Vitamin Supplementation

Currently, several large-scale intervention trials are underway to determine if B vitamin supplements (folic acid, B12, B6), which effectively lower blood homocysteine levels, reduce the incidence of vascular disease (Table 3). If proven effective, such supplements would be an inexpensive and relatively

Table 3 Intervention trials to determine the effect of B vitamin supplements on homocysteine and the risk of vascular disease

Study

Location Start date

Cambridge Heart Antioxidant Study 2 UK 1998

Heart Outcomes Prevention Evaluation 2 Canada 1999 (HOPE-2)

Norwegian Multi-Center B-Vitamin Norway 1998

Intervention Study (NORVIT) Prevention with a Combined Inhibitor and Australia 2000 Folate in Coronary Heart Disease (PACIFIC)

Study of Effectiveness of Additional UK 1999

Reductions in Cholesterol and Homocysteine (SEARCH) Vitamins in Stroke Prevention (VISP) USA 1998

Vitamins to Prevent Stroke (VITATOPS) Australia 1999 Western Norway B-Vitamin Intervention Norway 1999 Trial (WENBIT)

Women's Antioxidant and Cardiovascular USA 1998 Disease Study (WACS)

innocuous means by which the risk of vascular disease may be reduced. However, it must be recognized that if these trials are successful, they will not serve as definitive proof that homocysteine is a vascular toxin. It may be the case that one or more of the B vitamins influences vascular disease risk through separate mechanisms. For example, several studies have shown that low B6 status has an association with vascular disease independent of homo-cysteine. The uncertain relationship between hyperhomocysteinemia, B vitamins, and vascular disease is summarized in Figure 2. If homocysteine is not a vascular toxin, it may still serve as a marker of both vascular disease and as an indicator of the efficacy of B vitamin supplementation.

Hyperhomocysteinemia

Vascular disease

B vitamin deficiencies

Genetic polymorphisms

Folate

Methylenetetrahydrofolate reductase

Vitamin B12

Cystathionine ^-synthase

Vitamin B6

Methionine synthase

Riboflavin

Methionine synthase reductase

Figure 2 Hyperhomocysteinemia, B vitamins, genetic polymorphisms, and vascular disease. There is still some question whether elevated plasma homocysteine is a cause or consequence of vascular disease and whether there are influences of B vitamins and related polymorphisms on vascular disease risk that are independent of homocysteine.

Figure 2 Hyperhomocysteinemia, B vitamins, genetic polymorphisms, and vascular disease. There is still some question whether elevated plasma homocysteine is a cause or consequence of vascular disease and whether there are influences of B vitamins and related polymorphisms on vascular disease risk that are independent of homocysteine.

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