Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although a number of studies have reported raised total plasma homocysteine (tHcy) concentrations in free-living older people, there are no data on homocysteine response to a mixed nutrient supplement in older patients. A raised plasma homocysteine concentration in older patients is partly a reflection of their co-morbidity, including impaired renal function, and there is uncertainty about the extent to which dietary interventions can improve plasma tHcy. AIM: To determine the plasma tHcy response to dietary supplements during acute illness. METHODS: Two-hundred and thirty-six hospitalized, acutely ill older patients, who were part of a randomized double-blind placebo-controlled trial, were assigned to receive a daily oral nutritional supplement drink containing 1.3 mg of vitamin B2, 1.4 mg of vitamin B6, 1.5 µg of B12, 200 µg of folic acid, or a placebo, for 6 weeks. Outcome measures were plasma tHcy concentration at baseline, 6 weeks, and 6 months. RESULTS: The mean plasma tHcy concentration fell among patients given the supplements (mean difference 4.1 µmol/L [95 % C.I, 0.14 to 8.03), p = 0.043], but tHcy concentration increased between 6 weeks and 6 months, after patients stopped taking the supplements [mean difference -2.0 µmol/L (95 % C.I, -03.9 to -0.18), p = 0.033]. About 46 % of patients in the placebo group and 55 % of patients in the supplement group had hyperhomocysteinemia (>14 µmol/L) at baseline compared with 45 % and 29 % at the end of the treatment period. CONCLUSIONS: A mixed nutrient supplement containing physiological amounts of B vitamins significantly reduced plasma tHcy concentrations in older patients recovering from acute illness.

Antioxidant supplementation with or without B-group vitamins after acute ischemic stroke: a randomized controlled trial.

BACKGROUND: Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately after acute ischemic stroke and that endogenous antioxidant defenses are rapidly depleted, thus permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated total plasma homocysteine (tHcy). METHODS: To test whether supplementary antioxidants with or without B-group vitamins during this critical period enhance antioxidant capacity or mitigate oxidative damage, ninety-six acute ischemic stroke patients within 12 hours of symptom onset were randomly assigned to receive either daily oral 800 IU (727 mg) vitamin E and 500 mg vitamin C (n = 24), or B-group vitamins (5 mg folic acid, 5 mg vitamin B(2), 50 mg vitamin B(6), and 0.4 mg of vitamin B(12); n = 24), both vitamins together (n = 24), or no supplementation (n = 24) for 14 days. Treatment groups and controls were matched for stroke subtype and age. Blood was obtained before treatment, at day 7, and day 14 for measurements of plasma or blood vitamin status, plasma total antioxidant capacity (TAOC), malondialdehyde (MDA), tHcy and C-reactive protein (CRP). RESULTS: Supplementation with antioxidant vitamins and B-group vitamins separately or together significantly increased the plasma concentration of vitamin C, E, pyridoxal phosphate (B(6) status), red blood cell folate, and improved a measure of B(2) status (red cell glutathione reductase activation coefficient [EGRAC]), compared with the control group. Plasma TAOC increased significantly in the antioxidant treatment groups compared with the nonsignificant decline seen in the control group. tHcy concentrations decreased in subjects who received B-group vitamins and the control group compared with the rise seen in those who received antioxidants alone. There was a significant reduction in plasma MDA concentration in the 3 treatment groups, in contrast to the increase seen in the control group; however, the changes were most evident in antioxidant groups. CRP concentrations (a marker of tissue inflammation) were significantly lower in the 3 treatment groups compared with the control group. There were no additive or synergistic effects of antioxidants and B-group vitamins together on any outcome measure. CONCLUSIONS: Antioxidants supplementation with or without B-group vitamins enhances antioxidant capacity, mitigates oxidative damage, and may have an anti-inflammatory effect immediately postinfarct in stroke disease.

B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke.

Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately following acute stroke and that endogenous antioxidant defences are rapidly depleted, thus permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated plasma tHcy (total homocysteine). In the present study, we assessed whether supplementary B-group vitamins during this critical period will enhance antioxidant capacity and mitigate oxidative damage. Forty-eight patients with acute ischaemic stroke within 12 h of symptom onset were assigned to receive daily oral supplements of B-group vitamins comprising 5 mg of folate, 5 mg of vitamin B2, 50 mg of vitamin B6 and 0.4 mg of vitamin B12 (n=24) or no supplements (n=24) for 14 days. The treatment group and controls were matched for stroke subtype and age. Blood samples were obtained before intervention and also at 7 and 14 days post-recruitment for measurement of the following biomarkers: red cell folate (whole blood folate corrected with haematocrit), erythrocyte glutathione reductase activity coefficient (EGRAC; measure of vitamin B2 status), plasma pyridoxal phosphate (vitamin B6 status), plasma vitamin B12, plasma alpha-tocopherol, plasma ascorbic acid, plasma TAOC (total antioxidant capacity), plasma MDA (malondialdehyde), plasma tHcy and CRP (C-reactive protein). Supplementation for 14 days with B-group vitamins significantly increased the plasma concentrations of pyridoxal phosphate and red blood cell folate and improved a measure of B2 status compared with the control group (P<0.05). Plasma tHcy decreased in both groups albeit less in the control group, but differences in cumulative changes were not significant. There was, however, a decrease in plasma MDA concentration in the treatment group, in contrast with the increase seen in the control group and these differences were significant (P=0.05). CRP concentration, a marker of tissue inflammation, was significantly lower in the treatment group compared with controls (P<0.05). In conclusion, B-group vitamin supplementation immediately post-infarct may have antioxidant and anti-inflammatory effects in stroke disease independent of a homocysteine-lowering effect.