Nutrition, Metabolism & Cardiovascular Diseases (2010) 20, 326e331

available at www.sciencedirect.com

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

The efficacy of omega-3 fatty acid supplementation

on plasma homocysteine and malondialdehyde
levels of type 2 diabetic patients
Sh. Pooya, M. Djalali Jalali*, A. Djazayery Jazayery, A. Saedisomeolia,
M. Reza Eshraghian, F. Toorang

Department of Nutrition and Biochemistry, School of Health, Tehran University of Medical Sciences, Tehran, Iran

Received 22 July 2008; received in revised form 25 February 2009; accepted 1 April 2009

KEYWORDS Abstract Background and aims: Cardiovascular diseases are the major cause of mortality
Type II diabetes; among diabetic patients. The concentration of malondialdehyde (MDA) and homocysteine is
Omega-3 fatty acid; believed to play a role in cardiovascular diseases. Omega-3 fatty acid supplementation could
homocysteine; be effective in some diabetes complications and in the control of the glycemic index. However,
malondialdehyde; it may increase lipid peroxidation. The objective of this study was to determine the effect of
C-reactive protein omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients.
Methods and results: A randomized double-blind, placebo-controlled clinical trial was con-
ducted on 81 patients with type 2 diabetes. The patients were randomly assigned to either
the treatment or control groups. Each subject received three capsules of omega-3 fatty acids
or a placebo every day for a period of 2 months. The two groups were similar in terms of body
mass index and food intake. At the beginning of the study and after 2 months of supplementa-
tion their levels of HbA1c, homocysteine, MDA, C-reactive protein (CRP), total cholesterol,
LDL-cholesterol and fasting blood sugar (FBS) were determined. Due to omega-3 fatty acid
supplementation, homocysteine was changed significantly in both treatment and control
groups up to 3.10 mmol/L and 0.10 mmol/L respectively, and HbA1c decreased by 0.75% in
the treatment group and increased by 0.26% in the control group. However, the changes in
fasting blood sugar (FBS), malondialdehyde (MDA), C-reactive protein (CRP), total cholesterol
and LDL-cholesterol levels were not significant.
Conclusion: The consumption of omega-3 fatty acid supplements (3 g/day) for 2 months
decreases the levels of homocysteine in diabetic patients with no change in FBS, MDA and
CRP levels.
ª 2009 Elsevier B.V. All rights reserved.

* Corresponding author. Tel.: þ98 2188954911.

E-mail address: mjalali87@yahoo.com (M.D. Jalali).

0939-4753/$ - see front matter ª 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.numecd.2009.04.002
Omega-3 fatty acid, plasma homocysteine, plasma malondialdehyde, type II diabetes
Introduction
Diabetes is regarded as a serious condition that affects both
individuals and society as a whole. Its rapidly increasing
global prevalence is a primary cause of concern. It is esti-
mated that in 2030 around 366 million people could be
suffering from diabetes among the adult population of the
world [1]. Health problems associated with diabetes
contribute to an impaired quality of life and substantial
disability [2]. Increased body weight accompanying the
emergence of the metabolic syndrome and of type 2 dia-
betes as remarkably frequent clinical entities are among
the major epidemiological events of our time [3]. Epide-
miological studies have shown that the total blood homo-
cysteine concentration is a risk factor in cardiovascular
diseases [4]. A moderately elevated plasma concentration
of homocysteine is present in up to 8% of the general
population, and it is found in 20e40% of patients with
coronary and peripheral vascular diseases [5,6]. Malon-
dialdehyde (MDA) is also a highly toxic product formed by
lipid peroxidation due to the activity of free radicals. Many
studies have shown that the concentration of MDA increases
considerably in diabetes [7].
Consumption of omega-3 polyunsaturated fatty acids
may protect against metabolic diseases [8] such as
atherosclerosis, which has the most important effect on
mortality among diabetic patients [9]. Daily intake of
omega-3 fatty acids has a positive effect on the risk
factors for cardiovascular disease (CVD) [10]. Epidemio-
logical studies have assessed the relationship between C-
reactive protein (CRP) concentrations and omega-3 fatty
acid intakes [11,12]. These findings confirm the anti-
inflammatory effect of omega-3 fatty acid supplementa-
tion. It has also been reported that omega-3 fatty acid
supplementation could be effective in the control of
glycemic index [13]. However, it may increase oxidative
stress too [14]. It is suggested that the increasing omega-3
fatty acid content of phospholipids decreases the levels of
homocysteine. This study suggests that long-chain omega-
3 fatty acids may modulate gene expression of enzyme(s),
which are involved in the formation of homocysteine [15].
In recent years, numerous studies have been done on
omega-3 fatty acids, but due to the conflicting results, the
metabolic effect of these nutrients in patients with type 2
diabetes is still a matter of debate. Our study was carried
out in order to determine and compare the effects of
omega-3 fatty acid supplementation on MDA and homo-
cysteine in type 2 diabetic patients.
Methods
A randomized, double-blind, placebo-controlled clinical
trial was conducted on 81 subjects between the ages of
45 and 85 years with type 2 diabetes. All of the recruited
patients were diagnosed (by health staff) with type 2
diabetes for at least 2 years prior to participation.
Informed consent was obtained according to the guide-
lines of the Ethics Committee on Human Experimentation
at Tehran University of Medical Sciences. Inclusion criteria
for the study comprised: (1) negative past medical history
327
for myocardial infarction, cancer, renal and hepatic
diseases; and (2) no consumption of omega-3 fatty acids,
multi vitaminemineral supplements, or drugs which,
during intervention, interact with the lipid profile.
Anthropometric indices including body mass index (BMI),
past medical history, and current and past therapeutic
regimens were obtained through comprehensive inter-
views and thorough physical examinations. According to
the findings of previous studies, the supplementation
procedure for omega-3 fatty acids was set at three
capsules per day for 2 months [16]. This amount provided
a total daily dose of 2714 mg per day (eicosapentaenoic
acid (EPA), 1548 mg; docosahexaenoic acid (DHA), 828 mg;
and 338 mg of other omega-3 fatty acids). Capsules were
purchased from PBL Co. (PA, USA). Placebo capsules
contained 2100 mg of sunflower oil (12% SFA, 71% linoleic
acid, 16% MUFA). Placebo capsules were prepared for this
clinical trial by Zakaria Co. (Tehran, Iran) and had an
identical appearance to the omega-3 capsules. Ten milli-
liters of blood were taken from each subject before and
after 2 months of treatment. The blood samples were
collected after 12e14 h of overnight fasting, between 8
and 10 am and prior to any oral hypoglycemic agent
administration. Blood samples were aliquoted to serum
(without EDTA) and plasma (with EDTA) and immediately
stored at 70  C for subsequent analyses.
Biochemical assays
Serum MDA activities were determined using the thio-
barbituric acid method which is highly sensitive (with the
within-run coefficient of variance (CV Z 1.8e3.3%) and
between-run coefficient of variance (CV Z 3.3e4.4%)) [17].
Homocysteine was measured by Hitachi auto analyzer using
the enzymatic cycling method (Axis-Shield Enzymatic
Homocysteine Assay, Dundee, UK) (with the within-run
coefficient of variance (CV Z 1.02) and between-run
coefficient of variance (CV Z 1.91)). CRP was measured
using the immunoturbidimetrical method. Total cholesterol
and LDL-cholesterol were measured enzymatically by
Hitachi auto analyzer, fasting blood sugar (FBS) was
determined using MAN kit (Tehran, Iran) and hemoglobin
was measured by colorimetry and HbA1c by D-10 kites
(BioRad laboratories, Schilitigheim, France). Nutrient
intakes were estimated using the 24-h dietary recall ques-
tionnaire before and after supplementation. Food
Processor Ver. 2 software was employed in order to analyze
nutrient intake. Subjects were advised not to alter their
usual life style, including diet and physical activity
throughout the trial. They were also advised to avoid any
changes in their medications.
Statistical analysis
Differences between the two groups were determined by
a two tailed t-test using SPSS 11.5 software. All values
are expressed as mean  SD. A value of P < 0.05 was
considered as statistically significant. The power of the
study for homocysteine and MDA was calculated using
G*power 3 [18].
328
Results
At the beginning of the study, the groups shared similar age,
duration of diabetes and body mass index (BMI) (Table 1).
Nine out of the 90 subjects did not complete the study (five
people in the treatment group and four people in the
control group), mainly due to non-compliance. As Table 1
shows, the consumption of antidiabetic drugs was similar
among the groups. Table 2 shows the energy and nutrient
intakes before and after intervention. These data show that
there were no changes during the study; therefore, all
changes at the end of the study would be related to the
omega-3 fatty acid consumption. Table 3 shows the serum
HbA1c, homocysteine, MDA, CRP, total cholesterol, LDL-
cholesterol and fasting blood sugar (FBS) concentrations
before and after supplementation. This table shows that
following 2 months of supplementation with omega-3 fatty
acids, serum levels of homocysteine and HbA1c decreased
significantly in the treatment group. There were no changes
in the concentrations of MDA, CRP, total cholesterol, LDL-
cholesterol and FBS due to omega-3 fatty acid supplemen-
tation. This study shows that the Pearson correlation coef-
ficient between MDA vs homocysteine, CRP, LDL, HbA1c, FBS
and total cholesterol were 0.32 (P Z 0.24), 0.07 (P Z 0.74),
0.30 (P Z 0.15), 0.37 (P Z 0.15), 0.31 (P Z 0.15) and 0.31
(0.15), respectively (figures not shown), which were not
statistically significant. The Pearson correlation coefficient
between homocysteine vs CRP, LDL, HbA1c, FBS and total
cholesterol were 0.55 (P Z 0.03), 0.24 (P Z 0.38), 0.35
(P Z 0.19), 0.37 (0.16) and 0.15 (P Z 0.57), respectively,
which shows a significant positive correlation between
homocysteine and CRP levels. Our results also showed that
there was no significant correlation between homocysteine
and LDL, HbA1c and total cholesterol levels.
Discussion
Increased levels of homocysteine have been associated
with an increased risk of thrombosis and atherosclerosis
and stimulated platelet aggregation [19]. It is an indepen-
dent risk factor for atherosclerosis [20]. It has been
reported that omega-3 fatty acids can affect the produc-
tion of homocysteine [21,22]. Our study shows that homo-
cysteine levels were decreased significantly in the omega-3
fatty acid supplemented group and a significant difference
was found between the treatment and the control groups
Table 1 Initial demographic, anthropometric and biological data and consumption of antidiabetic drugs for the treatment and
control groups
Age (years) (means  SD)
Duration of diabetes (years) (means  SD)
BMI (kg/m2) (means  SD)
Metformin usage (mg/day)
(% of group using medication)
Glibenclamide usage (mg/day)
(% of group using medication)
a
NS, not significant.
b
Statistical test was independent t-test (P < 0.05).
Sh. Pooya et al.
before and after omega-3 fatty acid supplementation. The
power of the study to show the changes in homocysteine
and MDA were 0.9 and 0.9 respectively. A high power
confirms the significant difference in homocysteine and the
non-significant difference in MDA levels between the
groups. This fact indicates that our sample size is large
enough to show the differences. These results conclude
that omega-3 fatty acid supplementation can decrease the
amount of homocysteine. This confirms the results of other
studies showing that omega-3 fatty acids can possibly
decrease the formation of homocysteine [15]. Piolot [23]
reported the apparent interaction of omega-3 fatty acids
and NO on homocysteine metabolism in healthy people
[23]. This investigator also presented a probable mecha-
nism by which omega-3 fatty acid supplementation can
reduce the production of homocysteine. The reduced
homocysteine concentrations observed in their study are
attributed to possible oxidative stress induction by omega-3
fatty acids and stimulation of the oxidative catabolism of
homocysteine [24]. This increased susceptibility to oxida-
tive stress due to omega-3 fatty acid supplementation is
reported [25]. The observations of Li and Zeman confirm
the results of our study [26,27]. Zeman showed that omega-
3 fatty acid supplementation in combination with sta-
tin þ fibrate in diabetic patients can significantly decrease
the serum homocysteine [27]. Baro et al. investigated
whether the simultaneous effect of a daily intake of omega-
3 fatty acid and oleic acid fortified skimmed milk plus folic
acid and B-group vitamins would cause a decrease in
homocysteine levels [28]. We did not observe any signifi-
cant change in folate or vitamin B12 levels (Table 2) during
our study; therefore, we confirmed that the consumption of
omega-3 fatty acids may decrease the level of homo-
cysteine in diabetic patients.
Malondialdehyde (MDA) was determined for the first
time in the aqueous humor of glaucomatous eyes as
a product of lipid peroxidation [29]. MDA is a highly toxic
by-product formed by lipid peroxidation due to free radi-
cals and its concentration is increased in diabetes [30]. Our
study showed that omega-3 fatty acid supplementation
non-significantly decreases MDA levels. Therefore,
consumption of 3 g of pure omega-3 fatty acids does not
cause any significant change in MDA levels. Our study was
well powered (power > 0.90) to show a non-significant
change in MDA levels. Vaagenes reported that a high intake
of omega-3 fatty acids (1500 mg/day per kg body weight) in
Treatment group Control group P-valueb
56.38  9.24 (n Z 40) 52.7  10.65 (n Z 41) NSa
8.72  3.4 (n Z 40) 8.02  2.9 (n Z 41) NS
27.7  3.41 (n Z 40) 26.09  5.03 (n Z 41) NS
1.25  0.2 (55) 1.16  0.2 (51) NS
1.35  0.3 (45) 1.04  0.2 (49) NS
Omega-3 fatty acid, plasma homocysteine, plasma malondialdehyde, type II diabetes 329

Table 2 Daily energy and nutrient intakes of the treatment and control groups
Before intervention After intervention P-valuea
(means  SD) (means  SD)
Total energy (kcal)
Treatment group 1612.88  270.2 1718.65  407.33 NSb
Control group 1703.77  352.91 1793.92  423.12 NS
Total CHO (g)
Treatment group 322.61  46.9 (60) 326.88  68.6 (57) NS
(% of total calories)
Control group 338.50  68.01 (59) 341.09  54.2 (57) NS
(% of total calories)
Total protein (g)
Treatment group 93.5  16.3 (17) 87  12.6 (15) NS
Control group 89.07  11.8 (15.6) 86.9  13 (14.5) NS
Total fat (g)
Treatment group 26.1  21.44 (14) 27.56  20.7 (14.4) NS
Control group 23.6  17.06 (12.4) 22.88  25.8 (11.5) NS
Polyunsaturated fatty
acid (g)
Treatment group 7.23  5.9 7.19  5.9 NS
Control group 7.50  5.4 7.60  4.7 NS
Saturated fatty
acid (g)
Treatment group 9.6  7.09 9.8  6.9 NS
Control group 9.01  5.3 9.9  4.6 NS
Cholesterol (mg)
Treatment group 151.23  1.57 144.69  1.37 NS
Control group 140.97  6.5 144.04  6.2 NS
Vitamin B6 (mg)
Treatment group 1.5  0.9 1.6  0.7 NS
Control group 1.3  0.5 1.4  0.5 NS
Vitamin B12 (mg)
Treatment group 2.13  1.19 1.83  1.08 NS
Control group 3.02  3.6 2.9  2.65 NS
Folate (mg)
Treatment group 291.16  86.8 291.16  86 NS
Control group 316  44.2 313  63.02 NS
a
Statistical test was independent t-test (P < 0.05).
b
NS, not significant.

rats causes an increased fatty acyl-CoA oxidase (FAO)
enzyme activity, which increases lipid peroxidation and
leads to increased MDA levels. However, they reported that
a lower supplementation dose of omega-3 (250 mg/day per
kg body weight) has no effect on MDA and lipid peroxidation
[31]. Brude reported that daily consumption of 5 g of
omega-3 fatty acids for 6 weeks causes an increase in MDA
and LDL oxidation. They also showed that adding antioxi-
dants (75 mg vitamin E, 150 mg vitamin C, 15 mg b-caro-
tene, and 30 mg coenzyme Q10 per day) to omega-3 fatty
acid supplements prohibits changes [32]. Compared to
Brude’s study, our study had a longer experimental period
and lower omega-3 dosage, which showed that there is no
change in MDA levels due to omega-3 fatty acid
supplementation.
CRP is an inflammatory biomarker secreted from the
liver. Its level is increased in inflammatory conditions [33].
In our study we found a significant positive correlation
between homocysteine and CRP levels, which may indicate
the implication of systemic inflammation on homocysteine
levels. This is confirmed by Billups et al. [34]. Our results
also show that there is no significant effect of omega-3
fatty acids on the concentration of plasma CRP levels. Our
finding has been confirmed by other studies [10].
In conclusion, we found that consumption of omega-3
fatty acids (3 g/day) for 2 months decreases the production
of homocysteine in diabetic patients, which can lead to an
increased risk of cardiovascular disease. We also found no
change in MDA, FBS and CRP levels due to the consumption
of omega-3 fatty acids.
330 Sh. Pooya et al.

Table 3 Levels of HbA1c, homocysteine, malondialdehyde, C-reactive protein, total cholesterol, LDL-cholesterol and fasting
blood sugar before and after 2 months of omega-3 fatty acids supplementation in the treatment and control groups
Before (means  SD) After (means  SD) Difference (means  SD) P-valuec
HbA1c (%)
Treatment group 7.9  1.2 7.15  0.17 0.75  0.04 <0.001
Control group 7.64  0.98 7.90  0.16 0.26  0.07 NSa
P-valueb NS <0.001 <0.001
Homocysteine
(mmol/L)
Treatment group 14.40  4.07 11.29  2.12 3.10  2.7 <0.001
Control group 13.39  2.45 13.29  2.44 0.10  1.9 NS
P-value NS <0.001 <0.001
Malondialdehyde
(nmol/mL)
Treatment group 3.04  0.66 2.31  0.65 0.72  0.9 NS
Control group 2.94  1.07 2.37  0.87 0.57  1.10 NS
P-value NS NS NS
C-reactive protein
(mg/L)
Treatment group 2.70  0.02 2.48  0.23 0.22  0.06 NS
Control group 3.15  0.36 3.80  0.17 0.65  0.08 NS
P-value NS NS NS
Total cholesterol
(mg/dL)
Treatment group 154.9  41.27 159.1  39.45 4.1  0.4 NS
Control group 159.4  33.18 168.5  37.32 9.0  0.4 NS
P-value NS NS NS
LDL-cholesterol
(mg/dL)
Treatment group 127.7  36.5 125.8  34.0 1.9  0.7 NS
Control group 127.2  36.3 126.3  29.7 0.9  0.2 NS
P-value NS NS NS
FBS (mg/dL)
Treatment group 137.8  48.5 139.7  36.5 1.9  3.5 NS
Control group 129.2  28.3 126.2  34.2 3  1.3 NS
P-value NS NS NS
a
NS, not significant.
b
Independent t-test for comparing differences between the treatment and control groups (P < 0.05).
c
Paired t-test for comparing differences before and after intervention in the treatment and control groups.

Acknowledgments the SU.FOL.OM3 study: double-blind randomized placebo-

This work was supported by a grant from the vice-chan-
cellor for research of Tehran University of Medical Sciences
(no. 4302). We are indebted to the patients for their
cooperation. We would also like to thank Zakaria Co. and Dr
Navid Saadat.
References
[1] WHO. Prevalence of diabetes worldwide. Geneva: WHO; 2007.
[2] CDC. Diabetes surveillance. Atlanta, GA: HHS; 2007.
[3] Duncan BB, Schmidt MI. The epidemiology of low-grade
chronic systemic inflammation and type 2 diabetes. Diabetes
Technol Ther 2006;8(1):7e17.
[4] Galan P, de Bree A, Mennen L, Potier de Courcy G,
Preziozi P, Bertrais S, et al. Background and rationale of
controlled secondary prevention trial to test the impact of
supplementation with folate, vitamin B6 and B12 and/or
omega-3 fatty acids on the prevention of recurrent
ischemic events in subjects with atherosclerosis in the
coronary or cerebral arteries. J Nutr Health Aging 2003;7:
428e35.
[5] Slatter DA, Bolton CH, Bailey AJ. The importance of lipid-
derived malondialdehyde in diabetes mellitus. Diabetologia
2000;43:550e7.
[6] Vollset SE, Refsum H, Tverdal A, Nygard O, Nordrehaug JE,
Tell GS, et al. Plasma total homocysteine and cardiovascular
and noncardiovascular mortality: the Hordaland Homo-
cysteine Study. Am J Clin Nutr 2001;74:130e6.
[7] Rosato R, Ciccone G, Bo S, Pagano GF, Merletti F, Gregori D.
Evaluating cardiovascular mortality in type 2 diabetes
patients: an analysis based on competing risks Markov chains
and additive regression models. J Eval Clin Pract 2007;13:
422e8.
Omega-3 fatty acid, plasma homocysteine, plasma malondialdehyde, type II diabetes
[8] De Caterina R, Madonna R, Bertolotto A, Schmidt EB. n-3 fatty
acids in the treatment of diabetic patients: biological ratio-
nale and clinical data. Diabetes Care 2007;30:1012e26.
[9] Mahan, L.K., Escott-Stump, S. Krause’s food, Nutrition and
diet therapy. 11th ed. Nutrition in cardiovascular disease.
Philadelphia, PA; 2005, 592 p.
[10] Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P,
Lau J. Effects of omega-3 fatty acids on serum markers of
cardiovascular disease risk: a systematic review. Atheroscle-
rosis 2006;189:19e30.
[11] Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM,
Rifai N, et al. Consumption of (n-3) fatty acids is related to
plasma biomarkers of inflammation and endothelial activation
in women. J Nutr 2004;134:1806e11.
[12] Madsen T, Skou HA, Hansen VE, Fog L, Christensen JH, Toft E,
et al. C-reactive protein, dietary n-3 fatty acids, and the
extent of coronary artery disease. Am J Cardiol 2001;88:
1139e42.
[13] Frenoux JM, Prost ED, Belleville JL, Prost JL. A poly-
unsaturated fatty acid diet lowers blood pressure and
improves antioxidant status in spontaneously hypertensive
rats. J Nutr 2001;131:39e45.
[14] Wander RC, Du SH. Oxidation of plasma proteins is not
increased after supplementation with eicosapentaenoic and
docosahexaenoic acids. Am J Clin Nutr 2000;72:731e7.
[15] Li D, Yu XM, Xie HB, Zhang YH, Wang Q, Zhou XQ, et al.
Platelet phospholipid n-3 PUFA negatively associated with
plasma homocysteine in middle-aged and geriatric hyper-
lipaemia patients. Prostaglandins Leukot Essent Fatty Acids
2007;76:293e7.
[16] Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty
acids in type 2 diabetes: a review. J Am Diet Assoc 2005;
105(3):428e40.
[17] Richard MJ, Portal B, Meo J, Coudray C, Hadjian A, Favier A.
Malondialdehyde kit evaluated for determining plasma and
lipoprotein fractions that react with thiobarbituric acid. Clin
Chem 1992;38:704e9.
[18] Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible
statistical power analysis program for the social, behavioral,
and biomedical sciences. Behav Res Methods 2007;39:175e91.
[19] Signorello MG, Segantin A, Passalacqua M, Leoncini G.
Homocysteine decreases platelet NO level via protein kinase C
activation. Nitric Oxide 2009;20(2):104e13.
[20] Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K,
Stefanadis C. Homocysteine and coronary atherosclerosis:
from folate fortification to the recent clinical trials. Eur Heart
J 2009;30:6e15.
[21] Severus WE, Littman AB, Stoll AL. Omega-3 fatty acids,
homocysteine, and the increased risk of cardiovascular
mortality in major depressive disorder. Harv Rev Psychiatry
2001;9(6):280e93.
331
[22] Berstad P, Konstantinova SV, Refsum H, Nurk E, Vollset SE,
Tell GS, et al. Dietary fat and plasma total homocysteine
concentrations in 2 adult age groups: the Hordaland Homo-
cysteine Study. Am J Clin Nutr 2007;85:1598e605.
[23] Piolot A, Blache D, Boulet L, Fortin LJ, Dubreuil D, Marcoux C,
et al. Effect of fish oil on LDL oxidation and plasma homo-
cysteine concentrations in health. J Lab Clin Med 2003;141:
41e9.
[24] Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D.
Impaired homocysteine metabolism and atherothrombotic
disease. Lab Invest 2001;81:645e72.
[25] Saedisomeolia A, Wood GL, Garg ML, Gibson GP, Wark ABP.
Supplementation of long chain n-3 polyunsaturated fatty acids
increases the utilization of lycopene in cultured airway
epithelial cells. J Food Lipids 2008;15:421e32.
[26] Li D, Mann NJ, Sinclair AJ. A significant inverse relationship
between concentrations of plasma homocysteine and phos-
pholipid docosahexenoic acid in healthy male subjects. Lipids
2006;41(1):85e9.
[27] Zeman M, Zak A, Vecka M, Tvrzicka E, Pisarikova A,
Stankova B. Effect of n-3 polyunsaturated fatty acids on
plasma lipid, LDL lipoperoxidation, homocysteine and
inflammation indicators in diabetic dyslipidemia treated with
statin þ fibrate combination. Cas Lek Cesk 2005;144:737e41.
[28] Baro L, Fonolla J, Pena JL, Martinez-Ferez A, Lucena A,
Jimenez J, et al. n-3 Fatty acids plus oleic acid and vitamin
supplemented milk consumption reduces total and LDL
cholesterol, homocysteine and levels of endothelial adhesion
molecules in healthy humans. Clin Nutr 2003;22:175e82.
[29] Faschinger C, Schmut O, Wachswender C, Mossbock G. Glau-
coma and oxidative stress. Determination of malondialdehyde
e a product of lipid peroxidation. Ophthalmologe 2006;103:
953e9.
[30] Iraz M, Erdogan H, Ozyurt B, Ozugurlu F, Ozgocmen S,
Fadillioglu E. Brief communication: omega-3 essential fatty
acid supplementation and erythrocyte oxidant/antioxidant
status in rats. Ann Clin Lab Sci 2005;35:169e73.
[31] Vaagenes H, Muna ZA, Madsen L, Berge RK. Low doses of
eicosapentaenoic acid, docosahexaenoic acid, and hypolipi-
demic eicosapentaenoic acid derivatives have no effect on
lipid peroxidation in plasma. Lipids 1998;33:1131e7.
[32] Brude IR, Drevon CA, Hjermann I, Seljeflot I, Lund-Katz S,
Saarem K, et al. Peroxidation of LDL from combined-hyper-
lipidemic male smokers supplied with omega-3 fatty acids and
antioxidants. Arterioscler Thromb Vasc Biol 1997;17:2576e88.
[33] Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s
Illustrated biochemistry. 27th ed. McGraw-Hill; 2006.
[34] Billups KL, Kaiser DR, Kelly AS, Wetterling RA, Tsai MY, et al.
Relation of C-reactive protein and other cardiovascular risk
factors to penile vascular disease in men with erectile
dysfunction. Int J Impot Res 2003;15:231e6.