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Role of turmeric in oxidative modulation in
end-stage renal disease patients
Maryam PAKFETRAT,1Masoumeh AKMALI,2Leila MALEKMAKAN,3
Mojtaba DABAGHIMANESH,1Marjan KHORSAND4
1Department of Internal Medicine, 3Department of Community Medicine, Shiraz Nephro-Urology
Research Center, 2Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran;
4Department of Biochemistry, Shiraz University of Medical Sciences-Paramedical School, Shiraz, Iran
Abstract
Oxidative stress is considered as a major player in uremia-associated morbidity and mortality in
hemodialysis (HD) patients. The aim of this study was to evaluate the effects of turmeric on
oxidative stress markers in HD patients. This study was a prospective and double-blind randomized
clinical trial. Fifty HD patients aged 18–60 years were recruited after fulfilling the inclusion criteria.
Patients were randomly categorized into 2 groups: trial group received turmeric and control group
received placebo for 8 weeks. Each patient in the trial group received turmeric, whereas the control
group received starch for the same 8 weeks. Plasma malondialdehyde (MDA), red blood cell
(RBC) antioxidant enzyme activities as glutathione peroxidase (GPX), glutathione reductase (GR),
and catalase (CAT), cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-
cholesterol, triglyceride, albumin, and hemoglobin were also measured before and after study.
Although MDA level was reduced in both groups, the ratio of decrease was significantly higher in
the turmeric group (0.2 vs. 0.1, P = 0.040). Three enzymes of GPX, GR, and CAT levels were
increased in both groups; the ratio of increased was significantly higher in the turmeric group for
the CAT enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in the turmeric
group compared with the control group was observed (P = 0.001). Regular ingestion of turmeric
reduces plasma MDA and increases RBC CAT activity and plasma albumin levels in HD patients.
Turmeric showed no adverse effects.
Key words: Chronic renal failure, end-stage renal disease, hemodialysis, oxidative stress, turmeric
INTRODUCTION
End-stage renal disease (ESRD) is a state of oxidative stress
(OS) due to uremic oxidant mediator’s accumulation,1the
activation of phagocytic oxidative metabolism by the
dialysis membrane, intravenous iron therapy, and the anti-
oxidant depletion caused by hemodialysis (HD).2Oxida-
tive stress in these patients leads to a state of malnutrition
and accelerated atherosclerosis.3Some trials showed a
significant benefit from antioxidant therapy on cardiovas-
cular outcome in HD patients.4
Extensive research has focused on direct exogenous
antioxidants, including vitamin C and vitamin E, in the
treatment of cardiovascular disease (CVD).5Some clinical
trials showed no more beneficial effect of exogenous anti-
oxidant supplementation in CVD and recommended the
necessity for a new approach to regulating cellular redox
status.6
Correspondence to: L. Malekmakan, MD, MPH,
Department of Community Medicine, Shiraz
Nephro-Urology Research Center, Shiraz University of
Medical Sciences, PO Box 71348-14336, Shiraz 0711, Iran.
E-mail: malekl@sums.ac.ir
Hemodialysis International 2014; ••:••–••
© 2014 International Society for Hemodialysis
DOI:10.1111/hdi.12204
1
Turmeric, a dried powder derived from the rhizome of
Curcuma longa Linn., is an herb used as a dietary spice and
in traditional medicine for centuries.6,7 Curcuminoids,
a mixture of curcumin (diferuloylmethane), demethoxy-
curcumin, and bisdemethoxycurcumin, are vital constitu-
ents of turmeric.8Curcumin is perhaps the most active
and nontoxic component of turmeric (constitutes 2–5%
of turmeric),6,9 which has been extensively studied
for its therapeutic benefits, such as antioxidant,10,11
anti-inflammatory,12 cardioprotective,13 renoprotective,14
immunomodulatory,15 cancer chemopreventive,16 antide-
pressant,17 and neuroprotective activities.18
The other two constituents of the curcuminoid mixture
also contribute significantly to the effectiveness of cur-
cuminoids.8Also, the curcuminoid mixture represents
turmeric in its medicinal value better than curcumin
alone.8It is unclear whether all of the activities ascribed to
turmeric are due to curcumin or whether other com-
pounds in turmeric can manifest these activities uniquely,
additively, or synergistically with curcumin.9However,
studies have indicated that turmeric oil, present in tur-
meric, can enhance the bioavailability of curcumin.9
Studies over the past decade have indicated that
curcumin-free turmeric components possess numerous
biological activities including anti-inflammatory.9
In addition, pure drugs that are industrially produced
or isolated from plants may be chosen for their high
activity against a human disease, but they have disadvan-
tages.19 They rarely have the same degree of activity as the
unrefined extract at comparable concentrations or dose of
the active component. This phenomenon is attributed to
the absence of interacting substances present in the
extract.19 Therapeutic effect of turmeric on attenuation of
OS was evaluated in some conditions such attenuation of
proteinuria in diabetic nephropathy and lupus nephritis
patients,19–21 attenuated the release of reactive oxygen
species,22 thalassemia,23 in cancer treatment,24 against
gentamycin-induced nephrotoxicity, and OS in rat.25 Tu r -
meric appears to be nontoxic to humans even at high
doses.26
Due to paucity of information on the effect of turmeric
in HD population, we have, therefore, followed up this
study to determine the beneficial effect of turmeric as a
pure plant on OS in HD patients.
SUBJECTS AND MATERIALS
The study was a prospective and double-blind random-
ized clinical trial that was performed in a single center.
The protocol was in accordance with the Declaration of
Helsinki and the local committee, and all patients pro-
vided informed consent form before participating in the
study. Participants were recruited from among 183 HD
patients in Ebrahimi HD Center in Shiraz, Iran. Inclusion
criteria consisted of having the age of 18 years and more,
receiving 4-hour HD treatments 3 times per week at least
for 3 months and administering no other antioxidant
medications except for Nephrovit tablet (Nephrovit®;
OSVAH Pharmaceutical Company, Tehran, Iran) 1 tablet
per day for a minimum of 3 months. Each tablet of Neph-
rovit provides vitamin C (ascorbic acid 60 mg), niacin
(niacinamide 20 mg), pantothenic acid (10 mg), vitamin
B6 (pyridoxine hydrochloride 10 mg), vitamin B2 (ribo-
flavin 1.7 mg), vitamin B1 (thiamine mononitrate
1.5 mg), folic acid (5 mg), biotin (D-biotin 300 μg), and
vitamin B12 (cyanocobalamin 6 μg).
The membrane and the general dialysis prescription
were similar for all patients. Fifty patients who met the
study criteria were enrolled to the study and randomized
into 2 groups of trial (n = 25) and controls (n = 25). Each
patient in the trial group received a dose of turmeric (1
capsule with each meal containing 500 mg turmeric, of
which 22.1 mg was the active ingredient curcumin; 3
capsules daily), whereas the control group received starch
capsules for the same 8 weeks. The type and dose of the
individualized drugs remained unchanged during the
study. Also, all patients in both groups received Nephrovit
tablet as a previous regimen at least for 3 months. Each
patient was given an order number and received the medi-
cations in the corresponding prepacked bottles. All drug
and placebo tablets were similar in size, shape, weight,
and color. Patients were followed on-call weekly by 2 of
the investigators for detection of any side effects related to
the turmeric supplementation. Drug compliance was
evaluated by tablet counts. Clinical investigators, labora-
tory personnel, and patients were all masked to the treat-
ment assignment.
Turmeric rhizome was obtained from India market and
powdered rhizomes were encapsulated by Medical and
Natural Products Chemistry Research Center of Shiraz
University of Medical Sciences, using hard gelatin cap-
sules. Also, starch capsules were made by this center.
Curcumin as a standard was obtained from Sigma-Aldrich
(St. Louis, MO, USA); acetonitrile, methanol, and acetic
acid were high-performance liquid chromatography grade
(Merck, Darmstadt, Germany). Reagent-grade water
(Purelab, UHO, ELGA, Cheshire, UK) was used through-
out the study. Curcumin level of turmeric was measured
by methods described elsewhere.27
Blood samples were drawn from each patient just
before and at the end of the trial from the arterial line
Pakfetrat et al.
Hemodialysis International 2014; ••:••–••2
immediately before a midweek dialysis session and before
heparin administration. Samples were immediately centri-
fuged and frozen at −70°C.
Analytical procedures
Plasma malonyldialdehyde (MDA), an indirect index of
lipid peroxidation, was assayed as thiobarbituric acid
reactive substances (TBARS) using colorimetric method.
Briefly, 0.5 mL of diluted plasma (1:1, v/v) was mixed
with 2 mL TBA reagent containing trichloroacetic acid
(15% [w/v]), thiobarbituric acid (0.375% [w/v]), and
hydrochloric acid (0.25 N), and the mixture placed in a
boiling water bath for 15 minutes. The samples were
cooled and centrifuged at 3000 gfor 15 minutes at 4°C.
The absorbance of the supernatant was measured at
532 nm. The TBARS concentration was calculated using
1,1,3,3,-tetraethoxy propane as a standard. Results are
expressed as nmol/mL. The red blood cell glutathione
peroxidase (RBC GPX) activity was measured in RBC
hemolysate according to the method of Paglia and Val-
entine 23 by a decrease in absorption at 340 nm due to
oxidation of NADPH to NADP+, when oxidized gluta-
thione was reduced by glutathione reductase (GR). Oxi-
dized glutathione had been formed earlier by reaction
of its reduced form with t-butyl hydroperoxide
(t-BuOOH) and GPX. To obtain erythrocyte hemolysate,
100 μL of packed erythrocytes was hemolyzed by adding
9 volumes of cold distilled water. The resulting suspen-
sion was centrifuged twice to eliminate all of the cell
membranes. Each assay mixture was consisted of
0.25 mM GSH, 0.38 mM NaN3, 0.23 mM EDTA,
0.175 mM NADPH, 0.1 unit of GR, 0.05 mM t-BuOOH
in 37.6 mM phosphate buffer (pH 7.2), and an appro-
priate amount of hemolysate in a final volume of
600 μL. The units of enzyme activities were calculated
using an extinction coefficient of 6.22 mM/cm for
NADPH. One unit was equivalent to the oxidation of
1μmol of NADPH per minute. GPX activity in RBC was
expressed as IU/g Hb.
The RBC CAT activity was assessed by Aebi method and
red blood cell glutathione reductase (RBC GR) activity in
red blood cells was calculated by the method of Massey
and William and expressed in units/g Hb. The hemoglo-
bin concentration was determined using an autoanalyzer
SE-9000 (Sysmex KX-21N Instruments, Mundelein, IL,
USA). Serum and urinary creatinine were measured by an
autoanalyzer using the Jaffé method; lipid profiles, AST,
and ALT also were measured by autoanalyzer. Serum Alb
levels were measured using a bromocresol purple dye-
binding method.
Statistical analysis
Data were analyzed in Statistical Package for the Social
Sciences software, version 15.0 (SPSS, Inc., Chicago, IL,
USA). Association between categorical variables was ana-
lyzed using the chi-square test. Quantitative data were
presented as mean ±standard deviation and compared by
independent-samples t-test or Mann-Whitney test in 2
groups as nonparametric test. Also, we performed data
variations before and after administration of turmeric by
paired-sample t-test or Wilcoxon signed-rank test as non-
parametric test. All tests were two-sided, and P value less
than 0.05 were considered significant.
RESULTS
In this study, two patients of placebo group who under-
went renal transplantation were excluded. Eventually, 48
patients (25 in the turmeric group and 23 in the placebo
group) completed the 8-week treatment phase of the trial.
The 48 studied patients had a mean age of 53.6 ±14.7
years with dialysis duration of 29.3 ±13.4 months and
KT/V of 1.4 ±0.02 as a marker of dialysis quality. As
listed in Table 1, there were no statistically significant
Table 1 Comparison of the demographic data between control and trial in studied patients
Variable Trial (n = 25) Control (n = 23) P value
Age (years), mean ±SD 46.8 ±14.5 52.3 ±14.7 0.196
Sex (men), n (%) 15 (60.0) 11 (47.8) 0.185
History of diabetes, n (%) 8 (32.0) 9 (39.1) 0.106
History of smoking, n (%) 2 (8.0) 2 (8.7) 0.121
History of hypertension, n (%) 9 (36.0) 7 (30.4) 0.731
Dialysis duration, mean ±SD 30.7 ±13.0 31.9 ±14.0 0.750
KT/V, mean ±SD 1.5 ±0.2 1.4 ±0.1 0.181
±= mean and standard deviation; n = number.
Turmeric and oxidative modulation in end-stage renal disease
Hemodialysis International 2014; ••:••–•• 3
differences (P >0.05) between the 2 groups in terms of
baseline clinical and chemical characteristics.
After the end of the study, some oxidative activities
were compared in 2 groups, which are listed in Table 2
and Figure 1. Mean GRX and CAT enzyme activity levels
significantly increased in both groups (P <0.05);
however, GR enzyme activity also increased but it was
not significant in both groups (P >0.05). Moreover,
Table 2 Comparison of the oxidative parameters between control and trial in studied patients
Variable Trial (n = 25) Control (n = 23) P value
MDA (nmol/mL)
Before trial 7.5 ±2.5 8.6 ±1.4 0.072
After trial 6.0 ±2.4 7.5 ±1.1
P value 0.0001 0.001
Ratio 0.2 ±0.2 0.1 ±0.1 0.040
RBC GR (units/g Hb)
Before trial 31.2 ±19.3 32.9 ±20.2 0.778
After trial 37.7 ±19.8 35.4 ±18.7
P value 0.138 0.644
Ratio 0.7 ±1.8 0.5 ±1.2 0.658
RBC CAT (kilounits/g Hb)
Before trial 109.11 ±11.78 107.78 ±14.28 0.731
After trial 141.14 ±22.72 127.30 ±19.55
P value 0.0001 0.0001
Ratio 0.3 ±0.2 0.1 ±0.2 0.039
RBC GPX (units/g Hb)
Before trial 28.6 ±22.1 25.6 ±26.1 0.665
After trial 56.2 ±28.2 58.2 ±46.3
P value 0.0001 0.001
Ratio 1.7 ±2.3 1.8 ±1.8 0.819
Albumin (g/dL)
Before trial 4.1 ±0.3 4.1 ±0.2 0.931
After trial 4.4 ±0.3 4.2 ±0.3
P value 0.001 0.262
±= mean and standard deviation; MDA = plasma malonyldialdehyde; n = number; ratio = after–before value; RBC CAT = red blood cell
catalase activity; RBC GR = red blood cell glutathione reductase activity; RBC GPX = red blood cell glutathione peroxidase activity.
Figure 1 Comparison of the ratio of oxidative parameters between control (placebo) and trial (turmeric) in studied
patients.
Pakfetrat et al.
Hemodialysis International 2014; ••:••–••4
MDA decreased significantly in the 2 groups after the
trial (P <0.05).
Although MDA level was reduced significantly in both
groups, the ratio (after − before)/before of the decrease
was significantly higher in the turmeric group (0.2 vs. 0.1,
P = 0.040). Otherwise, three enzymes of GPX, GR, and
CAT levels were increased in both groups, the ratio of
increase was only statistically significant for CAT activity
enzyme in turmeric group in comparison to placebo
(0.3 ±0.2 vs. 0.1 ±0.2; P = 0.02). Significant elevation of
albumin level in the turmeric group (4.1–4.4, P = 0.001)
compared with that of the control group (4.1–4.2,
P = 0.262) was also observed. No adverse events of trial
and placebo were reported (Table 3).
DISCUSSION
Our result showed that, in comparison to placebo, tur-
meric was significantly more effective in attenuation of OS
and increased in antioxidative markers in ESRD patients.
To the best of our knowledge, this is the first study on
turmeric in ESRD patients.
Oxidative stress is an imbalance between generation of
reactive oxygen species (ROS) and antioxidants. A decrease
in oxygen tensions and hypoxia-inducible transcription
factors of the kidney was demonstrated in a number of
experimental models of chronic kidney disease (CKD).28
Oxidants are highly reactive compounds with a very
short half-life. Therefore, in vivo determination of
Table 3 Comparison of some parameters between control and trial in studied patients
Variable Trial (n = 25) Control (n = 23) P value
Hb (g/dL)
Before trial 11.3 ±2.1 10.9 ±1.6 0.425
After trial 11.5 ±1.9 12.3 ±1.5
P value 0.705 0.080
Cholesterol (mg/dL)
Before trial 182.04 ±64.2 162.5 ±31.8 0.195
After trial 179.1 ±45.4 179.3 ±37.7
P value 0.213 0.563
LDL (mg/dL)
Before trial 111.3 ±37.1 106.1 ±35.1 0.622
After trial 120.2 ±34.6 120.3 ±27.9
P value 0.079 0.089
Cholesterol (mg/dL)
Before trial 182.04 ±64.2 162.5 ±31.8 0.195
After trial 179.1 ±45.4 179.3 ±37.7
P value 0.213 0.563
HDL (mg/dL)
Before trial 30.8 ±8.2 28.9 ±6.3 0.390
After trial 32.4 ±6.3 30.9 ±5.9
P value 0.299 0.184
Triglyceride (mg/dL)
Before trial 167.1 ±100.5 148.5 ±78.3 0.481
After trial 161.2 ±80.0 160.5 ±75.6
P value 0.493 0.155
AST (units/mL)
Before trial 14.0 ±7.2 15.4 ±8.8 0.527
After trial 12.3 ±5.0 13.0 ±8.6
P value 0.071 0.098
ALT (units/mL)
Before trial 13.8 ±8.2 13.4 ±9.0 0.889
After trial 12.8 ±6.7 12.9 ±6.9
P value 0.239 0.557
±= mean and standard deviation; AST = aspartate aminotransferase; ALT = alanine aminotransferase; HDL = high-density lipoprotein;
LD = low-density lipoprotein; n = number.
Turmeric and oxidative modulation in end-stage renal disease
Hemodialysis International 2014; ••:••–•• 5
oxidants is generally not feasible. In contrast, lipids,
proteins, carbohydrates, and nucleic acids, after peroxida-
tion have longer lifetimes (hours to weeks), which makes
them perfect markers of OS. Throughout lipid peroxida-
tion, unstable hydroperoxides changed to smaller
and more stable products, such as MDA, acrolein,
4-hydroxynonenal, or TBARS.29 The association between
MDA levels and the progression of atherosclerosis was
demonstrated previously in dialysis patients.30 The
present study indicated that addition of turmeric to vita-
mins supplement decreased MDA level significantly more
than placebo (0.2 vs. 0.1, P = 0.040), showing that tur-
meric is more effective in decreasing MDA as a marker of
lipid peroxidation in this population.
Similar to our results, Acar et al. also reported that
curcumin reduced the MDA and OS index levels in the
brain and sciatic nerve tissues in the diabetic group.31
In our study, CAT enzyme increased more in the
turmeric-treated groups (P = 0.039). Also, changes for
glutathione reductase was more in patients who received
turmeric (Table 2), but it was not statistically significant.
Antioxidant systems, both enzymatic and non-
enzymatic, are naturally present and counteract free radi-
cals. Enzymatic antioxidants include catalase, superoxide
dismutase, and glutathione peroxidase. Nonenzymatic
antioxidants contain glutathione, vitamin E and vitamin
C, transferrin, and albumin.32
Sankar et al. reported that curcumin decreased lipid
peroxidation and increased the reduced glutathione, cata-
lase, and glutathione peroxidase level and protected the
normal histological architecture of the liver, kidney, and
brain.33 Iqbal et al. showed increased activities of gluta-
thione peroxidase, glutathione reductase, glucose-6-
phosphate dehydrogenase and CAT to 189%, 179%,
189%, and 181% in the liver, respectively, in the curcumin
fed mice as compared to the normal diet fed-matched
mice.34
A previous study indicated that curcumin protects mito-
chondria against OS both in vitro and in vivo.35 Curcumin
has a strong potential for scavenging superoxide radicals,
hydrogen peroxide, and inhibition of oxidative enzymes
such as cytochrome P450, and chelating and disarming
oxidative properties of metal ions such as iron.36,37
Alternatively, in vitro and in vivo studies have shown
that curcumin activates the appearance of some intracel-
lular antioxidative defense systems for free radicals.38
González-Salazar et al. suggested that the ROS scavenging
ability of curcumin is involved in the cardioprotective
effect.39
Hemodialysis patients have an abnormal production of
oxidants and defective antioxidant production. Bioincom-
patibility of dialysis membranes as an important source of
ROS and losses of antioxidants via dialysis membrane may
be responsible for the imbalance between oxidative and
antioxidative markers in HD patients.40 The role of ROS
and/or decreased antioxidant activity in development of
atherosclerosis and related cardiovascular disturbances is
well-established in the CKD population.30,41 Carbonylated
protein is the most extensively studied form of oxidized
protein, in which carbonyl groups are mainly formed by
direct oxidation at side chains of amino acids (lysine,
arginine, proline, and threonine). The carbonyl level as a
biomarker of OS increased in oxidative diseases including
aging, diabetes, atherosclerosis, and CKD.42,43 Highly car-
bonylated α-1-antitrypsin and fibrinogen may contribute
to endothelial cell dysfunction, a common phenomenon
in cardiovascular disease.44 As a result, theoretically anti-
oxidant therapy may be beneficial in reducing cardiovas-
cular complication in HD patients.
In our study, turmeric improved serum albumin level
significantly compared to no turmeric-treated patients.
Hemodialysis patients are subject to an acute phase
response occurring from a microinflammatory state,
which can be quantified by plasma levels of acute phase
proteins such as C-reactive protein and negative acute
phase proteins such as albumin.45
Hypoalbuminemia, acute phase inflammation, and OS
may act synergistically to increase cardiovascular morbid-
ity and mortality risk in maintenance HD patients.32,46
Antioxidants can either be of exogenous, such as vita-
mins, or endogenous type. In addition, among endog-
enous antioxidants, albumin represents a very important
circulating antioxidant in the plasma.47 Albumin acts
through its multiple-binding sites and free radical-
trapping properties. In physiological or pathological con-
ditions, function is associated with changes in the redox
status, the albumin structure, and its beneficial antioxi-
dant properties can be altered.48
Lim et al. demonstrated that the quality and integrity of
serum albumin molecule in HD patients were subtly
altered and this impaired its biological properties. Oxida-
tive alterations of this major plasma protein might
adversely affect its vasculoprotective effects in dialysis
patients.49
In agreement with previous studies, our result showed
that turmeric is effective in the improvement of plasma
albumin in the same way that it decreased MDA and
increased CAT enzyme that may confirm the association
between inflammation and OS.
Our study on turmeric in ESRD patients showed no
adverse reaction on general health and biochemical
marker including liver function tests. Thus, it seems that
Pakfetrat et al.
Hemodialysis International 2014; ••:••–••6
turmeric is a safe medication in this population. However,
the safety of turmeric therapy in ESRD patients should be
further evaluated in larger trials with longer duration of
therapy.
The main limitations of our study and interpretation of
its results are the small sample size and short duration of
the treatment phase. Moreover, in addition to oxidative
parameter, future studies should consider the outcome
measures, such as incidence of cardiovascular mortality
and morbidity.
In conclusion, to the best of our knowledge, this is the
first randomized, double-blind, clinical trial that demon-
strates the possible efficacy and safety of turmeric in
attenuating OS in ESRD patients. Future multicenter ran-
domized trials with larger sample sizes and longer dura-
tions of treatment are necessary to further ascertain the
long-term efficacy and safety of adding turmeric in HD
population.
ACKNOWLEDGMENTS
The Shiraz Nephro-Urology Research Center of Shiraz
University of Medical Sciences funded this study, which is
derived from the student thesis of Mojtaba Dabaghja-
manesh. The authors would like to thank Dr. Nasrin
Shokrpour at Center for Development of Clinical Research
of Nemazee Hospital for editorial assistance.
Conflict of interest: The authors declare that they have no
conflict of interest.
Manuscript received May 2014; revised July 2014.
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