Disturbance in uniformly C-13-labelled DHA metabolism in elderly human subjects carrying the apoE epsilon 4 allele

作者:Chouinard Watkins R; Rioux Perreault C; Fortier M; Tremblay Mercier J; Zhang Y; Lawrence P; Vohl M C; Perron P; Lorrain D; Brenna J T; Cunnane S C; Plourde M*
来源:British Journal of Nutrition, 2013, 110(10): 1751-1759.
DOI:10.1017/S0007114513001268

摘要

Carrying the apoE epsilon 4 allele (E4+) is the most important genetic risk for Alzheimer%26apos;s disease. Unlike non-carriers (E4-), E4+ seem not to be protected against Alzheimer%26apos;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 [C-13]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 [C-13]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 [C-13]DHA was 31% lower than that in E4-, and cumulative beta-oxidation of [C-13]DHA was higher than that in E4- 1-28 d post-dose (P %26lt;= 0.05). A genotype x time interaction was detected for cumulative beta-oxidation of [C-13]DHA (P %26lt;= 0.01). The whole-body half-life of [C-13]DHA was 77% lower in E4+ compared with E4- (P %26lt;= 0.01). In E4+ and E4-, the percentage dose of [C-13]DHA recovered/h as (CO2)-C-13 correlated with [C-13]DHA concentration in plasma, but the slope of linear regression was 117% steeper in E4+ compared with E4- (P %26lt;= 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 C-13-labelled fatty acids other than DHA cannot be deduced from the present study.

  • 出版日期2013-11-28