Interaction between BMI and APOE genotype is associated with changes in the plasma long-chain-PUFA response to a fish-oil supplement in healthy participants

Am J Clin Nutr. 2015 Aug;102(2):505-13. doi: 10.3945/ajcn.114.103507. Epub 2015 Jun 17.


Background: Carriers of the apolipoprotein E ɛ4 (APOE4) allele are lower responders to a docosahexaenoic acid (DHA) supplement than are noncarriers. This effect could be exacerbated in overweight individuals because DHA metabolism changes according to body mass index (BMI; in kg/m²).

Objectives: We evaluated the plasma fatty acid (FA) response to a DHA-rich supplement in APOE4 carriers and noncarriers consuming a high-saturated fat diet (HSF diet) and, in addition, evaluated whether being overweight changed this response.

Design: This study was part of the SATgenɛ trial. Forty-one APOE4 carriers and 41 noncarriers were prospectively recruited and consumed an HSF diet for 8-wk followed by 8 wk of consumption of an HSF diet with the addition of DHA and eicosapentaenoic acid (EPA) (HSF + DHA diet; 3.45 g DHA/d and 0.5 g EPA/d). Fasting plasma samples were collected at the end of each intervention diet. Plasma total lipids (TLs) were separated into free FAs, neutral lipids (NLs), and phospholipids by using solid-phase extraction, and FA profiles in each lipid class were quantified by using gas chromatography.

Results: Because the plasma FA response to the HSF + DHA diet was correlated with BMI in APOE4 carriers but not in noncarriers, the following 2 groups were formed according to the BMI median: low BMI (<25.5) and high BMI (≥25.5). In response to the HSF + DHA diet, there were significant BMI × genotype interactions for changes in plasma concentrations of arachidonic acid and DHA in phospholipids and TLs and of EPA in NLs and TLs (P ≤ 0.05). APOE4 carriers were lower plasma responders to the DHA supplement than were noncarriers but only in the high-BMI group.

Conclusions: Our findings indicate that apolipoprotein E genotype and BMI may be important variables that determine the plasma long-chain PUFA response to dietary fat manipulation. APOE4 carriers with BMI ≥25.5 may need higher intakes of DHA for cardiovascular or other health benefits than do noncarriers.

Trial registration: NCT01384032.

Keywords: BMI; DHA; apolipoprotein E ɛ4; fatty acid metabolism; lipids.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein E4 / genetics*
  • Body Mass Index
  • Dietary Supplements*
  • Fatty Acids, Unsaturated / blood*
  • Fatty Acids, Unsaturated / metabolism
  • Female
  • Fish Oils / administration & dosage*
  • Fish Oils / metabolism
  • Genetic Association Studies
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Overweight / blood
  • Overweight / genetics
  • Overweight / metabolism*
  • Polymorphism, Genetic*
  • Retrospective Studies
  • United Kingdom


  • Apolipoprotein E4
  • Fatty Acids, Unsaturated
  • Fish Oils

Associated data