Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats

Abstract

BackgroundFolate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats.MethodsIn a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4 weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4 weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4 weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins.ResultsPlasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (P = 0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (P = 0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (P > 0.05 vs. normal, P < 0.05 vs. enriched and high) and highest in rats consuming the B-vitamin-high diet (P < 0.05 vs. poor and normal, P > 0.05 vs. enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine.ConclusionThese data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.

Nutritional approaches in the risk reduction and management of Alzheimer's disease

“…Furthermore, data have shown uridine can stimulate phospholipid synthesis without diminishing acetylcholine synthesis or release in rat brain slices; and dietary supplementation with UMP increases acetylcholine level and release in striatum of aged rat [54,55]. Supplemental intakes of B vitamins (folate and vitamins B 12 and B 6 ) and dietary phospholipids may serve as cofactors to increase the availability of choline and DHA for neuronal membrane phospholipid synthesis [45,46,56]. Uridine or DHA, which promote phospholipids' synthesis, also have been shown to increase synaptic protein levels, enhance neurite outgrowth, and increase dendrite spine density, all indicative of synapse formation [52,[57][58][59][60].…”

“…In a recent systematic review, the pooled data from nine casecontrol studies showed that patients with AD have low serum levels of folate and vitamin B 12 , which are associated with increased homocysteine (Hcy) levels [43]. Increased Hcy and low B vitamin status are associated with reduced mobilization of DHA from liver to plasma and peripheral tissue [44,45], and with reduced choline synthesis and increased choline utilization [46][47][48].…”

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

“…Hypomethylation of IGF2 P3 is responsible for upregulated IGF2 transcription and has an active role in osteosarcoma and hepatoblastoma (12,27). Several clinical studies have shown a positive correlation between plasma DHA concentration and erythrocyte folate level or serum vitamin B 6 and B 12 , reported to be methylation modulators of imprinted genes (25,47,49). Interestingly, a choline-and methionine-deficient diet revealed a decrease of repressive dimethylation at histone H3 lysine 9 (H3K9) within H19 promoter as well as Igf2 P2 and P3 (6).…”

Does nutrition have a role in the prevention of Alzheimer's disease?

“…4 Certain B vitamins -specifically folate (vitamin B 9 ), B 6 and B 12 reduce blood homocysteine levels. 5 However, studies assessing the relationship between B vitamins and cognitive performance have produced mixed results. One study reported that taking high-dose B vitamin supplements (5mg folate, 25mg vitamin B 6 and 1mg vitamin B 12 daily) for 18 months did not slow the decline in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAScog) among patients with mild-to-moderate Alzheimer's disease.…”