![Significant decreases in remnant lipoprotein (intermediate density lipoprotein [IDL] + vLDL3) average percent change: T = −23.86, C = 8.33. LDL, low-density lipoprotein; T, treatment subjects; C, control subjects.](https://www.researchgate.net/profile/Daniel-Wecht/publication/231215518/figure/fig2/AS:202978020597769@1425405139475/Significant-decreases-in-remnant-lipoprotein-intermediate-density-lipoprotein-IDL_Q320.jpg)
Content uploaded by Daniel Wecht
Author content
All content in this area was uploaded by Daniel Wecht on Jun 09, 2016
Content may be subject to copyright.
21
vol. 1 • no. 1 SPORTS HEALTH
Evaluation of Lipid Profiles and the Use
of Omega-3 Essential Fatty Acid in
Professional Football Players
Anthony Yates, MD,* John Norwig, ATC,
† Joseph C. Maroon, MD,* Jeffrey Bost, PA-C,*‡
James P. Bradley, MD,* Mark Duca, MD,* Daniel A. Wecht, MD,* Ryan Grove, ATC,† Ariko Iso, ATC ,†
Ingrid Cobb, MD,§ Nathan Ross, BS,|| and Meghan Borden, BS¶
[ Primary Care ]
From the *University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, the †Pittsburgh Steelers Football Club, Pittsburgh, Pennsylvania, the §Case Western Reserve
Medical University School of Medicine, Cleveland, Ohio, the ||University of Rochester, Rochester, New York, and ¶Allegheny College, Meadville, Pennsylvania
‡Address correspondence to Jeffrey Bost, PA-C, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213 (e-mail: bostj@upmc.edu).
One or more authors has declared a potential conflict of interest. Dr Maroon is on the scientific advisory board of Nordic Naturals.
DOI: 10.1177/1941738108326978
© 2009 American Orthopaedic Society for Sports Medicine
Professional football players are some of the fittest ath-
letes in sports. Despite rigorous physical conditioning,
there is still a high risk for muscular, skeletal, and other
high-velocity contact injuries that result in acute and chronic
inflammation. The relationship between higher levels of cir-
culating inflammatory eicosanoids and the associated health
risk of vascular disease resulting in heart attack and strokes are
rarely considered in this young man’s game.
Background: Recent research showed 82% of 233 retired National Football League players under age 50 had abnormal
narrowing and blockages in arteries compared to the general population of the same age. It has been suggested that early
screening and intervention in this at-risk population be a priority.
Hypothesis: Omega-3 essential fatty acid has been shown to improve cardiovascular lipid risk factors and should
improve lipid profiles in professional football players to help reduce their recently shown accelerated risk of developing
cardiovascular disease.
Methods: A total of 36 active national football players were randomly assigned to 2 groups: the first group (n = 20) was
provided fish oil capsules (2200 mg of mixed docosahexaenoic acid and eicosapentaenoic acid and 360 mg of other omega-
3s), and the second group (n = 16) served as controls during a 60-day trial. Vertical Auto Profile cholesterol tests directly
measuring serum low-density lipoprotein, high-density lipoprotein, and other subfractions were performed. Compliance,
side effects, and seafood consumption data were also collected. Baseline, midpoint, and poststudy blood work measured
plasma docosahexaenoic acid and eicosapentaenoic acid.
Results: Treatment increased high-density lipoprotein (average percent change: +25.96, control +14.16), decreased triglycer-
ides treatment (–8.06, control +43.98), very low-density lipoprotein treatment (–13.98, control +23.18), intermediate density
lipoprotein (–27.58, control +12.07), remnant lipoproteins (–23.86, control +8.33), and very low-density lipoprotein-3 (–17.10,
control +7.77). An average increase of 106.67% for docosahexaenoic acid and 365.82% for eicosapentaenoic acid compared
to control was also shown.
Conclusion: Omega-3 supplementation significantly improved the lipid profile of active players randomized to treat-
ment. These results suggest that fish oil supplementation is an effective way to increase eicosapentaenoic acid and docosa-
hexaenoic acid levels in plasma and should be considered as a method to improve modifiable cardiovascular risk lipid fac-
tors in professional football players.
Clinical Relevance: A prospective study examining the effects of 60 days of a highly purified fish oil supplementation in
professional football players.
Keywords : cardiac risk factors; omega-3; professional football; vertical auto profile cholesterol test
22
Yates et al Jan • Feb 2009
The National Football League (NFL) has been the leader
among professional sports teams with regard to player safety
and health-related issues. From the introduction of protective
pads and helmets to the modern use of computers for
concussion testing and collision analysis, the NFL has sought
out the most modern, state-of-the-art capabilities to pro-
tect and improve the players’ well-being. Most of these previ-
ous technological improvements have involved equipment and
field improvements, which have resulted in longer NFL player
careers. Many players remain on active NFL rosters into their
early to mid-30s when the risk of cardiovascular disease (CVD)
starts to become significant in men.19
Cardiovascular Risks in NFL Players
In all organized sports the most devastating event that can
occur is the death of a player, on or off the field. Most sudden
deaths in athletes older than 30 years are due to a heart attack
from acute blockage of the coronary arteries.38,39 Athletes who
are older than 30 are at increased risk for heart attack if they
smoke, have high blood pressure, are obese or diabetic, have
elevated abnormal blood lipids, or a strong family history of
heart disease. In addition, low intakes or blood levels of eicos-
apentaenoic acid (EPA) and docosahexaenoic acid (DHA) have
been independently associated with increased risk of death
from coronary heart disease22 (Table 1). In randomized sec-
ondary prevention trials, fish or fish oil have reduced total and
CVD mortality.32,37
Hurst et al42 recently reported on 233 retired NFL football
players, ages 35 to 65. More than 80% had evidence of vascular
disease by the age of 50, which is higher than in the general
population. These authors suggested early screening and inter-
vention in this at-risk population.
Other research on retired NFL players of all ages has shown
players are more prone to obesity, obstructive sleep apnea, and
metabolic syndrome than the general population. Most disturb-
ingly, there is a higher mortality rate to age-matched controls
in some types of players.8, 20,45
Short of requiring a preseason cardiac catheterization on all
players, it has been difficult to determine an individual player’s
exact cardiac risk. This study focused on the effect of highly
purified fish oil supplementation on
2 modifiable risk markers of CVD.
The first is serum lipid levels, as
measured by low-density lipopro-
teins (LDL), high-density lipopro-
teins (HDL), and other lipid sub-
fractions. These lipid subfractions
include remnant lipoprotein (RLP)
cholesterol, small/dense LDL, and
lipoprotein a (Lp[a]). The second
is plasma levels of EPA and DHA
as a reflection of EPA/DHA intake
and presumed attainment of docu-
mented cardioprotective benefits of
omega-3 fatty acids.
Better Cardiac Risk Assessment
We are now entering a new era of cardiac risk assessment
where the concept of coronary artery plaque stabilization is
realized by understanding the biochemistry of blood vessels
becoming injured by vascular inflammation related to circula-
tion proinflammatory eicosanoids53 and the oxidation of fats,
as well as how this is a factor in the genesis of plaque for-
mation.28 Abnormalities of blood lipids are now universally
accepted as a significant risk factor for vascular disease due to
their ability to both precipitate plaque formation and also as an
inflammation-provoking substance upon entering the walls of
blood vessels.10
Emerging evidence suggests that not all lipids carry the same
risk for the development of CVD. Newer specialized blood
tests can fractionate blood lipids into many component mol-
ecules in order to better assess which lipid subfraction may
possess a greater risk for causing disease. Cardiotoxic LDL and
very low-density lipids (vLDL) are well known for blood ves-
sel damage, plaque formation, and ultimately vessel occlusion,
while increases in HDL are associated with less
cardiovascular risk.9,18,47
Omega-3 Fats EPA and DHA
The foundation of preventive medicine for cardiovascular dis-
ease is exercise and good nutrition. Possibly the most impor-
tant heart-healthy nutrients are the omega-3 fats EPA and DHA
from fish and fish oil. New and important findings are con-
tinually being reported about the benefits of fish oil for those
with cardiovascular disease. These include evidence from ran-
domized, controlled, clinical trials on how omega-3 fatty acids
improve heart health by reducing triglyceride levels, decreas-
ing the growth of atherosclerotic plaques, improving arterial
endothelial function, lowering blood pressure, and reducing
the risk of thrombosis.9,18,41,47
Fish oil is also a powerful supporter of the body’s natural
anti-inflammatory response, which counteracts the progres-
sion of heart disease.12 Omega-3 fats within the endothelium
reduce the inflammatory response that occurs from the oxi-
dization of blood lipids that have invaded blood vessels. This
Patient Population Recommendation
No documented history of CHD Eat a variety of fish (preferably cold-water, oily fish) at least twice per week. Include
oils and foods rich in alpha-linolenic acid (flaxseed, canola, and soybean oils;
flaxseeds; walnuts)
Documented history of CHD Consume approximately 1 g of EPA/DHA daily, preferably from oily fish. EPA/DHA
capsule supplements may be used in consultation with a physician
Need to lower triglyceride level Consume 2 to 4 grams of EPA/DHA daily in capsules, in consultation with a
physician
Table 1. Summary of American Heart Association recommendations for omega-3 fatty acid
intake relative to the incidence of coronary heart disease (CHD).a,1
aEPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.
23
vol. 1 • no. 1 SPORTS HEALTH
invasion typically promotes the process of plaque development
and initiates multiple atherogenic effects. Endothelial responses
to oxidizing lipids within the intima cause a migration and
activation of inflammatory cells, such as monocytes and mac-
rophages, which release chemotactic chemicals, in turn accel-
erating the inflammatory response. An increased proportion of
EPA and DHA within the cell membranes reduce the inflamma-
tory response by inhibiting the production of the proinflam-
matory eicosanoid PGE2 while supporting the production of
anti-inflammatory PGE3.22
Evidence from serum studies has shown that higher tissue
levels of omega-3 fats significantly reduce the risk for heart
attack. Red blood cell membrane omega-3 levels of 5% of total
fatty acids is associated with a remarkable 70% reduction in
the risk of heart attack.52
It is well established that fish oil directly improves heart
health. As new research emerges, it is becoming increasingly
evident that fish oil influences several additional parameters of
cardiovascular and metabolic health. When overweight individ-
uals (body mass index [BMI] > 25) combined fish oil (2 g total
omega-3) and regular exercise, this combination lowered
triglycerides, increased HDL cholesterol, and improved
endothelium-dependent arterial
vasodilatation when compared to
sunflower oil placebo. Both fish oil
and exercise independently reduced
body fat and improved cardiovascu-
lar and metabolic health.25
Evidence from prevention stud-
ies suggests that taking EPA and
DHA ranging from 500 mg to
about 1500 mg per day significantly
reduces deaths from heart disease
(all causes). A significant and ever-
growing body of scientific evidence
that shows how important omega-3
fats are for cardiovascular health
suggests that individuals with exist-
ing risk factors for cardiovascu-
lar disease should consume a min-
imum of 1 gram of EPA and DHA
per day. Individuals with elevated
serum lipids need 2 to 4 grams of
EPA and DHA daily.32,40 For many,
these recommendations cannot be
easily achieved through diet alone,
and a high-quality fish oil supple-
ment is recommended. For this
study the relatively short term of
intervention combined with rela-
tively large body mass of partici-
pants justified the selected omega-3
fatty acid dose of 2560 mg, which is
on the high end of what is recom-
mended for individuals with normal
lipid levels.
METHODS
Lipid Assessment
The Vertical Auto Profile or VAP Test (Atherotech Inc,
Birmingham, Alabama) provides all the information found in
a routine lipid panel plus measurements of all known choles-
terol subclasses that play important roles in the development of
CVD. The additional information provided by the VAP Test is
a more specific lipid analysis to predict heart disease risk and
was used in this study. Table 2 describes the components of
the VAP test measures in a blood sample.43
Plasma concentrations of the omega-3 fatty acids EPA and
DHA (Metametrix Clinical Laboratory, Duluth, Georgia) are
good biomarkers of dietary intake of these 2 essential fatty
acids. Plasma EPA and DHA concentrations provide an objec-
tive measurement of compliance in fish oil feeding studies. In
addition, plasma levels of EPA and DHA correlate with eryth-
rocyte cell membrane levels of EPA and DHA. Erythrocyte
cell membrane levels of EPA and DHA have been proposed as
a physiologically relevant, easily modified, independent, and
Table 2. Cholesterol subfractions, risk description, and normal values.
a
aLDL, low-density lipoprotein; Lp(a), lipoprotein a; IDL, intermediate density lipoprotein; LDL-R, low-density
lipoprotein–remnant; HDL, high-density lipoprotein; vLDL, very low-density lipoprotein.
Cholesterol
Type Description Major Components Desirable Score
Total cholesterol Total cholesterol circulation in body. All cholesterol <200 mg/dL
LDL cholesterol Considered to be the “bad” cholesterol
because it is a primary cause of heart disease.
Lp(a), IDL, LDL-R <130 mg/dL
HDL cholesterol Considered the “good” cholesterol because low
levels of this can lead to heart disease.
HDL2, HDL3 ≥40 mg/dL
vLDL cholesterol Carrier for triglycerides. If high it is a risk for
heart disease.
vLDL3 <30 mg/dL
Triglycerides Molecules that provide energy to the entire
body. If levels are high, triglycerides are a risk
for heart disease.
Several <150 mg/dL
Non-HDL cholesterol Contains all bad cholesterol components and
subclasses LDL and vLDL.
Several (see
description)
<160 mg/dL
Cholesterol Subfractions
Type Major Components Description Desirable Score
LDL
cholesterol
Lp(a) Very dangerous cholesterol that is harder than most to
treat effectively with drugs.
<10 mg/dL
IDL Dangerous if elevated. <20 mg/dL
Real LDL
cholesterol
Component of LDL cholesterol, measures the real
cholesterol circulation in the body.
<100 mg/dL
LDL cholesterol
pattern size
LDL cholesterol ranges from small and dense (pattern B)
to large and buoyant (pattern A). The smaller the LDL size,
the greater the risk for heart disease.
A
HDL
cholesterol
HDL2 The most protective form of HDL, large and buoyant. >10 mg/dL
HDL3 Least protective form of HDL, small and dense. >30 mg/dL
vLDL
cholesterol
vLDL3 Most dense form of vLDL, greater risk factor than both
vLDL1 and vLDL2.
<10 mg/dL
24
Yates et al Jan • Feb 2009
graded risk factor for death from CVD that could have signifi-
cant clinical implication.22,52 Therefore, lower levels of omega-3
in the red blood cell membrane indicate a higher risk of CVD.
Subjects
Following Institutional Review Board (IRB) approval, 36 pro-
fessional NFL football players from the Pittsburgh Steelers
Football Club, ages 23 to 41 years (average, 28.03 years), vol-
unteered to be randomly assigned to either the treatment (n
= 20) or the control (c = 16) arms of the study. Each group
contained similarly sized players, including BMI and position
played. After informed consent was given, baseline question-
naires were completed to assess any allergies to fish or sea-
food, family and personal medical history of cardiac disease
and risk factors, and dietary intake of fish and seafood. Vital
signs and baseline VAP cholesterol tests were also assessed
to directly measure the LDL, HDL, and other lipid subfrac-
tions, such as remnant lipoprotein cholesterol, small/dense
LDL, Lp(a), and plasma fatty acid concentrations (EPA/DHA)
(Table 2).
Study Design and Intervention
This study was designed to determine the effect of 2560 mg/
day of mixed EPA/DHA omega-3 fatty acid supplements (650
mg EPA; 450 mg DHA; 180 mg other omega-3 fatty acids
per 2 soft gels of ProOmega; Nordic Naturals, Watsonville,
California) in the form of fish oil soft gels on healthy, profes-
sional football players. Testing took place during a 2-month
period during the active 2006-2007 NFL season. Compliance,
side effects, and seafood consumption data were collected
using weekly questionnaires. Midpoint and poststudy VAP
and plasma fatty acid blood work was obtained after the
subjects fasted overnight.
The 20 players that were randomized to the treatment group
were provided individual bottles of 28 fish oil soft gels and
instructed to take 4 on a daily basis. These bottles were col-
lected on a weekly basis to access compliance and new bottles
were provided. The control subjects (n = 16) did not receive
any additional supplements and were asked not to take any
essential fatty acid supplements. All subjects were asked not to
take any omega-3 fatty acid supplements for at least 1 month
prior to the baseline blood work. A sample size estimate was
not performed.
RESULTS
Questionnaires revealed no significant difference in sea-
food and fish consumption between the treatment and con-
trol groups. In the treatment group there were no reported side
effects, and compliance overall was 80% for taking at least 24
of the provided 28 capsules per week.
The average baseline value, final test value, average value
change, and average percent changes of the VAP cholesterol
panel were calculated (Figures 1-6). The treatment subjects
(T) compared to the control subjects (C), using the unpaired
t test, had significant decreases in IDL (average percent change
[APC]: T = –27.58, C = 12.07), RLP (intermediate density
lipoprotein [IDL] + vLDL3) (APC: T = –23.86, C = 8.33), trig-
lycerides (APC: T = –8.06, C = 43.98), vLDL-3 (APC: T –17.10,
C = 7.77), and vLDL (APC: T = –13.98, C = 23.18). Total HDL-
cholesterol (HDL-C) direct (APC: T = 25.96, C = 14.16), HDL-2
(APC: T = 16.28, C = 1.164), and HDL-3 (APC: T = 35.52, C =
24.28) were greater in the treatment group but nonsignificant
(P = .067). Additionally, the LDL-C and Lp(a) subfractions had
nonsignificant improvement in the treatment group, and total
cholesterol, LDL, and Apolipoprotein (Apo) B100 changes
were similar in both groups.
There was an average increase of 106.67% for DHA and
365.82% for EPA in the treatment group. There was a 58.29%
increase in the EPA and no change in the DHA of the con-
trol group. Alpha-linolenic acid changes were similar in both
groups. There were no significant complications or side effects
in either group. (Figures 1-8; Table 2).
DISCUSSION
Coronary artery disease (CAD) is a leading cause of morbidity
and mortality in the United States.1 Professional football play-
ers, although often at the peak of physical conditioning, still
may possess significant CVD risk factors. Gender, family
history—including race—dietary excess, obesity, and other
disease conditions such as diabetes, hypertension, and abnor-
mal blood lipid profile are all risk factors for CVD in this select
population. Some of these risks are fixed, but the CVD risk fac-
tor of abnormal blood lipids is one of the most discriminating
factors for early detection of CVD.6
The size of blood lipids is very important with regard to
whether abnormal lipid values can increase CVD risk.2 Low-
density lipoproteins vary in particle size and density, which are
factors related to their ability to induce vascular oxidative dam-
age and cause blood vessel plaque formation. Lipid subtype
research now confirms that the predominance of small LDL is
a much more significant cardiovascular risk factor than other
subtypes. Larger LDL subfractions are less frequently associated
with CVD, while HDLs are often considered protective to the
development of CVD due to their large size.2,31
The therapeutic modulation of distinct LDL subspecies is
therefore of great benefit in reducing the risk of cardiovascu-
lar events. Low-density lipoprotein size correlates positively
with plasma HDL levels and negatively with plasma triglycer-
ide concentrations.3 ,17 The combination of small dense LDL,
decreased HDL cholesterol, and increased triglycerides has
been coined by Austin et al3 in 1990 as the “atherogenic lipo-
protein phenotype.”
By using an expanded cholesterol subfraction test for this
study (VAP) we demonstrated the possible effects of omega-3
essential fatty acid (EFA) dietary supplements as an interven-
tion for CVD.
Our evaluation using 2560 mg/day of mixed EPA/DHA
omega-3 fatty acid supplements for a 60-day period revealed
25
vol. 1 • no. 1 SPORTS HEALTH
the most significant blood lipid changes in
the IDL and RLP. The IDL showed a sig-
nificant decrease of 27.58% in the treat-
ment group compared to a 12.07% increase
in the control group (P = .0022). Increased
plasma IDL levels have been related to the
presence and severity of angiographically
determined CV D and to the progression of
arterial lesions.58
In addition, RLP had a significant decrease
of 23.86% in the treatment group compared
to an 8.33% increase in the control group
(P = .0042). Remnant lipoproteins are
formed intravascularly when chylomicrons
of intestinal origin and vLDL of hepatic
origin are converted by lipoprotein lipase
into smaller and denser particles. Remnant
lipoproteins are depleted of triglycerides,
enriched with cholesteryl esters and apoli-
poprotein E (a major component of vLDL)
and believed to be more atherogenic than
the larger size lipids. Evidence have impli-
cated RLPs in premature and accelerated
atherosclerosis.29
Omega-3 fatty acids have been shown to
reduce RLP levels. In 2007, Satoh et al51 eval-
uated 44 obese, type-2 diabetic Japanese
patients with metabolic syndrome and
reported significant reductions in RLP cho-
lesterol (P = .035) following 3 months of
1.8 g/day EPA supplementation.
Very low lipoprotein is the major carrier
of plasma triglycerides. They are a diverse
group of lipoprotein particles that vary in
triglyceride and cholesterol content, apoli-
poprotein C and apolipoprotein E, and in
their metabolism. The vLDL3, which is the
smallest of the vLDL subfractions, showed
a significant decrease of 17.10% in the treat-
ment group over time compared to a 7.77%
increase in the control group (P = .0343).
Since this entire lipoprotein particle can
enter the arterial intima, the vLDL concen-
tration and particle size are most impor-
tant variables. The vLDL3 subfraction is the
dense, cholesterol-laden portion with less
triglyceride that comprises the greatest risk
for cardiovascular disease. Lower vLDL3
levels correlate to decreased cardiovascu-
lar risk.43 Additionally, the treatment group’s
total vLDL demonstrated a significant
decrease of 13.98% compared to increases
of 23.18% in the control group (P = .0486).
Tornvall et al57 in 1993 confirmed that vLDL3
was the smallest of the vLDL particles and
IDL Cholesterol (p=0.0022)
18.89
13.09
13.33 13.43
−5.56
0.34
−27.58%
12.07%
−30.00
−20.00
−10.00
0.00
10.00
20.00
30.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Remnant Lipoproteins (IDL+VLDL3) (p=0.0042)
32.78
25.28
24.56 26.66
−8.22
1.38
8.33%
−23.86%
−30.00
−20.00
−10.00
0.00
10.00
20.00
30.00
40.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Figure 1. The average baseline value, final test value, average value change, and
average percent changes of Vertical Auto Profile cholesterol panel were calculated
comparing the treatment subjects (T) to the control subjects (C) using the unpaired
t test. Figure 1 shows a significant decreases in intermediate density lipoprotein
average percent change: T = –27.58, C = 12.07.
Figure 2. Significant decreases in remnant lipoprotein (intermediate density
lipoprotein [IDL] + vLDL3) average percent change: T = –23.86, C = 8.33. LDL,
low-density lipoprotein; T, treatment subjects; C, control subjects.
26
Yates et al Jan • Feb 2009
demonstrated a correlation between the
number of cholesteryl ester molecules
in vLDL3 and global coronary atherosclero-
sis in hypertriglyceridemic patients.
They concluded that it was the small
cholesterylester-rich vLDL3 particles that
predicted the CVD severity.
The treatment group’s triglyceride lipid
portion demonstrated a significant decrease
of 8.06% compared to increases of 43.98%
in the control group (P = .0298). Plasma
triglyceride concentration is a significant
predictor of coronary heart disease. A meta-
analysis by Hokanson and Austin26 of obser-
vational studies suggested that an 89-mg/
dL elevation in triglycerides was associated
with a 14% to 37% higher incidence of CVD
independent of other risk factors. Bucher
et al,6 in a meta-analysis of randomized,
controlled trials of omega-3 diets or supple-
mentation effects on CVD, found an aver-
age triglyceride reduction of 20% with
no significant effect on LDL-C or HDL-C.
Hamazaki et al21 performed a study evalu-
ating omega-3 supplementation on serum
levels of triglycerides and found a signifi-
cant decrease in triglyceride levels in the
omega-3 treated group compared to the
control group after 4, 8, and 12 weeks
(P < .05). Many studies of omega-3 fatty
acids have found marked lowering of vLDL
and triglycerides of 15% to 40%, depend-
ing on the dose. Our results are consistent
with the observations from these studies.
However, total cholesterol and LDL-C results
have been inconsistent among other stud-
ies. In general, decreases in LDL have been
found if dietary saturated fat intake was
decreased.13,23,27,50,54
The use of omega-3 EFA for the treat-
ment of hypertriglyceridemia has recently
been approved by the Food and Drug
Administration (FDA) using a prescrip-
tion form of EPA/DHA (Omacor; LOVAZA;
GlaxoSmithKline, Middlesex, United
Kingdom). Calabresi et al7 evaluated patients
who received 4 capsules daily of Omacor
(providing 3.4 g EPA and DHA per day)
or placebo for 8 weeks in a randomized,
double-blind, crossover study. They found
that Omacor significantly lowered plasma
triglycerides and vLDL-C levels by 27% and
18%, respectively.
Piolot et al46 reported significant reduc-
tions in vLDL triglyceride and vLDL-C
Triglycerides-Direct (p=0.0298)
108.75
88.70
92.50
129.82
−16.25
41.13 43.98%
−8.06%
−40.00
−20.00
0.00
20.00
40.00
60.00
80.00
100.00
120.00
140.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
VLDL-3 (Small Remnant) (p=0.0343)
13.89
12.19
11.22
13.22
−2.67
1.03
7.77%
−17.10%
−20.00
−15.00
−10.00
−5.00
0.00
5.00
10.00
15.00
20.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Figure 3. Significant decreases in triglycerides average percent change:
T = –8.06, C = 43.98. T, treatment subjects; C, control subjects.
Figure 4. Significant decreases in vLDL-3 average percent change: T = –17.10,
C = 7.77. LDL, low-density lipoprotein; T, treatment subjects; C, control subjects.
27
vol. 1 • no. 1 SPORTS HEALTH
concentrations following daily ingestion of
6 grams of omega-3 EFA (EPA/DHA) dur-
ing a 2-month period (P < .05). Rivellese
et al evaluated the effects of omega-3 EFA
on lipid metabolism in healthy individuals
undergoing either a diet rich in monoun-
saturated fats or one rich in saturated fatty
acids.49 They, too, discovered that the addi-
tion of omega-3 EFA supplements signifi-
cantly reduces triglyceride as well as vLDL
cholesterol, regardless of the type of diet.
Other authors have shown that the benefits
of omega-3 EFAs on coronary mortality are
due to their effects on cardiac arrhythmia,48
platelet aggregation,32, 37, 55 hemostatic vari-
ables,32 , 37, 55 and vascular reactivity37 in addi-
tion to how they affect lipid metabolism.35,44
High-density lipoprotein is considered the
“good” cholesterol because it forages cho-
lesterol from the tissues and delivers it to
the liver for degradation.59 It may be for this
reason that HDL and its subfractions are
acknowledged as protective factors against
coronary heart disease.36,54
The average total HDL cholesterol (direct)
showed a nearly significant increase of
25.96% in the treatment group compared
to a 14.16% increase the control group
(P = .0671). The subfraction of HDL, HDL2,
and HDL3 also increased in the treatment
group compared to the control, although
not statistically significant. This suggests
that a larger number of subjects may have
provided significant results.
Thomas et al56 also observed signifi-
cant increases in HDL and HDL2 con-
centrations following omega-3 EFA sup-
plementation of 4 g/day for 4 weeks in
recreationally active men. These increases
might be a means by which omega-3 EFA
supplementation improves the CVD risk
profile in patients.
Our results demonstrated no significant dif-
ference in HDL and subfractions HDL2 and
HDL3, which may confirm that the previ-
ously observed increases in HDL are asso-
ciated with exercise, for which both groups
of players are regular participants. Durstine
and Haskell14 reported elevations in HDL
and HDL3 concentrations following a ses-
sion of exercise independent of omega-3
EFA supplements. Thomas et al, while also
investigating the use of omega-3 EFA sup-
plementation and exercise, concluded that
both omega-3 EFA and exercise could raise
VLDL-Cholesterol-Direct (p=0.0486)
23.44
19.74
19.56
24.56
−3.89
4.81
23.18%
−13.98%
−20.00
−15.00
−10.00
−5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Total HDL-Cholesterol-Direct (p=0.0671)
44.83 45.00
56.17
49.33
11.33
5.40
14.16%
25.96%
0.00
10.00
20.00
30.00
40.00
50.00
60.00
ControlTreatment
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Figure 5. Significant decreases in vLDL average percent change: T = –13.98,
C = 23.18. LDL, low-density lipoprotein; T, treatment subjects; C, control subjects.
Figure 6. Total HDL cholesterol (HDL-C) direct (average percent change:
T = 25.96, C = 14.16) was improved but not significant (P = .067). HDL, high-
density lipoprotein; T, treatment subjects; C, control subjects.
28
Yates et al Jan • Feb 2009
HDL concentrations; the omega-3 EFA was
believed to be responsible for a greater
HDL2 increase, while HDL3-C was elevated
by exercise.56
Finally, both EPA and DHA plasma con-
centrations showed significant elevations
of (EPA 365.8% [P = .0207], DHA 106.67%
[P = .0555]) in the treatment group. These
increases confirm compliance among the
treatment group and show that a treatment
period of 60 days is long enough to allow
for a plasma increase in the proportion of
omega-3. Plasma concentrations of EPA and
DHA reflect current omega-3 status and are
predictors of future tissue status. Tissue sta-
tus of omega-3 fatty acids are currently
being investigated as a powerful indepen-
dent risk factor for death from coronary
heart disease.22 ,33 The plasma elevations of
EPA and DHA found in the treatment group
could be interpreted as therapeutic end-
points independent of changes in blood lip-
ids found among the treatment group.
The control group also experienced a
58.29% increase in EPA. Although less than
the treatment group, and despite dietary
diaries (suggest, recorded dietary intake)
showing similar seafood use, this result is
difficult to explain. The most likely expla-
nation is the metabolic conversion of the
vegetable or nut sources of omega-3 fatty
acids, such as walnuts or almonds, or alpha-
linolenic acid converted to EPA. It should
be noted that the majority of this average
increase in EPA was found in only 1 control
participant.
Omega-3 EFA and Lipids
In addition to omega-3 EFA, there are other
supplements that have been suggested as
possible adjuncts to the treatment of abnor-
mal blood lipids: antioxidant vitamins E and
C, garlic, soy products, plant stanols/sterols,
and fiber.30
Of this group omega-3 EFAs have had the
most success for improving blood lipid pro-
files. In fact Brown et al5 showed that some
antioxidants may inhibit HDL improvements
found with the combination therapy of nia-
cin and statin medication.
The omega-3 EFAs are believed to lower
lipids by inhibiting the synthesis of vLDL in
the liver. This results in smaller, less-dense
vLDL and LDL particles and, therefore, a
reduced plaque-producing lipid profile.34
Eicosapentaenoic (20:5n3) (p=0.0207)
35.71
15.57
115.86
25.00
80.14
9.43
365.82%
58.29%
0.00
50.00
100.00
150.00
200.00
250.00
300.00
350.00
400.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Docosahexaenoic (22:6n3) (p=0.0555)
108.29 89.57
192.29
103.43
84.00
13.8618.76%
106.67%
0.00
50.00
100.00
150.00
200.00
250.00
Treatment Control
units or percent
Average Baseline Value
Average End Value
Average Change Per Person
Average Percent Change Per Person
Figure 7. Average increase of 365.82% for EPA in the treatment group indicating
compliance. EPA, eicosapentaenoic acid.
Figure 8. Average increase of 106.67% for DHA in the treatment group indicating
compliance. DHA, docosahexaenoic acid.
29
vol. 1 • no. 1 SPORTS HEALTH
The dose used in this study was 2.2 g/day of mixed EPA
and DHA. Higher dosing of 3 to 4 grams a day have resulted
in greater blood lipid improvements in many clinical trials,
although current AHA guidelines recommend only 1 gram a
day of omega-3 EFA for CVD patients (Table 2). Omega-3 fatty
acid supplementation in doses of up to 3 grams a day is con-
sidered safe. Reported side effects have included gastrointes-
tinal upset and loose stool. At higher doses there is a possible
but low risk of bleeding.32
In 2001, the Adult Treatment Panel (ATP III) of the National
Cholesterol Education Program recommended that omega-3
fatty acids be used as an adjunct to pharmacological therapy
for lowering triglycerides. Additionally they concluded that the
most practical way to achieve this quantity of omega-3 fatty
acids is through the use of fish oil supplements.15,16
Finally, because of the lack of significant side effects and
complications associated with fish oil supplements, chronic or
lifelong use is very possible, as both a prevention and treat-
ment alternative in select cases to potentially toxic medications.
Statins remain an excellent means to reduce total cholesterol,
but subfraction lipid testing reveals that they are not effective
at reducing some harmful cholesterol subfractions. The pro-
portion of the smaller, potentially more dangerous vLDL lip-
ids may not be adequately reduced and the HDL fractions not
improved to the levels many believe are required to lessen car-
diac risk factors.24 The side effect profiles of statins are also not
insignificant and include potentially damaging myopathy and
increases in hepatic transaminases. Serious drug interactions
with statins are also a concern.4
CONCLUSION
This evaluation is limited by the relatively small number of par-
ticipants (N = 36). Despite this fact, rather dramatic improve-
ments in blood lipid profiles of professional football players
were achieved using a moderately high dose of omega-3 EFA
fish oil supplementation. Our results along with those cited in
the literature suggest that omega-3 EFA supplementation can
have a significant effect on improving blood lipid–related CVD
risk factors in professional football players.
Based on the results of our study population, the professional
NFL player should consider continued use of omega-3 EFA
supplementation throughout his active years as well as during
retirement, when additional risk factors for CVD become much
more prevalent as a function of aging.
ACKNOWLEDGMENTS
The authors would like to thank NFL Charities for their gener-
ous grant for this study and also the copyediting work
provided by Stephanie Bost.
REFERENCES
1. American Heart Association. Cardiovascular disease statistics. 20 06. http://
www.americanheart.org/presenter.jhtml?identifier=4478. Accessed August 8,
2007.
2. Austin MA, Hokanson JE, Brunzell JD. Characterization of low-
density lipoprotein subclasses: methodologic approaches and clinical rele-
vance. Curr Opin Lipidol. 1994;5:395-403.
3. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein
phenotype. A proposed genetic marker for coronary heart disease risk.
Circulation. 1990;82 :495-506.
4. Bellosta S, Paolet ti R, Corsini A. Safety of statins focus on clinical pharma-
cokinetics and drug interactions. Circulation. 2004;109:III-50-III-57.
5. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vita-
mins, or the combination for the prevention of coronary disease. N Engl J
Med. 20 01;34 5 :15 83 -1592 .
6. Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty
acids in coronary hear t disease: a meta-analysis of randomized controlled
trials. Am J Med. 2002;112:298-304.
7. Calabresi L, Donati D, Pazzucconi F, Sirtori CR, Franceschini G. Omacor
in familial combined hyperlipidemia: effects on lipids and low subclasses.
Atherosclerosis. 2000;148 (2):387-396.
8. Callahan LF, Currey SS, Jonas BL, et al. Osteoarthritis in retired national
football league (NFL) players: the role of injuries and playing position.
Arthritis Rheum. 2002 ;46 :S415.
9. Campos H, Genest JJ, Blijlevens E, et al. Low-density lipoprotein particle size
and coronar y arter y disease. Arterioscler Thromb. 199 2 ;12 :187-195.
10. Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary
heart disease. The Framingham Study. Ann Epidemiol. 1992 ;2 (1-2):23 -28.
11. Castelli WP. Lipids, risk factors, and ischaemic heart disease. Atherosclerosis.
1996;124(Suppl l):S1-S9.
12. Colussi G, Catena C, Baroselli S, et al. Omega-3 fatty acids: from biochem-
istry to their clinical use in the prevention of cardiovascular disease. Recent
Patents Cardiovasc Drug Discov. 2007;2 :13-21.
13. Connor WE, Conner SL. Diet, at herosclerosis, and fish oil. Adv Intern Med.
199 0 ;35 :13 9-171.
14. Durstine JL, Haskell WL. Effects of exercise training on plasma lipids and
lipoproteins. Exerc Sport Sci Rev. 1994;22:477-521.
15. Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Executive Summar y of the Third Report of The
National Cholesterol Education Program (NCEP) Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III). JAMA. 2001;285: 248 6-2497.
16. Fletcher B, Berra K, Ades P, et al. Managing abnormal blood lipids: a collab-
orative approach. Circulation. 2005 ;112:3184-3209.
17. Frost RJA, Otto C, Geiss HC, Schwandt P, Parhofer KG. Effects of Atorvastatin
versus Fenofibrate on lipoprotein profiles, low-density lipoprotei n subfrac-
tion distribution, and hemorheologic parameters in type 2 diabetes mellitus
with mixed hyperlipoproteinemia. Am J Cardiol. 2001;87:44-48.
18. Griffin BA, Freeman DJ, Tait GW, et al. Role of plasma triglyceride in the reg-
ulation of plasma low-density lipoprotein (LDL) subfractions: relative con-
tribution of small, dense LDL to coronary heart disease risk. Atherosclerosis.
1994 ;106 :241-253.
19. Grundy SM, Pasternak R, Greenland P, Smith S Jr, Fuster V. Assessment
of cardiovascular risk by use of multiple risk–factor assessment equa-
tions: a statement for healthcare professionals from the American Heart
Association and the American College of Cardiology. Circulation. 1999 ;
100: 148 1-1492.
20. Guskiewicz KM, Marshall SW, Bailes J, et al. Recurrent concussion and risk
of depression in retired professional football players. Med Sci Sports Ex erc.
2007;39 (6):903-909.
21. Hamazaki K, Itomura M, Huan M, et al. n-3 long-chain FA decrease serum
levels of TG and remnant-like particle-cholesterol in humans. Lipid s.
2003;38 (4):353-358.
22. Harris WS, Von Schacky C. The omega-3 index: a new risk factor for death
from coronar y heart disease ? Prev Med. 2004 ;39:212-220.
23. Haynes WG. Triglyceride-rich lipoproteins and vascular function. Arterioscler
Thromb Vasc Biol. 2 0 03 ;23 ;153 -155.
24. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection
Study of cholesterol lowering with si mvastati n in 20 536 high-risk individu-
als: a randomized, placebo-controlled trial. Lancet. 2002;360:7-22.
25. Hill AM, Buckley JD, Murphy KJ, Howe PR. Combining fish-oil supplements
with regular aerobic exercise i mproves body composition and cardiovascular
disease r isk factors. Am J Clin Nutr. 2007;85:1267-1274.
30
Yates et al Jan • Feb 2009
26. Hokanson JE, Austin M A. Plasma triglyceride level is a risk factor for cardio-
vascular disease independent of high-density lipoprotein cholesterol level:
a meta-analysis of population-based prospective studies. J Cardiovasc Risk.
199 6 ;3 : 213 -219.
27. Jeppesen J, Hein H, Suadicani P, et al. Triglyceride concentration and isch-
emic heart disease: an 8-year follow-up in the Copen hagen Male St udy.
Circulation. 1998 ;97:102 9-1036.
28. Jialal I, Devaraj S. The role of oxidized low-density lipoprotein in atherogen-
esis. J Nutr. 1996;126(4 Suppl):1053S-1057S.
29. Jialal I, Devaraj S. Remnant lipoproteins: measurement and clinical signifi-
cance. Clin Chem. 2002 ;4 8:217-219.
30. Katan MB, Gr undy SM, Jones P, Law M, Miettinen T, Paoletti R; Stresa
Workshop Participants. Efficacy and safety of plant stanols and ste-
rols in the management of blood cholesterol levels. Mayo Clin Proc.
2003;78(8):965-978.
31. Krauss RM. Low-density lipoprotei n subclasses and risk of coronary artery
disease. Curr Opin Lipidol. 19 91;2 :248-252 .
32. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association Nutrition
Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascu-
lar disease. Circulation. 2002;106:2747-2757.
33. Kuriki K, Nagaya T, Tokudome Y, et al. Plasma concentrations of (n-3)
highly unsaturated fatty acids are good biomarkers of relative dietary fatt y
acid intakes: a cross-sectional study. J Nutr. 2003;133 :3643-3650.
34. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med.
1988;318:549-557.
35. Luo J, R izkalla SW, Vidal H, et al. Moderate intake of n-3 fatty acids for 2
months has no detrimental effect on glucose metabolism and could amelio-
rate the lipid profile in type 2 diabetic men. Results of a controlled study.
Diabetes Care. 1998;21:717-724.
36. Mack WJ, Krauss RM, Hodis HN. Lipoprotein subclasses in the Monitored
Atherosclerosis Regression Study (MA RS): treatment effects and rela-
tion to coronar y angiographic progression. Ar terioscler Thromb Vasc Biol.
1996;16:697-704.
37. Marchioli R. Dietary supplementation with n-3 polyunsaturated fatty acids
and vitamin E after myocardial infarction: results of the GISSI-Prevenzione
trial. Lancet. 1999;354 :4 47-455.
38. Maron BJ, Chaitman BE, Ackerman MJ, et al. Recom mendations for physical
activity and recreational sport s participation for young patients with genetic
cardiovascular disease. Circulation. 2004;109:2807-2816.
39. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:
1064-1075.
40. Maroon JC, Bost J. Fish Oil: T he Natural Anti-Inflammatory. Laguna, CA:
Basic Health Books; 20 06.
41. Massaro M, Habib A, Lubrano L, et al. The omega-3 fatty acid
docosa-
hexaenoate attenuates endothelial cyclooxygenase-2 induction through
both NADP(H) oxidase and
PKCeqinhibition. Proc Natl Acad Sci U S A.
20 0 6 ;1 03 (4 1) :1518 4 -151 89 .
42. Mayo Clinic Press Release. Retired National Football League players at
increased risk for heart problems. Medical News Today Web site. http://
www.medicalnewstoday.com/articles/101971.php. Published March 29, 2008 ;
accessed October 23, 200 8.
43. Metamatrix Company Brochure. Basic description of lipids and lipoproteins.
http://www.cholesterol-tests.com/Description_L ipids.html. Accessed August
8, 2007.
44. Minihane AM, Khan S, Leigh-Firbank EC, et al. ApoE polymorphism and
fish oil supplementation in subjects with an atherogenic lipoprotein phe-
notype. Arter ioscler T hromb Vasc Biol. 200 0 ;20 :199 0 -199 7.
45. US Department of Health & Human Services. National Institute for
Occupational Safety and Health (NIOSH) NFL Mor tality Study. Januar y
199 4. http ://www.cdc.gov/niosh/pdfs/nflfactsheet.pdf. Accessed October
23, 2008.
46. Piolot A, Blache D, Boulet L, et al. Effect of fish oil on LDL oxida-
tion and plasma homocysteine concentrations in health. J Lab Clin Med.
2003;141(1):41-49.
47. Rajman I, Kendall MJ, Cramb R, et al. Investigation of low-densit y lipopro-
tein subfractions as a coronary risk factor in normotriglycer idemic men.
Atherosclerosis. 1996;125:231-242.
48. Reiffel WS, McDonald A. Antiarrhythmic effects of omega-3 fatty acids. Am J
Cardiol. 200 6;98(suppl) :50i-60i.
49. Rivellese AA, De Natale C, Lilli S. Type of dietary fat and insulin resistance.
Ann N Y Acad Sci. 2002;967:329-335.
50. Sacks FM, Alaupovic P, Moye LA, et al. VLDL , apolipoproteins B, CIII, and E,
and risk of recurrent coronary events in the cholesterol and recur rent events
(CARE) trial. Circulation. 2000;102:1886.
51. Satoh N, Shimatsu A, Kotani K, et al. Purified eicosapentaenoic acid reduces
small dense LDL, remnant lipoprotein par ticles, and C-Reactive protein in
metabolic syndrome. Diab etes Care. 20 07;3 0 :14 4 -146.
52. Siscovick DS, Raghunathan T E, King I, et al. Dietar y intake and cell mem-
brane levels of long-chain n-3 poly unsaturated fatt y acids and the risk of pri-
mary cardiac arrest. JAMA. 1995;274:1363 -1367.
53. Spagnoli LG, Bonanno E, Sangiorgi G, Mauriello A.
Role of inflammation in
atherosclerosis. J Nucl Med. 2007;4 8 (11):1800 -1815.
54. Stampfer MJ, Krauss RM, Ma J, et al. A prospective study of triglyceride level,
low-density lipoprotein particle diameter, and risk of myocardial infarction.
JAMA. 1996;276:882-888.
55. Stone NJ. Fish consumption, fish oil, lipids, and coronary heart disease.
Circulation. 1996;94:2337-2340.
56. Thomas TR, Smith BK, Donahue OM, Altena TS, James-Kracke M, Sun GY.
Effects of omega-3 fatty acid supplementation and exercise on low-den-
sity lipoprotein and high- density lipoprotein subfractions. Metabolism.
20 0 4;53 (6):749 -75 4.
57. Tornvall P, Bavenholm P, Landou C, de Faire U, Hamsten A. Relation of
plasma levels and composition of apolipoprotein B-containing lipoproteins
to angiographically defined coronary artery disease in young patients with
myocardial infarction. Circulation. 1993;88(5 Pt 1):2180-2189.
58. Sutherland WH, Restieaux NJ, Nye ER, et al. IDL composition and
angiographically determined progression of atherosclerotic lesions
during Simvastatin therapy. Arterioscler Thromb Vasc Biol. 1998;18:
577-5 83.
59. Yamashita S, Sakai N, Hirano K, Ishigami M, Maruyama T, Nakajima N,
Matsuzawa Y. Roles of plasma lipid transfer proteins in reverse cholesterol
transport. Front Biosci. 2001;6:D366-D387.
