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.

Highlights

  • Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity

  • The present results show that concurrently varying the dietary intake of folate, vitamin B-12, and vitamin B-6, across the range from inadequate to supra-physiological supplementation, can dose-dependently modify plasma docosahexaenoic acid (DHA) concentration

  • The present results show that concurrent dietary folate, vitamin B-12, and vitamin B-6 deficiency can lower plasma DHA concentration, which is in line with three previous experiments investigating effects of deficiencies of single B-vitamins in rats

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Summary

Introduction

Vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. Several clinical studies in different populations have found a negative correlation between serum, plasma or erythrocyte content of docosahexaenoic acid (DHA) and markers of B-vitamin deficiency such as plasma levels of homocysteine and/or S-adenosylhomocysteine (SAH) [13] In line with these observations, dietary deficiency studies in rats have shown that deficiencies of folate, vitamin B-12, or vitamin B-6 may reduce peripheral DHA levels [4,5,6]. It has been suggested that the methylation of PE to PC by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like DHA from the liver to the plasma and other tissues [3,9,10]. A factor that influences hepatic PEMT activity could potentially affect the availability of PUFAs such as DHA in plasma [9] and even their transport to the brain [16]

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