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) . 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 .
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 . 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 . Berstad, et al., reported that n-3 supplementation decreases plasma AA level . Polymorphism in codon 54 had no significant effect on serum fatty acids composition in adults Finns . In Pima, no significant difference between the long-chain fatty acids amount in adipose and muscle tissues was observed between Ala54 and Thr54 carriers . 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.