Email updates

Keep up to date with the latest news and content from Journal of Diabetes and Metabolic Disorders and BioMed Central.

Open Access Research article

Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes

Hamideh Pishva1*, Mohsen Amini2, Mohammad Reza Eshraghian3, Saeed Hosseini4 and Soltan Ali Mahboob5

Author Affiliations

1 Department of cellular, Molecular Nutrition, School of Nutrition Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Center, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

4 Endocrinology Metabolism Research Center (EMRC), Tehran University of Medical Sciences, Tehran, Iran

5 Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

For all author emails, please log on.

Journal of Diabetes & Metabolic Disorders 2012, 11:25  doi:10.1186/2251-6581-11-25

The electronic version of this article is the complete one and can be found online at:

Received:3 July 2012
Accepted:24 October 2012
Published:10 December 2012

© 2012 Pishva et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Fatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation.


Twenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured.


Although EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid.


EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.

Plasma fatty acids composition; Eicosapentaenoic acid; Polymorphism; Fatty acid binding protein-2; Peroxisome proliferator-activated receptor


Dietary fat intake is believed to contribute to development of chronic diseases, in particular cardiovascular disease [1]. No biomarkers reflect the absolute fat intake, however, measuring fatty acids concentrations in various biological samples reflect to some extent, the proportional intake of fatty acids [2]. Fatty acids can be measured as free fatty acids in serum, components of circulating triglycerides, components of erythrocyte membranes, phospholipids or cholesterol esters, or adipose tissue from different sites. The amount of serum or plasma fatty acids reflects the composition of dietary intakes of the past few hours (triglyceride) or the past few days (cholesterol ester and phospholipids fatty acids) [3].

Changes in plasma fatty acids composition reflect abnormalities in lipoprotein metabolism and dietary habits and have been widely studied in many animal and epidemiological [4,5] and clinical human studies [6,7].

Fatty acids of the n-3 family, particularly the long-chain n-3 fatty acids, are important nutrients throughout the life. Several epidemiological studies have shown that n-3 fatty acids in blood differ significantly among individuals [8-10]. This family of fatty acids has been historically associated with a lower risk of cardiovascular disease, including stroke [11] and coronary heart disease [12,13]. In children, cardiovascular benefits have been attributed to long-chain n-3 fatty acids [14,15]. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) two well-known long-chain n-3 fatty acids are important for their protective effects on cardiovascular disease; increased dietary intake of them has resulted in decreased cardiac mortality in a large secondary prevention study [16].

The composition of serum fatty acids can not only be used as an indicator of dietary fat quality [17], but can also be used as a biomarker for assessing metabolic and cardiovascular disease risk [18,19]. Intestinal fatty acid binding protein 2 (FABP2) is a small cytosolic protein involved in intracellular fatty acid (FA) transfer and metabolism. Peroxisome proliferator-activated receptor α (PPARα) is involved in glucose and lipid metabolism and thus may have a role in development of dyslipidemia, atherosclerosis, obesity, insulin resistance, and type II diabetes mellitus. We have shown that FABP2 genotypes influence the lipid-lowering effects of EPA supplementation in hypertriglyceridemic subjects [20]. We, therefore, conducted this study to determine the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation.

Subjects and methods


Participants were selected from the hypertriglyceridemic subjects referred from Tehran Central Laboratories to Endocrinology and Metabolism Research Center (EMRC). The inclusion criteria were a serum TG level >200 mg/dL (>2.3 mmol/L), and a fasting blood glucose of <110 mg/dL (<6.2 mmol/L). Those who had received lipid lowering agents, oral contraceptive pills, diuretics, sex hormones, thyroid medications, or omega-3 supplement, and patients with a history of gastrointestinal diseases, and smokers were excluded from the study.

After determination of their FABP2 genotypes, the first 23 eligible subjects who were found as Ala54 carriers and the first 23 eligible Thr54 carriers were enrolled in the study. Participants took two grams per day of pure EPA for eight weeks (four gel caps, each containing 500 mg ethyl ester EPA 90%, courtesy of Minami Nutrition, Edegem, Belgium). Two capsules were taken in the morning and two in the evening. The participants were followed weekly at the EMRC; a checklist for weekly consumption of capsules was filled and capsules for the next week were given to them. All of the subjects consumed controlled diet (Percentage of energy from carbohydrate, fat, and protein diets were similar).

A blood sample was drawn from each participant following a 14-hour overnight fasting at the baseline and after eight weeks of EPA supplementation. Height and weight were measured by a Seca scale (Germany) with light clothing and no shoes on. Body mass index (BMI) was then calculated. Waist circumference was measured with a flexible tape midway between the lowest rib and the iliac crest. The hip circumference was measured at the widest part of the gluteal region.

The study was approved by Ethics Committee of EMRC, Tehran University of Medical Sciences (TUMS). All participants were informed of the nature of the study and gave a written informed consent. The biochemical analyses were carried out at EMRC laboratory, TUMS. Genetic studies were conducted at the Department of Medical Genetics, TUMS. The plasma fatty acids composition was determined at the Department of Medicinal Chemistry and Pharmaceutical Sciences Laboratory, TUMS.

We calculated the sample size as fallow:

<a onClick="popup('','MathML',630,470);return false;" target="_blank" href="">View MathML</a>

<a onClick="popup('','MathML',630,470);return false;" target="_blank" href="">View MathML</a>

<a onClick="popup('','MathML',630,470);return false;" target="_blank" href="">View MathML</a>

Laboratory analyses

Plasma samples and sera were separated from blood samples by centrifuging at 4C and 1800 g for 15 min and stored in 1-mL aliquots in sterile tubes at -80C until used. Serum and plasma lipid and lipoprotein levels were measured as described previously [20].

Plasma fatty acid extraction and gas chromatography

Fatty acid extraction was done by Folch method [21] with some modifications. Plasma was homogenized in chloroform: methanol (2:1 vol/vol containing 50 mg/L butylated hydroxy toluene); normal saline was added to the solution, shacked vigorously and allowed for phase separation. The upper layer was drawn off by aspiration and washed several times; the lower phases were collected. Extracted lipids were dried under a stream of nitrogen. The dried lipids were soaponified by the method described previously [22]. Soaponified fatty acids were transesterified by boron trifluoride (BF3) in methanol. BF3 was added to the sample and incubated at 100°C in a water bath for an hour. After cooling to room temperature, hexane, HCl and water were added, shacked vigorously, centrifuged, and the upper phase was taken into a new tube and dried with nitrogen. Before injecting to the instrument, methanol and ethylated margaric acid (as an internal standard) were added to samples. Fatty acids methyl esters (FAMEs) were measured by gas chromatography. A capillary column with 60 m length, 0.25 mm internal diameter and 0.2 μM film thickness on an HP 6890 GC equipped with flame ionization detector was used to qualify and quantify FAMEs. The initial column temperature was set at 195°C for 2 min, which increased to 205°C by increments of 2°C/min, then to 214°C by 1°C/min, then to 240°C by 15°C/min and held for 10 min. Helium was used as the carrier gas at an initial flow rate of 1 mL/min for 8 min, which increased to 1.3 mL/min for 4.2 min and then to 1.9 mL/min. The detector temperature was set at 300°C and the injector temperature at 250°C. FAMEs were identified by comparison with the retention times of Supelco 37 component FAME mix standard. We focused on PUFAs in chromatogram and excluded short- and medium-chain saturated fatty acids from chromatogram. Different concentrations of FAME mix with added ethylated margaric acid were injected to gas chromatography machine (GC) to obtain the standard curve for each fatty acid. The peak area of a given fatty acid was divided by the peak area of the internal standard (ethylated margaric acid) then with respect to the standard curve, concentrations of fatty acids in plasma were estimated.


Ala54Thr (Gene ID: 2169)

Genomic DNA was extracted using the Flexi Gene DNA kit (Qiagen, GmbH, Hilden, Germany) as described previously [20]. A 180-bp DNA fragment containing the G to A nucleotide substitution in exon 2 (codon 54) of the FABP2 gene (Ala54Thr) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as described previously [20].

Leu162Val (gene ID: 55465)

The Leu162Val mutation of the PPARα gene is caused by a C to G transversion at nucleotide 484 in exon 5. The PCR-RFLP method was used as described earlier [23].

Intron 7

The PCR-RFLP method was used to determine intron 7 polymorphism (mutation) as described previously [23].

Statistical analyses

The normality of distribution of continuous variables was tested by one-sample Kolmogorov-Smirnov test. To normalize the continuous variables not normally distributed, a log transformation was applied. The mean plasma fatty acids concentrations between the two study groups with different FABP2 genotypes were compared by independent sample Student’s t test.

Since only few subjects with Thr54/Thr were found among the participants, they were pooled with Ala54/Thr subjects and analyses were carried out on the pooled data. Results are presented as Means±SE unless otherwise noted. Analyses were performed by SPSS® for Windows® ver 11.5. A p value <0.05 was considered statistically significant.


The baseline characteristics of subjects were described previously [20,23]. Table 1 shows the plasma fatty acids compositions in hypertriglyceridemic subjects.

Table 1. Plasma fatty acids composition in hypertriglyceridemic subjects

Table 2 shows plasma fatty acids levels of studied subjects stratified by their FABP2 genotypes. Concentrations of EPA (p<0.001), DHA (p<0.055), and some of n-3 fatty acids (p<0.001) were higher in those with Thr54 polymorphism than Ala54 after EPA supplementation. Changes in levels of other fatty acids did not significantly differ between subjects with G or A alleles.

Table 2. Plasma fatty acids concentration after 8 weeks of EPA supplementation in hypertriglyceridemic subjects stratified by FABP2 genotypes

Plasma fatty acids levels in hypertriglyceridemic subjects with Val162 polymorphism in PPARα genotypes are shown in Table 3. The concentrations of EPA (p<0.001), and n-3 fatty acids (p<0.001) were significantly higher and the n-6:n-3 ratio (p<0.01) was significantly lower in Val162 than in Leu162 polymorphism. Changes in levels of other fatty acids did not significantly differ between Leu or Val carriers. The levels of EPA (p<0.001) and n-3 fatty acids (p<0.02) were significantly different between GG and GC groups (Table 4).

Table 3. Plasma fatty acids concentration after 8 weeks of EPA supplementation in hypertriglyceridemic subjects stratified by PPARα genotypes

Table 4. Plasma fatty acids concentration after 8 weeks of EPA supplementation in hypertriglyceridemic subjects stratified by PPARα (GG/GC) genotypes


We found that EPA supplementation could increase the level of plasma EPA, in both FABP2 and PPARα genotypes with more effects on subjects with either Thr or Val162 alleles. These results are in keeping with the hypothesis which indicates that presence of the Thr54 allele may increase the binding affinity of FABP2 to long-chain fatty acids (LCFAs) [24]. Furthermore, enhanced intestinal absorption of fatty acids, higher levels of plasma lipids and the consequent enhanced lipid oxidation rates would inhibit in vivo tissue sensitivity to insulin. It was later confirmed, in a healthy white population with normal glucose tolerance, that the Thr54 allele was associated with insulin resistance [25].

In fact, in subjects with Thr54 allele, EPA supplementation results in absorption of EPA by entrocytes, which leads to a higher plasma EPA concentration. Although EPA is the precursor of DHA, we did not observe any increase in plasma level of DHA which might be due to poor enzymatic conversion of EPA to DHA. Arterburn, et al., previously reported that n-3 fatty acids consumption increased their levels in plasma. They showed that supplementation of adults with 4 g/day pure EPA ethyl ester results in significant increase in EPA concentration in whole plasma and plasma or serum phospholipids, but no increase was seen in DHA concentration, which is consistent with retro conversion of DHA to EPA [26-28]. In the present study, the levels of some fatty acids in plasma were changed. After EPA supplementation, the level of EPA, n-3 fatty acids, MUFA, PUFA and some saturated fatty acids such as miristic, palmitic, oleic, and stearic increased in both The54 and Ala54 carriers, the increase was more pronounced in Thr54 groups. These results were approved the Thr54 hypothesis which states increased fatty acids uptake and transport by Thr54 carriers. King, et al., reported that with consuming two different fat diets the level of fatty acids composition would be different [29]. There are some evidence that the level of n-6 fatty acids will decrease after consumption of n-3 fatty acids [26,30-32]. In the current study, the level of some plasma n-6 fatty acids such as arachidonic acid (AA) decreased in both Ala54 and Thr54 carriers after EPA supplementation; although we could not observe any interaction between EPA consumption and genotype. A decrease in the level of plasma AA after n-3 consumption has been reported previously [32-34]. Hlavaty, et al., reported that supplementing diet with n-3 fatty acids decreases plasma level of some n-6 fatty acids [35]. Berstad, et al., reported that n-3 supplementation decreases plasma AA level [33]. Polymorphism in codon 54 had no significant effect on serum fatty acids composition in adults Finns [36]. In Pima, no significant difference between the long-chain fatty acids amount in adipose and muscle tissues was observed between Ala54 and Thr54 carriers [37]. One study showed that in obese children who were Thr54 carriers, EPA consumption decreased the amount of plasma AA level. In the current study, AA concentrations were lower in Thr54 than Ala54 carriers after EPA supplementation. A decrease in n-6:n-3 fatty acids ratio was observed in both FABP2 and PPARα genotypes after EPA supplementation too. Although the n-6:n-3 fatty acids ratio decreased in both FABP2 and PPARα genotypes, these effects were more pronounced in Thr54 and Val162 than in Ala54 and Leu162 carriers. On the other hand, the ratio of AA: EPA decreased in both Thr54 and Ala54 after EPA supplementation, but no significant differences were observed between the two carriers. For nucleus receptors n-3 fatty acids are stronger ligands than n-6 fatty acids. In Greenland and Japanese people this ratio decreased in both Thr54 and Ala54 carriers after EPA supplementation [38,39].

There is increasing scientific evidence that genetic factors, conferring either protection or risk, also contribute importantly to the incidence of these diseases. SNPs are of particular interest because they can influence disease in a complex but largely unknown manner by interacting with environmental and lifestyle factors.

We showed that EPA supplementation could change the blood fatty acids composition, and thus it could be beneficial for lowering some plasma fatty acids. Since we observed more pronounced changes in blood fatty acids in Thr and Val than in Ala and Leu carriers, we suggest EPA supplementation to be used based on people genotypes.

In conclusion, EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, for high-risk people diet and micronutrients recommendation should be individualized.

Competing interests

All authors declare that they have no conflict of interests.

Authors’ contributions

HP contributed to conception of the idea and study design, interpretation of data, performing all experiments and writing the manuscript. MA provided assistance in study design of the GC analysis. MRE helped with statistical analysis and interpretation of data. SH helped in editing the manuscript. SAM provided assistant in the design of the study. All authors have read and approved the final form of the manuscript.


The authors would like to thank all the subjects who participated in this study, the staff of the Danesh, EMRC laboratories, and Shariaty Hospital Heart Diseases Center, Tehran. The EPA caps were a kind gift from Minami Nutrition, Belgium.


  1. Kris-Etherton PM, Harris WS, Appel LJ: Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.

    Circulation 2002, 106(21):2747-2757. PubMed Abstract | Publisher Full Text OpenURL

  2. Arab L: Biomarkers of fat and fatty acid intake.

    J Nutr 2003, 133(Suppl 3):925S-932S. PubMed Abstract | Publisher Full Text OpenURL

  3. Kohlmeier L: Future of dietary exposure assessment.

    Am J Clin Nutr 1995, 61(3 Suppl):702S-709S. PubMed Abstract | Publisher Full Text OpenURL

  4. Rossner S, Walldius G, Bjorvell H: Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss.

    Int J Obes 1989, 13(5):603-612. PubMed Abstract OpenURL

  5. Phinney SD, Tang AB, Thurmond DC, Nakamura MT, Stern JS: Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by gamma-linolenic acid administration.

    Metabolism: clinical and experimental 1993, 42(9):1127-1140. Publisher Full Text OpenURL

  6. Scaglioni S, Verduci E, Salvioni M, Bruzzese MG, Radaelli G, Zetterstrom R, Riva E, Agostoni C: Plasma long-chain fatty acids and the degree of obesity in Italian children.

    Acta Paediatr 2006, 95(8):964-969. PubMed Abstract | Publisher Full Text OpenURL

  7. Agostoni C, Riva E, Bellu R, Vincenzo SS, Grazia BM, Giovannini M: Relationships between the fatty acid status and insulinemic indexes in obese children.

    Prostaglandins Leukot Essent Fatty Acids 1994, 51(5):317-321. PubMed Abstract | Publisher Full Text OpenURL

  8. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH: Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.

    Lipids 2000, 35(12):1305-1312. PubMed Abstract | Publisher Full Text OpenURL

  9. Heude B, Ducimetiere P, Berr C: Cognitive decline and fatty acid composition of erythrocyte membranes–The EVA Study.

    Am J Clin Nutr 2003, 77(4):803-808. PubMed Abstract | Publisher Full Text OpenURL

  10. Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ: Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case–control study.

    Br J Nutr 2003, 89(4):483-489. PubMed Abstract | Publisher Full Text OpenURL

  11. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Goldbourt U, Greenland P: Fish consumption and incidence of stroke: a meta-analysis of cohort studies.

    Stroke; a journal of cerebral circulation 2004, 35(7):1538-1542. PubMed Abstract | Publisher Full Text OpenURL

  12. Whelton SP, He J, Whelton PK, Muntner P: Meta-analysis of observational studies on fish intake and coronary heart disease.

    Am J Cardiol 2004, 93(9):1119-1123. PubMed Abstract | Publisher Full Text OpenURL

  13. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P: Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies.

    Circulation 2004, 109(22):2705-2711. PubMed Abstract | Publisher Full Text OpenURL

  14. Engler MM, Engler MB, Malloy M, Chiu E, Besio D, Paul S, Stuehlinger M, Morrow J, Ridker P, Rifai N, Mietus-Snyder M: Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

    Int J Clin Pharmacol Ther 2004, 42(12):672-679. PubMed Abstract OpenURL

  15. Engler MM, Engler MB, Malloy MJ, Paul SM, Kulkarni KR, Mietus-Snyder ML: Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study).

    Am J Cardiol 2005, 95(7):869-871. PubMed Abstract | Publisher Full Text OpenURL

  16. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico.

    Lancet 1999, 354(9177):447-455. PubMed Abstract | Publisher Full Text OpenURL

  17. Aro A: Fatty acid composition of serum lipids: is this marker of fat intake still relevant for identifying metabolic and cardiovascular disorders?

    Nutr Metab Cardiovasc Dis 2003, 13(5):253-255. PubMed Abstract | Publisher Full Text OpenURL

  18. Riccardi G, Giacco R, Rivellese AA: Dietary fat, insulin sensitivity and the metabolic syndrome.

    Clinical nutrition (Edinburgh, Scotland) 2004, 23(4):447-456. Publisher Full Text OpenURL

  19. Vessby B: Dietary fat and insulin action in humans.

    Br J Nutr 2000, 83(Suppl 1):S91-96. PubMed Abstract | Publisher Full Text OpenURL

  20. Pishva H, Mahboob SA, Mehdipour P, Eshraghian MR, Mohammadi-Asl J, Hosseini S, Karimi F: Fatty acid-binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects. Burbank, Los Angeles County, Calif: Nutrition; OpenURL

  21. Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues.

    J Biol Chem 1957, 226(1):497-509. PubMed Abstract | Publisher Full Text OpenURL

  22. Wang Y, Sunwoo H, Cherian G, Sim JS: Fatty acid determination in chicken egg yolk: a comparison of different methods.

    Poult Sci 2000, 79(8):1168-1171. PubMed Abstract | Publisher Full Text OpenURL

  23. Pishva H, Mahboob SA, Mehdipour P, Eshraghian MR, Mohammadi-Asl J, Saeed Hosseini M, Rahmany M: Association between the FABP2 Ala54Thr, PPARa Leu162/Val, and PPARa intron7 polymorphisms and blood lipids, ApoB and ApoCIII in hypertriglyceridemic subjects in Tehran.

    J Clin Lipidol 2009, 3(2009):2187-2194. OpenURL

  24. Baier LJ, Sacchettini JC, Knowler WC, Eads J, Paolisso G, Tataranni PA, Mochizuki H, Bennett PH, Bogardus C, Prochazka M: An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

    J Clin Invest 1995, 95(3):1281-1287. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  25. Kim CH, Yun SK, Byun DW, Yoo MH, Lee KU, Suh KI: Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men.

    Metabolism: clinical and experimental 2001, 50(4):473-476. Publisher Full Text OpenURL

  26. Grimsgaard S, Bonaa KH, Hansen JB, Nordoy A: Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids.

    Am J Clin Nutr 1997, 66(3):649-659. PubMed Abstract | Publisher Full Text OpenURL

  27. Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ: Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension.

    Am J Clin Nutr 2002, 76(5):1007-1015. PubMed Abstract | Publisher Full Text OpenURL

  28. Nestel P, Shige H, Pomeroy S, Cehun M, Abbey M, Raederstorff D: The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans.

    Am J Clin Nutr 2002, 76(2):326-330. PubMed Abstract | Publisher Full Text OpenURL

  29. King IB, Lemaitre RN, Kestin M: Effect of a low-fat diet on fatty acid composition in red cells, plasma phospholipids, and cholesterol esters: investigation of a biomarker of total fat intake.

    Am J Clin Nutr 2006, 83(2):227-236. PubMed Abstract | Publisher Full Text OpenURL

  30. Arterburn LM, Hall EB, Oken H: Distribution, interconversion, and dose response of n-3 fatty acids in humans.

    Am J Clin Nutr 2006, 83(6 Suppl):1467S-1476S. PubMed Abstract | Publisher Full Text OpenURL

  31. Haban P, Zidekova E, Klvanova J: Supplementation with long-chain n-3 fatty acids in non-insulin-dependent diabetes mellitus (NIDDM) patients leads to the lowering of oleic acid content in serum phospholipids.

    Eur J Nutr 2000, 39(5):201-206. PubMed Abstract | Publisher Full Text OpenURL

  32. Horrobin DF: Interactions between n-3 and n-6 essential fatty acids (EFAs) in the regulation of cardiovascular disorders and inflammation.

    Prostaglandins Leukot Essent Fatty Acids 1991, 44(2):127-131. PubMed Abstract | Publisher Full Text OpenURL

  33. Berstad P, Seljeflot I, Veierod MB, Hjerkinn EM, Arnesen H, Pedersen JI: Supplementation with fish oil affects the association between very long-chain n-3 polyunsaturated fatty acids in serum non-esterified fatty acids and soluble vascular cell adhesion molecule-1.

    Clin Sci (Lond) 2003, 105(1):13-20. Publisher Full Text OpenURL

  34. Holler C, Auinger M, Ulberth F, Irsigler K: Eicosanoid precursors: potential factors for atherogenesis in diabetic CAPD patients?

    Perit Dial Int 1996, 16(Suppl 1):S250-253. PubMed Abstract | Publisher Full Text OpenURL

  35. Hlavaty P, Kunesova M, Gojova M, Tvrzicka E, Vecka M, Roubal P, Hill M, Hlavata K, Kalouskova P, Hainer V, Zak A, Drbohlav J: Change in fatty acid composition of serum lipids in obese females after short-term weight-reducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in comparison to controls.

    Physiological research/Academia Scientiarum Bohemoslovaca 2008, 57(Suppl 1):S57-65. PubMed Abstract | Publisher Full Text OpenURL

  36. Vidgren HM, Sipilainen RH, Heikkinen S, Laakso M, Uusitupa MI: Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects.

    Eur J Clin Invest 1997, 27(5):405-408. PubMed Abstract | Publisher Full Text OpenURL

  37. Pratley RE, Baier L, Pan DA, Salbe AD, Storlien L, Ravussin E, Bogardus C: Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans.

    J Lipid Res 2000, 41(12):2002-2008. PubMed Abstract | Publisher Full Text OpenURL

  38. Hirai A, Hamazaki T, Terano T, Nishikawa T, Tamura Y, Kamugai A, Jajiki J: Eicosapentaenoic acid and platelet function in Japanese.

    Lancet 1980, 2(8204):1132-1133. PubMed Abstract OpenURL

  39. Hegele RA, Young TK, Connelly PW: Are Canadian Inuit at increased genetic risk for coronary heart disease?

    J Mol Med (Berlin, Germany) 1997, 75(5):364-370. Publisher Full Text OpenURL