Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications.

Hyperinduced oxidant stress may have a role in the pathogenesis of diabetes and its micro- and macrovascular complications. Attaining euglycemia and the use of antioxidant vitamins could reduce oxidant stress and complications. In general, evidence does not support the use of supplements, and supplements are not recommended unless patients are deficient. Use of vitamins in excess may have adverse effects. Vitamin supplements are indicated in patients deficient in vitamins due to inadequate dietary intake or intestinal disease. Treatment with proper amounts of vitamins and antioxidants is best accomplished with a balanced diet including 3 servings of vegetables and 2 servings of fruits. Regarding supplementation of specific vitamins: carotene cannot be recommended in view of the possible harm and lack of benefit in clinical studies. Vitamin A (retinol) and Vitamin D should be repleted if deficient by laboratory assay. Excesses should be avoided. Vitamin A supplements, particularly in pregnancy, should not exceed 10,000 IU daily or a supplement should not exceed 25,000 units weekly. Vitamin E (alpha-tocopherol) alone in doses of 400 units is of questionable value, and larger doses may cause intracranial hemorrhage or interact negatively with lipid-lowering drugs. Vitamin E should not be used in patients who have bleeding disorders or patients on anticoagulants or acetylsalicylic acid (ASA). Vitamin C (ascorbic acid) losses in urine may be excessive in diabetic patients and may require repletion to 200 mg in nonsmokers and 250 mg in smokers. Further studies are needed testing: (1) vitamin supplementation in subgroups of patients at high risk for specific complications using tissue-specific indicators of oxidative stress; (2) the role of oxidative stress in nephropathy, diabetic myocardiopathy, dermopathy, joint limitation syndromes, peripheral edema, metabolic bone disease, and pregnancy; (3) the impact of renal failure on oxidative stress; and (4) the effects of diabetes and dietary vitamins on the relative amounts of retinoids, carotenoids, and vitamin E in the chylomicron and lipoproteins, and how this affects assimilation, oxidation of lipids, and atherosclerotic plaque formation.