Higher Increase in Plasma DHA in Females Compared to Males Following EPA Supplementation May Be Influenced by a Polymorphism in ELOVL2: An Exploratory Study

Lipids. 2021 Mar;56(2):211-228. doi: 10.1002/lipd.12291. Epub 2020 Nov 10.

Abstract

Young adult females have higher blood docosahexaenoic acid (DHA), 22:6n-3 levels than males, and this is believed to be due to higher DHA synthesis rates, although DHA may also accumulate due to a longer half-life or a combination of both. However, sex differences in blood fatty acid responses to eicosapentaenoic acid (EPA), 20:5n-3 or DHA supplementation have not been fully investigated. In this exploratory analysis, females and males (n = 14-15 per group) were supplemented with 3 g/day EPA, 3 g/day DHA, or olive oil control for 12 weeks. Plasma was analyzed for sex effects at baseline and changes following 12 weeks' supplementation for fatty acid levels and carbon-13 signature (δ13 C). Following EPA supplementation, the increase in plasma DHA in females (+23.8 ± 11.8, nmol/mL ± SEM) was higher than males (-13.8 ± 9.2, p < 0.01). The increase in plasma δ13 C-DHA of females (+2.79 ± 0.31, milliUrey (mUr ± SEM) compared with males (+1.88 ± 0.44) did not reach statistical significance (p = 0.10). The sex effect appears driven largely by increased plasma DHA in the AA genotype of females (+58.8 ± 11.5, nmol/mL ± SEM, n = 5) compared to GA + GG in females (+4.34 ± 13.5, n = 9) and AA in males (-29.1 ± 17.2, n = 6) for rs953413 in the ELOVL2 gene (p < 0.001). In conclusion, EPA supplementation increases plasma DHA levels in females compared to males, which may be dependent on the AA genotype for rs953413 in ELOVL2.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Elongation of very long-chain 2 (ELOVL2); Genetics; Nutrition; Sex.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dietary Supplements
  • Docosahexaenoic Acids / blood*
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / pharmacology
  • Fatty Acid Elongases / blood
  • Fatty Acid Elongases / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • ELOVL2 protein, human
  • Docosahexaenoic Acids
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid
  • Fatty Acid Elongases