Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele

Br J Nutr. 2013 Nov;110(10):1751-9. doi: 10.1017/S0007114513001268. Epub 2013 Apr 30.


Carrying the apoE ε4 allele (E4+ ) is the most important genetic risk for Alzheimer’s disease. Unlike non-carriers (E4- ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+ v. E4-. A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4-. In E4+, mean plasma [13C]DHA was 31% lower than that in E4-, and cumulative b-oxidation of [13C]DHA was higher than that in E4- 1–28 d post-dose (P ≤0·05). A genotype x time interaction was detected for cumulative b-oxidation of [13C]DHA (P ≤ 0·01). The whole-body half-life of [13C]DHA was 77% lower in E4+ compared with E4- (P ≤0·01). In E4+ and E4-, the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117% steeper in E4+ compared with E4- (P ≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study.

Publication types

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

MeSH terms

  • Aged
  • Alleles*
  • Alzheimer Disease / genetics*
  • Animals
  • Apolipoprotein E4 / genetics*
  • Carbon Dioxide / metabolism
  • Carbon Isotopes
  • Cognition
  • Cognition Disorders / genetics*
  • Diet
  • Dietary Fats / blood
  • Dietary Fats / metabolism
  • Docosahexaenoic Acids / blood
  • Docosahexaenoic Acids / genetics*
  • Docosahexaenoic Acids / metabolism
  • Female
  • Fishes
  • Genotype*
  • Half-Life
  • Humans
  • Linear Models
  • Lipid Peroxidation / genetics*
  • Male
  • Oxidation-Reduction


  • Apolipoprotein E4
  • Carbon Isotopes
  • Dietary Fats
  • Carbon Dioxide
  • Docosahexaenoic Acids