Folic Acid Fortification Ameliorates Hyperhomocysteinemia Caused by a Vitamin B₆-Deficient Diet Supplemented withL-Methionine

Abstract

Vitamin B 6 (B 6 ) deficiency affects homocysteine metabolism, and this leads to hyperhomocysteinemia. In this study, we examined i) the effects of B 6 -deficiency and graduated levels of dietary methionine on homocysteine metabolism, and ii) the effects of fortified folate on homocysteine metabolism. In experiment 1, Wistar male rats were fed a control or a B 6 -deficient diet supplemented with L-methionine at a level of 3, 6, or 9 g/kg of diet for 5 weeks. The resulting plasma homocysteine levels in the B 6 -deficient groups increased in relation to the increase in dietary methionine level. Next, in experiment 2, rats were fed a control, B 6 -deficient, or folate enriched (10 mg pteroylmonoglutamic acid/kg) B 6 -deficient diet containing L-methionine at 9 g/kg for 5 weeks. Although the B 6 -deficient diet induced hyperhomocysteinemia, folate fortification ameliorated the plasma homocysteine concentration. Overall, our results indicate that folate fortification ameliorates the hyperhomocysteinemia induced by B 6 deficiency and supplemental methionine intake.

Folic Acid Supplementation During Early Pregnancy and the Risk of Gestational Hypertension and Preeclampsia

“…Folic acid supplementation can effectively reduce homocysteine. [15][16][17][18] Thus, theoretically, if elevated homocysteine is a cause of gestational hypertension or preeclampsia, folic acid supplementation during early pregnancy may significantly reduce the risk of these outcomes or may change the distribution of the early-onset cases. However, our large cohort study results did not find a protective effect of folic acid supplementation on gestational hypertension or preeclampsia, and, thus, supports the hypothesis that elevated blood homocysteine during pregnancy may be a consequence or a concomitance rather than a cause of gestational hypertension.…”

“…13,14 Hyperhomocysteinemia usually can be corrected by supplementation with folic acid. [15][16][17][18] Thus, a major concern has been raised about whether folic acid supplementation can prevent the occurrence of gestational hypertension or preeclampsia. Three studies from the United States and Canada demonstrated that folic acid-containing multivitamins may greatly reduce the risk of gestational hypertension or preeclampsia.…”

Involvement of 5-Methyltetrahydrofolate in the Amelioration of Hyperhomocysteinemia Caused by Vitamin B₆ Deficiency and <small>L</small>-Methionine Supplementation

“…4) However, the role of folate fortification in this amelioration remained unknown. Folate is involved in the re-methylation pathway, in which 5-MTHF is required as a methyl donor.…”

“…Male Wistar rats, 4 weeks old and weighing 80-100 g, were obtained from Japan SLC (Hamamatsu, Japan). The rats were fed the following experimental diets: an AIN-76 diet-based control diet (C), 4) a B 6 -deficient diet (D), 4) and two kinds of B 6 -deficient folate-enriched diets (5 mg and 20 mg of pteroylmonoglutamic acid/kg of diet) containing either 2.5-or 10-fold the amount of folate compared to the control diet, respectively designated as F2.5 and F10. All the diets contained L-methionine at a dose of 9 g/kg of diet.…”

“…The liver was then immediately excised and the plasma was obtained by centrifugation. 4) L-Cystathionine, 5-MTHF disodium salt, THF and S-adenosylmethionine (SAM) iodide were purchased from Sigma-Aldrich (St. Louis, MO, USA). 4-Fluoro-7-sulfobenzofurazan ammonium salt (SBD-F), hydroxocobalamin acetate and dithiothreitol were purchased from Wako Pure Chemical Industries (Osaka, Japan), and methanol (HPLC grade), acetonitrile (HPLC grade) and tri-n-butylphosphine were purchased from Kanto Chemical (Tokyo, Japan).…”