Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial

Abstract

Mild hyperhomocysteinemia is accepted as a risk factor for premature cardiovascular disease. In a population with a high prevalence of cardiovascular disease, we screened a group of clinically healthy working men aged 30-49 y (n = 509) for plasma homocysteine and 5,10-methylene tetrahydrofolate reductase (MTHFR) genotype status. Those with mildly elevated homocysteine concentrations (> or = 8.34 micromol/L) were selected for intervention. In a randomized, factorial-design, controlled trial we assessed the effects of B-group vitamins and antioxidant vitamin supplementation on homocysteine concentrations. The 132 men were randomly assigned to one of four groups: supplementation with B-group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg cyanocobalamin), antioxidant vitamins alone (150 mg ascorbic acid, 67 mg RRR-alpha-tocopherol, and 9 mg beta-carotene), B-group vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-wk intervention. When homocysteine concentrations were analyzed by group, significant (P < 0.001) decreases (32.0% and 30.0%, respectively) were observed in both groups receiving B-group vitamins either with or without antioxidants. The effect of B-group vitamins alone over 8 wk was a reduction in homocysteine concentrations of 27.9% (95% CI: 22.0%, 33.3%; P < 0.001) whereas antioxidants alone produced a nonsignificant increase of 5.1% (95% CI: -2.8%, 13.6%; P = 0.21). There was no evidence of any interaction between the two groups of vitamins. The effect of B-group vitamin supplementation seemed to depend on MTHFR genotype. Supplementation with the B-group vitamins with or without antioxidants reduced homocysteine in the men with mildly elevated concentrations, and hence may be effective in reducing cardiovascular risk.

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

“…Supplementation for 8 weeks with B vitamins increased plasma folate, pyridoxal-5-phosphate and vitamin B 12 status significantly, which resulted in an expected, concomitant, lowering in plasma tHcy [13]. As expected, the antioxidant supplementation significantly improved the initially poor plasma vitamin C status and also significantly Eur J Nutr (2010) 49:483-492 485 increased vitamin E and b-carotene status [39].…”

“…Therefore, a possible lowering effect of tHcy with B vitamins may also lead to a reduction in ADMA concentrations. However, even though it has been shown that B vitamin supplementation leads to a significant decrease in tHcy concentrations [13], no effect has been reported on ADMA levels [44][45][46][47], with only one study showing an effect of B vitamin supplementation on lowering ADMA levels in human subjects [48]. This study was a relatively small-scale study (n = 42), uncontrolled, with no placebo group and suffers from the design weaknesses associated with this type of intervention.…”

“…This intervention study was originally designed to test the effect of B vitamins and antioxidant vitamins on tHcy concentrations in men with mildly elevated tHcy levels, and the results have previously been published [13]. Therefore, the analyses reported here represent analyses of secondary endpoints.…”

“…Therefore, as homocysteine (tHcy) is lowered through B vitamin supplementation [13], such treatment may also lead to a reduction in ADMA levels.…”

Connective tissue: Vascular and hematological (blood) support

“…An estimated 10-20% of all cardiovascular disease could be eliminated by simply lowering elevated Hcy levels, and studies show that simple key vitamins, such as folate and B12, are quite capable of doing so. These studies show a clear correlations between vitamin status and Hcy levels and that a combination of folate, B6, and B12 can lower Hcy by 50% (61)(62)(63)55,(64)(65)(66)(67)(68).…”