Homocysteine is a product of cellular methionine metabolism. Evidence suggests that high levels of plasma homocysteine are a risk factor for cardiovascular disease. Homocysteine may interfere with endothelial physiology through inhibition of nitric oxide synthesis, inducing endothelial dysfunction possibly via oxidative stress. In a healthy individual homocysteine levels remain controlled because a number reactions convert the homocysteine to other substances, limiting cellular accumulation. However, these reactions require a number of B vitamins as co-factors and low dietary intakes can reduces enzyme activity, causing cellular accumulation of homocysteine. Homocysteine can be metabolised to cystathionine by the enzyme cystathionine β-synthase which requires pyridoxine as a cofactor. Alternatively, homocysteine can be converted back to methionine via the enzyme methionine synthase, a reaction that requires vitamin B12 as a cofactor and a methyl group donated by the folic acid derived tetrahydrofolate.
Type 2 diabetics have a two to four-fold increased risk of cardiovascular disease which cannot be explained by traditional risk factors such as high lipid levels or hyperglycaemia. However, type 2 diabetes is associated with high plasma levels of homocysteine which might contribute to the risk of developing cardiovascular disease. Researchers have therefore investigated the effects of B vitamins on the homocysteine concentrations on type 2 diabetics. For example, one group of researchers1 assessed the effects of high intakes of folic acid on the homocysteine levels of type 2 diabetic subjects with elevated plasma concentrations of homocysteine. Subjects were administered either 5 mg per day folic acid or a placebo for eight weeks in a double-blind designed study. Supplementation with folic acid resulted in significant reductions in plasma homocysteine concentrations (15.1 to 12.1 µmol/L) and significant increases in plasma folic acid and vitamin B12 concentrations, when compared to the placebo.
Therefore, folic acid supplementation at pharmacological concentrations is effective at reducing plasma homocysteine concentrations in type 2 diabetics. Because homocysteine is associated with cardiovascular disease, these results suggest that folic acid is able to reduce the risk of cardiovascular disease in individuals with high homocysteine levels. In addition, the authors reported that plasma antioxidant status improved in the folic acid supplemented group, suggesting that reductions in homocysteine had reduced systemic oxidative stress, and therefore may have improved endothelial function. The improvement in the reducing capacity of the plasma was reflected in reductions in plasma malondialdehyde, a product of lipid peroxidation. These results therefore suggest that high homocysteine concentrations increase oxidative stress, and that reduction in plasma concentrations of homocysteine decrease oxidative stress. The benefits to cardiovascular disease likely derives from this improved reducing capacity of plasma.
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