Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake?

Hyperhomocysteinemia is considered as a risk factor for cardiovascular dise ases. Usually, an inverse relationship exists between homocysteine and fola te levels, and supplementation with folate lowers homocysteine concentratio ns in patients. Therefore, hyperhomocysteinemia is mainly ascribed to the i nsufficient dietary intake of folate. Hyperhomocysteinemia has also been ob served in infections and inflammatory diseases. Oxidative stress appears to be involved in the pathogenesis of these disorders, and associations have been found between homocysteine and e.g., neopterin concentration. Increase d neopterin concentration indicates immune system activation and also allow s an estimate of thus elicited oxidative stress. It may be relevant that th e active cofactor, tetrahydrofolate, is very susceptible to oxidation. Immu nologically induced oxidative stress could lead to folate depletion resulti ng in hyperhomocysteinemia. Thus, hyperhomocysteinemia in patients can be c onsidered as an indirect consequence of hyperconsumption of antioxidant vit amins during prolonged states of immune activation.