Key Findings
The n–3 PUFA DHA (22:6n–3) is highly concentrated in the brain where it regulates numerous functions, including cell survival and neuroinflammation. The main precursor to DHA in Western diets is alpha-linolenic acid (ALA). A recent study performed in rodents found that DHA synthesis from ALA appears sufficient to supply the brain. This study aimed to assess the potential impact of decreased ALA intake by performing a dietary dose-response to determine how different amounts of dietary ALA affect the rates of synthesis-secretion of ALA and LA to their long-chain PUFA (LCPUFA) products in rats. DHA synthesis was lowest in rats fed a ALA-deficient (D) diet, and no significant difference was observed between rats fed an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet. This indicates that the higher serum DHA concentrations observed in rats fed the ALA-A and ALA-H diets were at least in part due to increased DHA synthesis from ALA. The findings suggest that the body adapts to low substrate availability for DHA synthesis by increasing the capacity to synthesize DHA, therefore maintaining a stable DHA synthesis rate across a wide range of ALA intake amounts. Also there appears to be a minimum threshold of ALA intake below which this compensation no longer occurs and DHA synthesis is significantly reduced. Lowering dietary ALA may negatively affect rates of DHA synthesis.
ABSTRACT
BACKGROUND: Docosahexaenoic acid (DHA) is an omega-3 (n-3) polyunsaturated fatty acid (PUFA) thought to be important for brain function. Although the main dietary source of DHA is fish, DHA can also be synthesized from α-linolenic acid(ALA), which is derived from plants. Enzymes involved in DHA synthesis are also active toward ω-6 (n-6) PUFAs to synthesize docosapentaenoic acid n-6 (DPAn-6). It is unclear whether DHA synthesis from ALA is sufficient to maintain brain DHA. OBJECTIVE: The objective of this study was to determine how different amounts of dietary ALA would affect whole-body DHA and DPAn-6 synthesis rates. METHODS: Male Long-Evans rats were fed an ALA-deficient diet (ALA-D), an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet for 8 wk from weaning. Dietary ALA concentrations were 0.07%, 3%, and 10% of the fatty acids, and ALA was the only dietary PUFA that differed between the diets. After 8 wk, steady-state stable isotope infusion of labeled ALA and linoleic acid (LA) was performed to determine the in vivo synthesis-secretion rates of DHA and DPAn-6. RESULTS: Rats fed the ALA-A diet had an ∼2-fold greater capacity to synthesize DHA than did rats fed the ALA-H and ALA-D diets, and a DHA synthesis rate that was similar to that of rats fed the ALA-H diet. However, rats fed the ALA-D diet had a 750% lower DHA synthesis rate than rats fed the ALA-A and ALA-H diets. Despite enrichment into arachidonic acid, we did not detect any labeled LA appearing as DPAn-6. CONCLUSIONS: Increasing dietary ALA from 3% to 10% of fatty acids did not increase DHA synthesis rates, because of a decreased capacity to synthesize DHA in rats fed the ALA-H diet. Tissue concentrations of DPAn-6 may be explained at least in part by longer plasma half-lives.
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