Key Findings
A potential intervention strategy to counteract brain glucose hypometabolism in older individuals and lower the risk of conditions such as dementia, is to provide an alternative brain fuel such as ketones. The ketones, acetoacetate (AcAc) and b-hydroxybutyrate (b-HB), are produced via fatty acid beta-oxidation. In animals, ALA has a greater ketogenic effect than other18-carbon fatty acids such as oleic acid or linoleic acid. Rats given a very high-fat diet enriched with ALA achieve higher plasma b-HB concentrations compared with rats given a very high-fat diet enriched with saturated fats. The objective of this study was to evaluate the effect of an ALA-rich supplement (ALA-RS) on fasting plasma ketones and the plasma postprandial ketone response (ketogenesis) during a metabolic study day in healthy young and older adults. The secondary aim was to compare the effect of the ALA-RS on plasma long-chain n-3 PUFA, plasma lipids and metabolites, and total body fat mass in young and older adults. The flaxseed oil supplement rich in ALA had a differential effect according to age, mildly stimulating postprandial ketogenesis in young adults but favoring higher plasma ALA and EPA in older adults. The attenuated ketogenic effect of ALA in older adults may be in part due to their higher postprandial insulin response, which would inhibit ketogenesis, or to lower plasma lipoprotein lipase activity in older people. The modification of the ketogenic response in older adults seems specific to altered metabolism of long-chain fatty acids, because the ketogenic response to a medium-chain TG-rich supplement does not differ between young and older adults.
Abstract
Objectives: The aim of the present study was to compare the effects of an a-linolenic acid-rich supplement (ALA-RS) on the ketogenic response and plasma long-chain u-3 polyunsaturated fatty acid in healthy young adults and older individuals. Methods: Ten young and 10 older adults consumed a flaxseed oil supplement providing 2 g/d of ALA for 4 wk. Plasma ketones, nonesterified fatty acids (NEFA), triacylglycerols, glucose, and insulin were measured over 6 h, before and after supplementation. Total body fat mass was assessed before and after the ALA-RS. Results: The ALA-RS did not significantly modify fasting ketones but postprandial production of beta-hydroxybutyrate was increased by 26% only in the young adult group. Fasting plasma ketones were positively correlated to fasting plasma NEFA in both groups. However, the relation was shifted to the right in the older group, suggesting that older adults needed higher plasma NEFA levels to achieve the same ketone amounts as young adults. At baseline, the older group had 47% higher total plasma fatty acids than the young group. After the ALA-RS, plasma ALA doubled in both groups, an effect that was associated in the older group with a 40% higher eicosapentaenoic acid, but no difference in docosahexaenoic acid. The post supplementation increase in plasma ALA correlated positively with percent total body fat, especially in the older group. Conclusion: In young adults, ALA-RS mildly stimulated postprandial ketogenesis, whereas in the older group, it favored increased plasma ALA and EPA.
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