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

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- 1­28 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.

Metabolic response to a ketogenic breakfast in the healthy elderly.

OBJECTIVE: To determine whether the metabolism of glucose or ketones differs in the healthy elderly compared to young or middle-aged adults during mild, short-term ketosis induced by a ketogenic breakfast. DESIGN AND PARTICIPANTS: Healthy subjects in three age groups (23 +/- 1, 50 +/- 1 and 76 +/- 2 y old) were given a ketogenic meal and plasma beta -hydroxybutyrate, glucose, insulin, triacylglycerols, total cholesterol, non-esterified fatty acids and breath acetone were measured over the subsequent 6 h. Each subject completed the protocol twice in order to determine the oxidation of a tracer dose of both carbon-13 (13C) glucose and 13C-beta-hydroxybutyrate. The tracers were given separately in random order. Apolipoprotein E genotype was also determined in all subjects. RESULTS: Plasma glucose decreased and beta-hydroxybutyrate, acetone and insulin increased similarly over 6 h in all three groups after the ketogenic meal. There was no significant change in cholesterol, triacylglycerols or non-esterified fatty acids over the 6 h. 13C-glucose and 13C-beta-hydroxybutyrate oxidation peaked at 2-3 h postdose for all age groups. Cumulative 13C-glucose oxidation over 24 h was significantly higher in the elderly but only versus the middle-aged group. There was no difference in cumulative 13C-beta-hydroxybutyrate oxidation between the three groups. Apolipoprotein E (epsilon 4) was associated with elevated fasting cholesterol but was unrelated to the other plasma metabolites. CONCLUSION: Elderly people in relatively good health have a similar capacity to produce ketones and to oxidize 13C-beta-hydroxybutyrate as middle-aged or young adults, but oxidize 13C-glucose a little more rapidly than healthy middle-aged adults.

Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Québec: higher fish intake or aging-related change in n-3 fatty acid metabolism?

The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated.