n–6

20:2 n–6

18:3n–6

18:2n–6

24:1n–9

22:1n–9

20:1n–9

18:1 n–7

18:1 n–9

16:1 n–7

Fig. 2. Global blood levels of the sum of eicosapentaenoic acid and docosahexaenoic acid. *Fatty acid composition data from plasma total lipids, plasma phospholipids and whole blood

were assigned to categorical ranges that were estimated as equivalent to erythrocyte categories [314].

142 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

to ﬁnd EPA+ DHA blood data, although the one exception was the in-

clusion of blood data for Greenland where no dietary survey data was

reported. While low to high blood categorizations tend to agree with

low to high diet intake categorizations, there were some notable excep-

tions. A disconnect between dietary intake and blood levels could be the

result of documented limitations of determining fatty acid intakes from

databases [5], but it may also be due to challenges in blood fatty acid

analysis. Countries with the highest seafood omega-3 intake consump-

tion included the Paciﬁc island nations, the Mediterranean basin, Ice-

land, South Korea and Japan. Blood EPA+ DHA levels were also high in

South Korea, Japan, and the few countries we had for Paciﬁcislandna-

tions, but blood levels of EPA+DHA for the Mediterranean basin were

low to very low while Iceland blood levels were moderate. Given dietary

levels, moderate blood levels of EPA+ DHA for Iceland were somewhat

surprising and more data may be required to conﬁrm this assessment.

One of the four studies for Iceland that indicated moderate blood levels

of EPA+DHA in erythrocytes stored the blood samples at −20 °C for

15 weeks [175] which is known to promote EPA +DHA losses [319].

However, prior to storage, butylated hydroxyltoluene was added to

the samples that have the potential to protect samples from decreases

in EPA+ DHA [320,344]. In addition, one of the Icelandic studies was a

direct comparison to populations from Japan and Korea and while the

per capita consumption of ﬁsh and shellﬁsh was the highest in Iceland,

measured blood levels of EPA+ DHA were high in the Japan and South

Korea samples and moderate in the Iceland sample [252].FortheMed-

iterranean Basin, it is difﬁcult to determine the cause of discrepancies

between intakes of seafood omega-3 fat and blood levels. Blood level

data was available from several studies for these countries. The low

blood levels could indicate a bias in regard to the type of populations

that were sampled. For example, blood sampling itself might lend itself

to urban centers where the chance of shifts away from more traditional

diets is increased. It may also reﬂect differences in how we categorized

blood levels relative to how dietary intake levels were categorized and

they do not necessarily match. Based on calculations from a recent

study examining the relationship between dietary intakes and blood

levels of EPA + DHA with a typical North American background diet

[343], intakes of approximately 200 mg/day EPA + DHA would be re-

quired to shift blood EPA+DHA levels from the very low (red) to low

(orange) blood levels and approximately 500 mg/day to shift to moder-

ate (yellow) blood levels. Obtaining high blood levels of EPA+ DHA

(corresponding to N8% in erythrocytes) would appear to require at

least of 1250 mg/day EPA + DHA with a North American diet [343].

Background diet may inﬂuence this intake requirement as dietary

EPA+ DHA intake estimates from Japan can range from 669 to

1120 mg/day in adult populations [345] while studies in the present re-

view reported EPA+ DHA in erythrocytes ranging from 5.9 to 14.4%.The

highest category in the global seafood omega-3 fat intake mapping

study was N550 mg/day [4] which may not be high enough to discrim-

inate the global EPA+DHA status given that there are recommenda-

tions of ≥1000 mg/day EPA+ DHA from more than one expert group

[346,347].

5.4. Potential consequences of low blood levels of EPA+DHA

Low blood and dietary intake of EPA+ DHA can potentially increase

the risk of adverse health outcomes. While EPA+ DHA is often present-

ed as a panacea, the strongest evidence for health beneﬁts of increased

EPA+ DHA status have been found for reducing the risk of coronary

heart disease and possibly total mortality, and for supporting fetal/in-

fant neurodevelopment [348,349] and the latter is mechanistically re-

lated to cognitive function throughout the lifespan. While there are no

Dietary Reference Intakes for EPA and DHA, it has been proposed [346,

348] and several expert groups and international bodies have

established recommendations that typically range from 250 mg/day to

500 mg/day EPA + DHA for general health and 500 mg/day to

≥1000 mg/day EPA+ DHA for heart health as reviewed and discussed

previously [343,346,347]. These intake recommendations align closely

with the intakes associated with the erythrocyte blood level categories

that were used to develop the current global map, therefore we can con-

clude that global blood levels of EPA+ DHA are also low as a result of in-

takes lower than expert group recommendations.

The initial observations focusing on different blood lipids in the

Greenland Inuit [350,351] suggested cardiovascular beneﬁts of a marine

diet. The validity of the mortality records of the Greenland Inuit during

these initial observations been questioned in the past [352] and more

recently [353], but interpreting cardiovascular mortality prevalence in

Greenland during this period is challenging due to high rates of violent

death in males [354] and very high rates of smoking [355].Autopsy

studies,although limited,have suggested thatatherosclerosis is reduced

in Greenland and Alaskan natives as compared with non-natives [356,

357]. Nevertheless, these initial observations in Greenland led to inter-

vention studies examining oily ﬁsh intake [358] and ﬁsh oil

Table 6

Percentages of individual long chain omega-3 by stratiﬁcations within blood fraction.

EPA+ DHA categories Map color Number of studies EPA DPAn-3* DHA EPA +DHA DHA:EPA ratio DHA/EPA +DHA %

weight % of total fatty acids

Plasma total lipid

≤2.9 Red 43 0.57 0.49 1.55 2.12 2.71 73.0

N2.9–4.0 Orange 24 1.02 0.58 2.35 3.37 2.31 69.7

N4.0–5.2 Yellow 14 1.30 0.67 3.11 4.41 2.40 70.6

N5.2 Green 25 2.91 0.98 5.27 8.18 1.81 64.5

Plasma phospholipid

≤3.8 Red 25 0.66 0.86 2.18 2.85 3.29 76.7

N3.8–5.7 Orange 38 1.03 1.01 3.75 4.81 3.64 78.0

N5.7–7.6 Yellow 23 1.61 1.04 5.05 6.66 3.13 75.8

N7.6 Green 25 2.93 1.23 6.84 9.77 2.33 70.0

Erythrocytes

≤4.0 Red 40 0.49 2.01 2.71 3.20 5.48 84.6

N4.0–6.0 Orange 41 0.68 2.18 4.14 4.82 6.07 85.9

N6.0–8.0 Yellow 19 1.04 2.40 5.86 6.83 5.62 85.7

N8.0 Green 20 2.48 2.92 7.84 10.33 3.16 75.9

Whole blood

≤3.0 Red 5 0.59 0.88 1.92 2.51 3.28 76.6

N3.0–4.4 Orange 6 1.24 1.05 2.66 3.91 2.14 68.2

N4.4–5.9 Yellow 0 –– – – – –

N5.9 Green 0 –– – – – –

Fatty acid values are the average of values reported for each individual study. *Studies reporting DPAn-3 values for: Plasma total lipid were 24 red, 12 orange, 10 yellow and 17 green;

Plasma phospholipid were 10 red, 32 orange, 14 yellow and 15 green; erythrocytes were 31 red, 35 orange, 14 yellow, and 13 green; whole blood were 3 red and 4 orange. EPA,

eicosapentaenoic acid (20:5n-3); DPAn-3, docosapentaenoic acid n-3 (22:5n-3); DHA, docosapentaenoic acid (22:6n-3).

143K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

supplementation [359] that established a link between EPA+ DHA in-

take and reduced risk of coronary heart disease mortality with a major

proposed mechanism of a reduction in fatal arrhythmias and sudden

cardiac death. Various observational cohort studies that followed pro-

vided further support for the beneﬁts of EPA + DHA by linking blood

levels of EPA+DHA to cardiac events [13,14,360]. Numerous mecha-

nisms appear to be responsible for the cardiovascular effects of EPA+ -

DHA. These include altering biophysics properties of cellular

membranes, modulating membrane proteins and ion transport,

inﬂuencing gene expression directly and indirectly and serving as sub-

strates for the production of potent metabolites or lipid mediators

[361]. With these multiple mechanisms, omega-3 LCPUFA therefore

have numerous physiological effects that have been conﬁrmed by

meta-analyses and include reduced resting heart rate [362],inﬂuencing

heart rate variability [363], reduced blood pressure [364], reduced blood

triglycerides [365,366] and reduced thrombosis [361]. It has been pro-

posed that most of the beneﬁt of EPA+ DHA could be achieved with rel-

atively modest intakes of EPA+DHA (250–500 mg/day) [349] which

would be associated with modest increases in blood levels [343].How-

ever, the reduction of secondary coronary events through EPA supple-

mentation in a Japanese population with a high background diet of

EPA+ DHA [367] suggests higher dietary targets and blood levels

should be considered. A recent examination of the dietary intakes of

EPA+ DHA and blood levels indicates that intakes of 250–500 mg/day

EPA+ DHA do not increase blood EPA+DHA to levels associated with

reduced cardiac events in previous cohort studies [343]. Recently, the

beneﬁts of EPA+ DHA intake for reducing coronary heart disease mor-

tality have been questioned due to a lack of an effect in several recent

trials [325,326,368–370]. The recent clinical trials have been criticized

for being underpowered [371], low intervention doses [372], a lack of

attention to baseline intake of EPA + DHA [373,374] and for

overestimating adherence and compliance [7,373]. In addition, the rela-

tionship between EPA+DHA and arrhythmias has been shown to be in-

consistent which is in part due to considerable heterogeneity in study

populations and study design [375]. It has also been suggested that

the anti-arrhythmic effect may only be beneﬁcial in life threatening is-

chemia-induced ventricular ﬁbrillation and not recurrent ventricular

or atrial ﬁbrillation [361].

EPA and DHA are important for cognitive function throughout the

lifespan (reviewed recently [376]). The importance of omega-3 PUFA

and DHA in particular in supporting neurological development and

function in humans was ﬁrst established when the inclusion of alpha-

linolenic acid (ALA, 18:3n-3) in a total parental nutrition emulsion in-

creased DHA in serum phospholipid and corrected neurological symp-

toms that had developed during parental nutrition without ALA [377].

In adults, there is evidence that EPA and DHA may support or improve

cognitive function but study results are not consistent and appear to

be dependent on the type of the cognitive test, baseline cognitive func-

tion and dose and timing of EPA+ DHA intake [346,376,378].Lowlevels

of plasma EPA and DHA were ﬁrst observed in individuals with

Alzheimer's disease, other types of dementia and cognitive impairment

in 2000 [379] and an association between blood levels of EPA and DHA

and dementia has been conﬁrmed [380]. Higher blood DHA (DHA in

plasma phosphatidylcholine) has been associated with reduced risk of

all-cause dementia in a prospective follow-up study [15].Intervention

trials with EPA and/or DHA in individuals with Alzheimer's disease

have typically shown no beneﬁt[381], except in Alzheimer's patients

with very mild cognitive dysfunction [382]. A recent meta-analysis has

indicated that supplementation with EPA+DHA N1 g/day can improve

immediate recall or episodic memory in individuals with mild memory

complaints but not those with no complaints [378].Italsoappearsthat

sex of the subject may inﬂuence results as women may receive more

beneﬁts in episodic memory while men beneﬁt more from reaction

time and working memory [383] although body weight differences be-

tween sexes might result in different effective dosing of EPA and DHA

[384].

Cost-effectiveness assessment for the use of omega-3 PUFA treat-

ment completed usingoutcomes from the Gruppo Italiano per lo Studio

della Sopravvivenza nell'Infarto (GISSI) Prevenzione Trial estimated

that omega-3 PUFA was cost-effective [385,386] and the cost-effective-

ness was similar to other drugs prescribed at the time (simvastatin and

pravastatin) [386]. These assessments expanded to other studies and

countries for conﬁrmation [387,388]. The GISSI Prevenzione [359] and

the GISSI heart failure [389] trials were also used to determine the

cost-effectiveness of pharmaceutical grade EPA + DHA in the ethyl

ester form [390,391]. EPA+ DHA use was also determined to be cost-ef-

fective in the treatment of hypertriglyceridemia [392]. More recently

the use of EPA only omega-3 supplementation for secondary prevention

of cardiovascular disease [393] and reducing the incidence of coronary

heart disease in the elderly in Korea [394] have been associated with

cost savings. Cost-savings with omega-3 supplementation have also

been predicted in populations receiving parental nutrition [395,396]

and with perioperative strategies to reduce surgical morbidity in pa-

tients with gastrointestinal cancer [397,398].Although pregnant

women were not included in the present analysis, low blood levels of

EPA+ DHA in pregnant women has been documented [399,400] and a

recent econometric analysis also indicated that DHA supplementation

of pregnant women could save the Australianpublic hospital system be-

tween 15 and 51 million Australian dollars per year [401].

5.5. The challenge of increasing blood EPA + DHA levels through dietary

intakes

It is important to evaluate the feasibility of supplying the world's

population with the recommended amounts of EPA and DHA. That is,

to determine whether there are adequate sources of EPA and DHA avail-

able to support, for example, shifting all countries and regions to the

green category, a level of N8% EPA + DHA in their erythrocytes or the

equivalent in other blood fractions. The main dietary source of EPA

and DHA is ﬁsh and other marine foods [8,9,11,402]. Of course, this

may be supplied by fortiﬁed foods or supplements as well. A recent

analysis of omega-3 fatty acid sources has been recently published

[347]. It is clear from this and other such analyses that the total ﬁsh

availability had plateaued by the early 1990's and is inelastic [403].

Aquaculture has steadily increased relative to the wild ﬁsh catch but

most such species still depend upon dietary ﬁsh oil supplementation

from the wild catch, and thus the total cannot at present be increased

substantially. It was estimated that for theworld's population of 7.2 bil-

lion people, to supply 500 mg/day of DHA + EPA would require

1.3 million metric tons of EPA+DHA per annum. Human consumption

is now approximately 200 thousand metric tons, enough to supply 500

mg/day of EPA+ DHA to only 15% of the world's population. In order to

raise the world's population into the green range, it was estimated

above that 1250 mg/day of EPA+DHA would be required and at this

level of intake, a total of 3.12 million metric tons of EPA+DHA would

be needed every year. At this higher level of intake, the present produc-

tion would only support about 6% of the population.

How then might the omega-3 supply be increased to support health-

ful blood levels of EPA and DHA? One suggestion has been to increase

the consumption of ALA, the precursor of EPA and DHA as there is an

abundant supply of this fatty acid in vegetable oils. However, the

human conversion to EPA is limited and conversion to DHA is very

low [404] such that supplementation studies with ALA in humans

have shown little increases in EPA and DHA [405].Thereisthepotential

to increase the conversion of ALA to EPA and DHA by reducing the in-

take of linoleic acid (LA, 18:2n-6) [340]. However, in order to achieve

high (N8% in erythrocytes) blood levels of EPA+ DHA, total PUFA intake

levels would have to be drastically reduced (b2% of total energy) to

minimize competition for Δ6 desaturation [406] and removing

omega-6 PUFA would be controversial. This would also have a major

impact on the human food supply in regard to seed oil consumption,

and as already observed with efforts to remove trans fatty acids,

144 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

replacing types of fatty acids in the industrial food supply is a challeng-

ing and problematic endeavour [407]. The reduction in linoleic acid in-

take also serves to increase EPA and DHA content of tissues due to a

lower competition for incorporation into complex lipids [408]. In any

case, preformed sources of EPA and particularly of DHA are required

for the human diet to reach high blood levels of EPA+DHA, perhaps

in combination with lower linoleic acid intake.

It is certainly possible to increase heterotrophic fermentation of mi-

croorganisms such as Schizochytrium [409] and other Thraustochytrids

[410] to make both EPA and DHA. Although there are economic hurtles

for this source vs. ﬁsh oils, an economy of scale could signiﬁcantly lower

price and make it more generally accessible [347]. Algal biomass can be

used for aquaculture and animal feed rather than the extracted oil, as

well, supplying a lower cost but efﬁcacious source of EPA and DHA. An-

other possible source of EPA and DHA in the near future could be de-

rived from genetically modiﬁed oilseed crops such as canola or

soybeans [411]. Petrie et al., have estimated that there is an EPA/DHA

equivalence of one hectare of Brassica napus to 10,000 ﬁsh based on

an omega-3 content that has already been achieved in lab trials [412].

Although genetically modiﬁed food sources are not widely accepted at

this time, genome sequences for producing omega-3 LCPUFA have

been identiﬁed [413]. One could envisage an initial use in animal feed

and aquaculture, but also the development of productive EPA +DHA

microorganisms such that enriched foods and oils could be generated

on a much larger scale in order to potentially supply enough EPA and

DHA for the world's population.

6. Concluding remarks

Blood levels of EPA+ DHAare variable acrossthe globe, with mostof

the countries and regions of the world having levels that are considered

low to very low. While the global mapping of blood levels of EPA+ DHA

tend to agree with previous assessments of dietary intake of omega-3

PUFA from seafood [4], blood levels are less error prone and thus

blood level targets can be better linked to speciﬁc chronic disease out-

comes and events. The low and very low bloods levels observed for

most of the globe are associated with an increased risk in cardiovascular

related mortality based on previous observational studies [13,14].Itis

also highly likely that increased blood levels of EPA+DHA across the

globe would reduce the risk of cognitive decline with normal aging,

but further evidence is needed to identify speciﬁc blood level targets

[346,376]. It is also clear that data on blood levels of EPA+ DHAis need-

ed for large regions of the globe, particularly for developing countries.

Efforts to establish reference ranges in blood levels of fatty acids is need-

ed and this data would complement existing information on dietary in-

take but fatty acid data can also serve as phenotype information for

genome wide association studies. Given the challenges of fatty acid

analyses and reporting, an international initiative should be considered

to lead to standardized approaches and the development of a systematic

database.

Supplementary data to this article can be found online at http://dx.

doi.org/10.1016/j.plipres.2016.05.001.

Conﬂicts of interest

Financial support for this review was provided by DSM Nutritional

Products and Norman Salem, Jr. is employed by DSM, a manufacturer

of omega-3 fatty acids.

Acknowledgments

The authors would like to dedicate this manuscript to co-author

Mary “Roberta”Higgins who passed away on October 4th, 2015 during

the writing stage.

References

[1] Mendis S, Chestnov O, World HO. Global Status Report on Noncommunicable Dis-

eases 2014. Geneva: World Health Organization; 2014.

[2] Trikalinos TA, Lee J, Moorthy D, Yu WW,Lau J, Lichtenstein AH, etal. AHRQ Techni-

cal Reviews. Effects of Eicosapentanoic Acid and Docosahexanoic Acid on Mortality

Across Diverse Settings: Systematic Review and Meta-Analysis of Randomized Tri-

als and Prospective Cohorts: Nutritional Research Series. , vol 4Rockville (MD):

Agency for Healthcare Research and Quality (US); 2012.

[3] Williams JW, Plassman BL, Burke J, Benjamin S. Preventing Alzheimer's disease and

cognitive decline. Evid Rep Technol Assess 2010:1–727.

[4] Micha R, Khatibzadeh S, Shi P, Fahimi S, Lim S, Andrews KG, et al. Global, regional,

and national consumption levels of dietary fats and oils in 1990 and 2010: a sys-

tematic analysis including 266 country-speciﬁc nutrition surveys. BMJ 2014;348:

g2272.

[5] Patterson AC, Hogg RC, Kishi DM, Stark KD. Biomarker and dietary validation of a

Canadian food fre quency questionnaire to measure eicosapentaenoic and

docosahexaenoic acid intakes from whole food, functional food, and nutraceutical

sources. J Acad Nutr Diet 2012;11 2:1005–14.

[6] Fratesi JA, Hogg RC, Young-Newton GS, Patterson AC, Charkhzarin P, Block Thomas

K, et al. Direct quantitation of omega-3 fatty acid intake of Canadian residents of a

long-term care facility. Appl Physiol Nutr Metab=Physiol Appl Nutr Metab 2009;

34:1–9.

[7] Patterson AC, Metherel AH, Hanning RM, StarkKD. The percentage ofDHA in eryth-

rocytes can detect non-adherence to advice to increase EPA and DHA intakes. Br J

Nutr 2014;111:270–8.

[8] Block RC, Harris WS, Pottala JV. Determinants of blood cell omega-3 fatty acid con-

tent. Open Biomark J 2008;1:1–6.

[9] Flock MR, Skulas-Ray AC, Harris WS, Etherton TD, Fleming JA, Kris-Etherton PM.

Determinants of erythrocyte omega-3 fatty acid contentin response to ﬁsh oil sup-

plementation: a d ose–response randomized controlled trial. J Am Heart Assoc

2013;2:e000513.

[10] Stark KD, Beblo S, Murthy M, Whitty JE, Buda-Abela M, Janisse J, et al. Alcohol con-

sumption in pregnant, black wo men is associa ted with decre ased plasma and

erythrocyte docosahexaenoic acid. Alcohol Clin Exp Res 2005;29:130–40.

[11] Harris WS, Pottala JV, Lacey SM, Vasan RS, Larson MG, Robins SJ. Clinical correlates

and heritability of erythrocyte eicosapentaenoic and docosahexaenoicacid content

in the Framingham Heart Study. Atherosclerosis 2012;225:425–31.

[12] Crowe FL, Skeaff CM, Green TJ, Gray AR. Serum n-3 long-chain PUFA differ by sex

and age in a population-based survey of New Zealand adolescents and adults. Br

J Nutr 2008;99:1 68–74.

[13] Siscovick DS, Raghunathan TE, King I, Weinmann S, Wicklund KG, Albright J, et al.

Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty

acids and the risk of primary cardiac arrest. JAMA 1995;274:1363–7.

[14] Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, et al. Blood

levels of long-chain n-3fatty acids and the riskof sudden death. N EnglJ Med 2002;

346:1113–8.

[15] Schaefer EJ, Bongard V, Beiser AS,Lamon-Fava S, RobinsSJ, Au R, et al. Plasma phos-

phatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer

disease: the Framingham Heart Study. Arch Neurol 2006;63:1545–50.

[16] Abraham RA, Bahl VK, Parshad R, Seenu V,Roy A, Golandaz S, et al. Content of trans

fatty acids in human cheek epithelium: comparison with serumand adipose tissue.

Biomed Res Int 2013;276174:8.

[17] Allard JP, Kurian R, Aghdassi E, Muggli R, Royall D. Lipid peroxidation during n-3

fatty acid and vitamin E supplementation in humans. Lipids 1997;32:535–41.

[18] Almendingen K, Hostmark AT, Fausa O, Mosdol A, Aabakken L, Vatn MH. Familial

adenomatous polyposis patients h ave high levels of ar achidonic acid an d

docosahexaenoic acid and low levels of linoleic acid and alpha-linolenic acid in

serum phospholipids. Int J Cancer 2007;120:632–7.

[19] Alshatwi AA, Alrefai NA. A comparison of serum omega-3 fatty acid concentrations

between patients with coronary heart disease and healthy subjects. Pak J Nutr

2007;6:72–4.

[20] Ambring A, Johansson M, Axelsen M, Gan L, Strandvik B, Friberg P. Mediterranean-

inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the

number of leukocytes and platelet s, and vascular en dothelial grow th factor in

healthy subjects. Am J Clin Nutr 2006;83:575–81.

[21] Amiano P, Dorronsoro M, de Renobales M, de Gordoa JC R, Irigoien I. Very-long-

chain omega-3 fatty acids as markers for habitual ﬁsh intake in a population con-

suming mainlylean ﬁsh: the EPIC cohort of Gipuzkoa. European ProspectiveInves-

tigation into Cancer and Nutrition. Eur J Clin Nutr 2001;55:827–32.

[22] An WS, Kim SE, Kim KH, Lee S, Park Y, Kim HJ, et al. Comparison of fatty acid con-

tents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients. J

Ren Nutr 2009;19:267–74.

[23] Antalis CJ, Stevens LJ, Campbell M, Pazdro R, Ericson K, Burgess JR. Omega-3 fatty

acid statusin attention-deﬁcit/hyperactivity disorder. Prostaglandins LeukotEssent

Fat Acids 2006;75:299–308.

[24] Arterburn LM, Oken HA, Hoffman JP, Bailey-Hall E, Chung G, Rom D, et al. Bioequiv-

alence of docosahexaenoic acid from different algal oils in capsules and in a DHA-

fortiﬁed food. Lipids 2007;42:1011–24.

[25] Astorg P, Bertrais S, Alessandri JM, Guesnet P, Kesse-Guyot E, Linard A, et al. Long-

chain n-3 fatty acid levels in baseline serum phospholipids do not predict later oc-

currence of depressive episodes: a nested case–control study within a cohort of

middle-aged Fr ench men and women . Prostagland ins Leukot Essen t Fat Acids

2009;81:265–71.

[26] Astorg P, Bertrais S, Laporte F, Arnault N, Estaquio C, Galan P, et al. Plasma n-6 and

n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-

145K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

sectional study within a cohort of middle-aged French men and women. Eur J Clin

Nutr 2008;62:1155–61.

[27] Aupperle RL, Denney DR, Lynch SG, Carlson SE, Sullivan DK. Omega-3 fatty

acids and multiple sclerosis: relationship to depression. J Behav Med 2008;

31:127–35.

[28] Austria JA, RichardMN, Chahine MN, Edel AL, Malcolmson LJ,Dupasquier CM, et al.

Bioavailability of alpha-linolenic acid in subjects after ingestion of three different

forms of ﬂaxseed. J Am Coll Nutr 2008;27:214–21.

[29] Bagdade JD, Ritter MC, Davidson M, Su bbaiah PV. Effec t of marine lipids on

cholesteryl ester transfer and lipoprotein composition in patients with hypercho-

lesterolemia. Arterioscler Thromb:J Vasc Biol/Am Heart Assoc 1992;12:1146–52.

[30] Baghai TC, Varallo-Bedarida G, Born C, Hafner S, Schule C, Eser D, et al. Major de-

pressive disorder is associated with cardiovascular risk factors and low Omega-3

Index. J Clin Psychiatry 2011;72:1242–7.

[31] Barcelo-Coblijn G, Murphy EJ, Othman R, Moghadasian MH, Kashour T, Friel JK.

Flaxseed oil and ﬁsh-oil c apsule consumption alters human red blood cell n-3

fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty

acid. Am J Clin Nutr 2008;88:801–9.

[32] Barkia A, Mohamed K, Smaoui M, Zouari N, Hammami M, Nasri M. Change of diet,

plasma lipids, lipoproteins, and fatty acids during Ramadan: a controversial associ-

ation of the considered Ramadan model with atherosclerosis risk. J Health Popul

Nutr 2011;29:486–93.

[33] Berr C, Akbaraly T, Arnaud J, Hininger I, Roussel AM, Barberger GP. Increased sele-

nium intake in elderly high ﬁsh consumers may account for health beneﬁts previ-

ously ascribed to omega-3 fatty acids. J Nutr Health Aging 2009;13:14–8.

[34] BlockRC, Harris WS, Reid KJ, Sands SA, Spertus JA. EPA and DHAin blood cell mem-

branes from acute coronary syndrome patients and controls. Atherosclerosis 2008;

197:821–8.

[35] Bloomer RJ, Larso n DE, Fisher-We llman KH, Galpi n AJ, Schilling BK . Effect of

eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced in-

ﬂammatory and oxidative stress biomarkers: a randomized, placebo controlled,

cross-over study. Lipids Health Dis 2009;8:36.

[36] Bonaa KH, Bjerve KS, Nordoy A. Docosahexaenoic and eicosapentaenoic acids in

plasma phospholipids are divergently associated with high density lipoprotein in

humans. Arterioscler Thromb:J Vasc Biol/Am Heart Assoc 1992;12:675–81.

[37] Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, et al. Serum phos-

pholipid fatty acids and prostate cancer risk: results from the prostate cancer pre-

vention trial. Am J Epidemiol 2011;173:1429–39.

[38] Brignardello J, Morales P, Diaz E, Brunser O, Gotteland M. Increase of plasma fatty

acids without changes in n-6/n-3- PUFA ratio in asym ptomatic obese subjects.

Arch Latinoam Nutr 2011;61:149–53.

[39] Brown AJ, Pang E, Roberts DC. Erythrocyte ei cosapentaenoic acid versus

docosahexaenoic acid as a marker for ﬁsh and ﬁsh oil consumption. Prostaglandins

Leukot Essent Fat Acids 1991;44:103–6.

[40] Brox J, Olaussen K, Osterud B, Elvevoll EO, Bjornstad E, Brattebog G, et al. A long-

term seal- and cod-liver-oil supplementation in hypercholesterolemic su bjects.

Lipids 2001 ;36:7–13.

[41] Brude IR, Drevon CA, Hjermann I, Seljeﬂot I, Lund-Katz S, Saarem K, et al. Peroxida-

tion of LDL from combined-hyperlipidemic male smokers supplied with omega-3

fatty acids and antioxidants. Arterioscler Thromb Vasc Biol 1997;17:2576–88.

[42] Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of

omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin

Chem 2006;52:2265–72.

[43] Carrero JJ, Baro L, Fonolla J, Gonzalez-Santiago M, Martinez-FerezA, Castillo R, et al.

Cardiovascular effects of milk enriched with omega-3 polyunsaturated fatty acids,

oleic acid, folic acid, and vitamins E and B6 in volunteers with mild hyperlipidemia.

Nutrition, 20. Los Angeles County, Calif: Burbank; 2004 521–7.

[44] Caspar-Bauguil S, Garcia J, Galinier A, Periquet B, Ferrieres J, Allenbach S, et al. Pos-

itive impact of long-term lifestyle change on erythrocyte fatty acid proﬁle after

acute coronary syndromes. Arch Cardiovasc Dis 2010;103:106–14.

[45] Caspar-BauguilS, Montastier E, Galinon F, Frisch-BenarousD, Salvayre R, Ritz P.An-

orexia nervosa patients display a deﬁcit in membrane long chain poly-unsaturated

fatty acids. Clin Nutr (Edinburgh, Scotland 2012;31:386–90.

[46] Cazzola R, Rondanelli M, Russo-Volpe S, Ferrari E, Cestaro B. Decreased membrane

ﬂuidity and altered susceptibility to peroxidation and lipid composition in over-

weight and obese female erythrocytes. J Lipid Res 2004;45:1846–51.

[47] Cederholm TE, Berg AB, JohanssonEK, Hellstrom KH, Palmblad JE. Low levels of es-

sential fatty acids are related to impaireddelayed skin hypersensitivityin malnour-

ished chronically ill elderly people. Eur J Clin Investig 1994;24:615–20.

[48] Cherubini A, Andres-Lacueva C, Martin A, Lauretani F, Iorio AD, Bartali B, et al. Low

plasma N-3 fatty ac ids and dementia in older persons: th e InCHIANTI stu dy. J

Gerontol A Biol Sci Med Sci 2007;62:1120–6.

[49] Chien KL, Chao CL, Kuo CH, Lin HJ, Liu PH, Chen PR, et al. Plasma fatty acids and the

risk of metabolic syndrome in ethnic Chinese adults in Taiwan. Lipids Health Dis

2011;10:33.

[50] Coates AM, Sioutis S, Buckley JD, Howe PR. Regular consumption of n-3 fatty acid-

enriched pork modiﬁes cardiovascular risk factors. Br J Nutr 2009;101:592–7.

[51] Conklin SM, Harris JI, Manuck SB,Yao JK, Hibbeln JR, Muldoon MF. Serum omega-3

fatty acids are associated with variation in mood, personality and behavior in hy-

percholesterolemic community volunteers. Psychiatry Res 2007;152:1–10.

[52] Conquer JA, CherykLA, Chan E, Gentry PA, Holub BJ. Effectof supplementationwith

dietary seal oil on selected cardiovascular risk factors and hemostatic variables in

healthy male subjects. Thromb Res 1999;96:239–50.

[53] Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic

acid increases (n-3) fatty acid status and alters selected risk factors for heart dis-

ease in vegetarian subjects. J Nutr 1996;126:3032–9.

[54] Conquer JA, Roelfsema H, Zecevic J, Graham TE, Holub BJ. Effect of exercise on FA

proﬁles in n-3 FA-supplemented and -nonsupplemented premenopausal women.

Lipids 2002;37:947–51.

[55] Crispim SP, Geelen A, Souverein OW, Hulshof PJ, Ruprich J, Dofkova M, et al. Bio-

marker-based evaluation of two 24-h recalls for comparing usual ﬁsh, fruit and

vegetable intakes across European centers in the EFCOVAL Study. Eur J Clin Nutr

2011;65(Suppl. 1):S38–47.

[56] Crowe FL, Skeaff CM, Green TJ, Gray AR. Serum phospholipid n 3 long-chain

polyunsaturated fatty acids and physical and mental health in a population-

based survey of New Zealand adolescents and adults. Am J Clin Nutr 2007;86:

1278–85.

[57] Cunnane SC, Hamadeh MJ, Liede AC, Thompson LU, Wolever TM, Jenkins DJ. Nutri-

tional attributes of traditional ﬂaxseed in healthy young adults. Am J Clin Nutr

1995;61:62–8.

[58] Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA,

et al. Plasma and brain fatty acid proﬁles in mild cognitive imp airment and

Alzheimer's disease. J Alzheimers Dis 2012;29:691–7.

[59] Dahl L,Maeland CA, Bjorkkjaer T. A short foodfrequency questionnaire to assess in-

take of seafood and n-3 supplements: validation with biomarkers. Nutr J 2011;10:

127.

[60] DangourAD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P, et al. Effect of 2-y n-

3 long-chain polyunsaturated fatty acid supplementation on cognitive function in

older people: a randomized, double-blind, controlled trial. Am J Clin Nutr 2010;

91:1725–32.

[61] Dawczynski C, Martin L, Wagner A, JahreisG. n-3 LC-PUFA-enriched dairy products

are able to reduce cardiovascular risk factors: a double-blind, cross-over study. Clin

Nutr (Edinburgh, Scotland) 2010;29:592–9.

[62] de Groot RH, Hornstra G, Jolles J. Exploratory study into the relation between plas-

ma phospholipid fatty acid stat us and cognitive performance. Pr ostaglandins

Leukot Essent Fat Acids 2007;76:165–72.

[63] de Groot RH, van Boxtel MP, Schiepers OJ, Hornstra G, Jolles J. Age dependence of

plasma phospholipid fatty acid levels:potential role of linoleicacid in the age-asso-

ciated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations.

Br J Nutr 2009;102:1058–64.

[64] De Groote G, De Laporte A, Dhondt G, Christophe A. Improvement in the plasma

omega-3 index by the use of a ﬁsh oil-enriched spread. Ann Nut r Metab 2008;

53:23–8.

[65] de Oliveira Otto MC, Wu JH, Baylin A, Vaidya D, Rich SS, Tsai MY, et al. Circulat-

ing and dietary omega-3 and omega-6 polyunsaturated fatty acids and inci-

dence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc

2013;2:000506.

[66] DelyferMN, Buaud B, KorobelnikJF, Rougier MB, Schalch W, Etheve S, et al. Associ-

ation of macular pigment density with plasma omega-3 fatty acids: the PIMAVOSA

study. Investig Ophthalmol Vis Sci 2012;53:1204–10.

[67] Dewailly E, Blanchet C, Gingras S, Lemieux S, Holub BJ. Cardiovascular disease risk

factors and n-3fatty acid status in the adult population of James Bay Cree. Am J Clin

Nutr 2002;76:85–92.

[68] Dewailly E, Chateau-Degat L, Suhas E. Fish consumption and health in French Poly-

nesia. Asia Pac J Clin Nutr 2008;17:86–93.

[69] Dewailly EE, Blanchet C, Gingras S, Lemieux S, Sauve L, Bergeron J, et al. Relations

between n-3 fatty acid statu s and cardiovasc ular disease risk factors among

Quebecers. Am J Clin Nutr 2001;74:603–11.

[70] Di Stasi D, Bernasconi R, Marchioli R, Marﬁsi RM, Rossi G, Tognoni G, et al. Early

modiﬁcations of fatty acid composition in plasma ph ospholipids, platele ts and

mononucleates of healthy volunte ers after low dose s of n-3 polyunsat urated

fatty acids. Eur J Clin Pharmacol 2004;60:183–90.

[71] Dodin S, Cunnane SC, MasseB, Lemay A, Jacques H, AsselinG, et al. Flaxseed on car-

diovascular disease markers in healthy menopausal women: a randomized, dou-

ble-blind, plac ebo-controlled trial. Nutriti on, 24. Los Angel es County, Cali f:

Burbank; 2008 23–30.

[72] Duricic I, Sobajic S, Perunicic-PekovicG,StojanovM,RasicZ.Consumptionof

ﬁsh oil supplement alters erythrocyte fatty acid composition in overweight,

hypercholesterolemic, middle-aged Serbians. Nutr Res (N Y, NY) 2007;27:

529–34.

[73] Ebbesson SO, Devereux RB, Cole S, Ebbesson LO, Fabsitz RR, Haack K, et al. Heart

rate is associated with red blood cell fatty acid concentration: the genetics of cor-

onary artery disease in Alaska natives (GOCADAN) study. Am Heart J 2010;159:

1020–5.

[74] Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels

in the diet and in red blood cell membranes of depressed patients. J Affect Disord

1998;48:149–55.

[75] Elizondo A, Araya J, Rodrigo R, Poniachik J, Csendes A, Maluenda F, et al. Polyunsat-

urated fatty acid pattern in liver and erythrocyte phospholipids from obese pa-

tients. Obesity 2007;15:24–31.

[76] Emanuele E, Brondino N, Re S, Bertona M, Geroldi D. Serum omega-3 fatty acids

are associated with ultimatum bargaining behavior. Physiol Behav 2009;96:

180–3.

[77] Feart C, Peuchant E, Letenneur L, Samieri C, Montagnier D, Fourrier-Reglat A, et al.

Plasma eicosapentaenoic acid is inversely associated with severity of depressive

symptomatology in the elderly: data from the Bordeaux sample of the Three-City

Study. Am J Clin Nutr 2008;87:1156–62.

[78] Fernandez-Real JM, Broch M, Vendrell J, Ricart W. Insulin resistance, inﬂammation,

and serum fatty acid composition. Diabetes Care 2003;26:1362–8.

[79] Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F, et al. Relation-

ship of plasma polyunsaturated fatty acids to circulating inﬂammatory markers. J

Clin Endocrinol Metab 2006;91:439–46.

146 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

[80] Fillion M, Lemire M, PhilibertA, FrenetteB, Weiler HA, Deguire JR, et al. Visual acu-

ity in ﬁsh consumers of the Brazilian Amazon: risks and beneﬁts from local diet.

Public Health Nutr 2011;14:2236–44.

[81] Fortier M, Tremblay-Mercier J, Plourde M, Chouinard-Watkins R, Vandal M, Pifferi

F, et al. Higher plasma n-3 fatty acid status in the moderately healthy elderly in

southern Quebec: higher ﬁsh intake or aging-related change in n-3 fatty acid me-

tabolism? Prostaglandins Leukot Essent Fat Acids 2010;82:277–80.

[82] Freije A. Fatty acid proﬁle of the erythrocyte membranes of healthy Bahraini citi-

zens in comparison wi th coronary hear t disease patients. J Oleo Sci 2009;58:

379–88.

[83] Garneau V, Rudkowska I, Paradis AM, Godin G, Julien P, Perusse L, et al. Omega-3

fatty acids status in human subjects estimated using a food frequency question-

naire and plasma phospholipids levels. Nutr J 2012;11:46.

[84] Geppert J, Demmelmair H, Hornstra G, Koletzko B. Co-supplementation of healthy

women with ﬁsh oil and evening primrose oil increases plasma docosahexaenoic

acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without re-

ducing arachidonic acid concentrations. Br J Nutr 2008;99:360–9.

[85] Geppert J, Kraft V, Demmelmair H,Koletzko B. Docosahexaenoic acid supplementa-

tion in vegetarians effectively increases omega-3 index: a randomized trial. Lipids

2005;40:807–14.

[86] Gerasimova E, Perova N, Ozerova I, Polessky V, Metelskaya V, Sherbakova I, et al.

The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot

residents vs muscovites. Lipids 1991;26:261–5.

[87] GlewRH, Chuang LT, Berry T, OkolieH, Crossey MJ, VanderJagtDJ. Lipid proﬁles and

trans fatty acids in serum phospholipids of semi-nomadic Fulani in northern Nige-

ria. J Health Popul Nutr 2010;28:159–66.

[88] Gong J, Rosner B, Rees DG, Berson EL, We igel-DiFranco CA, Schaefer EJ. Plasma

docosahexaenoic acid levels i n various geneti c forms of retinitis pigmentos a.

Investig Ophthalmol Vis Sci 1992;33:2596–602.

[89] Green P, Hermesh H, Monselise A, Marom S, Presburger G, Weizman A. Red cell

membrane omega-3 fatty acids are decreased in nondepressed patients with social

anxiety disorder. Eur Neuropsychopharmacol 2006;16:107–13.

[90] Gronn M, Gorbitz C, Christensen E, Levorsen A, Ose L, Hagve TA, et al. Dietary n-6

fatty acids inhibit the incorporation of dietary n-3 fatty acids in thrombocyte and

serum phospholipids in humans: a controlled dietetic study. Scand J Clin Lab

Investig 1991;51:255–63.

[91] Grundt H, Nilsen DW, Hetland O, Aarsland T, Baksaas I, Grande T, et al. Improve-

ment of serum lipids and blood pressure during intervention with n-3 fatty acids

was not associated with changes in insulin levels in subjects with combined hyper-

lipidaemia. J Intern Med 1995;237:249–59.

[92] Guarini P, Stanzial AM, Olivieri O, Casaril M, Galvani S, Pantalena M, et al. Erythro-

cyte membrane lipids and serum selenium in post-viral and alcoholic cirrhosis. Clin

Chim Acta 1998;270:139–50.

[93] Gustafsson IB, Vessby B, Ohrvall M, Nydahl M. A diet rich in monounsaturated rape-

seed oil reduces the lipoprotein cholesterol concentration and increases the rela-

tive content of n-3 fatty acids in serum in hyperlipidemic subjects. Am J Clin Nutr

1994;59:667–74.

[94] Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, et al. Blood levels of

long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer.

Cancer Epidemiol Biomark Prev 2007;16:314–21.

[95] Hamazaki K, Itomura M, Sawazaki S, HamazakiT. Fish oil reduces tooth loss mainly

through its anti-inﬂammatory effects? Med Hypotheses 2006;67:868–70.

[96] Hamazaki-Fujita N, Hamazaki K, Tohno H, Itomura M, Terashima Y, Hamazaki T,

et al. Polyunsaturated fatty acids and blood circulation in the forebrain during a

mental arithmetic task. Brain Res 2011;1397:38–45.

[97] Harper CR, Edwards MJ, DeFilippisAP, JacobsonTA. Flaxseed oil increases the plas-

ma concentrations of cardioprotective (n-3) fatty acids in humans. J Nutr 2006;

136:83–7.

[98] Harris JI, Hibbeln JR, Mackey RH, Muldoon MF. Statin treatment alters serum n-3

and n-6 fatty acids in hypercholesterolemic patients. Prostaglandins Leukot Essent

Fat Acids 2004;71: 263–9.

[99] Harris WS, Lemke SL, Hansen SN, Goldstein DA, DiRienzo MA, Su H, et al.

Stearidonic acid-enriched soybean oil increased the omega-3 index, an emerging

cardiovascular risk marker. Lipids 2008;43:805–11.

[100] Harris WS, Pottala JV, Sands SA,Jones PG. Comparison of the effects of ﬁsh and ﬁsh-

oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids.

Am J Clin Nutr 2007;86:1621–5.

[101] Harris WS, Pottala JV, Vas an RS, Larson MG, Robins SJ. Changes in erythrocyte

membrane trans and marine fatty acids between 1999 and 2006 in older Ameri-

cans. J Nutr 2012;142:1297–303.

[102] Harris WS, Reid KJ, Sands SA, Spertus JA. Blood omega-3 and trans fatty acids

in middle-aged acute coronary syndrome patients. Am J Cardiol 2007;99:

154–8.

[103] Harvei S, Bjerve KS, Tretli S, Jellum E, Robsahm TE, Vatten L. Prediagnostic level of

fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk

of prostate cancer. Int J Cancer 1997;71:545–51.

[104] Haug A, Nyquist NF, Mosti TJ, Andersen M, Hostmark AT. Increased EPA levels in

serum phospholipids of humans after four weeks daily ingestion of one portion

chicken fed linseed and rapeseed oil. Lipids Health Dis 2012;11:104.

[105] Heude B, Ducimetiere P, Berr C. Cognitive decline and fatty acid compo-

sition of erythrocyte membranes—the EVA study. Am J Clin Nutr 2003;77:

803–8.

[106] Hibbeln JR, LinnoilaM, Umhau JC, Rawlings R, GeorgeDT, Salem Jr N. Essential fatty

acids predict metabolites of serotonin and dopamine in cerebrospinal ﬂuid among

healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry1998;

44:235–42.

[107] High KP, Sinclair J, Easter LH, Case D, Chilton FH. Advanced age, but not anergy, is

associated with altered serum polyunsaturated fatty acid levels. J Nutr Health

Aging 2003;7:378–84.

[108] Hirai K, Horiuchi R, Ohno Y, Higuchi H, Asano Y. Lower eicosapentaenoic acid and

higher arachidonic acid levels in sera of young adults in the Netherlands than in

Japan. Environ Health Prev Med 2000;5:60–5.

[109] Hjartaker A, Lund E, Bjerve KS. Serum phospholipid fatty acid composition and ha-

bitual intake of marine foods registered by a semi-quantitative food frequency

questionnaire. Eur J Clin Nutr 1997;51:736–42.

[110] Hlavaty P, Kunesova M, Gojova M, Tvrzicka E, Vecka M, Roubal P, et al. Change in

fatty acid composition of serum lipids in obese females after short-term weight-re-

ducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in

comparison to con trols. Physiol R es/Acad Sci Bohemoslov 2008;5 7(Suppl. 1):

S57–65.

[111] Hodge AM, Simpson JA, Gibson RA, Sinclair AJ, Makrides M, O'Dea K, et al. Plasma

phospholipid fatty acid composition as a biomarker of habitual dietary fat intake

in an ethnically diverse cohort. Nutr Metab Cardiovasc Dis 2007;17:415–26.

[112] Hodge J, Sanders K, Sinclair AJ. Differential utilization of eicosapentaenoic acid and

docosahexaenoic acid in human plasma. Lipids 1993;28:525–31.

[113] Hoffman DR, Uauy R, Birch DG. Red blood cell fatty acid levels in patients with au-

tosomal dominant retinitis pigmentosa. Exp Eye Res 1993;57:359–68.

[114] Hojo N, Fukushima T, Isobe A, Gao T, Shiwaku K, Ishida K, et al. Effect of serum

fatty acid composition on coronary atherosclerosis in Japan. Int J Cardiol 1998;

66:31–8.

[115] Huan M, Hamazaki K, Sun Y, Itomura M, Liu H, Kang W, et al. Suicide attempt and

n-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry

2004;56:490–6.

[116] Huang T, Shou T, Cai N, Wahlqvist ML, Li D. Associations of plasma n-3 polyunsat-

urated fatty acids with blood pressure and cardiovascular risk factors among Chi-

nese. Int J Food Sci Nutr 2012;63:667–73.

[117] Ikeya Y, Fukuyama N, Kitajima W, Ogushi Y, Mori H. Comparis on of

Eicosapentaenoic Acid Concentrations in Plasma Between Patients with Ischemic

Stroke and Control Subjects. Nutrition, 29. Los Angeles County, Calif: Burbank;

2013 127–31.

[118] Imre SG, Fekete I, Farkas T. Increased proportion of docosahexanoic acid and high

lipid peroxidation capacity in erythrocytes of stroke patients. Stroke J Cereb Circ

1994;25:24 16–20.

[119] Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, et al. Relation-

ships between plasma fatty acid composition and coronary artery dise ase. J

Atheroscler Thromb 2011;18:99–107.

[120] Ito Y, Shimizu H, Yoshimura T, Ross RK, Kabuto M, Takatsuka N, et al. Serum con-

centrations of carotenoids, alpha-tocopherol, fatty acids, and lipid pe roxides

among Japanese in Japan, and Japanese and Caucasians in the US. Int J Vitam

Nutr ResInt Z Vitam Ernahrungsforsch J Int Vitam Nutr 1999;69:385–95.

[121] Itomura M, Fujioka S, Hamazaki K, Kobayashi K, Nagasawa T, Sawazaki S, et al. Fac-

tors inﬂuencing EPA +DHA levels in red blood cells in Japan. In vivo 200 8;22:

131–5Athens,Greece.

[122] Iusupova IU. The fatty acid composition of the phospholipids of the erythrocyte

membranes, thrombocytes and alpha-lipoproteins in schizophrenia patients. Zh

Nevropatol Psikhiatr Im S S Korsakova 1995;95:58–62.

[123] Jabbar R, Saldeen T. A new predictor of risk for suddencardiac death. Ups J Med Sci

2006;111:169–77.

[124] James MJ,Ursin VM, Cleland LG. Metabolism of stearidonic acid in human subjects:

comparison with the metabolism of other n-3 fatty acids. Am J Clin Nutr 2003;77:

1140–5.

[125] Johnson EJ, Chung HY, CaldarellaSM, Snodderly DM. Theinﬂuence of supplemental

lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmenta-

tion. Am J Clin Nutr 2008;87:1521–9.

[126] Junshi C, TC C, Junyao L, Peto R, editors. Diet, lifestyle, and mortality in China: a

study of the characteristics of 65 Chinese counties. Oxford University Press; 1990.

[127] Kale A, Joshi S, Naphade N, Sapkale S, Raju MS, Pillai A, et al. Opposite changes in

predominantly docosahexaenoic acid (DHA) in cerebrospinal ﬂuid and red blood

cells from never-medicated ﬁrst-episode psychotic patients. Schizophr Res 2008;

98:295–301.

[128] Kalogeropoulos N, Panagiotakos DB, Pi tsavos C, Chrysohoou C, Rousinou G,

Toutouza M, et al. Unsaturated fatty acids are inversely associated and n-6/n-3 ra-

tios are positively related to inﬂammation and coagulation markers in plasma of

apparently healthy adults. Clin Chim Acta 2010;411:584–91.

[129] Karlsson J, Lindh G, Ronnebergh TR. Smoking, plasma antioxidants and essential

fatty acids before and after nutratherapy. Can J Cardiol 1996;12:665–70.

[130] Kawabata T, Hirota S, Hirayama T, Adachi N, Hagiwara C, Iwama N, et al. Age-relat-

ed changes of dietary intake and blood eicosapentaenoic acid, docosahexaenoic

acid, and arachidonic acid levels in Japanese men and women. Prostaglandins

Leukot Essent Fat Acids 2011;84:131–7.

[131] Keenan AH, Pedersen TL, Fillaus K, Larson MK, Shearer GC, Newman JW. Basal

omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose

n3-HUFA in healthy volunteers. J Lipid Res 2012;53:1662–9.

[132] Kelley DS, Siegel D, Vemuri M, Chung GH, Mackey BE. Docosahexaenoic acid sup-

plementation decreases remnant-like particle-cholesterol and increases the (n-3)

index in hypertriglyceridemic men. J Nutr 2008;138:30–5.

[133] Kew S, Mesa MD,Tricon S, Buckley R, Minihane AM, Yaqoob P. Effects of oils rich in

eicosapentaenoic and docosahexaenoic acids on immune cell composition and

function in healthy humans. Am J Clin Nutr 2004;79:674–81.

[134] Khanaki K, Nouri M, Ardekani AM, GhassemzadehA, Shahnazi V, Sadeghi MR, et al.

Evaluation of the relationship between endometriosis and omega-3 and omega-6

polyunsaturated fatty acids. Iran Biomed J 2012;16:38–43.

147K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

[135] Kibayashi E, Zhang M, Liu ZY, Sekine M, Sokejima S, Kagamimori S. Comparative

studies on serum taurine and plasma fatty acids in humans between the sea side

area in Toyama, Japan and the mountain areas in Inner Mongolia, China. Adv Exp

Med Biol 2000;483:143–8.

[136] Kim YJ, Kim OY, Cho Y, Chung JH, Jung YS, Hwang GS, et al. Plasma phospholipid

fatty acid composition in ischemic stroke: importance of docosahexaenoic acid in

the risk for intracranial atherosclerotic stenosis. Atherosclerosis 2012;225:418–24.

[137] Kitayama A, Arisawa K, Uemura H, Hiyoshi M, Takami H, Sawachika F, et al. Corre-

lations of ﬁsh intake and plasma docosahexaenoic acid levels with each congener

of PCDDs/PCDFs/dioxin-like PCBs in blood from the Japanese population. Int Arch

Occup Environ Health 2011;84:927–35.

[138] KnollN, Kuhnt K, Kyallo FM,Kiage-Mokua BN, Jahreis G. High content of long-chain

n-3 polyunsaturated fatty acids inred blood cells of Kenyan Maasai despite low di-

etary intake. Lipids Health Dis 2011;10:141.

[139] Kobayashi M, Sasaki S, Kawabata T, Hasegawa K, Akabane M, Tsugane S. Single

measurement of serum phospholipid fatty acid as a biomarker of speci ﬁc fatty

acid intake in middle-aged Japanese men. Eur J Clin Nutr 2001;55:643–50.

[140] Konagai C, Yanagimoto K, Hayamizu K, Han L, TsujiT, Koga Y. Effects of krilloil con-

taining n-3polyunsaturated fatty acids in phospholipid form on humanbrain func-

tion: a randomized controlled trial in healthy elderly volunteers. Clin Interv Aging

2013;8:1247–57.

[141] Kondo K, Morino K, Nishio Y, Kondo M, Fuke T, Ugi S, et al. Effects of a ﬁsh-based

diet on the serum adiponectin concentration in young, non-obese, healthy Japa-

nese subjects. J Atheroscler Thromb 2010;17:628–37.

[142] Kroger E, Verreault R, Carmichael PH, Lindsay J, Julien P, Dewailly E, et al. Omega-3

fatty acids andrisk of dementia: the Canadian Study of Health andAging. Am J Clin

Nutr 2009;90:184–92.

[143] Kroger J, ZietemannV ,Enzenbach C, Weikert C, Jansen EH, Doring F, et al. Eryth-

rocyte membrane phospholipid fatty acids, desaturase activity, and dietary

fatty acids in relation to risk of type 2 diabetes in the European Prospective In-

vestigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr

2011;93:127–42.

[144] Kuriki K, Nagaya T,Tokudome Y, Imaeda N, Fujiwara N, Sato J, et al. Plasma concen-

trations of (n-3) highly unsaturated fatty acids are good biomarkers of relative di-

etary fatty acid intakes: a cross-sectional study. J Nutr 2003;133:3643–50.

[145] Kuriki K, Wakai K, Hirose K, Matsuo K, Ito H, Suzuki T, et al. Risk of colorectal

cancer is linked to erythrocyte compositions of fatty acids as biomarkers for di-

etary intakes of ﬁsh, fat, and fatty acids. Cancer Epidemiol Biomark Prev 2006;

15:1791–8.

[146] Kuriki K, Wakai K, Matsuo K, Hiraki A, Suzuki T, Yamamura Y, et al. Gastric cancer

risk and erythrocyte composition of docosahexaenoic acid with anti-inﬂammatory

effects. Cancer Epidemiol Biomark Prev 2007;16:2406–15.

[147] Kuroki F, Iida M, Matsumoto T, Aoyagi K, Kanamoto K, Fujishima M. Serum n3 poly-

unsaturated fatty acids are depl eted in Crohn's disease. Dig Dis Sc i 1997;42:

1137–41.

[148] Kurotani K, Sato M, Ejima Y, Nanri A, Yi S, Pham NM, et al. High levels of stearic

acid, palmitoleic acid, and dihomo-gamma-linolenic acid and low levels of linoleic

acid in serum cholesterol esterare associated with highinsulin resistance. Nutr Res

(N Y, NY) 2012;32:669–75 e3.

[149] Kusumoto A, Ishik ura Y, Kawashima H, Kis o Y, Takai S, Miyazaki M. Effects o f

arachidonate-enriched triacylglycerol supplementation on serum fatty acids and

platelet aggregation in healthy male subjects with a ﬁsh diet. Br J Nutr 2007;98:

626–35.

[150] Laasonen M, Hokkanen L, Leppamaki S, Tani P, Erkkila AT. Project DyAdd: fatty

acids and cognition in adults with dyslexia, ADHD, or both. Prostaglandins Leukot

Essent Fat Acids 2009;81:79–88.

[151] Ladesich JB, Pottala JV, Romaker A, Ha rris WS. Membran e level of omega- 3

docosahexaenoic acid is associated with severity of obstructive sleep a pnea. J

Clin Sleep Med 2011;7:391–6.

[152] Lauretani F, Bandinelli S, Bartali B, Cherubini A, Iorio AD, Ble A, et al. Omega-6 and

omega-3 fatty acids predict accelerated decline of peripheral nerve func tion in

older persons. Eur J N eurol 2007;14:8 01–8.

[153] Laurin D, Verreault R, Lindsay J, Dewailly E, Holub BJ. Omega-3 fatty acids and risk

of cognitive impairment and dementia. J Alzheimers Dis 2003;5:315–22.

[154] Lauritzen L, Harslof LB, Hellgren LI, Pedersen MH, Molgaard C, Michaelsen KF. Fish

intake, erythrocyte n-3 fatty acid status and metabolic health in Danish adolescent

girls and boys. Br J Nutr 2012;107:697–704.

[155] Lee HY, Woo J, Chen ZY, Leung SF, Peng XH. Serum fatty acid, lipid proﬁle and die-

tary intake of Hong Kong Chinese omnivores and vegetarians. EurJ Clin Nutr 2000;

54:768–73.

[156] Leeson CP, Mann A, Kattenhorn M, Deanﬁeld JE, Lucas A, Muller DP. Relationship

between circulating n-3 fatty a cid concentrations and endoth elial function in

early adulthood. Eur Heart J 2002;23:216–22.

[157] Legrand P, Schmitt B,Mourot J, Catheline D, Chesneau G, MireauxM, et al. The con-

sumptionof food products from linseed-fedanimals maintainserythrocyte omega-

3 fatty acids in obese humans. Lipids 2010;45:11–9.

[158] Lemaitre RN, Siscovick DS, Berry EM, Kark JD, Friedlander Y.Familial aggregation of

red blood cell memb rane fatty acid com position: the Kibbutzim Family Study.

Metab Clin Exp 2008;57:662–8.

[159] LemkeSL, Vicini JL, Su H, Goldstein DA, Nemeth MA, Krul ES,et al. Dietary intake of

stearidonic acid-enriched soybean oil increases the omega-3 index: randomized,

double-blind clinical study of efﬁcacy and safety. Am J Clin Nutr 2010;92:766–75.

[160] Leng GC, Horrobin DF, Fowkes FG, Smith FB, LoweGD, Donnan PT, et al. Plasma es-

sential fatty acids, cigarette smoking, and dietary antioxidantsin peripheral arterial

disease. A population-based case–control study. Arterioscler Thromb:J Vasc Biol/

Am Heart Assoc 1994;14:471–8.

[161] Leng GC, Taylor GS, Lee AJ, Fowkes FG, Horrobin D. Essential fatty acids and cardio-

vascular disease: the Edinburgh Artery Study. Vasc Med 1999;4:219–26 London,

England.

[162] Lewis MD, Hibbeln JR, Johnson JE, Lin YH, Hyun DY, Loewke JD. Suicide deaths of

active-duty US military and omega-3 fatty-acid status: a case-control comparison.

J Clin Psychiatry 2011;72:1585–90.

[163] Lindberg M, Midthjell K, Bjerve KS. Long-term tracking of plasma phospholipid

fatty acid concentrations and their correlation with the dietary intake of marine

foods in newly diagnosed diabetic patients: results from a follow-up of the HUNT

Study, Norway. Br J Nutr 2013;109:1123–34.

[164] Lindqvist HM, Sandberg AS, Fagerberg B, Hulthe J. Plasma phospholipid EPA and

DHA in relation to atherosclerosis in 61-year-old men. Atherosclerosis 2009;205:

574–8.

[165] Liou YA, King DJ, Zibrik D, Innis SM. Decreasing linoleic acid with constant alpha-

linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phos-

pholipids in healthy men. J Nutr 2007;137:945–52.

[166] Liu JC, Conklin SM, Manuck SB, Yao JK, Muldoon MF. Long-chain omega-3 fatty

acids and blood pressure. Am J Hypertens 2011;24:1121–6.

[167] Liu Z, Wang D, Xue Q, Chen J, Li Y, Bai X, et al. Determination of fatty acid levels in

erythrocyte membranes of patients with chronic fatigue syndrome. Nutr Neurosci

2003;6:389–92.

[168] Lopez LB, Kritz-Silverstein D, Barrett CE. High dietary and plasma levels of the

omega-3 fatty acid docosahexaenoic acid are associated with decreased dementia

risk: the Rancho Bernardo study. J Nutr Health Aging 2011;15:25–31.

[169] Lucas M, Asselin G, Merette C, Poulin MJ, Dodin S. Validation of an FFQ for evalua-

tion of EPA and DHA intake. Public Health Nutr 2009;12:1783–90.

[170] Lucas M, Dewailly E, Blanchet C, Gingras S, Holub BJ. Plasma omega-3 and psycho-

logical distress among Nunavik Inuit (Canada). Psychiatry Res 2009;167:266–78.

[171] LucasM, Dewailly E, BlanchetC, Gingras S, Holub BJ. Plasman-3 fatty acids and psy-

chological distressin aboriginal Cree Indians (Canada). PublicHealth Nutr 2009;12:

2343–51.

[172] Lucas M, Kirmayer LJ, Dery S, Dewailly E. Erythrocyte n-3 is inversely correlated

with serious psychological distress among the Inuit: data from the Nunavik health

survey. J Am Coll Nutr 2010;29:211–21.

[173] Madsen T, Christensen JH, Svensson M, Witt PM, Toft E, Schmidt EB. Marine n-3

polyunsaturated fatty acids in patients with end-stage renal failure and in subjects

without kidney disease: a comparative study. J Ren Nutr 2011;21:169–75.

[174] Maes M, Christophe A , Delanghe J, Alta mura C, Neels H, Mel tzer HY. Lowered

omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters

of depressed patients. Psychiatry Res 1999;85:275–91.

[175] Magnusardottir A R, Steingrimsdottir L, Thorgeir sdottir H, Gunnl augsson G,

Skuladottir GV. Docosahexaenoic acid in red blood cells of women of reproductive

age is positively associated with oral contraceptive use and physical activity. Pros-

taglandins Leukot Essent Fat Acids 2009;80:27–32.

[176] Makhoul Z, Kristal AR, Gulati R, Luick B, Bersamin A,O'Brien D, et al. Associations of

obesity with triglycerides and C-reactive protein are attenuated in adults with high

red blood cell eicosapentaenoic and docosahexaenoic acids. Eur J Clin Nutr 2011;

65:808–17.

[177] MakiKC, Reeves MS, FarmerM, Griinari M, BergeK, Vik H, et al. Krill oilsupplemen-

tation increases plasma concentrations of eicosapentaenoic and docosahexaenoic

acids in overweight and obese me n and women. Nutr Res (N Y, NY) 2009 ;29:

609–15.

[178] ManavM, Su J, Hughes K, Lee HP, OngCN. Omega-3 fatty acids and selenium as cor-

onary heart disease risk modifying factors in Asian Indian and Chinese males. Nu-

trition, 20. Los Angeles County, Calif: Burbank; 2004 967–73.

[179] Mantzioris E, Cleland LG, Gibson RA, Neumann MA,Demasi M, James MJ. Biochem-

ical effects of a diet containing foods enriched with n-3 fatty acids. Am J Clin Nutr

2000;72:42–8.

[180] Marangoni F, Colombo C, Martiello A, Poli A, Paoletti R, Galli C. Levels of the n-3

fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are sig-

niﬁcantlyraised in blood lipids by the intake of four walnuts a day in humans. Nutr

Metab Cardiovasc Dis 2007:457–61.

[181] Masson S, Marchioli R, Mozaffarian D, Bernasconi R, MilaniV, Dragani L, et al. Plas-

ma n-3 polyunsaturated fatty acids in chronic heart failure in the GISSI-Heart Fail-

ure Trial: relation with ﬁsh intake, circulating biomarkers,and mortality. Am Heart

J 2013;16 5:208–15 e4.

[182] Mayneris-Perxachs J, Bondia-Pons I, Serra-Hajem L, Catellote AI, Lopez-Sabater MC.

Long-chain n-3 fatty acids and classical cardiovascular disease risk factors among

the Catalan population. Food Chem 2010;119:54–61.

[183] McAfee AJ, McSorley EM, Cuskelly GJ, Fearon AM, Moss BW, Beattie JA, et al. Red

meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in

healthy consumers. Br J Nutr 2011;105:80–9.

[184] McNamara RK, Jandacek R, Rider T, Tso P, Dwivedi Y, Pandey GN. Selective deﬁcits

in erythrocyte docosahexaenoic acid composition in adult patients with bipolar

disorder and major depressive disorder. J Affect Disord 2010;126:303–11.

[185] McNaughton SA, Hughes MC, Marks GC. Validation of a FFQ to estimate the intake

of PUFA usingplasma phospholipid fatty acids and weighedfoods records. Br J Nutr

2007;97:561–8.

[186] Mehendale SS, KilariBams AS, Deshmukh CS, Dhorepatil BS, NimbargiVN, Joshi SR.

Oxidative stress-mediated essential polyunsaturated fatty acid alterations in fe-

male infertility. Hum Fertil 2009;12:28–33.

[187] Merle BM, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Feart C, et al. High con-

centrations of plasma n3fatty acids are associated with decreased risk for late age-

related macular degeneration. J Nutr 2013;143:505–11.

[188] Messa P, Londero D, Massarino F, Paganin L, Mioni G, Zattoni F, et al. Abnormal ar-

achidonic acid content of red blood cell membranes and main lithogenic factors in

148 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

stone formers. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Ren

Assoc 2000;15:1388–93.

[189] Metcalf RG, James MJ, Mantzioris E, Cleland LG. A practical approach to increasing

intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3

fats. Eur J Clin Nutr 2003;57:1605–12.

[190] Metherel AH, Armstrong JM, Patterson AC,Stark KD. Assessment of blood measures

of n-3 polyunsaturatedfatty acids with acute ﬁsh oilsupplementationand washout

in men and women. Prostaglandins Leukot Essent Fat Acids 2009;81:23–9.

[191] Metherel AH, Buzikievich LM, Charkhzarin P, Patterson AC, Peel AC, Howorth AM,

et al. Omega-3 polyunsaturated fatty aci d proﬁling using ﬁngertip-prick whole

blood does not require overnight fasting before blood collection. Nutr Res (N Y,

NY) 2012;32:547–56.

[192] Meydani M, Natiello F, Goldin B, Free N, Woods M, Schaefer E, et al. Effect of long-

term ﬁsh oil supplemen tation on vitamin E status and lipid peroxidation in

women. J Nutr 1991;121:484–91.

[193] Moriguchi EH, Moriguchi Y, YamoriY. Impact of diet on the cardiovascular risk pro-

ﬁle of Japanese immigrants living in Brazil: contributions of World Health Organi-

zation CARDIAC an d MONALISA stud ies. Clin Exp Phar macol Physiol 2 004;

31(Suppl. 2):S5–7.

[194] Motoyama KR, Curb JD, Kadowaki T, El-Saed A, Abbott RD, Okamura T, et al. Asso-

ciation of serum n-6 and n-3 polyunsaturated fatty acids with lipids in 3 popula-

tions of middle-aged men. Am J Clin Nutr 2009;90:49–55.

[195] Mozaffarian D,Lemaitre RN, King IB,Song X, Huang H, Sacks FM, et al. Plasma phos-

pholipid long-chain omega-3 fatty acids and total and cause-speciﬁc mortality in

older adults: a cohort study. Ann Intern Med 2013;158:515–25.

[196] Mozaffarian D, Lemaitre RN, King IB, Song X, Spiegelman D, Sacks FM, et al. Circu-

lating long-chain omega-3 fatty acids and incidence of congestive heart failure in

older adults: the c ardiovascula r health study: a coh ort study. Ann Inte rn Med

2011;155:160–70.

[197] Muldoon MF, Ryan CM, Sheu L, Yao JK, Conklin SM, Manuck SB. Serum phospholip-

id docosahexaenonic acid is associated with cognitive functioning during middle

adulthood. J Nutr 2010;140:848–53.

[198] Munro IA, Garg ML. Dietary supplementation with n-3 PUFA does not promote

weight loss when combined wi th a very-low-energy diet. Br J Nutr 2012;108:

1466–74.

[199] Murphy KJ, Meyer BJ, Mori TA, Burke V, Mansour J, Patch CS, et al. Impact of foods

enriched with n-3 long-chain polyunsaturatedfatty acids on erythrocyte n-3 levels

and cardiovascular risk factors. Br J Nutr 2007;97:749–57.

[200] Nagasaka R, Gagnon C, Swist E, Rondeau I, Massarelli I, Cheung W, et al. EPA and

DHA status of South Asian and white Canadians living in the National Capital Re-

gion of Canada. Lipids 2014;49:1057–69.

[201] Nakamura T, Takebe K, Tando Y, Arai Y, Yamada N, Ishii M, et al. Serum fatty acid

composition in normal Japanese and its relationship with dietary ﬁsh and vegeta-

ble oil contents and blood lipid levels. Ann Nutr Metab 1995;39:261–70.

[202] Nenseter MS, Osterud B, Larsen T, Strom E, Bergei C, Hewitt S, et al. Effect of Norwe-

gian ﬁsh powder on risk factors for coronary heart disease among hypercholester-

olemic individuals. Nutr Metab Cardiovasc Dis 2000;10:323–30.

[203] Newcomer LM, King IB, Wicklund KG, Stanford JL. The association of fatty acids

with prostate cancer risk. Prostate 2001;47:262–8.

[204] Nikkari T, Luukkainen P, Pietinen P, Puska P. Fatty acid composition of serum

lipid fractions in relation to gender and quality of dietary fat. Ann Med 1995;

27:491–8.

[205] Njelekela M, Ikeda K, Mtabaji J, Yamori Y. Dietary habits, plasma polyunsaturated

fatty acids and selected coronary disease risk factors in Tanzania. East Afr Med J

2005;82:572–8.

[206] NogiA, Yang J, Li L, YamasakiM, Watanabe M, Hashimoto M, et al.Plasma n-3 poly-

unsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean

and Mongolian workers. J Occup Health 2007;49:205–16.

[207] Novgorodtseva TP , Denisenko YK, Zhukova NV, Antonyuk MV, Knyshova VV ,

Gvozdenko TA. Modiﬁcation of the fatty acid composition of the erythrocyte mem-

brane in patients with chronic respiratory diseases. Lipids Health Dis 2013;12:

12–117.

[208] Novgorodtseva TP, Karaman YK, Zhukova NV, Lobanova EG, Antonyuk MV, Kantur

TA. Composition of fatty acids in plasma and erythrocytes and eicosanoids level in

patients with metabolic syndrome. Lipids Health Dis 2011;10:10–82.

[209] O'Brien DM, Kristal AR, Jeannet MA, Wilkinson MJ, Bersamin A, Luick B. Red blood

cell delta15N: a novel biomarker o f dietary eicos apentaenoic acid and

docosahexaenoic acid intake. Am J Clin Nutr 2009;89:913–9.

[210] Oda E,Hatada K, Kimura J, Aizawa Y, Thanikachalam PV,Watanabe K. Relationships

between serum unsaturated fatty acids and coronary risk factors: negative rela-

tions between nervonic acid and obesity-related risk factors. Int Heart J 2005;46:

975–85.

[211] Ottestad I, Vogt G, Retterstol K, Myhrstad MC, Haugen JE, Nilsson A, et al. Oxidised

ﬁsh oil doesnot inﬂuence established markersof oxidative stress in healthy human

subjects: a randomised controlled trial. Br J Nutr 2012;108:315–26.

[212] Palozza P, Sgarlata E, Luberto C, Piccioni E, Anti M, Marra G, et al. n-3 fatty acids in-

duce oxidative modiﬁcations in human erythrocytes depending on dose and dura-

tion of dietary supplementation. Am J Clin Nutr 1996;64:297–304.

[213] Panagiotakos DB, Mamplekou E, Pits avos C, Kalogeropoulos N, Kastorini CM,

Papageorgiou C, et al. Fatty acids in take and depressive symptomato logy in a

Greek sample: an epidemiological analysis. J Am Coll Nutr 2010;29:586–94.

[214] ParkY, Kim M, Baek D, Kim SH. Erythrocyte n-3 polyunsaturated fatty acid and sea-

food intake decrease the risk of depression: case–control study in Korea. Ann Nutr

Metab 2012; 61:25–31.

[215] Park Y, Lim J, Lee J, Kim SG. Erythrocyte fatty acid proﬁles can predict acute non-

fatal myocardial infarction. Br J Nutr 2009;102:1355–61.

[216] Park Y, Park S, Yi H, Kim HY, Kang SJ, Kim J, et al. Low level of n-3 polyunsaturated

fatty acids in erythrocytes is a risk factor for both acute ischemic and hemorrhagic

stroke in Koreans. Nutr Res (N Y, NY) 2009;29:825–30.

[217] Parkinson AJ, Cruz AL, Heyward WL, Bulkow LR, Hall D, Barstaed L, et al. Elevated

concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan

Eskimos. Am J Clin Nutr 1994;59:384–8.

[218] Patenaude A, Rodriguez-Leyva D, Edel AL, Dibrov E, Dupasquier CM, Austria JA,

et al. Bioavailability of alpha-linolenic acid from ﬂaxseed diets as a function of

the age of the subject. Eur J Clin Nutr 2009;63:1123–9.

[219] Pauletto P, Puato M, Caroli MG, Casiglia E, Munhambo AE, Cazzolato G, et al. Blood

pressure and atherogenic lipoprotein proﬁles of ﬁsh-diet and vegetarian villagers

in Tanzania: the Lugalawa study. Lancet 1996;348:784–8.

[220] Paunescu AC, Ayotte P, Dewailly E, Dodin S, Pedersen HS, Mulvad G, et al. Polyun-

saturated fatty acids and calcaneal ultrasound parameters among Inuit women

from Nuuk (Greenland): a longitudinal study. Int J Circumpolar Health 2013;72.

[221] Peet M, Laugharne J, Rangarajan N, Horrobin D, Reynolds G. Depleted red cell mem-

brane essential fatty acids in drug-treated schizophrenic patients. J Psychiatr Res

1995;29:227–32.

[222] Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red

blood cell membranes of depressive patients. Biol Psychiatry 1998;43:315–9.

[223] Philibert A, Vanier C, Abdelouahab N, Chan HM, Mergler D. Fish intake and serum

fatty acid proﬁles from freshwater ﬁsh. Am J Clin Nutr 2006;84:1299–307.

[224] Phinney SD, Odin RS, Johnso n SB, Holman RT. Reduce d arachidonate in seru m

phospholipids and cholesteryl esters associated with vegetarian diets in humans.

Am J Clin Nutr 1990;51:385–92.

[225] Pottala JV, Garg S, Cohen BE, Whooley MA, Harris WS. Blood eicosapentaenoic and

docosahexaenoic acids predict all-cause mortality in patients with stable coronary

heart disease: the Heart and Soul study. Circ Cardiovasc Qual Outcomes 2010;3:

406–12.

[226] Prevention. CfDCa, Sciences. DoL, Health. NCfE. 2nd National report on biochemical

indicators of diet and nutrition in the U.S. population; 2012 1–495.

[227] Raatz SK,Redmon JB, Wimmergren N, Donadio JV, Bibus DM. Enhancedabsorption

of n-3 fatty acids from emulsiﬁed compared with encapsulated ﬁsh oil. J Am Diet

Assoc 2009;109: 1076–81.

[228] Raatz SK, Rosenberger TA, Johnson LK, Wolters WW, Burr GS, Picklo Sr MJ. Dose-

dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma

phospholipid n-3 fatty acids differentially. J Acad Nutr Diet 2013;113:282–7.

[229] Ramsden C, Gagnon C, Graciosa J, Faurot K, David R, Bralley JA, et al. Do omega-6

and trans fatty a cids play a role in complex regional pain synd rome? A pilot

study. Pain Med (Malden, Mass) 2010;11:1115–25.

[230] Rao S, Erasmus RT. A pilot study on plasma fatty acids in poorly controlled non in-

sulin dependent (type 2) Melanesian diabetics. Cent Afr J Med 1996;42:295–7.

[231] Reddy RD, Keshavan MS, Yao JK. Reduced red blood cell membrane essential poly-

unsatura ted fatty acids in ﬁrst episode schizophrenia at neuroleptic-naivebaseline.

Schizophr Bull 2004;30:901–11.

[232] Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, et al. Dose-related

effects of eicosapentaenoic acid on innate immune function in healthy humans: a

comparison of young and older men. Am J Clin Nutr 2006;83:331–42.

[233] Reinders I, Virtanen JK, Brouwer IA, Tuomainen TP. Association of serum n-3 poly-

unsaturated fatty acids with C-reactive protein in men. Eur J Clin Nutr 2012;66:

736–41.

[234] Rezvukhin AI, Shalaurova I, Berezovskaia EV. Effect of actual diet on fatty acid com-

position of blood serum and indicators of immunity in Siberian and Chukotka pop-

ulations. Vopr Med Khim 1996;42:59–64.

[235] Richardson AJ, Cyhlarova E, Ross MA. Omega-3 and omega-6 fatty acid concentra-

tions in red blood cell membranes relate to schizotypal traits in healthy adults.

Prostaglandins Leukot Essent Fat Acids 2003;69:461–6.

[236] Rissanen H, Knekt P, Jarvinen R, Salminen I, Hakulinen T. Serum fatty acids and

breast cancer incidence. Nutr Cancer 2003;45:168–75.

[237] Rizzo AM, Corsetto PA, Montorfano G, Opizzi A, Faliva M, Giacosa A, et al. Compar-

ison between the AA/EPA ratio in depressed and non depressed elderly females:

omega-3 fatty acid supplementation correlates with improved symptoms but

does not change immunological parameters. Nutr J 2012;11:82.

[238] Rizzo AM, Montorfano G, Negroni M, Adorni L, Berselli P, Corsetto P, et al. A rapid

method for determining arachidonic:eicosapentaenoic acid ratios in whole blood

lipids: correlation with erythrocyte membrane ratios and validation in a large Ital-

ian population of various ages and pathologies. Lipids Health Dis 2010;9:7.

[239] Rode A, Shephard RJ, Vloshinsky PE, KuksisA. Plasma fatty acid proﬁles of Canadian

Inuit and Siberian Ganasan. Arctic Med Res 1995;54:10–20.

[240] Rodriguez Y, Giri M, Rottiers R, ChristopheAB. Obese type 2 diabeticsand obese pa-

tients have comparable plasma phospholipid fatty acid compositions deviating

from that of healthy individuals. Prostaglandins Leukot Essent Fat Acids 2004;71:

303–8.

[241] RosellMS, Lloyd-Wright Z, Appleby PN, Sanders TA, Allen NE, Key TJ. Long-chain n-

3 polyunsaturated fatty acids in p lasma in British meat-eating, vege tarian, and

vegan men. Am J Clin Nutr 2005;82:327–34.

[242] Rusca A, Di Stefano AF, Doig MV, Scarsi C, Perucca E. Relative bioavailability and

pharmacokinetics of two oral fo rmulations of docosahexaenoic aci d/

eicosapentaenoic acid after multiple-dose administration in healthy volunteers.

Eur J Clin Pharmacol 2009;65:503–10.

[243] Ruusunen A, Virtanen JK, Lehto SM, Tolmunen T, Kauhanen J, Voutilainen S. Serum

polyunsaturated fatty acids are not associated with the risk ofsevere depression in

middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD)

study. Eur J Nutr 2011;50:89–96.

[244] Saadatian-Elahi M, Slimani N, Chajes V, Jenab M, Goudable J, Biessy C, et al. Plasma

phospholipid fatty acid proﬁles and their association with food intakes: results

149K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

from a cross-sectional study within the European Prospective Investigation into

Cancer and Nutrition. Am J Clin Nutr 2009;89:331–46.

[245] Sala-Vila A, Harris WS, Cofan M, Perez-Heras AM, Pinto X, Lamuela-Raventos RM,

et al. Determinants of the omega-3 index in a Mediterranean population at in-

creased risk for CHD. Br J Nutr 2011;106:425–31.

[246] Samieri C, Feart C, Letenneur L, Dartigues JF, Peres K, Auriacombe S, et al. Low plas-

ma eicosapentaenoic acid and depressive symptomatology are independent pre-

dictors of dementia risk. Am J Clin Nutr 2008;88:714–21.

[247] Samieri C, Feart C, Proust-Lima C, Peuchant E, Dartigues JF, Amieva H, et al. Omega-

3 fatty acids and cognitive decline: modulation byApoEepsilon4 allele and depres-

sion. Neurobiol Aging 2011;32 2317 e13-22.

[248] Samieri C, Maillard P, Crivello F, Proust-Lima C, Peuchant E, Helmer C, et al. Plasma

long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurolo-

gy 2012;79:642–50.

[249] Sanders TA, Gleason K, Grifﬁn B, Miller GJ. Inﬂuence of an algal triacylglycerol con-

taining docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) on

cardiovascular risk factors in healthy men and women. Br J Nutr 2006;95:525–31.

[250] Schloss I, Kidd MS, Tichelaar HY, Young GO, O'Keefe SJ. Dietary factors associated

with a low risk of colo n cancer in colo ured west coast ﬁsher men. S Afr Med J

1997;87:15 2–8.

[251] Sekikawa A, Curb JD, Ueshima H, El-Saed A, Kadowaki T, Abbott RD, et al. Marine-

derived n-3 fatty acids and atherosclerosis in Japanese, Japanese–American, and

white men: a cross-sectional study. J Am Coll Cardiol 2008;52:417–24.

[252] Sekikawa A, Steingrimsdottir L, Ueshima H, Shin C, Curb JD, Evans RW, et al. Serum

levels of marine-derived n-3 fa tty acids in Ic elanders, Jap anese, Koreans , and

Americans—a descriptive epidemiologic study. Prostaglandins Leukot Essent Fat

Acids 2012;87:11–6.

[253] Sfar S,Laporte F, Braham H, Jawed A, Amor S, Kerkeni A. Inﬂuence of dietary habits,

age and gender on plasmafatty acids levels ina population of healthyTunisian sub-

jects. Exp Gerontol 2010;45:719–25.

[254] Shannon J, King IB, MoshofskyR, Lampe JW, Gao DL, RayRM, et al. Erythrocyte fatty

acids and breast cancer risk: a case–control study in Shanghai, China. Am J Clin

Nutr 2007;85:1090–7.

[255] SirotV,DumasC,DesquilbetL,MariottiF,LegrandP,CathelineD,etal.Are-

stricted cubic spline approach to assess the association between high fat ﬁsh

intake and red blood cell EPA + DHA content. Nutr Metab Cardiovasc Dis

2012;22:318–26.

[256] Skuladottir GV, Gu dmundsdottir S, Olafsso n GB, Sigurdsson SB, Sigfusson N,

Axelsson J. Plasma fatty acids and lipids in two separate, but genetically compara-

ble, Icelandic populations. Lipids 1995;30:649–55.

[257] Sobczak S, Honig A, Christophe A, Maes M, Helsdingen RW, De Vriese SA, et al.

Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturat-

ed fatty acids in ﬁrst-degree relatives of bipolar patients. Psychol Med 2004;34:

103–12.

[258] Solakivi T, Kaukinen K, Kunnas T, Lehtimaki T, Maki M, Nikkari ST. Serum fatty acid

proﬁle in subjects with irritable bowel syndrome. Scand J Gastroenterol 2011;46:

299–303.

[259] Solomons NW, Bailey E, Soto Mendez MJ, Campos R, Kraemer K, Salem Jr N. Eryth-

rocyte fatty acid status in a convenience sampleof residents of the Guatemalan Pa-

ciﬁc coastal plain. Prostaglandins Leukot Essent Fat Acids 2015;98:21–7.

[260] Stark KD, Holub BJ. Differential eicosapentaenoic acid elevations and altered car-

diovascular di sease risk factor responses after supplementati on with

docosahexaenoic acid in postmenopausal women receiving and not receiving hor-

mone replacement therapy. Am J Clin Nutr 2004;79:765–73.

[261] Stark KD, Mulvad G, Pedersen HS, Park EJ, Dewailly E, Holub BJ. Fatty acid compo-

sitions of serum phospholipids of postmenopausal women:a comparison between

Greenland Inuit and Canadians before and after supplementation with ﬁsh oil. Nu-

trition, 18. Los Angeles County, Calif: Burbank; 2002 627–30.

[262] Stark KD, Park EJ, Maines VA, Holub BJ. Effect of a ﬁsh-oil concentrate on serum

lipids in postmenopausal women receiving and not receiving hormone replace-

ment therapy in a placebo-controlled, double-blind trial. Am J Clin Nutr 2000;72:

389–94.

[263] Stonehouse W, Pauga MR, Kruger R, Thomson CD, Wong M, Kruger MC. Consump-

tion of salmon v. salmon oil capsules: effects on n-3 PUFA and selenium status. Br J

Nutr 2011;106:1231–9.

[264] Stough C, Downey L, Silber B, Lloyd J, Kure C, Wesnes K, et al. The effects of 90-day

supplementati on with the omega-3 essential fa tty acid docosa hexaenoic acid

(DHA) on cogniti ve function an d visual acuity i n a healthy aging population.

Neurobiol Aging 2012;33 824 e1-3.

[265] Sublette ME, Bosetti F, DeMar JC, Ma K, Bell JM, Fagin-Jones S, et al. Plasma free

polyunsaturated fatty acid levels are associated with symptom severity in acute

mania. Bipolar Disord 2007;9:759–65.

[266] Sublette ME, Segal-Isaacson CJ, Cooper TB, Fekri S, Vanegas N, Galfalvy HC, et al.

Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturat-

ed fatty acids in subjects with and without major depressive disorder. J Am Diet

Assoc 2011;111 117-23 e1-2.

[267] Sullivan BL, Williams PG, Meyer BJ. Biomarker validation of a long-chain omega-3

polyunsaturated fatty acid food frequency questionnaire. Lipids 2006;41:845–50.

[268] Sun Q, Ma J, Campos H, Hankinson SE, Hu FB. Comparison between plasma and

erythrocyte fatty acid content as biomarke rs of fatty acid intake in US women.

Am J Clin Nutr 2007;86:74–81.

[269] Suominen-Taipale AL, Partonen T, Turunen AW, Mannisto S, Jula A, Verkasalo PK.

Fish consumption and omega-3 polyunsaturated fatty acids in relation to depres-

sive episodes: a cross-sectional analysis. PLoS ONE 2010;5, e10530.

[270] Surai PF, MacPherson A, Speake BK, Sparks NH. Designer egg evaluation in a con-

trolled trial. Eur J Clin Nutr 2000;54:298–305.

[271] Surette ME, Edens M, Chilton FH, Tramposch KM. Dietary echium oil increases plas-

ma and neutrophil long-chain (n-3) fatty acids and lowers serum triacylglycerols

in hypertriglyceridemic humans. J Nutr 2004;134:1406–11.

[272] Sutherland WH, Shilton ME, Nye ER, Gillies ME, Bakani I, Robertson MC. Urban/

rural differences in red blood cell fatty acid composition, plasma lipids and diet

in Melanesian Fijians. Eur J Clin Nutr 1995;49:233–41.

[273] Takita T, Nakmura K, Kimira M, Yamada N, Kobayashi Y, Innami S. Serum fatty acid

compositions and lipid concentrations and their correlations. J Clin Biochem Nutr

1996;20:149–59.

[274] Thorlaksdottir AY, Skuladottir GV, Petursdottir AL, Tryggvadottir L, Ogmundsdottir

HM, Eyfjord JE, et al. Positive association between plasma antioxidant capacity and

n-3 PUFA in red blood cells from women. Lipids 2006;41:119–25.

[275] Thorseng T, Witte DR, Vistisen D, Borch-Johnsen K, Bjerregaard P, Jorgensen ME.

The association between n-3 fatty acids in erythrocyte membranes and insulin re-

sistance: the Inuit Health in Transition Study. Int J Circumpolar Health 2009;68:

327–36.

[276] Tiemeier H, van Tuijl HR,Hofman A, Kiliaan AJ, Breteler MM. Plasmafatty acid com-

position and depression are associated in the elderly: the Rotterdam Study. Am J

Clin Nutr 2003;78:40–6.

[277] Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Jenssen T. Effects of n-3 polyunsaturat-

ed fatty acidson glucose homeostasisand blood pressure in essential hypertension.

A randomized, controlled trial. Ann Intern Med 1995;123:911–8.

[278] Tomiyama H, Matsumoto C, Odaira M, Yamada J, Yoshida M, Shiina K, et al. Rela-

tionshipsamong the serum omega fattyacid levels, serum C-reactive protein levels

and arterial stiffness/wave reﬂection in Japanese men. Atherosclerosis 2011;217:

433–6.

[279] Torres IC, Mira L, Ornelas CP, Melim A. Study of the effects of dietary ﬁsh intake on

serum lipids and lipoproteins in two populations with different dietary habits. Br J

Nutr 2000;83:371–9.

[280] Tremoli E, Maderna P, Marangoni F, Colli S, Eligini S, Catalano I, et al. Prolonged in-

hibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy

volunteers. Am J Clin Nutr 1995;61:607–13.

[281] Umemura U, Ishimori M, Kobayashi T, Tamura Y, Koike KA, Shimamoto T, et al.

Possible effects of diets on serum lipids, fatty acids and blood pressure levels in

male and female Japanese university students. Environ Health Prev Med 2005;

10:42–7.

[282] Vaddadi KS, Gilleard CJ, Soosai E, Polonowita AK, Gibson RA, Burrows GD. Schizo-

phrenia, tardive dyskinesia and essential fatty acids. Schizophr Res 1996;20:

287–94.

[283] Valera B, Dewailly E, Anassour-Laouan-Sidi E, Poirier P. Inﬂuence of n-3 fatty acids

on cardiac autonomic activity amongNunavik Inuit adults. Int J Circumpolar Health

2011;70:6–18.

[284] Valsta LM, SalminenI, Aro A, Mutanen M. Alpha-linolenic acid in rapeseed oil partly

compensates for the effect of ﬁsh restriction on plasma long chain n-3 fatty acids.

Eur J Clin Nutr 1996;50:229–35.

[285] van den Ham EC, van Houwelingen AC, Hornstra G. Evaluation of the relation be-

tween n-3 and n-6 fatty acid status and parity in nonpregnant women from the

Netherlands. Am J Clin Nutr 2001;73:622–7.

[286] van der Pols JC, Xu C, Boyle GM, Hughes MC, Carr SJ, Parsons PG, et al. Serum

omega-3 and omega-6 fatty acids and cutaneous p53 expression in an Australian

population. Cancer Epidemiol Biomark Prev 2011;20:530–6.

[287] Virtanen JK, Laukkanen JA, Mursu J, Voutilainen S, Tuomainen TP. Serumlong-chain

n-3 polyunsaturated fattyacids, mercury, and risk of sudden cardiac death in men:

a prospective population-based study. PLoS ONE 2012;7, e41046.

[288] VisioliF, Rise P, Barassi MC, Marangoni F, Galli C. Dietary intake of ﬁsh vs. formula-

tions leads to higher plasma concentrat ions of n-3 fatty aci ds. Lipids 2003;38:

415–8.

[289] Vognild E, Elvevoll EO, Brox J, Olsen RL, Barstad H, Aursand M, et al. Effects of

dietary marine oils and olive oil on fatty acid composition, platelet membrane

ﬂuidity, platelet responses, and serum lipids in healthy humans. Lipids 1998;

33:427–36.

[290] Wakai K, Ito Y, Kojima M, Tokudome S, Ozasa K, Inaba Y, et al. Intake frequency of

ﬁsh and serum levels of long-chain n-3 fatty acids: a cross-sectional study within

the Japan Collaborative Cohort Study. J Epidemiol Jpn Epidemiol Assoc 2005;15:

211–8.

[291] Wang L, Folsom AR, Eckfeldt JH. Plasma fatty acid composition and incidence of

coronary heart disease in middle aged adults: the Atherosclerosis Risk in Commu-

nities (ARIC) Study. Nutr Metab Cardiovasc Dis 2003;13:256–66.

[292] Watanabe N, Watanabe Y, Kumagai M, Fujimoto K. Administration of dietary ﬁsh

oil capsules in healthy middle-aged Japanese men with a high level of ﬁsh con-

sumption. Int J Food Sci Nutr 2009;60(Suppl. 5):136–42.

[293] Welch AA, Bingham SA, Ive J, Friesen MD, Wareham NJ, Riboli E, et al. Dietary ﬁsh

intake and plasma phospholipid n-3 polyunsaturated fatty acid concentrations in

men and women in the European Prospective Investigation into Cancer-Norfolk

United Kingdom cohort. Am J Clin Nutr 2006;84:1330–9.

[294] Wennberg M, Bergdahl IA, Hallmans G, Norberg M, Lundh T, Skerfving S, et al. Fish

consumption and myocardial infarction: a second prospective biomarker study

from northern Sweden. Am J Clin Nutr 2011;93:27–36.

[295] Whalley LJ, Fox HC, Wahle KW, Starr JM, Deary IJ. Cognitive aging, childhood intel-

ligence, and the use of food supplements: possible involvement of n-3 fatty acids.

Am J Clin Nutr 2004;80:1650–7.

[296] YamadaT, Strong JP, Ishii T, Ueno T, Koyama M, WagayamaH, et al. Atherosclerosis

and omega-3 fatty acids in the populations of a ﬁshing village and a farming village

in Japan. Atherosclerosis 2000;153:469–81.

[297] YaqoobP, Pala HS, Cortina-Borja M, NewsholmeEA, Calder PC. Encapsulated ﬁsh oil

enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell

150 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

fatty acid compositions but not mononuclear cell functions. Eur J Clin Investig

2000;30:260–74.

[298] Yeh LL, Kuller LH, Bunker CH, Ukoli FA, Huston SL, Terrell DF. The role of socioeco-

nomic status and serum fatty acids in the relationship between intake of animal

foods and cardiovascular risk factors. Ann Epidemiol 1996;6:290–8.

[299] Yerlikaya FH, Mehmetoglu I, Kurban S, Tonbul Z. Plasma fatty acid composition in

continuous amb ulatory perito neal dialysis patients: an increased omega-6/

omega-3 ratio and deﬁciency of essential fatty acids. Ren Fail 2011;33:819–23.

[300] Young LR, Kurzer MS, Thomas W, Redmon JB, Raatz SK. Effect of dietary fat and

omega-3 fatty acids on urinary eicosanoids and sex hormone concentrations in

postmenopausa l women: a randomized control led feeding tr ial. Nutr Cancer

2011;63:930–9.

[301] Young LR, Raatz SK, Thomas W, Redmon JB, Kurzer MS. Total dietary fat and

omega-3 fatty acids have modest effects on urinary sex hormones in postmeno-

pausal women. Nutr Metab 2013;10:1743–7075.

[302] Zhang J, Wang C, Li L, Man Q, Song P, Meng L, et al. Inclusion of Atlantic salmon in

the Chinese diet reduces cardiovascular disease risk markers in dyslipidemic adult

men. Nutr Res (N Y, NY) 2010;30:447–54.

[303] ZhaoM, Lamers Y, Ralat MA, Coats BS, Chi YY, Muller KE, et al. Marginal vitamin B-6

deﬁciency decreases plasma (n-3) and (n-6) PUFA concentrations in healthy men

and women. J Nutr 2012;142:1791–7.

[304] Zheng JS, Xu A, Huang T, Yu X, Li D. Low docosahexaenoic acid content in plasma

phospholipids is associated with increased non-alcoholic fatty liver disease in

China. Lipids 2012;47:549–56.

[305] Zhou YE, Kubow S, Egeland GM. Highly unsaturated n-3 fatty acids status of Cana-

dian Inuit:InternationalPolar Year Inuit Health Survey,2007–2008 . Int J Circumpo-

lar Health 2011;70:498–510.

[306] Zhu J, Sun Q, Zong G, Si Y, Liu C, Qi Q, et al. Interaction between a common variant

in FADS1 and erythrocyte polyunsaturated fatty acids on lipid proﬁle in Chinese

Hans. J Lipid Res 2013;54:1477–83.

[307] Zhukova NV, Novgorodtseva TP. Lipid Composition of Erythrocytes at Cardiovascu-

lar and Hepatobiliary Diseases. In: Gilmore PL, editor. Lipids: Categories, Biological

Functions and Metabolism; 2009.

[308] Zuijdgeest-van Leeuwen SD, van der He ijden MS, Rietveld T, van den Berg JW,

Tilanus HW, Burgers JA, et al. Fatty acid composition of plasma lipids in patients

with pancreatic, lung and oesophageal cancer in comparisonwith healthy subjects.

Clin Nutr (Edinburgh, Scotland) 2002;21:225–30.

[309] Assies J, Lieverse R, Vreken P, Wanders RJ, Dingemans PM,Linszen DH. Signiﬁcantly

reduced docosahexaenoic and docosapentaenoic acid concentrations in erythro-

cyte membranes from schizophrenic patients compared with a carefully matched

control group. Biol Psychiatry 2001;49:510–22.

[310] Lee E, Lee S, Park Y. n-3 Polyunsaturated fattyacids and trans fatty acids in patients

with the metabolic syndrome: a case-control study in Korea. Br J Nutr 2008;100:

609–14.

[311] Armstrong JM, Metherel AH, Stark KD. Direct microwave transesteriﬁcation of ﬁn-

gertip prick blood samples for fatty acid determinations. Lipids 2008;43:187–96.

[312] Alexander LR, Justice Jr JB, Madden J. Fatty acid composition of human erythrocyte

membranes by capillary gas chromatography-mass spectrometry. J Chromatogr

1985;342:1–12.

[313] Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from

coronary heart disease? Prev Med 2004;39:212–20.

[314] StarkKD, Aristizabal HenaoJJ, Metherel AH, Pilote L. Translating plasma and whole

blood fatty acid compositional data into the sum o f eicosapentaenoic and

docosahexaenoic acid in eryth rocytes. Pros taglandins Leukot Essent Fat Acids

2015;104:1–10.

[315] United Nations. Statistical Ofﬁce. Population and Vital Statistics Report. Statistical

Papers Series A. New York: United Nations; 2015. p. 1–23.

[316] Parra MS, Schnaas L, Meydani M, Perroni E, Martinez S, Romieu I. Erythrocyte cell

membrane phospholipid levels compared against reported dietary intakes of polyun-

saturated fatty acids in pregnant Mexican women. Public Health Nutr 2002;5:931–7.

[317] Abdelmagid SA, Clarke SE, Nielsen DE, Badawi A, El-Sohemy A, Mutch DM, et al.

Comprehe nsive proﬁling of plasma fatty acid concentrations in young healthy Ca-

nadian adults. PLoS ONE 2015;10, e0116195.

[318] Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in con-

sumption of omega-3 and omega-6 fatty acids in the Unit ed States during the

20th century. Am J Clin Nutr 2011;93:950–62.

[319] Metherel AH, Aristizabal Henao JJ,Stark KD. EPA and DHA levels in wholeblood de-

crease more rapidly when stored at −20 degrees C as compared with room tem-

perature, 4 and −75 degrees C. Lipids 2013;48:1079–91.

[320] Metherel AH, Stark KD. Cryopreservation prevents iron-initiated highly unsaturat-

ed fatty acid loss duringstorage of human blood on chromatography paper at −20

degrees C. J Nutr 2015;145:654–60.

[321] Stark KD. Analytical implications of routine clinical testing for omega-3 fatty acid

biomarkers. Lipid Technol 2008;20:177–9.

[322] Lacher DA, Hughes JP, Carroll MD. Estimate of biological variation of laboratory

analytes based on the third nat ional health and nutrition ex amination survey.

Clin Chem 2005;51:450–2.

[323] Schantz MM, Powers CD, Sch leicher RL. Interlaboratory Analytical Comparison

Study of Total Fatty Acid Concentrations in Human Serum: Results for Exercise

01: QA12FASER01. In: USDoC NIST, editor. NIST Interagency/Internal Repor t

(NISTIR) - 79532013; 2013. p. 1–79.

[324] vonSchacky C. The Omega-3 Index as a risk factor forcardiovascular diseases. Pros-

taglandins Other Lipid Mediat 2011;96:94–8.

[325] Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S, et al. Ef-

fects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a

randomised placebo controlled trial. BMJ 2010;341:c6273.

[326] Kromhout D, Giltay EJ, Geleijnse JM. Alpha Omega Trial G. n-3 fatty acids and car-

diovascular events after myocardial infarction. N Engl J Med 2010;363:2015–26.

[327] Brenna JT. Fatty acid analysis by high resolution gas chromatography and mass

spectrometry for clinical and experimental applications. Curr Opin Clin Nutr

Metab Care 2013;16:548–54.

[328] Hedengran A, Szecsi PB, Dyerberg J, Harris WS, Stender S. n-3 PUFA esteriﬁed to

glycerol or as ethyl esters reduce non-fasting plasma triacylglycerol in subjects

with hypertriglyceridemia: a randomized trial. Lipids 2015;50:165–75.

[329] Browning LM, WalkerCG, Mander AP, West AL, Madden J, GambellJM, et al. Incor-

poration of eicosapentaenoic and docosahexaenoic acids into lipid pools when

given as supplements providing doses equivalent to typical intakes of oily ﬁsh.

Am J Clin Nutr 2012;96:748–58.

[330] Marangoni F, ColomboC, Galli C. A method for the directevaluation of the fatty acid

status in a drop of blood from a ﬁngertipin humans: applicability to nutritional and

epidemiological studies. Anal Biochem 2004;326:267–72.

[331] Galli C, Rise P, Ghezzi S, Marangoni F. Fast determination of fatty acids in whole

blood collected from ﬁngertips: application to the assessment of fatty acid patterns

(and variousindexes) in populationstudies. World Rev Nutr Diet2009;100:35–45.

[332] Nurhasan M, Roos N, Aristizabal Henao JJ, Chamnan C, Stark KD, Lauritzen L. Effect

of storage temperature in a Cambodian ﬁeld setting on the fatty acid composition

in whole blood. Prostaglandins Leukot Essent Fat Acids 2015;96:57–61.

[333] Bjerve KS, Brubakk AM, Fougner KJ, Johnsen H, Midthjell K, Vik T. Omega-3 fatty

acids: essential fatty acids with important biological effects, and serum phospho-

lipid fatty acids as markers of dietary omega 3-fatty acid intake. Am J Clin Nutr

1993;57 (801S-5S; discussion 5S-6).

[334] Lands WE. Long-term fat intake and biomarkers. Am J Clin Nutr 1995;61:721S–5S.

[335] Ameur A, Enroth S, Johansson A, Zaboli G, Igl W, Johansson AC, et al. Genetic adap-

tation of fatty-acid metabolism: a human-speciﬁc haplotype increasingthe biosyn-

thesis of long-chain omega-3 and omega-6 fatty acids. Am J Hum Genet 2012;90:

809–20.

[336] Merino DM, Johnston H, Clarke S, Roke K, Nielsen D , Badawi A, et al. Polymor-

phisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and

Asian adults. Mol Genet Metab 2011;103:171–8.

[337] Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, GuralnikJM, et al. Genome-

wide association study of plasma pol yunsaturated fatty acids in the InCHIANTI

Study. PLoS Genet 2009;5, e1000338.

[338] Crawford MA. The early development and evolution of the human brain. Ups J Med

Sci Suppl 1990;48:43–78.

[339] Lands WE, Morris A, Libelt B. Quantitative effects of dietary polyunsaturated fats on

the composition of fatty acids in rat tissues. Lipids 1990;25:505–16.

[340] LandsWE, Libelt B, Morris A, Kramer NC, Prewitt TE, Bowen P, et al.Maintenance of

lower proportions of (n - 6) eicosanoid precursors in phospholipids of human plas-

ma in response to added dietary (n - 3) fatty acids. Biochim Biophys Acta 1992;

1180:147–62.

[341] Lands B. A critique of paradoxes in current advice on dietary lipids. Prog Lipid Res

2008;47:77–106.

[342] Burr ML, Ashﬁeld-Watt PA, Dunstan FD, Fehily AM, Breay P, Ashton T, et al. Lack of

beneﬁt of dietary advice to men with angina: results of a controlled trial. Eur J Clin

Nutr 2003;57:193–200.

[343] Patterson AC, Chalil A, Aristizabal Henao JJ, Streit IT, Stark KD. Omega-3 polyunsat-

urated fattyacid blood biomarkers increase linearly in men and women after tight-

ly controlledintakes of 0.25, 0.5, and 1 g/dof EPA + DHA. Nutr Res (N Y, NY) 2015;

35:1040–51.

[344] Metherel AH, Hogg RC, Buzikievich LM, Stark KD. Butylated hydroxytoluene can

protect polyunsaturated fatty acids in dried blood spots from degradation for up

to 8 weeks at room temperature. Lipids Health Dis 2013;12:22.

[345] Otsuka R, Kato Y, Imai T, Ando F, Shimokata H. Higher serum EPA or DHA, and

lower ARA compositions with age independent fatty acid intake in Japanese aged

40 to 79. Lipids 2013;48:719–27.

[346] FlockMR, Harris WS, Kris-Etherton PM. Long-chain omega-3fatty acids: time to es-

tablish a dietary reference intake. Nutr Rev 2013;71:692–707.

[347] Salem Jr N, EggersdorferM. Is the world supply of omega-3 fattyacids adequate for

optimal human nutrition? Curr Opin Clin Nutr Metab Care 2015;18:147–54.

[348] Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, Cunnane SC, et al. To-

wards establishing dietary r eference inta kes for eicosapentaenoic and

docosahexaenoic acids. J Nutr 2009;139:804S–19S.

[349] Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating

the risks and the beneﬁts. JAMA 2006;296:1885–99.

[350] Dyerberg J, Bang HO, Hjorne N. Fatty a cid composition of the p lasma lipids in

Greenland Eskimos. Am J Clin Nutr 1975;28:958–66.

[351] Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Green-

landic West-coast Eskimos. Lancet 1971;1:1143–5.

[352] Bjerregaard P, Young TK, Hegele RA. Low incidence of cardi ovascular dise ase

among the Inuit—what is the evidence? Atherosclerosis 2003;166:351–7.

[353] Fodor JG, Helis E, Yaz dekhasti N, Vohnout B. “Fishing”for the origins of the

“Eskimos and heart disease”story: facts or wishful thinking? Can J Cardiol 2014;

30:864–8.

[354] Bjerregaard P. Fatal accidents in Greenland. Arctic Med Res 1990;49:132–41.

[355] Bjerregaard P, Mulvad G, PedersenHS. Cardiovascular risk factorsin Inuit of Green-

land. Int J Epidemiol 1997;26:1182–90.

[356] Newman3rd WP, Middaugh JP, Guzman MA, Propst MT, Rogers DR. Comparison of

atherosclerosis in alaska Natives and nonnatives. Arch Pathol Lab Med 1997;121:

1069–75.

[357] Pedersen HS, Mulvad G, Newman 3rd WP, Boudreau DA. Atherosclerosis in coro-

nary arteries and aorta among Greenlanders: an autopsy study. Atherosclerosis

2003;170:9 3–103.

151K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

[358] BurrML, Fehily AM, Gilbert JF, RogersS, Holliday RM, Sweetnam PM, et al. Effects of

changes in fat, ﬁsh, and ﬁbre intakes on death and myocardial reinfarction: diet

and reinfarction trial (DART). Lancet 1989;2:757–61.

[359] Investigators G-P. Dietary supplementation with n-3 polyunsaturated fatty acids

and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial.

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet

1999;354:447–55.

[360] Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. n-3 Polyun-

saturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarc-

tion in older adults: the Cardiovascular Health Study. Am J Clin Nutr 2003;77:

319–25.

[361] Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on

risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011;58:

2047–67.

[362] Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of ﬁsh

oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circu-

lation 2005;112:1945–52.

[363] Xin W, Wei W, Li XY. Short-term effects of ﬁsh-oil supplementation on heart rate

variability in humans: a meta-analysis of randomized controlled trials. Am J Clin

Nutr 2013;97:926–35 .

[364] Miller PE, Van Elsw yk M, Alexande r DD. Long-chain omega-3 fatty acids

eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-anal-

ysis of randomized controlled trials. Am J Hypertens 2014;27:885–96.

[365] Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A. Beneﬁts of ﬁsh oil supplemen-

tation in hyperlipidemia: a systematic reviewand meta-analysis. Int J Cardiol 2009;

136:4–16.

[366] Wei MY,Jacobson TA. Effects of eicosapentaenoicacid versus docosahexaenoic acid

on serum lipids: a systematic review and meta-an alysis. Curr Ath eroscler Rep

2011;13:474–83.

[367] Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Ef-

fects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic

patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;

369:1090–8.

[368] Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, et al. OMEGA, a ran-

domized, placebo -controlled trial to test the effect of highly puriﬁed omega-3

fatty acids on top of modern guideline-adjusted therapy after myocardial infarc-

tion. Circulation 2010;122:2152–9.

[369] Investigators OT, Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, et al. n-3 Fatty

acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med

2012;367:309–18.

[370] Roncaglioni MC, Tombesi M, Silletta MG. n-3 Fatty acids in patients with cardiac

risk factors. N Engl J Med 2013;369:781–2.

[371] Hu FB, Manson JE. Omega-3 fatty acids and secondary prevention of cardiovascular

disease-is it just a ﬁsh tale?: comment on “Efﬁcacy of omega-3 fatty acid supple-

ments (eicosapentaenoic acid and docosahexaenoic acid)in the secondary preven-

tion of cardiovascular disease”. Arch Intern Med 2012;172:694–6.

[372] Lewis EJ. Omega-3 fatty acid supplementation and cardiovascular disease events.

JAMA 2013;309:27.

[373] Galli C, Brenna JT. Omega-3 fatty acid supplementation and cardiovascular disease

events. JAMA 2013;309:28–9.

[374] von Schacky C. Omega-3 fatty acids in cardio vascular disease—an uphill battle.

Prostaglandins Leukot Essent Fat Acids 2015;92:41–7.

[375] Khoueiry G, Abi Rafeh N, Sullivan E, Saiful F, Jaffery Z, Kenigsberg DN, et al. Do

omega-3 polyunsaturated fatty acids reduce risk of sudden cardiac death and ven-

tricular arrhythmias? A meta-analysis of randomized trials. Heart Lung 2013;42:

251–6.

[376] Joffre C, Nadjar A, Lebbadi M, Calon F, Laye S. n-3 LCPUFA improves cognition: the

young, the old and the sick. Prostaglandins Leukot Essent Fatty Acids 2014;91:

1–20.

[377] Holman RT, JohnsonSB, Hatch TF. A case of human linolenic aciddeﬁciency involv-

ing neurological abnormalities. Am J Clin Nutr 1982;35:617–23.

[378] Yurko-Mauro K, Alexander DD, Van Elswyk ME. Docosahexaenoic acid and adult

memory: a systematic review and meta-analysis. PLoS ONE 2015;10, e0120391.

[379] Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of

blood plasma of patients with Alzheimer's disease, other types of dementia, and

cognitive impairment. Lipids 2000;35:1305–12.

[380] Lin PY, Chiu CC, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty

acid compositions in dementia. J Clin Psychiatry 2012;73:1245–54.

[381] de Souza Fernandes DP, Canaan Rezende FA, Pereira Rocha G, De Santis FM, Silva

Moreira PR, Goncalves Alfenas Rd e C. Effect of eicos apentaenoic ac id and

docosahexaenoic acid supplementations to control cognitive decline in dementia

and Alzheimer's disease: a systematic review. Nutr Hosp 2015;32:528–33.

[382] Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G,

Garlind A, et al. Omega-3 fatty acid treatment in 174 patients with mild to moder-

ate Alzheimer di sease: OmegAD st udy: a randomi zed double-bli nd trial. Arch

Neurol 2006;6 3:1402–8.

[383] Stonehouse W, Conlon CA, Podd J, HillSR, MinihaneAM, Haskell C, et al. DHA sup-

plementation improved both memory andreaction time in healthyyoung adults: a

randomized controlled trial. Am J Clin Nutr 2013;97:1134–43.

[384] Eriksdotter M, Vedin I, Falahati F, Freund-Levi Y, Hjorth E, Faxen-Irving G, et al.

Plasma fatty acid proﬁles in relation to cognition and genderin Alzheimer's disease

patients during oral omega-3 fatty acid supplementation: the OmegAD Study. J

Alzheimers Dis 2015;48:805–12.

[385] Verboom CN. Critical analysis of G-PT. highly puriﬁed omega-3 polyunsaturated

fatty acids are effective as adjunct therapy for secondary prevention of myocardial

infarction. Herz 2006;31(Suppl. 3):49–59.

[386] Franzosi MG, Brunetti M, Marchioli R, Marﬁsi RM, Tognoni G, Valagussa F, et al.

Cost-effectiveness analysis ofn-3 polyunsaturatedfatty acids (PUFA)after myocar-

dial infarction: results from Gruppo Italiano per lo Studio del la Sopravvivenza

nell'Infarto (GISSI)-Prevenzione Trial. PharmacoEconomics 2001;19:411–20.

[387] Schmier JK, Rachman NJ, Halpern MT. The cost-effectiveness of omega-3 supple-

ments for prevention of secondary coronary events. Manag Care 2006;15:43–50.

[388] Lamotte M, Annemans L, Kawalec P, Zoellners Y. A multi-country health-economic

evaluation of highly concentrated n-3 polyunsaturated fatty acids in the secondary

prevention after myocardial infarction. Herz 2006;31(Suppl. 3):74–82.

[389] Gissi HFI, Tavazzi L, Maggioni AP, MarchioliR, Barlera S, Franzosi MG, et al. Effect of

n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF

trial): a randomi sed, double-b lind, placebo- controlled trial. Lancet 2008; 372:

1223–30.

[390] Cowie MR, Cure S, Bianic F, McGuire A, Goodall G, Tavazzi L. Cost-effectiveness of

highly puriﬁed omega-3 polyunsaturated fatty acid ethyl esters in the treatment

of chronic heart failure: results of Markov modelling in a UK setting. Eur J Heart

Fail 2011;13:681–9.

[391] Quilici S, Martin M,McGuire A, ZoellnerY. A cost-effectiveness analysis of n-3 PUFA

(Omacor) treatment in post-MI patients. Int J Clin Pract 2006;60:922–32.

[392] Samuel S, Peskin B, Arondekar B, Alperin P, Johnson S, Blumenfeld I, et al. Estimat-

ing health and economic beneﬁts from using prescription omega-3 fatty acids in

patients with severe hypertriglyceridemia. Am J Cardiol 2011;108:691–7.

[393] Schmier JK, Hulme-Lowe C, Nelson JR, Chowdhury S, Everett PB, Philip S. Abstract

243: a novel cost effectiveness model of eicosapentaenoic acid (EPA) for secondary

prevention in the United States. Circ Cardiovasc Qual Outcomes 2015;8:A243.

[394] Hwang JY, Kim WS, Jeong S, Kwon O. Evidence-based estimation of health carecost

savings from the use of omega-3 supplementation among the elderly in Korea.

Nutr Res Pract 2015;9:400–3.

[395] Pradelli L, Eandi M, Povero M, Mayer K, Muscaritoli M, Heller AR, et al. Cost-effec-

tiveness of omega-3 fatty acid supplements in parenteral nutrition therapy in hos-

pitals: a discrete event simulation model. Clin Nutr(Edinburgh, Scotland) 2014;33:

785–92.

[396] Wu GH, Gao J, Ji CY, Pradelli L, Xi QL, Zhuang QL. Cost and effectiveness of omega-3

fatty acid supplementation in Chinese ICU patients receiving parenteral nutrition.

Clinicoecon Outcomes Res 2015;7:369–75.

[397] Braga M, Gianotti L, Vignali A, Schmid A, Nespoli L, Di Carlo V. Hospital Resources

Consumed for Surgical Morbidity: Effects of Preoperative Arginine and Omega-3

Fatty Acid Supplementation on Costs. Nutritiron, 21. Los Angeles County, Calif: Bur-

bank; 2005 1078–86.

[398] Chevrou-Severac H, Pinget C, Cerantola Y, Demartines N, Wasserfallen JB,

Schafer M. Cost-effectiveness analysis of immune-modulating nutritional sup-

port for gastrointestinal cancer patients. Clin Nutr (Edinburgh, Scotland)

2014;33:649–54.

[399] Stark KD, Beblo S, Murthy M, Buda-Abela M, Janisse J, Rockett H, et al. Comparison

of bloodstream fatty acid composition fromAfrican–Americanwomen at gestation,

delivery, and postpartum. J Lipid Res 2005;46:516–25.

[400] Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation.Am

J Clin Nutr 2009;89:678S–84S.

[401] Ahmed S, Makrides M, Sim N, McPhee A, Quinlivan J, Gibson R, et al. Analysis of

hospital cost outcome of DHA-rich ﬁsh-oil suppleme ntation in pregnancy: evi-

dence from a rando mized controlled trial. Prostaglandins Leuko t Essent Fatty

Acids 201 5;102-103:5–11.

[402] Stark KD, Patterson AC. EPA and DHA—protein, not fat is “where it's at”?Prosta-

glandins Leukot Essent Fat Acids 2012;87:49–51.

[403] The state of world ﬁsheries and aquaculture/FAO Fisheries Department. 2014.

[404] Brenna JT, Salem Jr N, Sinclair AJ, Cunnane SC. International Society for the study of

fatty A, lipids I. alpha-linolenic acid supplementation and conversion to n-3 long-

chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty

Acids 2009;80:85–91.

[405] Egert S, Lindenmeier M, Harnack K, Krome K, Erbersdobler HF, Wahrburg U, et al.

Margarines for tiﬁed with alpha-linolenic acid, eicosapentaenoic acid, or

docosahexaenoic acidalter the fatty acid compositionof erythrocytes butdo not af-

fect the antioxidant status of healthy adults. J Nutr 2012;142:1638–44.

[406] Gibson RA, Neumann MA, Lien EL, Boyd KA, Tu WC. Docosahexaenoic acid synthe-

sis from alpha-linolenic acid is inhibited by diet s high in polyunsaturated fatty

acids. Prostaglandins Leukot Essent Fat Acids 2013;88:139–46.

[407] Arcand J, Scourboutakos MJ, Au JT, L'Abbe MR. Trans fatty acids in the Canadian

food supply: an updated analysis. Am J Clin Nutr 2014;100:1116–23.

[408] Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE. Healthy intakes of n-3

and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr

2006;83:1483S–93S.

[409] Kuratko C, Abril JR, Hoffman JP, Salem Jr N. 13 - Enrichment of infant formula with

omega-3 fatty acids. In: Jacobsen C, Nielsen NS, Horn AF, Sørensen A-DM, editors.

Food enrichment with omega-3 fat ty acids. Woodhead Publishing; 2013.

p. 353–86.

[410] Gupta A, Barrow CJ, Puri M. Omega-3 biotechnology: thraustochytrids as a novel

source of omega-3 oils. Biotechnol Adv 2012;30:1733–45.

[411] Damude HG, Kinney AJ. Engineering oilseed plants for a sustainable, land-based

source of long chain polyunsaturated fatty acids. Lipids 2007;42:179–85.

[412] Petrie JR, Shrestha P, Zhou XR, Mansour MP, Liu Q, Belide S, et al. Metabolic engi-

neering plant seeds with ﬁsh oil-like levels of DHA. PLoS ONE 2012;7, e49165.

[413] Ji XJ, Mo KQ, Ren LJ, Li GL, Huang JZ, Huang H. Genome sequence of Schizochytrium

sp. CCTCC M209059, an effective producer of docosahexaenoic acid-rich lipids. Ge-

nome Announc 2015:3.

152 K.D. Stark et al. / Progress in Lipid Research 63 (2016) 132–152

Table S1.

PubMed search strategy1

Terms

Items

(((("Epidemiology"[Mesh]) OR "Biological Markers"[Mesh]) OR "Cohort

Studies"[Mesh]) OR "Longitudinal Studies"[Mesh]) OR ( "Health

Surveys"[Mesh] OR "Diet Surveys"[Mesh] OR "Nutrition Surveys"[Mesh]

OR "Cross-Sectional Studies"[Mesh] )

2153631

("Fatty Acids, Omega-3/blood"[Mesh:noexp] OR "Docosahexaenoic

Acids/blood"[Mesh:noexp]) OR "Eicosapentaenoic

Acid/blood"[Mesh:noexp] AND (("1990/01/01"[PDAT] :

"2013/12/31"[PDAT]) AND "humans"[MeSH Terms] AND ("aged, 80 and

over"[MeSH Terms] OR "aged"[MeSH Terms] OR "middle aged"[MeSH

Terms] OR ("middle aged"[MeSH Terms] OR "aged"[MeSH Terms]) OR

"adult"[MeSH Terms:noexp] OR "young adult"[MeSH Terms] OR

"adult"[MeSH Terms]))

877

1Completed April 2014

Table S2.

Studies identified in search strategy but excluded after screening and eligibility assessment1

“no author” Summaries for patients. Omega-3 fatty acids and congestive heart failure in older adults. Annals of internal medicine. 2011;155:I-29.

Aarsetoey H, Aarsetoey R, Lindner T, Staines H, Harris WS, Nilsen DW. Low levels of the omega-3 index are associated with sudden cardiac arrest and remain stable

in survivors in the subacute phase. Lipids. 2011;46:151-61.

Aarsetoy H, Ponitz V, Nilsen OB, Grundt H, Harris WS, Nilsen DW. Low levels of cellular omega-3 increase the risk of ventricular fibrillation during the acute

ischaemic phase of a myocardial infarction. Resuscitation. 2008;78:258-64.

Abelsohn A, Vanderlinden LD, Scott F, Archbold JA, Brown TL. Healthy fish consumption and reduced mercury exposure: counseling women in their reproductive

years. Canadian family physician Medecin de famille canadien. 2011;57:26-30.

Acar N, Berdeaux O, Juaneda P, Gregoire S, Cabaret S, Joffre C, et al. Red blood cell plasmalogens and docosahexaenoic acid are independently reduced in primary

open-angle glaucoma. Experimental eye research. 2009;89:840-53.

Adamkova V, Kacer P, Mraz J, Suchanek P, Pickova J, Kralova Lesna I, et al. The consumption of the carp meat and plasma lipids in secondary prevention in the heart

ischemic disease patients. Neuro endocrinology letters. 2011;32 Suppl 2:17-20.

Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.

Lipids. 1996;31 Suppl:S157-61.

Al MD, van Houwelingen AC, Hornstra G. Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome. The American journal of clinical nutrition.

2000;71:285S-91S.

Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to

the neonatal essential fatty acid status. The British journal of nutrition. 1995;74:55-68.

Alexander JW, Goodman HR, Succop P, Light JA, Kuo PC, Moser AB, et al. Influence of long chain polyunsaturated fatty acids and ornithine concentrations on

complications after renal transplant. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2008;6:118-26.

Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Smith AW, Meeske K, et al. Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among

breast cancer survivors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:1280-7.

Allard JP, Royall D, Kurian R, Muggli R, Jeejeebhoy KN. Effect of omega 3 fatty acids and vitamin E supplements on lipid peroxidation measured by breath ethane and

pentane output: a randomized controlled trial. World review of nutrition and dietetics. 1994;75:162-5.

Amano T, Matsubara T, Uetani T, Kato M, Kato B, Yoshida T, et al. Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated

backscatter intravascular ultrasound study. Atherosclerosis. 2011;218:110-6.

Amiano P, Dorronsoro M, Larranaga N, Renobales M, Ruiz de Gordoa JC. Very-long-chain omega-3 fatty acids as markers for habitual fish intake in Spain. IARC

scientific publications. 2002;156:201-2.

Amin AA, Menon RA, Reid KJ, Harris WS, Spertus JA. Acute coronary syndrome patients with depression have low blood cell membrane omega-3 fatty acid levels.

Psychosomatic medicine. 2008;70:856-62.

An WS, Lee SM, Son YK, Kim SE, Kim KH, Han JY, et al. Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis

patients. Nutrition research (New York, NY). 2012;32:495-502.

An WS, Son YK, Kim SE, Kim KH, Bae HR, Lee S, et al. Association of adiponectin and leptin with serum lipids and erythrocyte omega-3 and omega-6 fatty acids in

dialysis patients. Clinical nephrology. 2011;75:195-203.

Andersen LF, Solvoll K, Drevon CA. Very-long-chain n-3 fatty acids as biomarkers for intake of fish and n-3 fatty acid concentrates. The American journal of clinical

nutrition. 1996;64:305-11.

Andersen LF, Solvoll K, Johansson LR, Salminen I, Aro A, Drevon CA. Evaluation of a food frequency questionnaire with weighed records, fatty acids, and alpha-

tocopherol in adipose tissue and serum. American journal of epidemiology. 1999;150:75-87.

Anderson JS, Nettleton JA, Herrington DM, Johnson WC, Tsai MY, Siscovick D. Relation of omega-3 fatty acid and dietary fish intake with brachial artery flow-

mediated vasodilation in the Multi-Ethnic Study of Atherosclerosis. The American journal of clinical nutrition. 2010;92:1204-13.

Andreassen AK, Hartmann A, Offstad J, Geiran O, Kvernebo K, Simonsen S. Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients. Journal

of the American College of Cardiology. 1997;29:1324-31.

Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, Fezeu L, Hercberg S, Galan P. Cognitive function after supplementation with B vitamins and long-chain omega-3

fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. The American journal of clinical nutrition. 2011;94:278-86.

Antoniuk MV, Novgorodtseva TP. [Possible use of balneotherapy for atherosclerosis prevention]. Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury.

2001:3-5.

Antypa N, Van der Does AJ, Smelt AH, Rogers RD. Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy volunteers. Journal of

psychopharmacology (Oxford, England). 2009;23:831-40.

Appleton KM, Fraser WD, Rogers PJ, Ness AR, Tobias JH. Supplementation with a low-moderate dose of n-3 long-chain PUFA has no short-term effect on bone

resorption in human adults. The British journal of nutrition. 2011;105:1145-9.

Appleton KM, Gunnell D, Peters TJ, Ness AR, Kessler D, Rogers PJ. No clear evidence of an association between plasma concentrations of n-3 long-chain

polyunsaturated fatty acids and depressed mood in a non-clinical population. Prostaglandins, leukotrienes, and essential fatty acids. 2008;78:337-42.

Araya Araya J, Rojas Garcia M, Fernandez Fraile P, Mateluna Acevedo A. [Differences in percent composition of long chain polyunsaturated fatty acids in maternal-

fetal erythrocytes in term and preterm infants]. Archivos latinoamericanos de nutricion. 1998;48:210-5.

Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D. Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate

cancer. Urology. 2001;58:283-8.

Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, et al. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in

men undergoing radical prostatectomy. Cancer prevention research (Philadelphia, Pa). 2011;4:2062-71.

Attar-Bashi NM, Weisinger RS, Begg DP, Li D, Sinclair AJ. Failure of conjugated linoleic acid supplementation to enhance biosynthesis of docosahexaenoic acid from

alpha-linolenic acid in healthy human volunteers. Prostaglandins, leukotrienes, and essential fatty acids. 2007;76:121-30.

Austria JA, Richard MN, Chahine MN, Edel AL, Malcolmson LJ, Dupasquier CM, et al. Bioavailability of alpha-linolenic acid in subjects after ingestion of three

different forms of flaxseed. Journal of the American College of Nutrition. 2008;27:214-21.

Ayotte P, Carrier A, Ouellet N, Boiteau V, Abdous B, Sidi EA, et al. Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from

Nunavik. Environmental health perspectives. 2011;119:1077-83.

Badjatia N, Seres D, Carpenter A, Schmidt JM, Lee K, Mayer SA, et al. Free Fatty acids and delayed cerebral ischemia after subarachnoid hemorrhage. Stroke; a journal

of cerebral circulation. 2012;43:691-6.

Bagga D, Capone S, Wang HJ, Heber D, Lill M, Chap L, et al. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.

Journal of the National Cancer Institute. 1997;89:1123-31.

Baggio B, Budakovic A, Ferraro A, Checchetto S, Priante G, Musacchio E, et al. Relationship between plasma phospholipid polyunsaturated fatty acid composition and

bone disease in renal transplantation. Transplantation. 2005;80:1349-52.

Baker KR, Matthan NR, Lichtenstein AH, Niu J, Guermazi A, Roemer F, et al. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee:

the MOST study. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2012;20:382-7.

Bakewell L, Burdge GC, Calder PC. Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets. The British journal of nutrition.

2006;96:93-9.

Bakken AM, Farstad M, Holmsen H. Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. Journal of applied physiology

(Bethesda, Md : 1985). 1991;70:2669-72.

Balk E, Chung M, Lichtenstein A, Chew P, Kupelnick B, Lawrence A, et al. Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of

cardiovascular disease. Evidence report/technology assessment (Summary). 2004:1-6.

Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic

cancer. British journal of cancer. 1999;81:80-6.

Barbosa VM, Miles EA, Calhau C, Lafuente E, Calder PC. Effects of a fish oil containing lipid emulsion on plasma phospholipid fatty acids, inflammatory markers, and

clinical outcomes in septic patients: a randomized, controlled clinical trial. Critical care (London, England). 2010;14:R5.

Bazan HA, Lu Y, Thoppil D, Fitzgerald TN, Hong S, Dardik A. Diminished omega-3 fatty acids are associated with carotid plaques from neurologically symptomatic

patients: Implications for carotid interventions. Vascular pharmacology. 2009;51:331-6.

Beblo S, Stark KD, Murthy M, Janisse J, Rockett H, Whitty JE, et al. Effects of alcohol intake during pregnancy on docosahexaenoic acid and arachidonic acid in

umbilical cord vessels of black women. Pediatrics. 2005;115:e194-203.

Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. The New England

journal of medicine. 1996;334:1557-60.

Berg JP, Glattre E, Haldorsen T, Hostmark AT, Bay IG, Johansen AF, et al. Longchain serum fatty acids and risk of thyroid cancer: a population-based case-control

study in Norway. Cancer causes & control : CCC. 1994;5:433-9.

Bergmann RL, Haschke-Becher E, Klassen-Wigger P, Bergmann KE, Richter R, Dudenhausen JW, et al. Supplementation with 200 mg/day docosahexaenoic acid from

mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Annals of nutrition &

metabolism. 2008;52:157-66.

Berstad P, Seljeflot I, Veierod MB, Hjerkinn EM, Arnesen H, Pedersen JI. Supplementation with fish oil affects the association between very long-chain n-3

polyunsaturated fatty acids in serum non-esterified fatty acids and soluble vascular cell adhesion molecule-1. Clinical science (London, England : 1979). 2003;105:13-

20.

Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in

Communities Study. The American journal of clinical nutrition. 2007;85:1103-11.

Bianconi L, Calo L, Mennuni M, Santini L, Morosetti P, Azzolini P, et al. n-3 polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical

cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study. Europace : European pacing, arrhythmias, and cardiac

electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

2011;13:174-81.

Bierenbaum ML, Chen Y, Lei H, Watkins T. Relationship between dietary fatty acid, selenium, and degenerative cardiomyopathy. Medical hypotheses. 1992;39:58-62.

Bierenbaum ML, Reichstein RP, Watkins TR, Maginnis WP, Geller M. Effects of canola oil on serum lipids in humans. Journal of the American College of Nutrition.

1991;10:228-33.

Birlouez-Aragon I, Saavedra G, Tessier FJ, Galinier A, Ait-Ameur L, Lacoste F, et al. A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus

and cardiovascular diseases. The American journal of clinical nutrition. 2010;91:1220-6.

Bjerregaard P, Pedersen HS, Mulvad G. The associations of a marine diet with plasma lipids, blood glucose, blood pressure and obesity among the inuit in Greenland.

European journal of clinical nutrition. 2000;54:732-7.

Bjerve KS, Brubakk AM, Fougner KJ, Johnsen H, Midthjell K, Vik T. Omega-3 fatty acids: essential fatty acids with important biological effects, and serum

phospholipid fatty acids as markers of dietary omega 3-fatty acid intake. The American journal of clinical nutrition. 1993;57:801S-5S; discussion 5S-6.

Blankenship J. Increasing maternal docosahexaenoic acid levels. Journal of the American Dietetic Association. 2005;105:1103-4.

Bohles H, Arndt S, Ohlenschlager U, Beeg T, Gebhardt B, Sewell AC. Maternal plasma homocysteine, placenta status and docosahexaenoic acid concentration in

erythrocyte phospholipids of the newborn. European journal of pediatrics. 1999;158:243-6.

Bohov P, Gelienova K, Sebokova E, Klimes I. Abnormal serum fatty acid composition in non-insulin-dependent diabetes mellitus. Annals of the New York Academy of

Sciences. 1993;683:367-70.

Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based

intervention trial from the Tromso study. The New England journal of medicine. 1990;322:795-801.

Bonham MP, Duffy EM, Wallace JM, Robson PJ, Myers GJ, Davidson PW, et al. Habitual fish consumption does not prevent a decrease in LCPUFA status in pregnant

women (the Seychelles Child Development Nutrition Study). Prostaglandins, leukotrienes, and essential fatty acids. 2008;78:343-50.

Boudreau DA, Middaugh JP, Mulvad G, Pedersen HS, Hansen JC, Malcom GT, et al. Project meeting report: atherosclerosis & omega 3 fatty acids in Arctic Natives.

Arctic medical research. 1996;55:27-31.

Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a

phase II trial. British journal of cancer. 2009;101:1978-85.

Bouzidi N, Mekki K, Boukaddoum A, Dida N, Kaddous A, Bouchenak M. Effects of omega-3 polyunsaturated fatty-acid supplementation on redox status in chronic

renal failure patients with dyslipidemia. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

2010;20:321-8.

Bower RH, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides,

and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Critical care medicine. 1995;23:436-49.

Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging.

Neurology. 2012;78:241-9.

Brouwer IA, Zock PL, van Amelsvoort LG, Katan MB, Schouten EG. Association between n-3 fatty acid status in blood and electrocardiographic predictors of

arrhythmia risk in healthy volunteers. The American journal of cardiology. 2002;89:629-31.

Browne JC, Scott KM, Silvers KM. Fish consumption in pregnancy and omega-3 status after birth are not associated with postnatal depression. Journal of affective

disorders. 2006;90:131-9.

Browning LM, Krebs JD, Moore CS, Mishra GD, O'Connell MA, Jebb SA. The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation,

insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes, obesity & metabolism. 2007;9:70-80.

Browning LM, Walker CG, Mander AP, West AL, Madden J, Gambell JM, et al. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when

given as supplements providing doses equivalent to typical intakes of oily fish. The American journal of clinical nutrition. 2012;96:748-58.

Brude IR, Finstad HS, Seljeflot I, Drevon CA, Solvoll K, Sandstad B, et al. Plasma homocysteine concentration related to diet, endothelial function and mononuclear

cell gene expression among male hyperlipidaemic smokers. European journal of clinical investigation. 1999;29:100-8.

Brunborg LA, Madland TM, Lind RA, Arslan G, Berstad A, Froyland L. Effects of short-term oral administration of dietary marine oils in patients with inflammatory

bowel disease and joint pain: a pilot study comparing seal oil and cod liver oil. Clinical nutrition (Edinburgh, Scotland). 2008;27:614-22.

Burdge GC. Polyunsaturated fatty acid intakes and alpha-linolenic acid metabolism. The American journal of clinical nutrition. 2011;93:665-6; author reply 6-7.

Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. The British journal of

nutrition. 2002;88:411-20.

Burns T, Maciejewski SR, Hamilton WR, Zheng M, Mooss AN, Hilleman DE. Effect of omega-3 fatty acid supplementation on the arachidonic acid:eicosapentaenoic

acid ratio. Pharmacotherapy. 2007;27:633-8.

Buydens-Branchey L, Branchey M, Hibbeln JR. Low plasma levels of docosahexaenoic acid are associated with an increased relapse vulnerability in substance abusers.

The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2009;18:73-80.

Buydens-Branchey L, Branchey M, Hibbeln JR. Higher n-3 fatty acids are associated with more intense fenfluramine-induced ACTH and cortisol responses among

cocaine-abusing men. Psychiatry research. 2011;188:422-7.

Buydens-Branchey L, Branchey M, McMakin DL, Hibbeln JR. Polyunsaturated fatty acid status and relapse vulnerability in cocaine addicts. Psychiatry research.

2003;120:29-35.

Cabre E, Navarro E, de Ramon M, Klaassen J, Planas R, Mingorance MD, et al. Impact of portacaval anastomosis on plasma fatty acid profile in cirrhosis: a randomized

24-month follow-up study. JPEN Journal of parenteral and enteral nutrition. 1996;20:198-205.

Cabre E, Periago JL, Gonzalez J, Gonzalez-Huix F, Abad-Lacruz A, Gil A, et al. Plasma polyunsaturated fatty acids in liver cirrhosis with or without chronic hepatic

encephalopathy: a preliminary study. JPEN Journal of parenteral and enteral nutrition. 1992;16:359-63.

Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation. The American journal of clinical nutrition. 2009;89:678S-84S.

Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, et al. DHA supplementation and pregnancy outcomes. The American journal of clinical

nutrition. 2013;97:808-15.

Carpentier YA, Hacquebard M, Portois L, Dupont IE, Deckelbaum RJ, Malaisse WJ. Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection

of a novel medium-chain triacylglycerol:fish-oil emulsion in humans. The American journal of clinical nutrition. 2010;91:875-82.

Caspar-Bauguil S, Fioroni A, Galinier A, Allenbach S, Pujol MC, Salvayre R, et al. Pro-inflammatory phospholipid arachidonic acid/eicosapentaenoic acid ratio of

dysmetabolic severely obese women. Obesity surgery. 2012;22:935-44.

Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is

incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis.

2010;212:252-9.

Chambrier C, Bastard JP, Rieusset J, Chevillotte E, Bonnefont-Rousselot D, Therond P, et al. Eicosapentaenoic acid induces mRNA expression of peroxisome

proliferator-activated receptor gamma. Obesity research. 2002;10:518-25.

Cheruku SR, Montgomery-Downs HE, Farkas SL, Thoman EB, Lammi-Keefe CJ. Higher maternal plasma docosahexaenoic acid during pregnancy is associated with

more mature neonatal sleep-state patterning. The American journal of clinical nutrition. 2002;76:608-13.

Chilton FH, Patel M, Fonteh AN, Hubbard WC, Triggiani M. Dietary n-3 fatty acid effects on neutrophil lipid composition and mediator production. Influence of

duration and dosage. The Journal of clinical investigation. 1993;91:115-22.

Chiu CC, Frangou S, Chang CJ, Chiu WC, Liu HC, Sun IW, et al. Associations between n-3 PUFA concentrations and cognitive function after recovery from late-life

depression. The American journal of clinical nutrition. 2012;95:420-7.

Christensen JH, Dyerberg J, Schmidt EB. n-3 fatty acids and the risk of sudden cardiac death assessed by 24-hour heart rate variability. Lipids. 1999;34 Suppl:S197.

Christensen JH, Korup E, Aaroe J, Toft E, Moller J, Rasmussen K, et al. Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of

myocardial infarction with left ventricular dysfunction. The American journal of cardiology. 1997;79:1670-3.

Christensen JH, Riahi S, Schmidt EB, Molgaard H, Kirstein Pedersen A, Heath F, et al. n-3 Fatty acids and ventricular arrhythmias in patients with ischaemic heart

disease and implantable cardioverter defibrillators. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac

pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2005;7:338-44.

Christensen JH, Skou HA, Madsen T, Torring I, Schmidt EB. Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus. Journal of

internal medicine. 2001;249:545-52.

Christophe A, Robberecht E, De Baets F, Franckx H. Increase of long chain omega-3 fatty acids in the major serum lipid classes of patients with cystic fibrosis. Annals

of nutrition & metabolism. 1992;36:304-12.

Chung H, Nettleton JA, Lemaitre RN, Barr RG, Tsai MY, Tracy RP, et al. Frequency and type of seafood consumed influence plasma (n-3) fatty acid concentrations.

The Journal of nutrition. 2008;138:2422-7.

Clarke G, Fitzgerald P, Hennessy AA, Cassidy EM, Quigley EM, Ross P, et al. Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females

with irritable bowel syndrome. Journal of lipid research. 2010;51:1186-92.

Cohen BE, Garg SK, Ali S, Harris WS, Whooley MA. Red blood cell docosahexaenoic acid and eicosapentaenoic acid concentrations are positively associated with

socioeconomic status in patients with established coronary artery disease: data from the Heart and Soul Study. The Journal of nutrition. 2008;138:1135-40.

Collier PM, Ursell A, Zaremba K, Payne CM, Staughton RC, Sanders T. Effect of regular consumption of oily fish compared with white fish on chronic plaque

psoriasis. European journal of clinical nutrition. 1993;47:251-4.

Conklin SM, Manuck SB, Yao JK, Flory JD, Hibbeln JR, Muldoon MF. High omega-6 and low omega-3 fatty acids are associated with depressive symptoms and

neuroticism. Psychosomatic medicine. 2007;69:932-4.

Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and

cognitive impairment. Lipids. 2000;35:1305-12.

Craig-Schmidt MC, Carlson SE, Crocker L, Sibai BM. Plasma total phospholipid arachidonic acid and eicosapentaenoic acid in normal and hypertensive pregnancy.

World review of nutrition and dietetics. 1994;76:126-9.

Crawford M. Placental delivery of arachidonic and docosahexaenoic acids: implications for the lipid nutrition of preterm infants. The American journal of clinical

nutrition. 2000;71:275S-84S.

Crowe FL, Skeaff CM, Green TJ, Gray AR. Serum n-3 long-chain PUFA differ by sex and age in a population-based survey of New Zealand adolescents and adults. The

British journal of nutrition. 2008;99:168-74.

da Costa KA, Sanders LM, Fischer LM, Zeisel SH. Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo

phosphatidylethanolamine N-methyltransferase activity in humans. The American journal of clinical nutrition. 2011;93:968-74.

Dabadie H, Peuchant E, Bernard M, LeRuyet P, Mendy F. Moderate intake of myristic acid in sn-2 position has beneficial lipidic effects and enhances DHA of

cholesteryl esters in an interventional study. The Journal of nutritional biochemistry. 2005;16:375-82.

Dahm CC, Gorst-Rasmussen A, Crowe FL, Roswall N, Tjonneland A, Drogan D, et al. Fatty acid patterns and risk of prostate cancer in a case-control study nested

within the European Prospective Investigation into Cancer and Nutrition. The American journal of clinical nutrition. 2012;96:1354-61.

Das UN, Kumar KV, Ramesh G. Essential fatty acid metabolism in south Indians. Prostaglandins, leukotrienes, and essential fatty acids. 1994;50:253-5.

Dawczynski C, Hackermeier U, Viehweger M, Stange R, Springer M, Jahreis G. Incorporation of n-3 PUFA and gamma-linolenic acid in blood lipids and red blood cell

lipids together with their influence on disease activity in patients with chronic inflammatory arthritis--a randomized controlled human intervention trial. Lipids in health

and disease. 2011;10:130.

de Batlle J, Sauleda J, Balcells E, Gomez FP, Mendez M, Rodriguez E, et al. Association between Omega3 and Omega6 fatty acid intakes and serum inflammatory

markers in COPD. The Journal of nutritional biochemistry. 2012;23:817-21.

de Groot RH, Hornstra G, van Houwelingen AC, Roumen F. Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated

fatty acid status and pregnancy outcome. The American journal of clinical nutrition. 2004;79:251-60.

de Lorgeril M, Salen P, Guiraud A, Zeghichi S, Boucher F, de Leiris J. Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary

heart disease. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2005;15:36-41.

de Lorgeril M, Salen P, Martin JL, Boucher F, de Leiris J. Interactions of wine drinking with omega-3 fatty acids in patients with coronary heart disease: a fish-like

effect of moderate wine drinking. American heart journal. 2008;155:175-81.

de Mello VD, Erkkila AT, Schwab US, Pulkkinen L, Kolehmainen M, Atalay M, et al. The effect of fatty or lean fish intake on inflammatory gene expression in

peripheral blood mononuclear cells of patients with coronary heart disease. European journal of nutrition. 2009;48:447-55.

Decsi T, Campoy C, Koletzko B. Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial. Advances in experimental medicine and

biology. 2005;569:109-13.

DeFilippis AP, Harper CR, Cotsonis GA, Jacobson TA. Effect of baseline plasma fatty acids on eicosapentaenoic acid levels in individuals supplemented with alpha-

linolenic acid. International journal of food sciences and nutrition. 2009;60 Suppl 5:28-37.

Deike E, Bowden RG, Moreillon JJ, Griggs JO, Wilson RL, Cooke M, et al. The effects of fish oil supplementation on markers of inflammation in chronic kidney

disease patients. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2012;22:572-7.

Delarue J, Guillodo MP, Guillerm S, Elbaz A, Marty Y, Cledes J. Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose

load in haemodialysis patients. The British journal of nutrition. 2008;99:1041-7.

Denzlinger C, Kless T, Sagebiel-Kohler S, Lemmen C, Jacob K, Wilmanns W, et al. Modulation of the endogenous leukotriene production by fish oil and vitamin E.

Journal of lipid mediators and cell signalling. 1995;11:119-32.

Dewailly E, Blanchet C, Gingras S, Lemieux S, Holub BJ. Fish consumption and blood lipids in three ethnic groups of Quebec (Canada). Lipids. 2003;38:359-65.

Dewell A, Marvasti FF, Harris WS, Tsao P, Gardner CD. Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults

with metabolic syndrome. The Journal of nutrition. 2011;141:2166-71.

di Giuseppe R, de Lorgeril M, Salen P, Laporte F, Di Castelnuovo A, Krogh V, et al. Alcohol consumption and n-3 polyunsaturated fatty acids in healthy men and

women from 3 European populations. The American journal of clinical nutrition. 2009;89:354-62.

Diboune M, Ferard G, Ingenbleek Y, Tulasne PA, Calon B, Hasselmann M, et al. Composition of phospholipid fatty acids in red blood cell membranes of patients in

intensive care units: effects of different intakes of soybean oil, medium-chain triglycerides, and black-currant seed oil. JPEN Journal of parenteral and enteral nutrition.

1992;16:136-41.

Dinan T, Siggins L, Scully P, O'Brien S, Ross P, Stanton C. Investigating the inflammatory phenotype of major depression: focus on cytokines and polyunsaturated fatty

acids. Journal of psychiatric research. 2009;43:471-6.

Dirix CE, Kester AD, Hornstra G. Associations between term birth dimensions and prenatal exposure to essential and trans fatty acids. Early human development.

2009;85:525-30.

Dirix CE, Kester AD, Hornstra G. Associations between neonatal birth dimensions and maternal essential and trans fatty acid contents during pregnancy and at delivery.

The British journal of nutrition. 2009;101:399-407.

Djousse L, Biggs ML, Lemaitre RN, King IB, Song X, Ix JH, et al. Plasma omega-3 fatty acids and incident diabetes in older adults. The American journal of clinical

nutrition. 2011;94:527-33.

Domei T, Yokoi H, Kuramitsu S, Soga Y, Arita T, Ando K, et al. Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events

in patients undergoing percutaneous coronary intervention. Circulation journal : official journal of the Japanese Circulation Society. 2012;76:423-9.

Donahue SM, Rifas-Shiman SL, Gold DR, Jouni ZE, Gillman MW, Oken E. Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort.

The American journal of clinical nutrition. 2011;93:780-8.

Doornbos B, van Goor SA, Dijck-Brouwer DA, Schaafsma A, Korf J, Muskiet FA. Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum

depressive symptoms in a small population based sample. Progress in neuro-psychopharmacology & biological psychiatry. 2009;33:49-52.

Dullemeijer C, Durga J, Brouwer IA, van de Rest O, Kok FJ, Brummer RJ, et al. n 3 fatty acid proportions in plasma and cognitive performance in older adults. The

American journal of clinical nutrition. 2007;86:1479-85.

Dullemeijer C, Verhoef P, Brouwer IA, Kok FJ, Brummer RJ, Durga J. Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older

adults. The journal of nutrition, health & aging. 2010;14:347-51.

Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R. Maternal vitamin D, folate, and polyunsaturated fatty acid status and bacterial vaginosis during

pregnancy. Infectious diseases in obstetrics and gynecology. 2011;2011:216217.

Dunstan JA, Mori TA, Barden A, Beilin LJ, Holt PG, Calder PC, et al. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal

erythrocyte fatty acid composition. European journal of clinical nutrition. 2004;58:429-37.

Dwarkanath P, Muthayya S, Thomas T, Vaz M, Parikh P, Mehra R, et al. Polyunsaturated fatty acid consumption and concentration among South Indian women during

pregnancy. Asia Pacific journal of clinical nutrition. 2009;18:389-94.

Dyerberg J, Christensen JH, Eskesen D, Astrup A, Stender S. Trans, and n-3 polyunsaturated fatty acids and vascular function-a yin yang situation? Atherosclerosis

Supplements. 2006;7:33-5..

Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM. Eskimos have CHD despite high consumption of omega-3 fatty acids: the Alaska Siberia project. International

journal of circumpolar health. 2005;64:387-95.

Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM, Tejero ME. Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in

Alaskan Eskimos: the Alaska Siberia project. International journal of circumpolar health. 2005;64:396-408.

Ebbesson SO, Tejero ME, Nobmann ED, Lopez-Alvarenga JC, Ebbesson L, Romenesko T, et al. Fatty acid consumption and metabolic syndrome components: the

GOCADAN study. Journal of the cardiometabolic syndrome. 2007;2:244-9.

Emken EA, Adlof RO, Duval SM, Nelson GJ. Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic, and linolenic

acids by male subjects. Lipids. 1999;34:785-91.

Engstrom K, Wallin R, Saldeen T. Effect of low-dose aspirin in combination with stable fish oil on whole blood production of eicosanoids. Prostaglandins, leukotrienes,

and essential fatty acids. 2001;64:291-7.

Engstrom KS, Wennberg M, Stromberg U, Bergdahl IA, Hallmans G, Jansson JH, et al. Evaluation of the impact of genetic polymorphisms in glutathione-related genes

on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study. Environmental health : a

global access science source. 2011;10:33.

Eritsland J, Arnesen H, Gronseth K, Fjeld NB, Abdelnoor M. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. The

American journal of cardiology. 1996;77:31-6.

Erkkila AT, Lehto S, Pyorala K, Uusitupa MI. n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease. The

American journal of clinical nutrition. 2003;78:65-71.

Erkkila AT, Matthan NR, Herrington DM, Lichtenstein AH. Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in

women with CAD. Journal of lipid research. 2006;47:2814-9.

Erkkila AT, Schwab US, de Mello VD, Lappalainen T, Mussalo H, Lehto S, et al. Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart

disease using multiple medications. European journal of nutrition. 2008;47:319-28.

Eschen O, Christensen JH, De Caterina R, Schmidt EB. Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids. Nutrition,

metabolism, and cardiovascular diseases : NMCD. 2004;14:180-5.

Escolano-Margarit MV, Ramos R, Beyer J, Csabi G, Parrilla-Roure M, Cruz F, et al. Prenatal DHA status and neurological outcome in children at age 5.5 years are

positively associated. The Journal of nutrition. 2011;141:1216-23.

Evans SJ, Kamali M, Prossin AR, Harrington GJ, Ellingrod VL, McInnis MG, et al. Association of plasma omega-3 and omega-6 lipids with burden of disease measures

in bipolar subjects. Journal of psychiatric research. 2012;46:1435-41.

Evans SJ, Prossin AR, Harrington GJ, Kamali M, Ellingrod VL, Burant CF, et al. Fats and factors: lipid profiles associate with personality factors and suicidal history in

bipolar subjects. PloS one. 2012;7:e29297.

Faber J, Berkhout M, Vos AP, Sijben JW, Calder PC, Garssen J, et al. Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation

of EPA into white blood cells and modulates immune responses within one week in healthy men and women. The Journal of nutrition. 2011;141:964-70.

Fahrmann JF, Ballester OF, Ballester G, Witte TR, Salazar AJ, Kordusky B, et al. Inhibition of nuclear factor kappa B activation in early-stage chronic lymphocytic

leukemia by omega-3 fatty acids. Cancer investigation. 2013;31:24-38.

Fakhrzadeh H, Poorebrahim R, Shooshtarizadeh P, Raza M, Hosseini S. The effects of consumption of omega3 fatty acid-enriched eggs on insulin and CRP. Nutrition,

metabolism, and cardiovascular diseases : NMCD. 2005;15:329-30.

Farrell DJ. Enrichment of hen eggs with n-3 long-chain fatty acids and evaluation of enriched eggs in humans. The American journal of clinical nutrition. 1998;68:538-

44.

Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA. Association of marine omega-3 fatty acid levels with telomeric aging in patients with

coronary heart disease. JAMA : the journal of the American Medical Association. 2010;303:250-7.

Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on

loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003;52:1479-86.

Fernandez-Real JM, Vayreda M, Casamitjana R, Gonzalez-Huix F, Ricart W. Circulating granulocyte-macrophage colony-stimulating factor and serum fatty acid

composition in men and women. Metabolism: clinical and experimental. 2001;50:1479-83.

Fernandez-Real JM, Vendrell J, Ricart W. Circulating adiponectin and plasma fatty acid profile. Clinical chemistry. 2005;51:603-9.

Fiedorowicz JG, Hale N, Spector AA, Coryell WH. Neuroticism but not omega-3 fatty acid levels correlate with early responsiveness to escitalopram. Annals of clinical

psychiatry : official journal of the American Academy of Clinical Psychiatrists. 2010;22:157-63.

Figler M, Gasztonyi B, Cseh J, Horvath G, Kisbenedek AG, Bokor S, et al. Association of n-3 and n-6 long-chain polyunsaturated fatty acids in plasma lipid classes

with inflammatory bowel diseases. The British journal of nutrition. 2007;97:1154-61.

Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, et al. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes.

International journal of sport nutrition and exercise metabolism. 2010;20:496-506.

Fitten LJ, Ortiz F, Fairbanks L, Rosenthal M, Cole GN, Nourhashemi F, et al. Depression, diabetes and metabolic-nutritional factors in elderly Hispanics. The journal of

nutrition, health & aging. 2008;12:634-40.

Fokkema MR, Brouwer DA, Hasperhoven MB, Martini IA, Muskiet FA. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid

(ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent. Prostaglandins, leukotrienes, and essential fatty acids.

2000;63:287-92.

Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, et al. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented

with Omega-3 polyunsaturated fatty acids. European journal of clinical investigation. 2005;35:499-507.

Frasure-Smith N, Lesperance F, Julien P. Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes.

Biological psychiatry. 2004;55:891-6.

Freeman MP, Hibbeln JR, Silver M, Hirschberg AM, Wang B, Yule AM, et al. Omega-3 fatty acids for major depressive disorder associated with the menopausal

transition: a preliminary open trial. Menopause (New York, NY). 2011;18:279-84.

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate

Alzheimer disease: OmegAD study: a randomized double-blind trial. Archives of neurology. 2006;63:1402-8.

Friday KE, Failor RA, Childs MT, Bierman EL. Effects of n-3 and n-6 fatty acid-enriched diets on plasma lipoproteins and apolipoproteins in heterozygous familial

hypercholesterolemia. Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. 1991;11:47-54.

Friedman AN, Moe SM, Perkins SM, Li Y, Watkins BA. Fish consumption and omega-3 fatty acid status and determinants in long-term hemodialysis. American journal

of kidney diseases : the official journal of the National Kidney Foundation. 2006;47:1064-71.

Friedman AN, Saha C, Watkins BA. Feasibility study of erythrocyte long-chain omega-3 polyunsaturated fatty acid content and mortality risk in hemodialysis patients.

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2008;18:509-12.

Friedman AN, Yu Z, Tabbey R, Denski C, Tamez H, Wenger J, et al. Low blood levels of long-chain n-3 polyunsaturated fatty acids in US hemodialysis patients:

clinical implications. American journal of nephrology. 2012;36:451-8.

Friesen RW, Innis SM. Linoleic acid is associated with lower long-chain n-6 and n-3 fatty acids in red blood cell lipids of Canadian pregnant women. The American

journal of clinical nutrition. 2010;91:23-31.

Fujihara M, Fukata M, Odashiro K, Maruyama T, Akashi K, Yokoi Y. Reduced plasma eicosapentaenoic acid-arachidonic acid ratio in peripheral artery disease.

Angiology. 2013;64:112-8.

Furuhjelm C, Warstedt K, Fageras M, Falth-Magnusson K, Larsson J, Fredriksson M, et al. Allergic disease in infants up to 2 years of age in relation to plasma omega-3

fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatric allergy and immunology : official publication of the European Society of Pediatric

Allergy and Immunology. 2011;22:505-14.

Garcia Osle M, Mourente G, Mangas A, Santi MJ, Baraibar E, Garcia Calzado MC, et al. [Effects of pharmacological doses of polyunsaturated fatty acids of the series 3

on the concentration of plasma lipoproteins]. Anales de medicina interna (Madrid, Spain : 1984). 1994;11:473-8.

Garcia-Larsen V, Luczynska M, Kowalski ML, Voutilainen H, Ahlstrom M, Haahtela T, et al. Use of a common food frequency questionnaire (FFQ) to assess dietary

patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ. European journal of clinical nutrition. 2011;65:750-6.

Gerasimova EN, Perova NV, Ozerova IN, Kulakova SN, Levachev MM, Shal'nova SA, et al. [Possible relationship between polyunsaturated fatty acids and signs of left

ventricle hypertrophy]. Kardiologiia. 1990;30:61-5.

Gerber MJ, Scali JD, Michaud A, Durand MD, Astre CM, Dallongeville J, et al. Profiles of a healthful diet and its relationship to biomarkers in a population sample

from Mediterranean southern France. Journal of the American Dietetic Association. 2000;100:1164-71.

Gerstenblith AT, Baskin DE, Shah CP, Wolfe JD, Fineman MS, Kaiser RS, et al. Electroretinographic effects of omega-3 Fatty Acid supplementation on dry age-related

macular degeneration. JAMA ophthalmology. 2013;131:365-9.

Ghebremeskel K, Crawford MA, Lowy C, Min Y, Thomas B, Golfetto I, et al. Arachidonic and docosahexaenoic acids are strongly associated in maternal and neonatal

blood. European journal of clinical nutrition. 2000;54:50-6.

Ghebremeskel K, Min Y, Crawford MA, Nam JH, Kim A, Koo JN, et al. Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as

a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus. Lipids. 2000;35:567-74.

Ghebremeskel K, Thomas B, Lowy C, Min Y, Crawford MA. Type 1 diabetes compromises plasma arachidonic and docosahexaenoic acids in newborn babies. Lipids.

2004;39:335-42.

Gillingham LG, Harding SV, Rideout TC, Yurkova N, Cunnane SC, Eck PK, et al. Dietary oils and FADS1-FADS2 genetic variants modulate [13C]alpha-linolenic acid

metabolism and plasma fatty acid composition. The American journal of clinical nutrition. 2013;97:195-207.

Gil-Sanchez A, Larque E, Demmelmair H, Acien MI, Faber FL, Parrilla JJ, et al. Maternal-fetal in vivo transfer of [13C]docosahexaenoic and other fatty acids across

the human placenta 12 h after maternal oral intake. The American journal of clinical nutrition. 2010;92:115-22.

Giltay EJ, Duschek EJ, Katan MB, Zock PL, Neele SJ, Netelenbos JC. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic

acid levels in postmenopausal women. The Journal of endocrinology. 2004;182:399-408.

Giltay EJ, Gooren LJ, Toorians AW, Katan MB, Zock PL. Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects. The

American journal of clinical nutrition. 2004;80:1167-74.

Glen AI, Cooper SJ, Rybakowski J, Vaddadi K, Brayshaw N, Horrobin DF. Membrane fatty acids, niacin flushing and clinical parameters. Prostaglandins, leukotrienes,

and essential fatty acids. 1996;55:9-15.

Glick NR, Fischer MH. Essential fatty acid-deprived tube-fed adults synthesize arachidonic and docosahexaenoic acids: a pilot analysis of the fatty acid status of people

with profound developmental disabilities. Clinical biochemistry. 2008;41:1019-21.

Glick NR, Fischer MH. Low DHA and plasmalogens associated with a precise PUFA-rich diet devoid of DHA. Clinical biochemistry. 2010;43:1305-8.

Golding J, Steer C, Emmett P, Davis JM, Hibbeln JR. High levels of depressive symptoms in pregnancy with low omega-3 fatty acid intake from fish. Epidemiology

(Cambridge, Mass). 2009;20:598-603.

Goyens PL, Mensink RP. Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects. European journal of

clinical nutrition. 2006;60:978-84.

Granot E, Jakobovich E, Rabinowitz R, Levy P, Schlesinger M. DHA supplementation during pregnancy and lactation affects infants' cellular but not humoral immune

response. Mediators of inflammation. 2011;2011:493925.

Gray DR, Gozzip CG, Eastham JH, Kashyap ML. Fish oil as an adjuvant in the treatment of hypertension. Pharmacotherapy. 1996;16:295-300.

Griffin MD, Sanders TA, Davies IG, Morgan LM, Millward DJ, Lewis F, et al. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity,

lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study. The American journal of clinical nutrition.

2006;84:1290-8.

Gronowitz E, Lorentzon M, Ohlsson C, Mellstrom D, Strandvik B. Docosahexaenoic acid is associated with endosteal circumference in long bones in young males with

cystic fibrosis. The British journal of nutrition. 2008;99:160-7.

Guallar E, Hennekens CH, Sacks FM, Willett WC, Stampfer MJ. A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male

physicians. Journal of the American College of Cardiology. 1995;25:387-94.

Guarini P, Bellavite P, Biasi D, Carletto A, Galvani S, Caramaschi P, et al. Effects of dietary fish oil and soy phosphatidylcholine on neutrophil fatty acid composition,

superoxide release, and adhesion. Inflammation. 1998;22:381-91.

Guebre-Egziabher F, Rabasa-Lhoret R, Bonnet F, Bastard JP, Desage M, Skilton MR, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases

adiponectin concentration and fatty acid oxidation in healthy subjects. European journal of clinical nutrition. 2008;62:1287-93.

Guilbault C, Wojewodka G, Saeed Z, Hajduch M, Matouk E, De Sanctis JB, et al. Cystic fibrosis fatty acid imbalance is linked to ceramide deficiency and corrected by

fenretinide. American journal of respiratory cell and molecular biology. 2009;41:100-6.

Gutierrez-Mata AP, Vilaseca MA, Capdevila-Cirera A, Vidal-Oller M, Alonso-Colmenero I, Colome R, et al. [Neurological, neuropsychological, and ophthalmological

evolution after one year of docosahexaenoic acid supplementation in phenylketonuric patients]. Revista de neurologia. 2012;55:200-6.

Hamazaki K, Terashima Y, Itomura M, Sawazaki S, Inagaki H, Kuroda M, et al. The relationship between n-3 long-chain polyunsaturated fatty acids and pulse wave

velocity in diabetic and non-diabetic patients under long-term hemodialysis. A horizontal study. Clinical nephrology. 2009;71:508-13.

Hamazaki K, Terashima Y, Itomura M, Sawazaki S, Inagaki H, Kuroda M, et al. Docosahexaenoic acid is an independent predictor of all-cause mortality in

hemodialysis patients. American journal of nephrology. 2011;33:105-10.

Hansen JB, Svensson B, Wilsgard L, Osterud B. Serum enriched with n-3 polyunsaturated fatty acids inhibits procoagulant activity in endothelial cells. Blood

coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 1991;2:515-9.

Hanwell HE, Kay CD, Lampe JW, Holub BJ, Duncan AM. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty

acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. The Journal of nutrition.

2009;139:1128-34.

Harper KN, Hibbeln JR, Deckelbaum R, Quesenberry CP, Jr., Schaefer CA, Brown AS. Maternal serum docosahexaenoic acid and schizophrenia spectrum disorders in

adult offspring. Schizophrenia research. 2011;128:30-6.

Harris W. Omega-3 fatty acids: the "Japanese" factor?. Journal of the American College of Cardiology. 2008;52:425-7.

Harris WS, Pottala JV, Lacey SM, Vasan RS, Larson MG, Robins SJ. Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid

content in the Framingham Heart Study. Atherosclerosis. 2012;225:425-31.

Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, et al. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with

erythrocytes and response to supplementation. Circulation. 2004;110:1645-9.

Harris WS, Thomas RM. Biological variability of blood omega-3 biomarkers. Clinical biochemistry. 2010;43:338-40.

Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? . Preventive medicine. 2004;39:212-20.

Hartwich J, Malec MM, Partyka L, Perez-Martinez P, Marin C, Lopez-Miranda J, et al. The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary

LDL phenotype transformation - insights from the LIPGENE study. Clinical nutrition (Edinburgh, Scotland). 2009;28:510-5.

Harvey N, Dhanwal D, Robinson S, Kim M, Inskip H, Godfrey K, et al. Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone

health of children? The Southampton Women's Survey. Osteoporosis international : a journal established as result of cooperation between the European Foundation for

Osteoporosis and the National Osteoporosis Foundation of the USA. 2012;23:2359-67.

Hawkes JS, Bryan DL, Makrides M, Neumann MA, Gibson RA. A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the

human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. The American journal of clinical nutrition. 2002;75:754-60.

Hayakawa S, Yoshikawa D, Ishii H, Tanaka M, Kumagai S, Matsumoto M, et al. Association of plasma omega-3 to omega-6 polyunsaturated fatty acid ratio with

complexity of coronary artery lesion. Internal medicine (Tokyo, Japan). 2012;51:1009-14.

Healy DA, Wallace FA, Miles EA, Calder PC, Newsholm P. Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids.

2000;35:763-8.

Heath RB, Karpe F, Milne RW, Burdge GC, Wootton SA, Frayn KN. Selective partitioning of dietary fatty acids into the VLDL TG pool in the early postprandial

period. Journal of lipid research. 2003;44:2065-72.

Helland IB, Saarem K, Saugstad OD, Drevon CA. Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil. European journal of

clinical nutrition. 1998;52:839-45.

Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, et al. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating

women. Pediatrics. 2001;108:E82.

Helmersson-Karlqvist J, Miles EA, Vlachava M, Kremmyda LS, Noakes PS, Diaper ND, et al. Enhanced prostaglandin F2alpha formation in human pregnancy and the

effect of increased oily fish intake: results from the Salmon in Pregnancy Study. Prostaglandins, leukotrienes, and essential fatty acids. 2012;86:35-8.

Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition

among patients with schizophrenia or schizoaffective disorder. Biological psychiatry. 2003;53:431-41.

Hibbeln JR, Umhau JC, George DT, Salem N, Jr. Do plasma polyunsaturates predict hostility and depression?. World review of nutrition and dietetics. 1997;82:175-86.

Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE, et al. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of

serotonin and dopamine are predicted by plasma essential fatty acids. Biological psychiatry. 1998;44:243-9.

Hirai K, Asano Y, Kakesu M, Higuchi H, Nakanishi M, Maeda M, et al. [Reduction in n-3 PUFA levels and EPA/AA ratio in serum after desert travels in China]. Nihon

eiseigaku zasshi Japanese journal of hygiene. 2003;58:275-80.

Hjerkinn EM, Seljeflot I, Ellingsen I, Berstad P, Hjermann I, Sandvik L, et al. Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid

supplements, or both on circulating markers of endothelial activation in men with long-standing hyperlipidemia. The American journal of clinical nutrition.

2005;81:583-9.

Hoffman DR, DeMar JC, Heird WC, Birch DG, Anderson RE. Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. Journal of lipid research.

2001;42:1395-401.

Hoffman DR, Uauy R, Birch DG. Metabolism of omega-3 fatty acids in patients with autosomal dominant retinitis pigmentosa. Experimental eye research. 1995;60:279-

89.

Holler C, Auinger M, Ulberth F, Irsigler K. Eicosanoid precursors: potential factors for atherogenesis in diabetic CAPD patients? . Peritoneal dialysis international :

journal of the International Society for Peritoneal Dialysis. 1996;16 Suppl 1:S250-3.

Holub BJ, Wlodek M, Rowe W, Piekarski J. Correlation of omega-3 levels in serum phospholipid from 2053 human blood samples with key fatty acid ratios. Nutrition

journal. 2009;8:58.

Hon G, Hassan M, van Rensburg SJ, Abel S, Marais de W, van Jaarsveld P, et al. Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in

patients with multiple sclerosis. The British journal of nutrition. 2009;102:1334-40.

Hongtong K, Boonnim D, Pakpeankitwatana R, Hamroongroj T, Chantaranipapong Y, Changbumrung S. Platelet fatty acids in coronary heart disease, dyslipidemia,

hypertension and healthy controls. The Southeast Asian journal of tropical medicine and public health. 2003;34:675-81.

Horrobin D, Fokkema MR, Muskiet FA. The effects on plasma, red cell and platelet fatty acids of taking 12 g/day of ethyl-eicosapentaenoate for 16 months:

dihomogammalinolenic, arachidonic and docosahexaenoic acids and relevance to Inuit metabolism. Prostaglandins, leukotrienes, and essential fatty acids. 2003;68:301-

Huang T, Asimi S, Lou D, Li D. Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients. Asia Pacific journal of clinical

nutrition. 2012;21:394-9.

Huang T, Bhulaidok S, Cai Z, Xu T, Xu F, Wahlqvist ML, et al. Plasma phospholipids n-3 polyunsaturated fatty acid is associated with metabolic syndrome. Molecular

nutrition & food research. 2010;54:1628-35.

Huang T, Wahlqvist ML, Xu T, Xu A, Zhang A, Li D. Increased plasma n-3 polyunsaturated fatty acid is associated with improved insulin sensitivity in type 2 diabetes

in China. Molecular nutrition & food research. 2010;54 Suppl 1:S112-9.

Hughes GS, Jr., Ringer TV, Francom SF, Caswell KC, DeLoof MJ, Spillers CR. Effects of fish oil and endorphins on the cold pressor test in hypertension. Clinical

pharmacology and therapeutics. 1991;50:538-46.

Ikehata A, Hiwatashi N, Kinouchi Y, Yamazaki H, Kumagai Y, Ito K, et al. Effect of intravenously infused eicosapentaenoic acid on the leukotriene generation in

patients with active Crohn's disease. The American journal of clinical nutrition. 1992;56:938-42.

Imhoff-Kunsch B, Stein AD, Villalpando S, Martorell R, Ramakrishnan U. Docosahexaenoic acid supplementation from mid-pregnancy to parturition influenced breast

milk fatty acid concentrations at 1 month postpartum in Mexican women. The Journal of nutrition. 2011;141:321-6.

Innis SM, Elias SL. Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women. The American journal of clinical nutrition.

2003;77:473-8.

Innis SM, Friesen RW. Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. The American journal of clinical nutrition.

2008;87:548-57.

Innis SM, Hansen JW. Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy

adults. The American journal of clinical nutrition. 1996;64:159-67.

Iso H, Sato S, Umemura U, Kudo M, Koike K, Kitamura A, et al. Linoleic acid, other fatty acids, and the risk of stroke. Stroke; a journal of cerebral circulation.

2002;33:2086-93.

Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, et al. The change in low-density lipoprotein cholesterol concentration is positively related to

plasma docosahexaenoic acid but not eicosapentaenoic acid. Journal of atherosclerosis and thrombosis. 2012;19:673-9.

Ito Y, Suzuki K, Imai H, Sakamoto H, Nakano H. Effects of polyunsaturated fatty acids on atrophic gastritis in a Japanese population. Cancer letters. 2001;163:171-8.

Jackson KG, Lockyer S, Carvalho-Wells AL, Williams CM, Minihane AM, Lovegrove JA. Dietary fat manipulation has a greater impact on postprandial lipid

metabolism than the apolipoprotein E (epsilon) genotype-insights from the SATgenepsilon study. Molecular nutrition & food research. 2012;56:1761-70.

Jadoon A, Chiu CC, McDermott L, Cunningham P, Frangou S, Chang CJ, et al. Associations of polyunsaturated fatty acids with residual depression or anxiety in older

people with major depression. Journal of affective disorders. 2012;136:918-25.

Jakobik V, Burus I, Decsi T. Fatty acid composition of erythrocyte membrane lipids in healthy subjects from birth to young adulthood. European journal of pediatrics.

2009;168:141-7.

Jakobsen MU, Dethlefsen C, Due KM, Slimani N, Chajes V, May AM, et al. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change.

Obesity facts. 2011;4:312-8.

Jensen CL, Maude M, Anderson RE, Heird WC. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids

and maternal and infant plasma phospholipids. The American journal of clinical nutrition. 2000;71:292S-9S.

Jiang W, Oken H, Fiuzat M, Shaw LK, Martsberger C, Kuchibhatla M, et al. Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart

failure and major depressive disorder. Journal of cardiovascular translational research. 2012;5:92-9.

Jin F, Nieman DC, Sha W, Xie G, Qiu Y, Jia W. Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women. Plant foods for

human nutrition (Dordrecht, Netherlands). 2012;67:105-10.

Joffe YT, van der Merwe L, Evans J, Collins M, Lambert EV, September A, et al. The tumor necrosis factor-alpha gene -238G>A polymorphism, dietary fat intake,

obesity risk and serum lipid concentrations in black and white South African women. European journal of clinical nutrition. 2012;66:1295-302.

Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, Sears B. Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate

diets. The American journal of clinical nutrition. 2006;83:1055-61.

Kale A, Naphade N, Sapkale S, Kamaraju M, Pillai A, Joshi S, et al. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol

in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry research. 2010;175:47-53.

Karlsson J, Lundgren G, Ronneberg R. Plasma selenium in healthy man before and after nutratherapy. International journal for vitamin and nutrition research

Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition. 1997;67:27-33.

Kashiyama T, Ueda Y, Nemoto T, Wada M, Masumura Y, Matsuo K, et al. Relationship between coronary plaque vulnerability and serum n-3/n-6 polyunsaturated fatty

acid ratio. Circulation journal : official journal of the Japanese Circulation Society. 2011;75:2432-8.

Keen C, Olin AC, Eriksson S, Ekman A, Lindblad A, Basu S, et al. Supplementation with fatty acids influences the airway nitric oxide and inflammatory markers in

patients with cystic fibrosis. Journal of pediatric gastroenterology and nutrition. 2010;50:537-44.

Khair-El-Din T, Sicher SC, Vazquez MA, Chung GW, Stallworth KA, Kitamura K, et al. Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a

major constituent of fetal and neonatal sera as well as fish oils. The Journal of experimental medicine. 1996;183:1241-6.

Kilari A, Mehendale S, Dangat K, Pisal H, Joshi S. Associations of long-chain polyunsaturated fatty acid concentrations with birth outcome in term Indian mothers and

their neonates. American journal of human biology : the official journal of the Human Biology Council. 2011;23:319-24.

Kilari AS, Mehendale SS, Dangat KD, Yadav HR, Gupta A, Taralekar VS, et al. Long chain polyunsaturated fatty acids in mothers of preterm babies. Journal of

perinatal medicine. 2010;38:659-64.

Kilari AS, Mehendale SS, Dangat KD, Yadav HR, Kulakarni AV, Dhobale MV, et al. Long chain polyunsaturated fatty acids in mothers and term babies. Journal of

perinatal medicine. 2009;37:513-8.

Kim M, Nam JH, Oh DH, Park Y. Erythrocyte alpha-linolenic acid is associated with the risk for mild dementia in Korean elderly. Nutrition research (New York, NY).

2010;30:756-61.

Kimura Y, Sato M, Kurotani K, Nanri A, Kawai K, Kasai H, et al. PUFAs in serum cholesterol ester and oxidative DNA damage in Japanese men and women. The

American journal of clinical nutrition. 2012;95:1209-14.

Kirkegaard E, Svensson M, Strandhave C, Schmidt EB, Jorgensen KA, Christensen JH. Marine n-3 fatty acids, atrial fibrillation and QT interval in haemodialysis

patients. The British journal of nutrition. 2012;107:903-9.

Kishino T, Ohnishi H, Ohtsuka K, Matsushima S, Urata T, Watanebe K, et al. Low concentrations of serum n-3 polyunsaturated fatty acids in non-alcoholic fatty liver

disease patients with liver injury. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2011;49:159-62.

Klingler M, Klem S, Demmelmair H, Koletzko B. Comparison of the incorporation of orally administered DHA into plasma, erythrocyte and cheek cell

glycerophospholipids. The British journal of nutrition. 2013;109:962-8.

Kobayakawa M, Yamawaki S, Hamazaki K, Akechi T, Inagaki M, Uchitomi Y. Levels of omega-3 fatty acid in serum phospholipids and depression in patients with

lung cancer. British journal of cancer. 2005;93:1329-33.

Kohler A, Bittner D, Low A, von Schacky C. Effects of a convenience drink fortified with n-3 fatty acids on the n-3 index. The British journal of nutrition.

2010;104:729-36.

Kohlschutter A, Schade B, Blomer B, Hubner C. Low erythrocyte plasmalogen and plasma docosahexaenoic acid (DHA) in juvenile neuronal ceroid-lipofuscinosis

(JNCL). Journal of inherited metabolic disease. 1993;16:299-304.

Kojima M, Wakai K, Tokudome S, Suzuki K, Tamakoshi K, Watanabe Y, et al. Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a prospective

study. American journal of epidemiology. 2005;161:462-71.

Kompauer I, Demmelmair H, Koletzko B, Bolte G, Linseisen J, Heinrich J. Association of fatty acids in serum phospholipids with hay fever, specific and total

immunoglobulin E. The British journal of nutrition. 2005;93:529-35.

Konrad M, Nieman DC, Henson DA, Kennerly KM, Jin F, Wallner-Liebmann SJ. The acute effect of ingesting a quercetin-based supplement on exercise-induced

inflammation and immune changes in runners. International journal of sport nutrition and exercise metabolism. 2011;21:338-46.

Kooshki A, Taleban FA, Tabibi H, Hedayati M. Effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in

hemodialysis patients. Annals of nutrition & metabolism. 2011;58:197-202.

Korpela R, Seppo L, Laakso J, Lilja J, Karjala K, Lahteenmaki T, et al. Dietary habits affect the susceptibility of low-density lipoprotein to oxidation. European journal

of clinical nutrition. 1999;53:802-7.

Kottke TE, Wu LA, Brekke LN, Brekke MJ, White RD. Preventing sudden death with n-3 (omega-3) fatty acids and defibrillators. American journal of preventive

medicine. 2006;31:316-23.

Krasevec JM, Jones PJ, Cabrera-Hernandez A, Mayer DL, Connor WE. Maternal and infant essential fatty acid status in Havana, Cuba. The American journal of clinical

nutrition. 2002;76:834-44.

Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jimenez M, et al. Effects of fish-oil and folate supplementation of pregnant women on maternal

and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. The American journal of clinical nutrition.

2007;85:1392-400.

Kuipers RS, Luxwolda MF, Sango WS, Kwesigabo G, Dijck-Brouwer DA, Muskiet FA. Maternal DHA equilibrium during pregnancy and lactation is reached at an

erythrocyte DHA content of 8 g/100 g fatty acids. The Journal of nutrition. 2011;141:418-27.

Kulkarni A, Mehendale S, Pisal H, Kilari A, Dangat K, Salunkhe S, et al. Association of omega-3 fatty acids and homocysteine concentrations in pre-eclampsia. Clinical

nutrition (Edinburgh, Scotland). 2011;30:60-4.

Kulkarni AV, Mehendale SS, Yadav HR, Kilari AS, Taralekar VS, Joshi SR. Circulating angiogenic factors and their association with birth outcomes in preeclampsia.

Hypertension research : official journal of the Japanese Society of Hypertension. 2010;33:561-7.

Kuratko CN, Salem N, Jr. Biomarkers of DHA status. Prostaglandins, leukotrienes, and essential fatty acids. 2009;81:111-8.

Kurisu S, Kato Y, Mitsuba N, Ishibashi K, Dohi Y, Nishioka K, et al. Short-term effects of eicosapentaenoic acid on P wave signal-averaged electrocardiogram in

patients with coronary artery disease. International journal of cardiology. 2012;154:200-2.

Kyle DJ, Schaefer E, Patton G, Beiser A. Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids. 1999;34 Suppl:S245.

Laasonen M, Hokkanen L, Leppamaki S, Tani P, Erkkila AT. Project DyAdd: Fatty acids in adult dyslexia, ADHD, and their comorbid combination. Prostaglandins,

leukotrienes, and essential fatty acids. 2009;81:89-96.

Lasztity N, Hamvas J, Biro L, Nemeth E, Marosvolgyi T, Decsi T, et al. Effect of enterally administered n-3 polyunsaturated fatty acids in acute pancreatitis--a

prospective randomized clinical trial. Clinical nutrition (Edinburgh, Scotland). 2005;24:198-205.

Lau CS, McLaren M, Belch JJ. Effects of fish oil on plasma fibrinolysis in patients with mild rheumatoid arthritis. Clinical and experimental rheumatology. 1995;13:87-

90.

Lauretani F, Maggio M, Pizzarelli F, Michelassi S, Ruggiero C, Ceda GP, et al. Omega-3 and renal function in older adults. Current pharmaceutical design.

2009;15:4149-56.

Lee SH, Shin MJ, Kim JS, Ko YG, Kang SM, Choi D, et al. Blood eicosapentaenoic acid and docosahexaenoic acid as predictors of all-cause mortality in patients with

acute myocardial infarction--data from Infarction Prognosis Study (IPS) Registry. Circulation journal : official journal of the Japanese Circulation Society.

2009;73:2250-7.

Lee TK, Clandinin MT, Hebert M, MacDonald IM. Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular

dystrophy: randomized clinical trial. Canadian journal of ophthalmology Journal canadien d'ophtalmologie. 2010;45:514-9.

Leeson CP, Hingorani AD, Mullen MJ, Jeerooburkhan N, Kattenhorn M, Cole TJ, et al. Glu298Asp endothelial nitric oxide synthase gene polymorphism interacts with

environmental and dietary factors to influence endothelial function. Circulation research. 2002;90:1153-8.

Leigh-Firbank EC, Minihane AM, Leake DS, Wright JW, Murphy MC, Griffin BA, et al. Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential

associations with lipid responses. The British journal of nutrition. 2002;87:435-45.

Lemaitre-Delaunay D, Pachiaudi C, Laville M, Pousin J, Armstrong M, Lagarde M. Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after

ingestion of a single dose of [(13)C]DHA in phosphatidylcholine. Journal of lipid research. 1999;40:1867-74.

Lemas DJ, Wiener HW, O'Brien DM, Hopkins S, Stanhope KL, Havel PJ, et al. Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with

variation in body composition and fasting lipid traits in Yup'ik Eskimos. Journal of lipid research. 2012;53:175-84.

Leng GC, Smith FB, Fowkes FG, Horrobin DF, Ells K, Morse-Fisher N, et al. Relationship between plasma essential fatty acids and smoking, serum lipids, blood

pressure and haemostatic and rheological factors. Prostaglandins, leukotrienes, and essential fatty acids. 1994;51:101-8.

Li D, Mann NJ, Sinclair AJ. Comparison of n-3 polyunsaturated fatty acids from vegetable oils, meat, and fish in raising platelet eicosapentaenoic acid levels in humans.

Lipids. 1999;34 Suppl:S309.

Lindberg M, Saltvedt I, Sletvold O, Bjerve KS. Long-chain n-3 fatty acids and mortality in elderly patients. The American journal of clinical nutrition. 2008;88:722-9.

Lishinevs'ka V, Briuzhina TS, Korkushko OV. [Age-related changes in fatty acid composition of the erythrocyte membrane]. Fiziolohichnyi zhurnal (Kiev, Ukraine :

1994). 2003;49:47-51.

Llorente AM, Jensen CL, Voigt RG, Fraley JK, Berretta MC, Heird WC. Effect of maternal docosahexaenoic acid supplementation on postpartum depression and

information processing. American journal of obstetrics and gynecology. 2003;188:1348-53.

Lloyd DA, Paynton SE, Bassett P, Mateos AR, Lovegrove JA, Gabe SM, et al. Assessment of long chain n-3 polyunsaturated fatty acid status and clinical outcome in

adults receiving home parenteral nutrition. Clinical nutrition (Edinburgh, Scotland). 2008;27:822-31.

Lloyd-Still JD, Powers CA, Hoffman DR, Boyd-Trull K, Lester LA, Benisek DC, et al. Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol

of algal origin in cystic fibrosis patients: a randomized, controlled study. Nutrition (Burbank, Los Angeles County, Calif). 2006;22:36-46.

Lockyer S, Tzanetou M, Carvalho-Wells AL, Jackson KG, Minihane AM, Lovegrove JA. SATgenepsilon dietary model to implement diets of differing fat composition

in prospectively genotyped groups (apoE) using commercially available foods. The British journal of nutrition. 2012;108:1705-13.

Lossl K, Skou HA, Christensen JH, Schmidt EB. The effect of n-3 fatty acids on leukotriene formation from neutrophils in patients on hemodialysis. Lipids. 1999;34

Suppl:S185.

Lucas M, Proust F, Blanchet C, Ferland A, Dery S, Abdous B, et al. Is marine mammal fat or fish intake most strongly associated with omega-3 blood levels among the

Nunavik Inuit? . Prostaglandins, leukotrienes, and essential fatty acids. 2010;83:143-50.

Luley C, Lelieur I, Hanisch M, Vohwinkel M, Lodde A, Wieland H, et al. Fish oil treatment and apolipoprotein(a). Arzneimittel-Forschung. 1992;42:77-80.

Luxwolda MF, Kuipers RS, Smit EN, Velzing-Aarts FV, Dijck-Brouwer DA, Muskiet FA. The relation between the omega-3 index and arachidonic acid is bell shaped:

synergistic at low EPA+DHA status and antagonistic at high EPA+DHA status. Prostaglandins, leukotrienes, and essential fatty acids. 2011;85:171-8.

Macasek J, Vecka M, Zak A, Urbanek M, Krechler T, Petruzelka L, et al. Plasma fatty acid composition in patients with pancreatic cancer: correlations to clinical

parameters. Nutrition and cancer. 2012;64:946-55.

Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Transactions of the American

Ophthalmological Society. 2008;106:336-56.

Madden J, Carrero JJ, Brunner A, Dastur N, Shearman CP, Calder PC, et al. Polymorphisms in the CD36 gene modulate the ability of fish oil supplements to lower

fasting plasma triacyl glycerol and raise HDL cholesterol concentrations in healthy middle-aged men. Prostaglandins, leukotrienes, and essential fatty acids.

2008;78:327-35.

Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and

increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. Journal of affective disorders. 1996;38:35-46.

Magnusardottir AR, Steingrimsdottir L, Thorgeirsdottir H, Hauksson A, Skuladottir GV. Red blood cell n-3 polyunsaturated fatty acids in first trimester of pregnancy

are inversely associated with placental weight. Acta obstetricia et gynecologica Scandinavica. 2009;88:91-7.

Mahadik SP, Mukherjee S, Horrobin DF, Jenkins K, Correnti EE, Scheffer RE. Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from

schizophrenic patients: comparison with bipolar patients and normal subjects. Psychiatry research. 1996;63:133-42.

Mahomed K, Williams MA, King IB, Mudzamiri S, Woelk GB. Erythrocyte omega-3, omega-6 and trans fatty acids in relation to risk of preeclampsia among women

delivering at Harare Maternity Hospital, Zimbabwe. Physiological research / Academia Scientiarum Bohemoslovaca. 2007;56:37-50.

Makhoul Z, Kristal AR, Gulati R, Luick B, Bersamin A, Boyer B, et al. Associations of very high intakes of eicosapentaenoic and docosahexaenoic acids with

biomarkers of chronic disease risk among Yup'ik Eskimos. The American journal of clinical nutrition. 2010;91:777-85.

Maki KC, Van Elswyk ME, McCarthy D, Hess SP, Veith PE, Bell M, et al. Lipid responses to a dietary docosahexaenoic acid supplement in men and women with

below average levels of high density lipoprotein cholesterol. Journal of the American College of Nutrition. 2005;24:189-99.

Maki KC, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, et al. Lipid responses in mildly hypertriglyceridemic men and women to consumption of

docosahexaenoic acid-enriched eggs. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal

international de vitaminologie et de nutrition. 2003;73:357-68.

Makrides M, Gibson RA. Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation. The American journal of clinical nutrition. 2000;71:307S-

11S.

Malcolm CA, Hamilton R, McCulloch DL, Montgomery C, Weaver LT. Scotopic electroretinogram in term infants born of mothers supplemented with

docosahexaenoic acid during pregnancy. Investigative ophthalmology & visual science. 2003;44:3685-91.

Marc I, Plourde M, Lucas M, Sterescu A, Piedboeuf B, Dufresne A, et al. Early docosahexaenoic acid supplementation of mothers during lactation leads to high plasma

concentrations in very preterm infants. The Journal of nutrition. 2011;141:231-6.

Marcovina SM, Kennedy H, Bittolo Bon G, Cazzolato G, Galli C, Casiglia E, et al. Fish intake, independent of apo(a) size, accounts for lower plasma lipoprotein(a)

levels in Bantu fishermen of Tanzania: The Lugalawa Study. Arteriosclerosis, thrombosis, and vascular biology. 1999;19:1250-6.

Marosvolgyi T, Horvath G, Dittrich A, Cseh J, Lelovics Z, Szabo E, et al. Fatty acid composition of plasma lipid classes in chronic alcoholic pancreatitis. Pancreatology

: official journal of the International Association of Pancreatology (IAP) [et al]. 2010;10:580-5.

Marsen TA, Pollok M, Oette K, Baldamus CA. Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations. Prostaglandins, leukotrienes, and

essential fatty acids. 1992;46:191-6.

Martinez M, Mougan I, Roig M, Ballabriga A. Blood polyunsaturated fatty acids in patients with peroxisomal disorders. A multicenter study. Lipids. 1994;29:273-80.

Mas E, Croft KD, Zahra P, Barden A, Mori TA. Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty

acid supplementation. Clinical chemistry. 2012;58:1476-84.

Matorras R, Perteagudo L, Sanjurjo P. Biochemical markers of n-3 long chain polyunsaturated fatty acid intake during pregnancy. Clinical and experimental obstetrics

& gynecology. 1998;25:135-8.

Matorras R, Ruiz JI, Perteagudo L, Barbazan MJ, Diaz A, Valladolid A, et al. Longitudinal study of fatty acids in plasma and erythrocyte phospholipids during

pregnancy. Journal of perinatal medicine. 2001;29:293-7.

Mawatari S, Saito K, Murakami K, Fujino T. Absence of correlation between glycated hemoglobin and lipid composition of erythrocyte membrane in type 2 diabetic

patients. Metabolism: clinical and experimental. 2004;53:123-7.

Mayser P, Mayer K, Mahloudjian M, Benzing S, Kramer HJ, Schill WB, et al. A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based

lipid infusion in atopic dermatitis. JPEN Journal of parenteral and enteral nutrition. 2002;26:151-8.

Mayser P, Mrowietz U, Arenberger P, Bartak P, Buchvald J, Christophers E, et al. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis:

results of a double-blind, randomized, placebo-controlled, multicenter trial. Journal of the American Academy of Dermatology. 1998;38:539-47.

Mazer LM, Yi SH, Singh RH. Docosahexaenoic acid status in females of reproductive age with maple syrup urine disease. Journal of inherited metabolic disease.

2010;33:121-7.

McCowen KC, Ling PR, Ollero M, Tawa N, Bistrian BR. Effect of a fish oil-containing beverage on changes in plasma lipid fatty acids in patients with malabsorption.

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2010;25:517-23.

McNamara RK. Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: current status, future directions, and dietary

recommendations. Prostaglandins, leukotrienes, and essential fatty acids. 2009;81:223-31.

McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, et al. Dietary fish oil augments nitric oxide production or release in patients with

type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1993;36:33-8.

Mehmetoglu I, Yerlikaya FH, Kurban S, Polat H. Plasma omega-3 fatty acid levels negatively and omega-6 fatty acid levels positively associated with other

cardiovascular risk factors including homocysteine in severe obese subjects. Asia Pacific journal of clinical nutrition. 2012;21:519-25.

Meneses F, Torres AG, Trugo NM. Essential and long-chain polyunsaturated fatty acid status and fatty acid composition of breast milk of lactating adolescents. The

British journal of nutrition. 2008;100:1029-37.

Mezzano D, Kosiel K, Martinez C, Cuevas A, Panes O, Aranda E, et al. Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with

vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids. Thrombosis research. 2000;100:153-60.

Micallef M, Munro I, Phang M, Garg M. Plasma n-3 Polyunsaturated Fatty Acids are negatively associated with obesity. The British journal of nutrition.

2009;102:1370-4.

Micallef MA, Garg ML. The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and

women. The Journal of nutrition. 2008;138:1086-90.

Micallef MA, Garg ML. Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals.

Atherosclerosis. 2009;204:476-82.

Micallef MA, Munro IA, Garg ML. An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. European journal of clinical

nutrition. 2009;63:1154-6.

Mikagi K, Kawahara R, Kinoshita H, Aoyagi S. Effect of preoperative immunonutrition in patients undergoing hepatectomy; a randomized controlled trial. The Kurume

medical journal. 2011;58:1-8.

Miles EA, Banerjee T, Dooper MM, M'Rabet L, Graus YM, Calder PC. The influence of different combinations of gamma-linolenic acid, stearidonic acid and EPA on

immune function in healthy young male subjects. The British journal of nutrition. 2004;91:893-903.

Miles EA, Noakes PS, Kremmyda LS, Vlachava M, Diaper ND, Rosenlund G, et al. The Salmon in Pregnancy Study: study design, subject characteristics, maternal fish

and marine n-3 fatty acid intake, and marine n-3 fatty acid status in maternal and umbilical cord blood. The American journal of clinical nutrition. 2011;94:1986S-92S.

Miles EA, Thies F, Wallace FA, Powell JR, Hurst TL, Newsholme EA, et al. Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations.

Clinical science (London, England : 1979). 2001;100:91-100.

Milte CM, Coates AM, Buckley JD, Hill AM, Howe PR. Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood

lipid levels. The British journal of nutrition. 2008;99:1083-8.

Min Y, Ghebremeskel K, Crawford MA, Nam JH, Kim A, Koo JN, et al. Pregnancy reduces arachidonic and docosahexaenoic in plasma triacylglycerols of Korean

women. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie

et de nutrition. 2000;70:70-5.

Min Y, Ghebremeskel K, Lowy C, Thomas B, Crawford MA. Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational

diabetes. Diabetologia. 2004;47:75-81.

Min Y, Lowy C, Ghebremeskel K, Thomas B, Bitsanis D, Crawford MA. Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of

compromised insulin sensitivity in offspring of gestational diabetic women. Diabetic medicine : a journal of the British Diabetic Association. 2005;22:914-20.

Min Y, Lowy C, Ghebremeskel K, Thomas B, Offley-Shore B, Crawford M. Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid

status: a potential marker of fetal insulin resistance. The American journal of clinical nutrition. 2005;82:1162-8.

Min Y, Lowy C, Islam S, Khan FS, Swaminathan R. Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity.

European journal of clinical nutrition. 2011;65:690-5.

Minihane AM, Brady LM, Lovegrove SS, Lesauvage SV, Williams CM, Lovegrove JA. Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of

insulin responses in Indian Asians living in the UK. European journal of nutrition. 2005;44:26-32.

Mischoulon D, Best-Popescu C, Laposata M, Merens W, Murakami JL, Wu SL, et al. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major

depressive disorder. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2008;18:639-45.

Miyake Y, Sasaki S, Tanaka K, Ohya Y, Matsunaga I, Yoshida T, et al. Relationship between dietary fat and fish intake and the prevalence of atopic eczema in pregnant

Japanese females: baseline data from the Osaka Maternal and Child Health Study. Asia Pacific journal of clinical nutrition. 2008;17:612-9.

Miyata H, Yano M, Yasuda T, Hamano R, Yamasaki M, Hou E, et al. Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy

on chemotherapy-related toxicity in patients with esophageal cancer. Clinical nutrition (Edinburgh, Scotland). 2012;31:330-6.

Moller JM, Nielsen GL, Ekelund S, Schmidt EB, Dyerberg J. Homocysteine in Greenland Inuits. Thrombosis research. 1997;86:333-5.

Moodley T, Vella C, Djahanbakhch O, Branford-White CJ, Crawford MA. Arachidonic and docosahexaenoic acid deficits in preterm neonatal mononuclear cell

membranes. Implications for the immune response at birth. Nutrition and health. 2009;20:167-85.

Moon HJ, Kim TH, Byun DW, Park Y. Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean

women with osteoporosis. Annals of nutrition & metabolism. 2012;60:146-53.

Mori TA, Beilin LJ, Burke V, Morris J, Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular

disease. Arteriosclerosis, thrombosis, and vascular biology. 1997;17:279-86.

Mori TA, Burke V, Puddey IB, Watts GF, O'Neal DN, Best JD, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and

lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. The American journal of clinical nutrition. 2000;71:1085-94.

Mori TA, Vandongen R, Douglas AJ, McCulloch RK, Burke V. Differential effect of aspirin on platelet aggregation in IDDM. Diabetes. 1992;41:261-6.

Mori TA, Vandongen R, Mahanian F, Douglas A. Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive

oil supplementation. Metabolism: clinical and experimental. 1992;41:1059-67.

Moseley K, Koch R, Moser AB. Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-

restricted diet. Journal of inherited metabolic disease. 2002;25:56-64.

Moses AG, Maingay J, Sangster K, Fearon KC, Ross JA. Pro-inflammatory cytokine release by peripheral blood mononuclear cells from patients with advanced

pancreatic cancer: relationship to acute phase response and survival. Oncology reports. 2009;21:1091-5.

Moses AW, Slater C, Preston T, Barber MD, Fearon KC. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be

modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. British journal of cancer. 2004;90:996-1002.

Moyers B, Farzaneh-Far R, Harris WS, Garg S, Na B, Whooley MA. Relation of whole blood n-3 fatty acid levels to exercise parameters in patients with stable

coronary artery disease (from the heart and soul study). The American journal of cardiology. 2011;107:1149-54.

Mozaffarian D, Lemaitre RN, Kuller LH, Burke GL, Tracy RP, Siscovick DS. Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the

Cardiovascular Health Study. Circulation. 2003;107:1372-7.

Mozaffarian D, Longstreth WT, Jr., Lemaitre RN, Manolio TA, Kuller LH, Burke GL, et al. Fish consumption and stroke risk in elderly individuals: the cardiovascular

health study. Archives of internal medicine. 2005;165:200-6.

Munakata M, Nishikawa M, Togashi N, Nio E, Kobayashi Y, Omura K, et al. The nutrient formula containing eicosapentaenoic acid and docosahexaenoic acid benefits

the fatty acid status of patients receiving long-term enteral nutrition. The Tohoku journal of experimental medicine. 2009;217:23-8.

Mundal HH, Meltzer HM, Aursnes I. Bleeding times related to serum triglyceride levels in healthy young adults. Thrombosis research. 1994;75:285-91.

Murphy KJ, Galvin K, Kiely M, Morrissey PA, Mann NJ, Sinclair AJ. Low dose supplementation with two different marine oils does not reduce pro-inflammatory

eicosanoids and cytokines in vivo. Asia Pacific journal of clinical nutrition. 2006;15:418-24.

Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with

advanced nonsmall cell lung cancer. Cancer. 2011;117:3774-80.

Murphy RA, Mourtzakis M, Chu QS, Reiman T, Mazurak VC. Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung

cancer patients. The Journal of nutrition. 2010;140:1602-6.

Nakabou M, Kai T, Maeshima T, Kanamasa K. [Relationship between EPA or EPA/AA and arteriosclerosis in elderly patients over 80 years old]. Nihon Ronen Igakkai

zasshi Japanese journal of geriatrics. 2011;48:672-8.

Nakamura K, Kariyazono H, Komokata T, Hamada N, Sakata R, Yamada K. Influence of preoperative administration of omega-3 fatty acid-enriched supplement on

inflammatory and immune responses in patients undergoing major surgery for cancer. Nutrition (Burbank, Los Angeles County, Calif). 2005;21:639-49.

Nakamura M, Iwahashi M, Takifuji K, Nakamori M, Naka T, Ishida K, et al. Optimal dose of preoperative enteral immunonutrition for patients with esophageal cancer.

Surgery today. 2009;39:855-60.

Nestares T, Lopez-Jurado M, Urbano G, Seiquer I, Ramirez-Tortosa MC, Ros E, et al. Effects of lifestyle modification and lipid intake variations on patients with

peripheral vascular disease. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal

international de vitaminologie et de nutrition. 2003;73:389-98.

Neubronner J, Schuchardt JP, Kressel G, Merkel M, von Schacky C, Hahn A. Enhanced increase of omega-3 index in response to long-term n-3 fatty acid

supplementation from triacylglycerides versus ethyl esters. European journal of clinical nutrition. 2011;65:247-54.

Nieman DC, Gillitt N, Jin F, Henson DA, Kennerly K, Shanely RA, et al. Chia seed supplementation and disease risk factors in overweight women: a metabolomics

investigation. Journal of alternative and complementary medicine (New York, NY). 2012;18:700-8.

Nieman DC, Henson DA, McAnulty SR, Jin F, Maxwell KR. n-3 polyunsaturated fatty acids do not alter immune and inflammation measures in endurance athletes.

International journal of sport nutrition and exercise metabolism. 2009;19:536-46.

Nigam A, Frasure-Smith N, Lesperance F, Julien P. Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance in coronary patients with and

without metabolic syndrome. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2009;19:264-70.

Niinivirta K, Isolauri E, Laakso P, Linderborg K, Laitinen K. Dietary counseling to improve fat quality during pregnancy alters maternal fat intake and infant essential

fatty acid status. The Journal of nutrition. 2011;141:1281-5.

Nishinaga M, Takata J, Doi Y, Okumiya K, Matsubayashi K, Ozawa T. [Nutritional factors and functional assessment]. Nihon Ronen Igakkai zasshi Japanese journal of

geriatrics. 2005;42:174-6.

Niu K, Hozawa A, Kuriyama S, Ohmori-Matsuda K, Shimazu T, Nakaya N, et al. Dietary long-chain n-3 fatty acids of marine origin and serum C-reactive protein

concentrations are associated in a population with a diet rich in marine products. The American journal of clinical nutrition. 2006;84:223-9.

Nordoy A, Barstad L, Connor WE, Hatcher L. Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans. The

American journal of clinical nutrition. 1991;53:1185-90.

Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta neurologica Scandinavica.

2000;102:143-9.

Novak EM, King DJ, Innis SM. Low linoleic acid may facilitate Delta6 desaturase activity and docosahexaenoic acid accretion in human fetal development.

Prostaglandins, leukotrienes, and essential fatty acids. 2012;86:93-8.

Novak F, Borovska J, Vecka M, Vavrova L, Kodydkova J, Mrackova M, et al. [Alterations in fatty acid composition of plasma and erythrocyte lipids in critically ill

patients during sepsis]. Casopis lekaru ceskych. 2010;149:324-31.

Novgorodtseva TP, Endakova EA, Kozycheva EV, Kitaiskaia LS. [Modification to the erythrocyte membrane lipids in patients with cardiovascular pathology during

balneotherapy]. Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury. 1999:12-5.

Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, et al. Effects of serum n-3 to n-6 polyunsaturated fatty acids ratios on coronary atherosclerosis in

statin-treated patients with coronary artery disease. The American journal of cardiology. 2013;111:6-11.

Oda E, Hatada K, Katoh K, Kodama M, Nakamura Y, Aizawa Y. A case-control pilot study on n-3 polyunsaturated fatty acid as a negative risk factor for myocardial

infarction. International heart journal. 2005;46:583-91.

Ogunleiye AJ, Muraoka A, Niizeki S, Tojo H, Hosokawa Y, Sato I, et al. Effect of fish oil and safflower oil in common Japanese diet on human plasma fatty acid

composition. Journal of nutritional science and vitaminology. 1990;36:423-30.

Oken E, Radesky JS, Wright RO, Bellinger DC, Amarasiriwardena CJ, Kleinman KP, et al. Maternal fish intake during pregnancy, blood mercury levels, and child

cognition at age 3 years in a US cohort. American journal of epidemiology. 2008;167:1171-81.

Olza J, Mesa MD, Aguilera CM, Moreno-Torres R, Jimenez A, Perez de la Cruz A, et al. Influence of an eicosapentaenoic and docosahexaenoic acid-enriched enteral

nutrition formula on plasma fatty acid composition and biomarkers of insulin resistance in the elderly. Clinical nutrition (Edinburgh, Scotland). 2010;29:31-7.

Ota Y, Sasagawa T, Suzuki K, Tomioka K, Nagai A, Niiyama G, et al. Vitamin E supplementation increases polyunsaturated fatty acids of RBC membrane in HCV-

infected patients. Nutrition (Burbank, Los Angeles County, Calif). 2004;20:358-63.

Otto SJ, de Groot RH, Hornstra G. Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional

docosahexaenoic acid status. Prostaglandins, leukotrienes, and essential fatty acids. 2003;69:237-43.

Otto SJ, Houwelingen AC, Antal M, Manninen A, Godfrey K, Lopez-Jaramillo P, et al. Maternal and neonatal essential fatty acid status in phospholipids: an

international comparative study. European journal of clinical nutrition. 1997;51:232-42.

Otto SJ, van Houwelingen AC, Badart-Smook A, Hornstra G. The postpartum docosahexaenoic acid status of lactating and nonlactating mothers. Lipids. 1999;34

Suppl:S227.

Otto SJ, van Houwelingen AC, Badart-Smook A, Hornstra G. Comparison of the peripartum and postpartum phospholipid polyunsaturated fatty acid profiles of lactating

and nonlactating women. The American journal of clinical nutrition. 2001;73:1074-9.

Otto SJ, van Houwelingen AC, Badart-Smook A, Hornstra G. Changes in the maternal essential fatty acid profile during early pregnancy and the relation of the profile

to diet. The American journal of clinical nutrition. 2001;73:302-7.

Overgaard J, Porsgaard T, Guo Z, Lauritzen L, Mu H. Postprandial lipid responses of butter blend containing fish oil in a single-meal study in humans. Molecular

nutrition & food research. 2008;52:1140-6.

Panagiotakos DB, Kastorini CM, Pitsavos C, Stefanadis C. The current Greek diet and the omega-6/omega-3 balance: the Mediterranean diet score is inversely

associated with the omega-6/omega-3 ratio. World review of nutrition and dietetics. 2011;102:53-6.

Panchaud A, Sauty A, Kernen Y, Decosterd LA, Buclin T, Boulat O, et al. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic

fibrosis patients: a randomized, crossover placebo-controlled trial. Clinical nutrition (Edinburgh, Scotland). 2006;25:418-27.

Panza F, Frisardi V, Seripa D, Pilotto A, Solfrizzi V. Plasma levels of n-3 polyunsaturated fatty acids and cognitive decline: possible role of depressive symptoms and

apolipoprotein E genotyping. Journal of the American Geriatrics Society. 2010;58:2249-51.

Park Y, Harris W. EPA, but not DHA, decreases mean platelet volume in normal subjects. Lipids. 2002;37:941-6.

Park Y, Harris WS. Dose-response of n-3 polyunsaturated fatty acids on lipid profile and tolerability in mildly hypertriglyceridemic subjects. Journal of medicinal food.

2009;12:803-8.

Park Y, Kim M. Serum 25-hydroxyvitamin D concentrations are associated with erythrocyte levels of n-3 PUFA but not risk of CVD. The British journal of nutrition.

2011;106:1529-34.

Park Y, Oh SH, Rhee MY. Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with

hypertension. Nutrition research (New York, NY). 2010;30:807-14.

Parker GB, Heruc GA, Hilton TM, Olley A, Brotchie H, Hadzi-Pavlovic D, et al. Low levels of docosahexaenoic acid identified in acute coronary syndrome patients

with depression. Psychiatry research. 2006;141:279-86.

Pawlosky RJ, Hibbeln JR, Herion D, Kleiner DE, Salem N, Jr. Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during

withdrawal. Journal of lipid research. 2009;50:154-61.

Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N, Jr. Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. Journal of lipid research.

2001;42:1257-65.

Payet M, Esmail MH, Polichetti E, Le Brun G, Adjemout L, Donnarel G, et al. Docosahexaenoic acid-enriched egg consumption induces accretion of arachidonic acid

in erythrocytes of elderly patients. The British journal of nutrition. 2004;91:789-96.

Pazirandeh S, Ling PR, Ollero M, Gordon F, Burns DL, Bistrian BR. Supplementation of arachidonic acid plus docosahexaenoic acid in cirrhotic patients awaiting liver

transplantation: a preliminary study. JPEN Journal of parenteral and enteral nutrition. 2007;31:511-6.

Pedersen MW, Koenig W, Christensen JH, Schmidt EB. The effect of marine n-3 fatty acids in different doses on plasma concentrations of Lp-PLA2 in healthy adults.

European journal of nutrition. 2009;48:1-5.

Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with

standard drugs. Archives of general psychiatry. 2002;59:913-9.

Pelikanova T, Kazdova L, Chvojkova S, Base J. Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients. Metabolism: clinical and

experimental. 2001;50:1472-8.

Perez-Martinez P, Delgado-Lista J, Garcia-Rios A, Tierney AC, Gulseth HL, Williams CM, et al. Insulin receptor substrate-2 gene variants in subjects with metabolic

syndrome: association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance. Molecular nutrition & food research. 2012;56:309-

15.

Petersen MM, Eschen RB, Aardestrup I, Obel T, Schmidt EB. Flow-mediated vasodilation and dietary intake of n-3 polyunsaturated acids in healthy subjects. Cellular

and molecular biology (Noisy-le-Grand, France). 2010;56:38-44.

Petit JM, Guiu B, Duvillard L, Jooste V, Brindisi MC, Athias A, et al. Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a

lower prevalence of steatosis in patients with type 2 diabetes. Clinical nutrition (Edinburgh, Scotland). 2012;31:520-5.

Phang M, Lincz LF, Garg ML. Eicosapentaenoic and docosahexaenoic acid supplementations reduce platelet aggregation and hemostatic markers differentially in men

and women. The Journal of nutrition. 2013;143:457-63.

Phelan N, O'Connor A, Kyaw Tun T, Correia N, Boran G, Roche HM, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with

polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial. The American journal of clinical nutrition.

2011;93:652-62.

Philibert A, Bouchard M, Mergler D. Neuropsychiatric symptoms, omega-3, and mercury exposure in freshwater fish-eaters. Archives of environmental & occupational

health. 2008;63:143-53.

Phillips CM, Goumidi L, Bertrais S, Field MR, Ordovas JM, Cupples LA, et al. Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk

of insulin resistance and metabolic syndrome in adults. The Journal of nutrition. 2010;140:238-44.

Pike KC, Calder PC, Inskip HM, Robinson SM, Roberts GC, Cooper C, et al. Maternal plasma phosphatidylcholine fatty acids and atopy and wheeze in the offspring at

age of 6 years. Clinical & developmental immunology. 2012;2012:474613.

Pilkington SM, Massey KA, Bennett SP, Al-Aasswad NM, Roshdy K, Gibbs NK, et al. Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-

induced suppression of human cutaneous immune responses. The American journal of clinical nutrition. 2013;97:646-52.

Piolot A, Blache D, Boulet L, Fortin LJ, Dubreuil D, Marcoux C, et al. Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health. The

Journal of laboratory and clinical medicine. 2003;141:41-9.

Pishva H, Mahboob SA, Mehdipour P, Eshraghian MR, Mohammadi-Asl J, Hosseini S, et al. Fatty acid-binding protein-2 genotype influences lipid and lipoprotein

response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects. Nutrition (Burbank, Los Angeles County, Calif). 2010;26:1117-21.

Popichev MI, Tolkacheva NV, Kulakova SN, Konoshenko SV. [Lipid composition of blood plasma and erythrocyte membrane of volleyball players under intensive

physical load]. Ukrainskii biokhimicheskii zhurnal. 1997;69:83-7.

Pot GK, Geelen A, van Heijningen EM, Siezen CL, van Kranen HJ, Kampman E. Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with

colorectal adenoma risk: an endoscopy-based case-control study. International journal of cancer Journal international du cancer. 2008;123:1974-7.

Poulia KA, Panagiotakos DB, Tourlede E, Rezou A, Stamatiadis D, Boletis J, et al. Omega-3 fatty acids supplementation does not affect serum lipids in chronic

hemodialysis patients. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2011;21:479-84.

Pratt VC, Tredget EE, Clandinin MT, Field CJ. Fatty acid content of plasma lipids and erythrocyte phospholipids are altered following burn injury. Lipids. 2001;36:675-

82.

Pratt VC, Watanabe S, Bruera E, Mackey J, Clandinin MT, Baracos VE, et al. Plasma and neutrophil fatty acid composition in advanced cancer patients and response to

fish oil supplementation. British journal of cancer. 2002;87:1370-8.

Prisco D, Filippini M, Francalanci I, Paniccia R, Gensini GF, Abbate K, et al. Effect of n-3 polyunsaturated fatty acid intake on phospholipid fatty acid composition in

plasma and erythrocytes. The American journal of clinical nutrition. 1996;63:925-32.

Prisco D, Paniccia R, Coppo M, Filippini M, Francalanci I, Brunelli T, et al. Platelet activation and platelet lipid composition in pulmonary cancer. Prostaglandins,

leukotrienes, and essential fatty acids. 1995;53:65-8.

Puri BK, Richardson AJ, Horrobin DF, Easton T, Saeed N, Oatridge A, et al. Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission,

normalisation of blood fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes. International journal of clinical practice.

2000;54:57-63.

Pyzh MV, Gratsianskii NA, Areshev G, Kulakova SN. [Dietary effect of omega-3 polyunsaturated fatty acid supplementation on blood fatty acids, lipid and lipoproteins

in patients with ischemic heart disease]. Kardiologiia. 1993;33:21-6.

Querques G, Benlian P, Chanu B, Portal C, Coscas G, Soubrane G, et al. Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age-

related macular degeneration. European journal of ophthalmology. 2009;19:100-6.

Raatz SK, Bibus D, Thomas W, Kris-Etherton P. Total fat intake modifies plasma fatty acid composition in humans. The Journal of nutrition. 2001;131:231-4.

Raatz SK, Young LR, Picklo MJ, Sr., Sauter ER, Qin W, Kurzer MS. Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase

activity indices, and urinary prostaglandin E in women. Nutrition research (New York, NY). 2012;32:1-7.

Radack K, Deck C, Huster G. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial.

Archives of internal medicine. 1991;151:1173-80.

Raitt MH, Connor WE, Morris C, Kron J, Halperin B, Chugh SS, et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients

with implantable defibrillators: a randomized controlled trial. JAMA : the journal of the American Medical Association. 2005;293:2884-91.

Ramel A, Martinez JA, Kiely M, Bandarra NM, Thorsdottir I. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European

young adults during energy restriction. Nutrition (Burbank, Los Angeles County, Calif). 2010;26:168-74.

Rao S, Erasmus RT. Pilot study on plasma fatty acids in poorly controlled non insulin dependent diabetic Melanesians. East African medical journal. 1996;73:816-8.

Rapp JH, Connor WE, Lin DS, Porter JM. Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human

atherosclerotic plaques. Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. 1991;11:903-11.

Rasic-Milutinovic Z, Popovic T, Perunicic-Pekovic G, Arsic A, Borozan S, Glibetic M. Lower serum paraoxonase-1 activity is related to linoleic and docosahexanoic

fatty acids in type 2 diabetic patients. Archives of medical research. 2012;43:75-82.

Rasmussen LE, Svensson M, Jorgensen KA, Schmidt EB, Christensen JH. The content of docosahexaenoic acid in serum phospholipid is inversely correlated with

plasma homocysteine levels in patients with end-stage renal disease. Nutrition research (New York, NY). 2010;30:535-40.

Reece MS, McGregor JA, Allen KG, Harris MA. Maternal and perinatal long-chain fatty acids: possible roles in preterm birth. American journal of obstetrics and

gynecology. 1997;176:907-14.

Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry research. 2009;166:254-9.

Remans PH, Sont JK, Wagenaar LW, Wouters-Wesseling W, Zuijderduin WM, Jongma A, et al. Nutrient supplementation with polyunsaturated fatty acids and

micronutrients in rheumatoid arthritis: clinical and biochemical effects. European journal of clinical nutrition. 2004;58:839-45.

Ren H, Ghebremeskel K, Okpala I, Lee A, Ibegbulam O, Crawford M. Patients with sickle cell disease have reduced blood antioxidant protection. International journal

for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition. 2008;78:139-

47.

Ren H, Ghebremeskel K, Okpala I, Ugochukwu CC, Crawford M, Ibegbulam O. Abnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in

sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS). Prostaglandins, leukotrienes, and essential fatty acids. 2006;74:1-6.

Ren H, Magulike N, Ghebremeskel K, Crawford M. Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids.

Prostaglandins, leukotrienes, and essential fatty acids. 2006;74:157-63.

Rey M, Turcotte F, Lapointe C, Dewailly E. High blood cadmium levels are not associated with consumption of traditional food among the Inuit of Nunavik. Journal of

toxicology and environmental health. 1997;51:5-14.

Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in

acute lung injury. JAMA : the journal of the American Medical Association. 2011;306:1574-81.

Richardson AJ, Easton T, Puri BK. Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with

eicosapentaenoic acid. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2000;10:189-93.

Riemer S, Maes M, Christophe A, Rief W. Lowered omega-3 PUFAs are related to major depression, but not to somatization syndrome. Journal of affective disorders.

2010;123:173-80.

Rioux FM, Belanger-Plourde J, Leblanc CP, Vigneau F. Relationship between maternal DHA and iron status and infants' cognitive performance. Canadian journal of

dietetic practice and research : a publication of Dietitians of Canada = Revue canadienne de la pratique et de la recherche en dietetique : une publication des Dietetistes

du Canada. 2011;72:76.

Rissanen T, Voutilainen S, Nyyssonen K, Lakka TA, Salonen JT. Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute

coronary events: the Kuopio ischaemic heart disease risk factor study. Circulation. 2000;102:2677-9.

Ritch CR, Wan RL, Stephens LB, Taxy JB, Huo D, Gong EM, et al. Dietary fatty acids correlate with prostate cancer biopsy grade and volume in Jamaican men. The

Journal of urology. 2007;177:97-101; discussion .

Rodriguez-Palmero M, Lopez-Sabater MC, Castellote-Bargallo AI, de la Torre-Boronat MC, Rivero-Urgell M. Administration of low doses of fish oil derived N-3 fatty

acids to elderly subjects. European journal of clinical nutrition. 1997;51:554-60.

Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation

on depressed mood and cognitive function: a randomised controlled trial. The British journal of nutrition. 2008;99:421-31.

Romieu I, Garcia-Esteban R, Sunyer J, Rios C, Alcaraz-Zubeldia M, Velasco SR, et al. The effect of supplementation with omega-3 polyunsaturated fatty acids on

markers of oxidative stress in elderly exposed to PM(2.5). Environmental health perspectives. 2008;116:1237-42.

Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, et al. Effect of omega-3 fatty acids supplementation on depressive symptoms and on

health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. Journal of the American

College of Nutrition. 2010;29:55-64.

Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, et al. Long chain omega 3 polyunsaturated fatty acids supplementation in the treatment

of elderly depression: effects on depressive symptoms, on phospholipids fatty acids profile and on health-related quality of life. The journal of nutrition, health & aging.

2011;15:37-44.

Rudkowska I, Caron-Dorval D, Verreault M, Couture P, Deshaies Y, Barbier O, et al. PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase

lipoprotein lipase activity. Molecular nutrition & food research. 2010;54:543-50.

Rudkowska I, Paradis AM, Thifault E, Julien P, Tchernof A, Couture P, et al. Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids

supplementation in a normolipidemic/normocholesterolemic Caucasian population. The Journal of nutritional biochemistry. 2013;24:54-61.

Rum P, Hornstra G. The n-3 and n-6 polyunsaturated fatty acid composition of plasma phospholipids in pregnant women and their infants. Relationship with maternal

linoleic acid intake. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2002;40:32-9.

Rupp H, Rupp TP, Alter P, Maisch B. Inverse shift in serum polyunsaturated and monounsaturated fatty acids is associated with adverse dilatation of the heart. Heart

(British Cardiac Society). 2010;96:595-8.

Rupp H, Rupp TP, Alter P, Maisch B. Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart

disease resulting in "HUFA deficiency". Canadian journal of physiology and pharmacology. 2012;90:55-73.

Rylander C, Lund E, Froyland L, Sandanger TM. Predictors of PCP, OH-PCBs, PCBs and chlorinated pesticides in a general female Norwegian population.

Environment international. 2012;43:13-20.

Rytter D, Schmidt EB, Bech BH, Christensen JH, Henriksen TB, Olsen SF. Fish oil supplementation during late pregnancy does not influence plasma lipids or

lipoprotein levels in young adult offspring. Lipids. 2011;46:1091-9.

Sacks FM, Hebert P, Appel LJ, Borhani NO, Applegate WB, Cohen JD, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-

cholesterol levels in phase I of the Trials of Hypertension Prevention. Journal of hypertension. 1994;12:209-13.

Sadou H, Leger CL, Descomps B, Barjon JN, Monnier L, Crastes de Paulet A. Differential incorporation of fish-oil eicosapentaenoate and docosahexaenoate into lipids

of lipoprotein fractions as related to their glyceryl esterification: a short-term (postprandial) and long-term study in healthy humans. The American journal of clinical

nutrition. 1995;62:1193-200.

Safarinejad MR, Hosseini SY, Dadkhah F, Asgari MA. Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal

plasma: a comparison between fertile and infertile men. Clinical nutrition (Edinburgh, Scotland). 2010;29:100-5.

Saifullah A, Watkins BA, Saha C, Li Y, Moe SM, Friedman AN. Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in

haemodialysis patients--a pilot study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal

Association. 2007;22:3561-7.

Sakamoto M, Chan HM, Domingo JL, Kawakami S, Murata K. Mercury and docosahexaenoic acid levels in maternal and cord blood in relation to segmental maternal

hair mercury concentrations at parturition. Environment international. 2012;44:112-7.

Sakamoto M, Kubota M, Liu XJ, Murata K, Nakai K, Satoh H. Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption

to fetus. Environmental science & technology. 2004;38:3860-3.

Sakurai T, Matsui T, Yao T, Takagi Y, Hirai F, Aoyagi K, et al. Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized,

controlled trial comparing nutrient formulas. JPEN Journal of parenteral and enteral nutrition. 2002;26:98-103.

Sala-Vila A, Cofan M, Perez-Heras A, Nunez I, Gilabert R, Junyent M, et al. Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects

with primary dyslipidemia. The American journal of clinical nutrition. 2010;92:186-93.

Salem N, Jr., Kuratko CN. Lack of evidence for increased alpha-linolenic acid metabolism in vegetarians. The American journal of clinical nutrition. 2011;93:1154-5;

author reply 5-6.

Salisbury AC, Amin AP, Harris WS, Chan PS, Gosch KL, Rich MW, et al. Predictors of omega-3 index in patients with acute myocardial infarction. Mayo Clinic

proceedings Mayo Clinic. 2011;86:626-32.

Salisbury AC, Harris WS, Amin AP, Reid KJ, O'Keefe JH, Jr., Spertus JA. Relation between red blood cell omega-3 fatty acid index and bleeding during acute

myocardial infarction. The American journal of cardiology. 2012;109:13-8.

Salm P, Taylor PJ, Kostner K. Simultaneous quantification of total eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid in plasma by high-performance

liquid chromatography-tandem mass spectrometry. Biomedical chromatography : BMC. 2011;25:652-9.

Sanders TA, Hall WL, Maniou Z, Lewis F, Seed PT, Chowienczyk PJ. Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a

randomized controlled trial. The American journal of clinical nutrition. 2011;94:973-80.

Sanders TA, Hinds A. The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy

male volunteers. The British journal of nutrition. 1992;68:163-73.

Sanders TA, Lewis F, Slaughter S, Griffin BA, Griffin M, Davies I, et al. Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-

linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study. The

American journal of clinical nutrition. 2006;84:513-22.

Sanjurjo P, Matorras R, Ingunza N, Alonso M, Rodriguez-Alarcon J, Perteagudo L. Cross-sectional study of percentual changes in total plasmatic fatty acids during

pregnancy. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 1993;25:590-2.

Sanjurjo P, Perteagudo L, Rodriguez Soriano J, Vilaseca A, Campistol J. Polyunsaturated fatty acid status in patients with phenylketonuria. Journal of inherited

metabolic disease. 1994;17:704-9.

Sanjurjo P, Ruiz-Sanz JI, Jimeno P, Aldamiz-Echevarria L, Aquino L, Matorras R, et al. Supplementation with docosahexaenoic acid in the last trimester of pregnancy:

maternal-fetal biochemical findings. Journal of perinatal medicine. 2004;32:132-6.

Santos FS, Chaves CR, Costa RS, Oliveira OR, Santana MG, Conceicao FD, et al. Status of cis and trans fatty acids in Brazilian adolescent mothers and their newborns.

Journal of pediatric and adolescent gynecology. 2012;25:270-6.

Santos MJ, Llopis J, Mataix FJ, Urbano G, Lopez Jurado M. Influence of dietary fish on fatty acid composition of the erythrocyte membrane in coronary heart disease

patients. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie

et de nutrition. 1996;66:378-85.

Santos MJ, Lopez-Jurado M, Llopis J, Urbano G, Mataix FJ. Influence of dietary supplementation with fish on plasma fatty acid composition in coronary heart disease

patients. Annals of nutrition & metabolism. 1995;39:52-62.

Saravanan P, Bridgewater B, West AL, O'Neill SC, Calder PC, Davidson NC. Omega-3 fatty acid supplementation does not reduce risk of atrial fibrillation after

coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. Circulation Arrhythmia and electrophysiology. 2010;3:46-53.

Scambi C, Guarini P, De Franceschi L, Bambara LM. Can 5-methyltetrahydrofolate modify the phospholipid fatty acid pattern in cystic fibrosis pediatric patients?.

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2006;5:197-9.

Scarpa M, Romanato G, Manzato E, Ruffolo C, Marin R, Basato S, et al. Restorative proctocolectomy for ulcerative colitis: impact on lipid metabolism and adipose

tissue and serum fatty acids. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2008;12:279-87.

Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and

Alzheimer disease: the Framingham Heart Study. Archives of neurology. 2006;63:1545-50.

Schaefer EJ, Robins SJ, Patton GM, Sandberg MA, Weigel-DiFranco CA, Rosner B, et al. Red blood cell membrane phosphatidylethanolamine fatty acid content in

various forms of retinitis pigmentosa. Journal of lipid research. 1995;36:1427-33.

Scheltens P, Twisk JW, Blesa R, Scarpini E, von Arnim CA, Bongers A, et al. Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled

trial. Journal of Alzheimer's disease : JAD. 2012;31:225-36.

Schins A, Crijns HJ, Brummer RJ, Wichers M, Lousberg R, Celis S, et al. Altered omega-3 polyunsaturated fatty acid status in depressed post-myocardial infarction

patients. Acta psychiatrica Scandinavica. 2007;115:35-40.

Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Different gene expression profiles in normo- and dyslipidemic men after fish oil supplementation:

results from a randomized controlled trial. Lipids in health and disease. 2012;11:105.

Schmitt Y, Schneider H. [The effect of highly unsaturated fatty acids on the parameters of lipoprotein metabolism and rheology during their administration to patients

undergoing chronic hemodialysis treatment]. Zeitschrift fur Ernahrungswissenschaft. 1993;32:209-18.

Schubert R, Kitz R, Beermann C, Rose MA, Lieb A, Sommerer PC, et al. Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge.

International archives of allergy and immunology. 2009;148:321-9.

Sekikawa A, Kadowaki T, Curb JD, Evans RW, Maegawa H, Abbott RD, et al. Circulating levels of 8 cytokines and marine n-3 fatty acids and indices of obesity in

Japanese, white, and Japanese American middle-aged men. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and

Cytokine Research. 2010;30:541-8.

Sekikawa A, Kadowaki T, El-Saed A, Okamura T, Sutton-Tyrrell K, Nakamura Y, et al. Differential association of docosahexaenoic and eicosapentaenoic acids with

carotid intima-media thickness. Stroke; a journal of cerebral circulation. 2011;42:2538-43.

Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing

elective upper gastrointestinal tract surgery: a prospective randomized study. Archives of surgery (Chicago, Ill : 1960). 1999;134:1309-16.

Sergeant S, Hugenschmidt CE, Rudock ME, Ziegler JT, Ivester P, Ainsworth HC, et al. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene

variants in African Americans and European Americans with diabetes or the metabolic syndrome. The British journal of nutrition. 2012;107:547-55.

Shahar E, Boland LL, Folsom AR, Tockman MS, McGovern PG, Eckfeldt JH. Docosahexaenoic acid and smoking-related chronic obstructive pulmonary disease. The

Atherosclerosis Risk in Communities Study Investigators. American journal of respiratory and critical care medicine. 1999;159:1780-5.

Shearer GC, Harris WS, Pedersen TL, Newman JW. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters. Journal

of lipid research. 2010;51:2074-81.

Shin MJ, Shim E, Kang B, Park S, Lee SH, Shim CY, et al. Increased inflammation, reduced plasma phospholipid eicosapentaenoic acid and reduced antioxidant

potential of treated hypertensive patients with metabolic syndrome. Yonsei medical journal. 2009;50:757-63.

Shoji H, Hisata K, Suzuki M, Yoshikawa N, Suganuma H, Ohkawa N, et al. Effects of parenteral soybean oil lipid emulsion on the long-chain polyunsaturated fatty acid

profile in very-low-birth-weight infants. Acta paediatrica (Oslo, Norway : 1992). 2011;100:972-6.

Siener R, Alteheld B, Terjung B, Junghans B, Bitterlich N, Stehle P, et al. Change in the fatty acid pattern of erythrocyte membrane phospholipids after oral

supplementation of specific fatty acids in patients with gastrointestinal diseases. European journal of clinical nutrition. 2010;64:410-8.

Siguel EN, Lerman RH. Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Metabolism: clinical and experimental.

1996;45:12-23.

Silverman DI, Reis GJ, Sacks FM, Boucher TM, Pasternak RC. Usefulness of plasma phospholipid N-3 fatty acid levels in predicting dietary fish intake in patients with

coronary artery disease. The American journal of cardiology. 1990;66:860-2.

Silverman DI, Ware JA, Sacks FM, Pasternak RC. Comparison of the absorption and effect on platelet function of a single dose of n-3 fatty acids given as fish or fish

oil. The American journal of clinical nutrition. 1991;53:1165-70.

Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression.

Prostaglandins, leukotrienes, and essential fatty acids. 2005;72:211-8.

Sirtori CR, Paoletti R, Mancini M, Crepaldi G, Manzato E, Rivellese A, et al. N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and

abnormal glucose tolerance. Italian Fish Oil Multicenter Study. The American journal of clinical nutrition. 1997;65:1874-81.

Skilton MR, Mikkila V, Wurtz P, Ala-Korpela M, Sim KA, Soininen P, et al. Fetal growth, omega-3 (n-3) fatty acids, and progression of subclinical atherosclerosis:

preventing fetal origins of disease? The Cardiovascular Risk in Young Finns Study. The American journal of clinical nutrition. 2013;97:58-65.

Skuladottir G, Reynisdottir M, Gudbjarnason S, Sigurdsson SB, Axelsson J. The fatty acid profile in plasma phospholipids of two separate but genetically-comparable

populations. Arctic medical research. 1991;Suppl:512-4.

Skuladottir GV, Heidarsdottir R, Arnar DO, Torfason B, Edvardsson V, Gottskalksson G, et al. Plasma n-3 and n-6 fatty acids and the incidence of atrial fibrillation

following coronary artery bypass graft surgery. European journal of clinical investigation. 2011;41:995-1003.

Sliwinski S, Croonenberghs J, Christophe A, Deboutte D, Maes M. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism?. Neuro

endocrinology letters. 2006;27:465-71.

Smaoui M, Koubaa N, Hammami S, Abid N, Feki M, Chaaba R, et al. Association between dietary fat and antioxidant status of Tunisian type 2 diabetic patients.

Prostaglandins, leukotrienes, and essential fatty acids. 2006;74:323-9.

Smuts CM, Borod E, Peeples JM, Carlson SE. High-DHA eggs: feasibility as a means to enhance circulating DHA in mother and infant. Lipids. 2003;38:407-14.

Sofi F, Giorgi G, Cesari F, Gori AM, Mannini L, Parisi G, et al. The atherosclerotic risk profile is affected differently by fish flesh with a similar EPA and DHA content

but different n-6/n-3 ratio. Asia Pacific journal of clinical nutrition. 2013;22:32-40.

Son YK, Lee SM, Kim SE, Kim KH, Lee SY, Bae HR, et al. Association between vascular calcification scores on plain radiographs and fatty acid contents of

erythrocyte membrane in hemodialysis patients. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

2012;22:58-66.

Sontrop J, Campbell MK. Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Preventive medicine. 2006;42:4-

13.

Sorensen IM, Joner G, Jenum PA, Eskild A, Stene LC. Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are independent of risk of type 1

diabetes in the offspring. Diabetes/metabolism research and reviews. 2012;28:431-8.

Sorokovoi KV, Pogozheva AV, Kulakova SN, Lupinovich VL, Karagodina ZV, Levachev MM, et al. [Study of metabolic and clinical effects of polyunsaturated fatty

acids omega-3 from "Eicovit" in patients with ischemic heart disease and familial hyperlipoproteinemia]. Voprosy pitaniia. 1998:29-31.

Stanke-Labesque F, Moliere P, Bessard J, Laville M, Vericel E, Lagarde M. Effect of dietary supplementation with increasing doses of docosahexaenoic acid on

neutrophil lipid composition and leukotriene production in human healthy volunteers. The British journal of nutrition. 2008;100:829-33.

Stapleton RD, Martin TR, Weiss NS, Crowley JJ, Gundel SJ, Nathens AB, et al. A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment

of acute lung injury. Critical care medicine. 2011;39:1655-62.

Stark KD, Beblo S, Murthy M, Whitty JE, Buda-Abela M, Janisse J, et al. Alcohol consumption in pregnant, black women is associated with decreased plasma and

erythrocyte docosahexaenoic acid. Alcoholism, clinical and experimental research. 2005;29:130-40.

Steffen BT, Steffen LM, Tracy R, Siscovick D, Hanson NQ, Nettleton J, et al. Obesity modifies the association between plasma phospholipid polyunsaturated fatty acids

and markers of inflammation: the Multi-Ethnic Study of Atherosclerosis. International journal of obesity (2005). 2012;36:797-804.

Steffen BT, Steffen LM, Tracy R, Siscovick D, Jacobs D, Liu K, et al. Ethnicity, plasma phospholipid fatty acid composition and inflammatory/endothelial activation

biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA). European journal of clinical nutrition. 2012;66:600-5.

Stiefel P, Ruiz-Gutierrez V, Gajon E, Acosta D, Garcia-Donas MA, Madrazo J, et al. Sodium transport kinetics, cell membrane lipid composition, neural conduction and

metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention. Annals of nutrition & metabolism. 1999;43:113-20.

Stokes-Riner A, Thurston SW, Myers GJ, Duffy EM, Wallace J, Bonham M, et al. A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the

Seychelles. Neurotoxicology and teratology. 2011;33:325-8.

Strandvik B, Chen Y, Dangardt F, Eriksson S, Friberg P, Garemo M, et al. From the Swedish to the Mediterranean diet and the omega-6/omega-3 balance. World review

of nutrition and dietetics. 2011;102:73-80.

Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, et al. Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized,

double-blind, placebo-controlled trial. The Journal of clinical psychiatry. 2008;69:644-51.

Subbaiah PV, Kaufman D, Bagdade JD. Incorporation of dietary n-3 fatty acids into molecular species of phosphatidyl choline and cholesteryl ester in normal human

plasma. The American journal of clinical nutrition. 1993;58:360-8.

Sublette ME, Hibbeln JR, Galfalvy H, Oquendo MA, Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. The American

journal of psychiatry. 2006;163:1100-2.

Sumino H, Ichikawa S, Murakami M, Nakamura T, Kanda T, Sakamaki T, et al. Effects of hormone replacement therapy on circulating docosahexaenoic acid and

eicosapentaenoic acid levels in postmenopausal women. Endocrine journal. 2003;50:51-9.

Sun Q, Ma J, Campos H, Rexrode KM, Albert CM, Mozaffarian D, et al. Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial

infarction. The American journal of clinical nutrition. 2008;88:216-23.

Sungurtekin H, Degirmenci S, Sungurtekin U, Oguz BE, Sabir N, Kaptanoglu B. Comparison of the effects of different intravenous fat emulsions in patients with

systemic inflammatory response syndrome and sepsis. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

2011;26:665-71.

Svensson M, Schmidt EB, Jorgensen KA, Christensen JH. The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: a

randomized placebo-controlled intervention study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association -

European Renal Association. 2008;23:2918-24.

Swierk M, Williams PG, Wilcox J, Russell KG, Meyer BJ. Validation of an Australian electronic food frequency questionnaire to measure polyunsaturated fatty acid

intake. Nutrition (Burbank, Los Angeles County, Calif). 2011;27:641-6.

Szklarek-Kubicka M, Fijalkowska-Morawska J, Zaremba-Drobnik D, Ucinski A, Czekalski S, Nowicki M. Effect of intradialytic intravenous administration of omega-3

fatty acids on nutritional status and inflammatory response in hemodialysis patients: a pilot study. Journal of renal nutrition : the official journal of the Council on Renal

Nutrition of the National Kidney Foundation. 2009;19:487-93.

Tanaka T, Kakutani S, Horikawa C, Kawashima H, Kiso Y. Oral supplementation with dihomo-gamma-linolenic acid (DGLA)-enriched oil increases serum DGLA

content in healthy adults. Lipids. 2012;47:643-6.

Taylor CG, Noto AD, Stringer DM, Froese S, Malcolmson L. Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control

in individuals with well-controlled type 2 diabetes. Journal of the American College of Nutrition. 2010;29:72-80.

Terano T. Effect of omega 3 polyunsaturated fatty acid ingestion on bone metabolism and osteoporosis. World review of nutrition and dietetics. 2001;88:141-7.

Terre'Blanche G, van der Walt MM, Bergh JJ, Mienie LJ. Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with

docosahexaenoic acid--a case report. Lipids in health and disease. 2011;10:152.

Theobald HE, Chowienczyk PJ, Whittall R, Humphries SE, Sanders TA. LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and

women. The American journal of clinical nutrition. 2004;79:558-63.

Theobald HE, Goodall AH, Sattar N, Talbot DC, Chowienczyk PJ, Sanders TA. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men

and women. The Journal of nutrition. 2007;137:973-8.

Thomas B, Ghebremeskel K, Lowy C, Crawford M, Offley-Shore B. Nutrient intake of women with and without gestational diabetes with a specific focus on fatty acids.

Nutrition (Burbank, Los Angeles County, Calif). 2006;22:230-6.

Thomas B, Ghebremeskel K, Lowy C, Min Y, Crawford MA. Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women.

European journal of clinical nutrition. 2004;58:1492-7.

Thomas TR, Liu Y, Linden MA, Rector RS. Interaction of exercise training and n-3 fatty acid supplementation on postprandial lipemia. Applied physiology, nutrition,

and metabolism = Physiologie appliquee, nutrition et metabolisme. 2007;32:473-80.

Thorsdottir I, Birgisdottir B, Kiely M, Martinez J, Bandarra N. Fish consumption among young overweight European adults and compliance to varying seafood content

in four weight loss intervention diets. Public health nutrition. 2009;12:592-8.

Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Jenssen T. Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids. Arteriosclerosis,

thrombosis, and vascular biology. 1997;17:814-9.

Tsuji M, Ando T, Kitano T, Wakamiya J, Koriyama C, Akiba S. Relationship between RBC mercury levels and serum n3 polyunsaturated fatty acid concentrations

among Japanese men and women. Journal of environmental and public health. 2012;2012:849305.

Tulk HM, Robinson LE. Modifying the n-6/n-3 polyunsaturated fatty acid ratio of a high-saturated fat challenge does not acutely attenuate postprandial changes in

inflammatory markers in men with metabolic syndrome. Metabolism: clinical and experimental. 2009;58:1709-16.

Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, et al. Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control

study. The British journal of nutrition. 2003;89:483-9.

Turunen AW, Jula A, Suominen AL, Mannisto S, Marniemi J, Kiviranta H, et al. Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to

low-grade inflammation and early atherosclerosis. Environmental research. 2013;120:43-54.

Turunen AW, Mannisto S, Kiviranta H, Marniemi J, Jula A, Tiittanen P, et al. Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty

acids as biomarkers of fish consumption. European journal of clinical nutrition. 2010;64:313-23.

Ueeda M, Doumei T, Takaya Y, Ohnishi N, Takaishi A, Hirohata S, et al. Association of serum levels of arachidonic acid and eicosapentaenoic acid with prevalence of

major adverse cardiac events after acute myocardial infarction. Heart and vessels. 2011;26:145-52.

Umemura U, Koike KA, Iso H, Sankai T, Shimamoto T, Sato S, et al. [Population-based comparative study on dietary habits and serum fatty acid compositions]. Nihon

eiseigaku zasshi Japanese journal of hygiene. 1993;48:939-54.

Umhau JC, Dauphinais KM, Patel SH, Nahrwold DA, Hibbeln JR, Rawlings RR, et al. The relationship between folate and docosahexaenoic acid in men. European

journal of clinical nutrition. 2006;60:352-7.

Urano S, Hoshi-Hashizume M, Tochigi N, Matsuo M, Shiraki M, Ito H. Vitamin E and the susceptibility of erythrocytes and reconstituted liposomes to oxidative stress

in aged diabetics. Lipids. 1991;26:58-61.

van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, et al. Effect of fish-oil supplementation on mental well-being in older subjects:

a randomized, double-blind, placebo-controlled trial. The American journal of clinical nutrition. 2008;88:706-13.

van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Olderikkert MG, Beekman AT, et al. Effect of fish oil supplementation on quality of life in a general

population of older Dutch subjects: a randomized, double-blind, placebo-controlled trial. Journal of the American Geriatrics Society. 2009;57:1481-6.

van der Meij BS, Langius JA, Smit EF, Spreeuwenberg MD, von Blomberg BM, Heijboer AC, et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty

acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. The Journal of nutrition. 2010;140:1774-80.

van Eijsden M, Hornstra G, van der Wal MF, Bonsel GJ. Ethnic differences in early pregnancy maternal n-3 and n-6 fatty acid concentrations: an explorative analysis.

The British journal of nutrition. 2009;101:1761-8.

van Eijsden M, Hornstra G, van der Wal MF, Vrijkotte TG, Bonsel GJ. Maternal n-3, n-6, and trans fatty acid profile early in pregnancy and term birth weight: a

prospective cohort study. The American journal of clinical nutrition. 2008;87:887-95.

van Goor SA, Schaafsma A, Erwich JJ, Dijck-Brouwer DA, Muskiet FA. Mildly abnormal general movement quality in infants is associated with higher Mead acid and

lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio. Prostaglandins, leukotrienes, and essential fatty acids. 2010;82:15-20.

van Houwelingen AC, Sorensen JD, Hornstra G, Simonis MM, Boris J, Olsen SF, et al. Essential fatty acid status in neonates after fish-oil supplementation during late

pregnancy. The British journal of nutrition. 1995;74:723-31.

Vancassel S, Durand G, Barthelemy C, Lejeune B, Martineau J, Guilloteau D, et al. Plasma fatty acid levels in autistic children. Prostaglandins, leukotrienes, and

essential fatty acids. 2001;65:1-7.

Vandal M, Freemantle E, Tremblay-Mercier J, Plourde M, Fortier M, Bruneau J, et al. Plasma omega-3 fatty acid response to a fish oil supplement in the healthy

elderly. Lipids. 2008;43:1085-9.

VanderJagt DJ, Arndt CD, Okolo SN, Huang YS, Chuang LT, Glew RH. Fatty acid composition of the milk lipids of Fulani women and the serum phospholipids of

their exclusively breast-fed infants. Early human development. 2000;60:73-87.

Vanhala M, Saltevo J, Soininen P, Kautiainen H, Kangas AJ, Ala-Korpela M, et al. Serum omega-6 polyunsaturated fatty acids and the metabolic syndrome: a

longitudinal population-based cohort study. American journal of epidemiology. 2012;176:253-60.

Varming K, Schmidt EB, Svaneborg N, Moller JM, Lervang HH, Grunnet N, et al. The effect of n-3 fatty acids on neutrophil chemiluminescence. Scandinavian journal

of clinical and laboratory investigation. 1995;55:47-52.

Vedin I, Cederholm T, Freund-Levi Y, Basun H, Garlind A, Irving GF, et al. Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood

mononuclear leukocytes: the OmegAD study. PloS one. 2012;7:e35425.

Vedin I, Cederholm T, Freund-Levi Y, Basun H, Hjorth E, Irving GF, et al. Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral

supplementation of omega3 fatty acids: the OmegAD study. Journal of lipid research. 2010;51:1179-85.

Vega-Lopez S, Kaul N, Devaraj S, Cai RY, German B, Jialal I. Supplementation with omega3 polyunsaturated fatty acids and all-rac alpha-tocopherol alone and in

combination failed to exert an anti-inflammatory effect in human volunteers. Metabolism: clinical and experimental. 2004;53:236-40.

Vermunt SH, Mensink RP, Simonis MM, Hornstra G. Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid. Lipids.

2000;35:137-42.

Versleijen MW, Roelofs HM, Rombouts C, Hermans PW, Noakes PS, Calder PC, et al. Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status,

but not immune function or (anti)oxidant balance: a randomized cross-over study. European journal of clinical investigation. 2012;42:290-302.

Virtanen JK, Mursu J, Voutilainen S, Tuomainen TP. Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men.

Circulation. 2009;120:2315-21.

Virtanen JK, Voutilainen S, Rissanen TH, Mursu J, Tuomainen TP, Korhonen MJ, et al. Mercury, fish oils, and risk of acute coronary events and cardiovascular disease,

coronary heart disease, and all-cause mortality in men in eastern Finland. Arteriosclerosis, thrombosis, and vascular biology. 2005;25:228-33.

Volker D, Fitzgerald P, Major G, Garg M. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. The Journal of rheumatology. 2000;27:2343-6.

Vors C, Pineau G, Gabert L, Drai J, Louche-Pelissier C, Defoort C, et al. Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the

meal: a randomized crossover clinical trial. The American journal of clinical nutrition. 2013;97:23-36.

Wakil A, Mir M, Mellor DD, Mellor SF, Atkin SL. The bioavailability of eicosapentaenoic acid from reconstituted triglyceride fish oil is higher than that obtained from

the triglyceride and monoglyceride forms. Asia Pacific journal of clinical nutrition. 2010;19:499-505.

Walkowiak J, Lisowska A, Blaszczynski M, Przyslawski J, Walczak M. Polyunsaturated fatty acids in cystic fibrosis are related to nutrition and clinical expression of

the disease. Journal of pediatric gastroenterology and nutrition. 2007;45:488-9; author reply 9.

Wander RC, Du SH, Ketchum SO, Rowe KE. alpha-Tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil. The Journal of

nutrition. 1996;126:643-52.

Wander RC, Du SH, Thomas DR. Influence of long-chain polyunsaturated fatty acids on oxidation of low density lipoprotein. Prostaglandins, leukotrienes, and essential

fatty acids. 1998;59:143-51.

Wang DC, Sun CH, Liu LY, Sun XH, Jin XW, Song WL, et al. Serum fatty acid profiles using GC-MS and multivariate statistical analysis: potential biomarkers of

Alzheimer's disease. Neurobiology of aging. 2012;33:1057-66.

Wang J, Yu JC, Kang WM, Ma ZQ. Superiority of a fish oil-enriched emulsion to medium-chain triacylglycerols/long-chain triacylglycerols in gastrointestinal surgery

patients: a randomized clinical trial. Nutrition (Burbank, Los Angeles County, Calif). 2012;28:623-9.

Wang J, Zhang Y. [Effect of the long chain polyunsaturated fatty acids levels in mothers on fetuses]. Zhonghua fu chan ke za zhi. 1998;33:722-3.

Wang X, Li W, Li N, Li J. Omega-3 fatty acids-supplemented parenteral nutrition decreases hyperinflammatory response and attenuates systemic disease sequelae in

severe acute pancreatitis: a randomized and controlled study. JPEN Journal of parenteral and enteral nutrition. 2008;32:236-41.

Wang YP, Kay HH, Killam AP. Decreased levels of polyunsaturated fatty acids in preeclampsia. American journal of obstetrics and gynecology. 1991;164:812-8.

Ward PE, Sutherland J, Glen EM, Glen AI. Niacin skin flush in schizophrenia: a preliminary report. Schizophrenia research. 1998;29:269-74.

Watanabe A, Saito S, Tsuchida T, Higuchi K, Okita M. Low plasma levels of docosahexaenoic acid in patients with liver cirrhosis and its correction with a

polyunsaturated fatty acid-enriched soft oil capsule. Nutrition (Burbank, Los Angeles County, Calif). 1999;15:284-8.

Watanabe E, Sobue Y, Sano K, Okuda K, Yamamoto M, Ozaki Y. Eicosapentaenoic acid for the prevention of recurrent atrial fibrillation. Annals of noninvasive

electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2011;16:373-8.

Watson TA, Blake RJ, Callister R, Garg ML. Antioxidant-restricted diet reduces plasma nonesterified fatty acids in trained athletes. Lipids. 2005;40:433-5.

Weaver BJ, Corner EJ, Bruce VM, McDonald BE, Holub BJ. Dietary canola oil: effect on the accumulation of eicosapentaenoic acid in the alkenylacyl fraction of

human platelet ethanolamine phosphoglyceride. The American journal of clinical nutrition. 1990;51:594-8.

Welch AA, Shakya-Shrestha S, Lentjes MA, Wareham NJ, Khaw KT. Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-

fish-eating meat-eaters, vegetarians, and vegans and the product-precursor ratio [corrected] of alpha-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results

from the EPIC-Norfolk cohort. The American journal of clinical nutrition. 2010;92:1040-51.

Wells EM, Jarrett JM, Lin YH, Caldwell KL, Hibbeln JR, Apelberg BJ, et al. Body burdens of mercury, lead, selenium and copper among Baltimore newborns.

Environmental research. 2011;111:411-7.

Wennberg M, Bergdahl IA, Stegmayr B, Hallmans G, Lundh T, Skerfving S, et al. Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in

northern Sweden. The British journal of nutrition. 2007;98:1038-45.

Wennberg M, Stromberg U, Bergdahl IA, Jansson JH, Kauhanen J, Norberg M, et al. Myocardial infarction in relation to mercury and fatty acids from fish: a risk-

benefit analysis based on pooled Finnish and Swedish data in men. The American journal of clinical nutrition. 2012;96:706-13.

Wheaton DH, Hoffman DR, Locke KG, Watkins RB, Birch DG. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for

X-linked retinitis pigmentosa. Archives of ophthalmology. 2003;121:1269-78.

Wichmann MW, Thul P, Czarnetzki HD, Morlion BJ, Kemen M, Jauch KW. Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion

(Lipoplus, MLF541): data from a prospective, randomized, multicenter trial. Critical care medicine. 2007;35:700-6.

Wiese DM, Lashner BA, Lerner E, DeMichele SJ, Seidner DL. The effects of an oral supplement enriched with fish oil, prebiotics, and antioxidants on nutrition status

in Crohn's disease patients. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2011;26:463-73.

Wijendran V, Bendel RB, Couch SC, Philipson EH, Cheruku S, Lammi-Keefe CJ. Fetal erythrocyte phospholipid polyunsaturated fatty acids are altered in pregnancy

complicated with gestational diabetes mellitus. Lipids. 2000;35:927-31.

Wilk JB, Tsai MY, Hanson NQ, Gaziano JM, Djousse L. Plasma and dietary omega-3 fatty acids, fish intake, and heart failure risk in the Physicians' Health Study. The

American journal of clinical nutrition. 2012;96:882-8.

Wilkinson P, Leach C, Ah-Sing EE, Hussain N, Miller GJ, Millward DJ, et al. Influence of alpha-linolenic acid and fish-oil on markers of cardiovascular risk in subjects

with an atherogenic lipoprotein phenotype. Atherosclerosis. 2005;181:115-24.

Wilkinson T, Aukema HM, Thomas LM, Holub BJ. Marked enrichment of the alkenylacyl subclass of plasma ethanolamine glycerophospholipid with eicosapentaenoic

acid in human subjects consuming a fish oil concentrate. Lipids. 1996;31 Suppl:S211-5.

Williams MA, Frederick IO, Qiu C, Meryman LJ, King IB, Walsh SW, et al. Maternal erythrocyte omega-3 and omega-6 fatty acids, and plasma lipid concentrations,

are associated with habitual dietary fish consumption in early pregnancy. Clinical biochemistry. 2006;39:1063-70.

Williams MA, Zingheim RW, King IB, Zebelman AM. Omega-3 fatty acids in maternal erythrocytes and risk of preeclampsia. Epidemiology (Cambridge, Mass).

1995;6:232-7.

Wood PL, Mankidy R, Ritchie S, Heath D, Wood JA, Flax J, et al. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale-Cognitive scores in

Alzheimer patients. Journal of psychiatry & neuroscience : JPN. 2010;35:59-62.

Wu BT, Dyer RA, King DJ, Innis SM. Low fish intake is associated with low blood concentrations of vitamin D, choline and n-3 DHA in pregnant women. The British

journal of nutrition. 2013;109:936-43.

Wu JH, Lemaitre RN, King IB, Song X, Sacks FM, Rimm EB, et al. Association of plasma phospholipid long-chain omega-3 fatty acids with incident atrial fibrillation

in older adults: the cardiovascular health study. Circulation. 2012;125:1084-93.

Yamori Y. Worldwide epidemic of obesity: hope for Japanese diets. Clinical and experimental pharmacology & physiology. 2004;31 Suppl 2:S2-4.

Yamori Y, Liu L, Mizushima S, Ikeda K, Nara Y. Male cardiovascular mortality and dietary markers in 25 population samples of 16 countries. Journal of hypertension.

2006;24:1499-505.

Yang ZH, Miyahara H, Takeo J, Katayama M. Ingestion of a single serving of saury alters postprandial levels of plasma n-3 polyunsaturated fatty acids and long-chain

monounsaturated fatty acids in healthy human adults. Lipids in health and disease. 2012;11:95.

Yano Y, Hoshide S, Tamaki N, Inokuchi T, Nagata M, Yokota N, et al. Regional differences in hypertensive cardiovascular remodeling between fishing and farming

communities in Japan. American journal of hypertension. 2011;24:437-43.

Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, et al. Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects

on breast adipose tissue fatty acid composition. The American journal of clinical nutrition. 2010;91:1185-94.

Yep YL, Li D, Mann NJ, Bode O, Sinclair AJ. Bread enriched with microencapsulated tuna oil increases plasma docosahexaenoic acid and total omega-3 fatty acids in

humans. Asia Pacific journal of clinical nutrition. 2002;11:285-91.

Ylonen SK, Salminen I, Lyssenko V, Virtanen SM, Groop L, Aro A, et al. The Pro12Ala polymorphism of the PPAR-gamma2 gene affects associations of fish intake

and marine n-3 fatty acids with glucose metabolism. European journal of clinical nutrition. 2008;62:1432-9.

Young GS, Conquer JA, Thomas R. Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with

attention deficit hyperactivity disorder. Reproduction, nutrition, development. 2005;45:549-58.

Yuen AW, Sander JW, Fluegel D, Patsalos PN, Bell GS, Johnson T, et al. Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial.

Epilepsy & behavior : E&B. 2005;7:253-8.

Zabel R, Ash S, King N, Bauer J. Adherence to fish oil intervention in patients with chronic kidney disease. Journal of renal nutrition : the official journal of the Council

on Renal Nutrition of the National Kidney Foundation. 2010;20:329-33.

Zhang B, Wang P, Zhou Q, Chen C, Zhuo S, Ye Y, et al. The relationships between erythrocyte membrane n-6 to n-3 polyunsaturated fatty acids ratio and blood lipids

and C-reactive protein in Chinese adults: an observational study. Biomedical and environmental sciences : BES. 2011;24:234-42.

Zhang J, Wang C, Li L, Man Q, Meng L, Song P, et al. Dietary inclusion of salmon, herring and pompano as oily fish reduces CVD risk markers in dyslipidaemic

middle-aged and elderly Chinese women. The British journal of nutrition. 2012;108:1455-65.

Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in

hypercholesterolemic men and women. The Journal of nutrition. 2004;134:2991-7.

Zhou Q, Zhang B, Wang P, Mei F, Chen CG, Sun LN, et al. Association of interleukin-6 gene -572 C > G polymorphism with dietary intake of n-3 fatty acids on plasma

HDL-c level in Chinese male adults. Asia Pacific journal of clinical nutrition. 2010;19:506-12.

Zhou YE, Kubow S, Dewailly E, Julien P, Egeland GM. Decreased activity of desaturase 5 in association with obesity and insulin resistance aggravates declining long-

chain n-3 fatty acid status in Cree undergoing dietary transition. The British journal of nutrition. 2009;102:888-94.

Zhou YE, Kubow S, Egeland GM. Is iron status associated with highly unsaturated fatty acid status among Canadian Arctic Inuit?. Food & function. 2011;2:381-5.

Zhu QQ, Lou DJ, Si XW, Guan LL, You QY, Yu ZM, et al. [Serum omega-3 polyunsaturated fatty acid and insulin resistance in type 2 diabetes mellitus and non-

alcoholic fatty liver disease]. Zhonghua nei ke za zhi [Chinese journal of internal medicine]. 2010;49:305-8.

1Studies listed alphabetically by first author

Effects of Omega-3 for children’s health: an integrative literature review

Article

Jun 2024

Background: Omega-3 is a set of essential fatty acids, related to brain development and is beneficial to adult health. It is necessary to understand whether the benefits of these fatty acids extend to children because they have low omega-3 consumption, not reaching the daily recommendations established by public health dietary guidelines. The knowledge about the benefits of omega-3 for children can help to identify the necessity to increase the consumption of omega-3 by this population, encouraging the promotion of dietary interventions for child health. This integrative review aimed to gather the main scientific findings that describe the benefits of omega-3 consumption by preschool and school-age children. Methods: The terms: “Fatty Acids, Omega-3, AND Child” were investigated in four databases: PubMed, Web of Science, Cochrane, and Virtual Health Library. Subsequently, the inclusion and exclusion criteria were applied. Results: 53 scientific articles that responded to this investigation were selected. They reported several benefits from omega-3 to children's physical, mental, and cognitive health. Conclusion: The results highlight the importance of omega-3 for this age group's health and development, encouraging adequate consumption.

Aggregation Behavior of Amyloid Beta Peptide Depends Upon the Membrane Lipid Composition

Article

Full-text available

Jun 2024
J MEMBRANE BIOL

Lipika Mirdha

Protein aggregation plays a crucial role in the development of several neurodegenerative diseases. It is important to understand the aggregation process for the detection of the onset of these diseases. Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative diseases caused by the aggregation of Aβ-40 and Aβ-42 peptides. The smaller oligomers lead to the formation of protein plaque at the neural membranes leading to memory loss and other disorders. Interestingly, aggregation takes place at the neural membranes, therefore the membrane composition seems to play an important role in the aggregation process. Despite a large number of literatures on the effect of lipid composition on protein aggregation, there are very few concise reviews that highlight the role of membrane composition in protein aggregation. In this review, we have discussed the implication of membrane composition on the aggregation of amyloid beta peptide with a special emphasis on cholesterol. We have further discussed the role of the degree of unsaturation of fatty acids and the participation of apolipoprotein E4 (ApoE4) in the onset of AD. Graphical Abstract

THE ROLE OF FATTY ACIDS IN THE LIPID METABOLISM DISORDERS MECHANISMS IN INDIVIDUALS WITH ALCOHOL DEPENDENT SYNDROME

Article

Dec 2022

SVETLANA N. LEIKHTER

Introduction. The determination of blood serum fatty acid composition is promising in lipid metabolism disorders study in narcological patients. Aim. The study aim was to establish the fatty acids role in lipid metabolism disorders mechanisms in patients with alcohol dependence syndrome. Material and methods. 208 people were examined, including 96 patients with the second stage alcohol dependence syndrome; 112 people were practically healthy persons during professional examinations. Saturated, monounsaturated, polyunsaturated fatty acids were determined by gas-liquid chromatography. The total polyunsaturated content, omega-3 and omega-6 acids was calculated. Statistical processing was carried out using the SPSS 15.0 application software package. Results and discussion. In narcological patients, a low saturated fatty acids content was revealed, which, against the liver dysfunction background, leads to their insufficient inclusion in the triglycerides and low-density lipoproteins structure. The low content of ω-3 α-linolenic, docosahexaenoic and ω-6-linoleic, arachidonic acids helps to reduce the biologically active substances synthesis with pro- and anti-inflammatory activity. The necessity of blood serum fatty acid composition purposeful study to clarify the comorbid alcohol-attributive morbidity development is substantiated. Conclusion. To identify the lipid metabolism disorders mechanisms in narcological patients, it is more important to determine not the lipid metabolism «traditional» parameters, but the blood serum fatty acid composition. The low ω-3 and ω-6 fatty acids content affects the biologically active substances synthesis with pro- and anti-inflammatory activity, which may explain the decrease in reactivity in patients with somatic pathology. The identified alcohol-associated violation the fatty acid composition signs can be considered as chronic alcohol intoxication screening markers when conducting lipid metabolism study in drug-related risk groups, for example, when they are in somatic hospitals.

Relação dos sinais de depressão pós-parto e sono com a qualidade da dieta em mulheres no período do pós parto

Article

Full-text available

Jun 2024

Introdução: após o nascimento de um filho, ocorrem inúmeras mudanças na rotina dos envolvidos, algumas das quais são percebidas apenas pela mãe, destacando-se a deterioração do sono e da qualidade nutricional, além do risco de depressão pós-parto. Objetivo: avaliar a relação da qualidade da dieta de mulheres no período pós-parto com sinais de depressão pós-parto e qualidade do sono. Metodologia: mulheres de uma cidade do sudeste do Brasil foram recrutadas durante a gravidez e convidadas a continuar o estudo três a quatro meses após o parto. Dados sociodemográficos, obstétricos, antropométricos e dietéticos foram coletados, e os índices de avaliação foram: Índice Adaptado de Qualidade da Dieta para Gestantes (IQDAG), Escala de Depressão Pós-Natal de Edimburgo (EPDS) e Índice de Qualidade do Sono de Pittsburgh (PSQI). Os testes Qui-quadrado e Kruskal-Wallis foram realizados para comparação dos dados, e a correlação de Spearman foi usada para examinar a associação entre os sinais de depressão pós-parto das mulheres, a qualidade do sono e a qualidade da dieta. Resultados: o grupo das frutas foi o menos consumido pelas mulheres, e apenas 1,9%,10,6% e 9,6% atingiram a pontuação máxima para os nutrientes ômega-3, cálcio e ácido fólico, respectivamente. Em contraste, mais de 70% das mulheres atingiram a pontuação máxima para o consumo de leguminosas. Conclusão: não foram encontrados resultados significativos ou correlações ao analisar sinais de depressão pós-parto e qualidade do sono em relação à qualidade da dieta.

Omega-3 world map: 2024 update

Article

Jun 2024
PROG LIPID RES

An Up-to-date Marker of Heart Health - The Omega-3 Index!

Article

Jun 2024

Fatty acid composition in erythrocytes and coronary artery disease risk: a case-control study in China

Article

Jun 2024

Background & aims: There is limited and conflicting evidence about the association of erythrocyte fatty acids with coronary artery disease (CAD), particularly in China where the CAD rates are high....

The effect of fish oil rich in cetoleic acid on the omega-3 index and skin quality

Article

May 2024

Lipidomic and Fatty Acid Biomarkers in Whole Blood Can Predict the Dietary Intake of Eicosapentaenoic and Docosahexaenoic Acids in a Danish Population

Article

May 2024
J NUTR

Inclusion of oil from transgenic Camelina sativa in feed effectively supplies EPA and DHA to Atlantic salmon (Salmo salar) grown to market size in seawater pens

Article

Apr 2024
FOOD CHEM

A Long-Term Seal- and Cod-Liver-Oil Supplementation in Hypercholesterolemic Subjects

Article

Full-text available

Feb 2001

In this long-term study, we wanted to explore the effect of dietary supplementation of seal oil (SO) as compared cod-liver oil (CLO) on subjects with moderate hypercholes-terolemia. The test parameters included fatty acid composition in serum, blood lipids, platelet aggregation, and the activity of blood monocytes. After a run-in period of 6 mon, 120 clinically healthy hypercholesterolemic (7.0-9.5 mmol/L; 270-366 mg/dL) subjects were randomly selected to consume either 15 mL of SO or CLO daily for 14 mon followed by a 4-mon wash-out period. A third group was not given any dietary supplement (con-trol). Consumption of marine oils (SO and CLO) changed the fatty acid composition of serum significantly. Maximal levels were achieved after 10 mon. No further changes were seen after 14 mon. A wash-out period of 4 mon hardly altered the level of n-3 fatty acids in serum. Addition of SO gave 30% higher level of eicosapentaenoic acid, as compared to CLO. Subjects taking SO or CLO had lower whole-blood platelet aggregation than the control group. Neither SO nor CLO had any effects on the levels of serum total cholesterol, high-density lipoprotein cholesterol , postprandial triacylglycerol, apolipoproteins A1 and B100

Long-chain n–3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men

Article

Full-text available

Aug 2005

Background: Plasma concentrations of long-chain n−3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. Objectives: We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n–3; EPA), docosapentaenoic acid (22:5n–3; DPA), and docosahexaenoic acid (22:6n–3; DHA) were related to the subjects’ duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n–6; LA) and α-linolenic acid (18:3n-3; ALA). Design: The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. Results: The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. Conclusions: The proportions of plasma long-chain n−3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.

Docosahexaenoic Acid Supplementation Decreases Remnant-Like Particle-Cholesterol and Increases the (n-3) Index in Hypertriglyceridemic Men

Article

Full-text available

Jan 2008

Plasma remnant-like particle-cholesterol (RLP-C) and the RBC (n-3) index are novel risk factors for cardiovascular disease. Effects of docosahexaenoic acid (DHA) supplementation on these risk factors in hypertriglyceridemic men have not been studied. We determined effects of DHA supplementation on concentrations of plasma RLP-C, the RBC (n-3) index, and associations between concentrations of plasma RLP-C with those of plasma lipids and fatty acids. Hypertriglyceridemic men aged 39–66 y, participated in a randomized, placebo-controlled, parallel study. They received no supplements for 8 d and then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the last 90 d. Fasting blood samples were collected on study d −7, 0 (baseline), 45 (mid-intervention), 84, and 91 (end-intervention). DHA supplementation for 45 d decreased (P < 0.05) fasting RLP-C (36%) and increased plasma eicosapentaenoic acid (EPA):arachidonic acid (AA) (100%) and the RBC (n-3) index (109%). Continued supplementation with DHA between d 45 and 91 further increased the RBC (n-3) index (162%) and plasma EPA:AA (137%) compared with baseline values. RLP-C concentration was positively associated (P < 0.01) with the plasma concentrations of triacylglycerols (Kendall's correlation coefficient or r = 0.46), triacylglycerol:HDL cholesterol (HDL-C) (r = 0.44), total cholesterol:HDL-C (r = 0.26), Apo B (r = 0.22), C III (r = 0.41), and E (r = 0.17), and 18:1(n-9) (r = 0.32); it was negatively associated (P < 0.05) with plasma concentrations of DHA (r = −0.32), EPA (r = −0.25), HDL-C (r = −0.21), LDL cholesterol:Apo B (r = −0.30), and HDL-C:Apo A (r = −0.25). Supplementation with placebo oil did not alter any of the response variables tested. Decreased atherogenic RLP-C and increased cardio-protective (n-3) index may improve cardio-vascular health.

Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy

Article

Full-text available

Dec 1995

Healthy pregnant women (n 23) were supplemented with fish-oil capsules (2.7 g n-3 polyunsaturated fatty acids/d) from the 30th week of gestation until delivery. Subjects in a control group were either supplemented with olive-oil capsules (4 g/d, n 6) or received no supplementation (n 10). Fatty acid compositions of the phospholipids isolated from umbilical plasma and umbilical arterial and venous vessel walls were determined. Fatty acid compositions of maternal venous plasma phospholipids were determined as well. Maternal plasma phospholipids of the fish-okupplemented group contained more n-3 fatty acids and less n-6 fatty acids. Moreover, the amounts of the essential fatty acid deficiency markers Mead acid (20:3n-9) and Osbond acid (22:5n-6) were significantly lower. The extra amount of n-3 fatty acids consumed by the mothers resulted in higher contents of n-3 fatty acids, and of docosahexaenoic acid (22 : 6n-3) in particular, in the phospholipids of umbilical plasma and vessel walls. It is, indeed, possible to interfere with the docosahexaenoic acid status at birth: children born to mothers supplemented with fish oil in the last trimester of pregnancy start with a better d d e x a e n o i c acid status at birth, which may be beneficial to neonatal neurodevelopment.

Comparison of the effects of fish and fish-oil capsules on the n–3 fatty acid content of blood cells and plasma phospholipids

Article

Dec 2007

Background: n–3 Fatty acids (FAs) have been shown to be beneficial for cardiovascular health. Whether n–3 FAs from oily fish consumed weekly or from fish-oil capsules taken daily are equally bioavailable is not clear. Objective: The purpose of this study was to compare the rate and extent of enrichment of blood cell membranes [ie, red blood cells (RBCs)] and plasma phospholipids with n–3 FAs from these 2 sources. Design: Healthy premenopausal female volunteers were randomly assigned to consume a daily average of 485 mg eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids either from 2 servings of oily fish (ie, salmon and albacore tuna) per week or from 1–2 capsules/d. Results: After 16 wk, EPA+DHA in RBCs in the fish group (n = 11) increased from 4.0 ± 0.6% of total FAs to 6.2 ± 1.4%, whereas it rose from 4.3 ± 1.0% to 6.2 ± 1.4% in the capsule group (P < 0.0001 for both; NS for group effect). Similar results were observed in plasma phospholipids. EPA+DHA stabilized in the latter after 4 wk but continued to rise through week 16 in RBCs. EPA in RBCs increased significantly (P = 0.01) more rapidly in the fish group than in the capsule group during the first 4 wk, but rates did not differ significantly between groups thereafter. Total FA variances were less in RBCs than in plasma phospholipids (P = 0.04). Conclusion: These findings suggest that the consumption of equal amounts of EPA and DHA from oily fish on a weekly basis or from fish-oil capsules on a daily basis is equally effective at enriching blood lipids with n–3 FAs.

Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk

Article

Jun 2006

Objective: Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behavior. Predicting risk of future suicidal behaviors by essential fatty acid status merits examination. Method: Plasma polyunsaturated fatty acid levels in phospholipids were measured in 33 medication-free depressed subjects monitored for suicide attempt over a 2-year period. Survival analysis examined the association of plasma polyunsaturated fatty acid status and pathological outcome. Results: Seven subjects attempted suicide on follow-up. A lower docosahexaenoic acid percentage of total plasma polyunsaturated fatty acids and a higher omega-6/omega-3 ratio predicted suicide attempt. Conclusions: A low docosahexaenoic acid percentage and low omega-3 proportions of lipid profile predicted risk of suicidal behavior among depressed patients over the 2-year period. If confirmed, this finding would have implications for the neurobiology of suicide and reduction of suicide risk.

The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation

Article

May 2008

Background: Lutein and docosahexaenoic acid (DHA) may protect against age-related macular degeneration (AMD). Lutein is a component of macular pigment. DHA is in the retina. Objective: The objective of this 4-mo study was to determine the effects of lutein (12 mg/d) and DHA (800 mg/d) on their serum concentrations and macular pigment optical density (MPOD). Design: Forty-nine women (60–80 y) were randomly assigned to placebo, DHA, lutein, or lutein + DHA supplement. Serum was analyzed for lutein and DHA (0, 2, and 4 mo). MPOD was determined (0 and 4 mo) at 0.4, 1.5, 3, and 5° temporal retinal eccentricities. Serum was analyzed for lipoproteins (4 mo). Results: There was no interaction between lutein and DHA supplementations for serum lutein and MPOD. The lutein supplementation × DHA supplementation × month interaction was significant for serum DHA response (P < 0.05). In the lutein group, serum lutein increased from baseline at 2 and 4 mo (P < 0.001), and MPOD increased at 3.0° (P < 0.01). In the DHA group, serum DHA increased at 2 and 4 mo (P < 0.0001), and MPOD increased at 0.4° (P < 0.05). In the lutein + DHA group, serum lutein and DHA increased at 2 and 4 mo (P < 0.01), and MPOD increased at 0.4, 1.5, and 3° (P = 0.06, 0.08, and 0.09, respectively). Differences from placebo in lipoprotein subfractions were greatest for the lutein + DHA group (4 mo). Conclusions: Lutein supplementation increased MPOD eccentrically. DHA resulted in central increases. These results may be due to changes in lipoproteins. Lutein and DHA may aid in prevention of age-related macular degeneration.

Cardiovascular disease risk factors and n−3 fatty acid status in the adult population of James Bay Cree1–3

Article

Jul 2002

Background: Canadian native populations, which traditionally consume large amounts of fish, have lower rates of mortality from heart disease than do Canadian nonnative populations, which have low fish intakes. Fish oils rich in n−3 fatty acids may have a protective effect against cardiovascular disease (CVD) risk factors. Objectives: The purposes were to examine the profile of plasma phospholipid concentrations of the n−3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) among James Bay Cree and to verify the relation between these concentrations and CVD risk factors. Design: The study population consisted of 917 subjects aged 18–74 y who participated in the 1991 Santé Québec Health Survey. Data were obtained through home interviews and clinic visits. Plasma samples were analyzed for phospholipid fatty acid composition. Results: The mean fish consumption on the day before the survey was 60 g among the adult Cree population. Expressed as a percentage of total fatty acids, relative concentrations of EPA and DHA were 0.65% and 2.80%, respectively. n−3 Fatty acids were higher among coastal residents than among inland residents. A positive association was observed between plasma HDL and n−3 fatty acids. EPA and EPA+DHA were inversely associated with triacylglycerols. Among subjects aged 50–74 y, an inverse association between EPA and EPA:AA and total:HDL cholesterol was observed. Conclusions: n−3 Fatty acids may favorably influence some CVD risk factors. The Cree population must be encouraged to maintain their traditional fish-based diet, which may be one of the factors protecting them against mortality from CVD.

A case of human linolenic acid deficiency involving neurological abnormalities

Article

Mar 1982

A 6-yr-old girl who lost 300 cm of intestine was maintained by total parenteral nutrition. After 5 months on a preparation rich in linoleic acid but low in linolenic acid she experienced episodes of numbness, paresthesia, weakness, inability to walk, pain in the legs, and blurring of vision. Diagnostic analysis of fatty acids of serum lipids revealed marginal linoleate deficiency and significant deficiency of linolenate. When the regimen was changed to emulsion containing linolenic acid neurological symptoms disappeared. Analysis indicated that linoleate deficiency had worsened but linolenate deficiency had been corrected. The requirement for linolenic acid is estimated to be about 0.54% of calories.

Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: The OPTILIP study

Article

Jan 2006

Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults

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