British Journal of Nutrition

Full Papers

Metabolism and Metabolic Studies

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

R. Chouinard-Watkinsa1a2, C. Rioux-Perreaulta1, M. Fortiera1, J. Tremblay-Merciera1, Y. Zhanga3, P. Lawrencea3, M. C. Vohla4, P. Perrona5, D. Lorraina1a6, J. T. Brennaa3, S. C. Cunnanea1a2a4a5 and M. Plourdea1a4a5 c1

a1 Research Center on Aging, Health and Social Services Centre, University Institute of Geriatrics of Sherbrooke, 1036 Belvédère Sud, Sherbrooke, QC, Canada J1H 4C4

a2 Department of Physiology, Université de Sherbrooke, Sherbrooke, QC, Canada

a3 Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA

a4 Institute of Nutraceuticals and Functional Foods and Department of Food Science and Nutrition, Université Laval, Québec, QC, Canada

a5 Department of Medecine, Université de Sherbrooke, Sherbrooke, QC, Canada

a6 Départment of Psychology, Université de Sherbrooke, Sherbrooke, QC, Canada

Abstract

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.

(Received September 28 2012)

(Revised March 19 2013)

(Accepted March 20 2013)

(Online publication April 30 2013)

Key Words:

  • DHA;
  • ApoE ε4;
  • Metabolism;
  • β-Oxidation

Correspondence

c1 Corresponding author: Dr M. Plourde, fax +1 819 829 7141, email melanie.plourde2@usherbrooke.ca

Footnotes

  Abbreviations: ALA, α-linolenic acid; APOE, apoE gene; E4+, apoE ε4 allele carriers; E4 − , apoE ε4 non-carriers

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