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The interaction between omega-3 fatty acid intake and genotype is an active area of study, and a recent study published in Lipids in Health and Disease aimed to evaluate the effects of two specific genetic variants on fish oil supplementation. Eighty-six healthy adults received 2.2g EPA and 1.4g DHA per day for 4 weeks (in divided doses with meals). Lipid profiles were evaluated using dried blood spots before and after supplementation, and 2 specific polymorphisms in the FADS1 and ELOVL2 genes were genotyped, rs174537 and rs953413, respectively.
For context, the FADS1 gene encodes the enzyme delta-5 desaturase (D5D), and ELOVL2 encodes ELOVL fatty acid elongase-2, both of which are rate-limiting enzymes in the conversion of polyunsaturated fatty acids (PUFAs, such as plant-based alpha-linolenic acid) to longer-chain acids, including EPA, DHA, and arachidonic acid. Notably, EPA and DHA are the final products in a series of conversions; i.e., they are metabolically downstream of D5D, and only the conversion of EPA to DHA depends on the elongase enzyme.
As might be expected, in this recent study, a number of omega-3 fatty acids significantly increased after fish oil supplementation, especially EPA and DHA. There were also some significant decreases in omega-6 fatty acid levels, including dihomo-γ-linolenic acid, arachidonic acid, and docosatetraenoic acid. The omega-3 index also significantly increased after only 4 weeks of supplementation, from 3.14 to 4.69. The omega-3 index, an important biomarker of cardiovascular disease risk, is defined as the percentage of EPA and DHA to total plasma fatty acids.
The FADS1 rs174537 polymorphism did not significantly influence EPA, DHA, or the omega-3 index when comparing baseline to post-supplementation (only eicosadienoic acid was significantly increased among carriers of the minor T allele). This was not surprising, given that FADS1 is only needed for the conversion of PUFAs to EPA and DHA, and not likely to influence their metabolism, absorption, etc.
However, among carriers of the A allele (e.g., the AA or GA genotype) of the ELOVL2 rs953413 polymorphism, there was a significantly higher post-supplementation omega-3 fatty acid percentage when compared to people with the GG genotype. For example, among carriers of the A allele vs. GG, EPA was 1.28% vs. 0.67%, DHA was 2.82% vs. 2.33%, and the omega-3 index was 5.06% vs. 3.83%.
The authors concluded that carriers of the minor (A) allele of the ELOVL2 rs953413 polymorphism may benefit more from fish oil supplementation, at least in terms of increasing EPA and DHA levels. This also means that people with the GG genotype may require higher doses of fish oil supplementation to achieve the same benefits. While the short-term nature of this most recent study limits its conclusions, it highlights the importance of having reliable biomarkers, such as the omega-3 index, to determine the efficacy of any omega-3 supplementation. It’s worth mentioning that EPA/DHA supplementation may be even more important among people with both a low intake and genetic polymorphisms related to fatty acid metabolism. For example, previous research has shown that EPA/DHA supplementation is especially important among people with the FADS1 rs174537 polymorphism, as a means to bypass the rate-limiting step in their synthesis.
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