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

  • R. Chouinard-Watkins (a1) (a2), C. Rioux-Perreault (a1), M. Fortier (a1), J. Tremblay-Mercier (a1), Y. Zhang (a3), P. Lawrence (a3), M. C. Vohl (a4), P. Perron (a5), D. Lorrain (a1) (a6), J. T. Brenna (a3), S. C. Cunnane (a1) (a2) (a4) (a5) and M. Plourde (a1) (a4) (a5)...

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 β-oxidation of [13C]DHA was higher than that in E4 −  1–28 d post-dose (P≤ 0·05). A genotype × time interaction was detected for cumulative β-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.

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*Corresponding author: Dr M. Plourde, fax +1 819 829 7141, email
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