10-YEAR RETROSPECTIVE ON THE ANTIOXIDANT HYPOTHESIS OF ARTERIOSCLEROSIS - THRESHOLD PLASMA-LEVELS OF ANTIOXIDANT MICRONUTRIENTS RELATED TO MINIMUM CARDIOVASCULAR RISK

The antioxidant hypothesis postulates that suboptimal levels of principal antioxidant micronutrients are hitherto underrated risk factors for cardiovascular diseases. Complementary observational data consistently suggest optimal, i.e., potentially protective plasma levels of approximately >50 mu mol/L of vitamin C, >30 mu mol/L of lipid-standardized vitamin E (alpha-tocopherol/cholesterol ratio >5.2 mu mol/mmol), and >0.4 mu mol/L beta (>0.5 mu mol/L total)-carotene. Relative risks are doubled at >25 to 50% lower values. Suboptimal levels of each factor increase the risk singly, or in combination risk increases multiplicatively. They can be stronger predictors of coronary heart disease than classical risk factors such as hypercholesterolemia and hypertension, at least in Northern Europe. In male Americans, the relative risk of cardiovascular diseases was substantially reduced by daily intake of >130 mg of vitamin C, >100 IU of vitamin E (100 mg of d,l- or 74 mg of d-alpha-acetyl-tocopherol) in all subjects, and by >9 mg of beta-carotene, but only in smokers-in comparison with a suboptimal intake that very probably permits only suboptimal plasma levels. Antioxidant deficits can be avoided by ''prudent diets'' rich in fruits/vegetables, and net vitamin E (high vitamin E/polyunsaturated fatty acids ratio) as is common in European communities where premature cardiovascular death is low. These essential antioxidants may be crucial components of such protective diets but other, presumably synergistic constituents await evaluation, e.g., carotenoids other than beta-carotene, phenols/bioflavonoids, minerals such as potassium and selenium, fibers, mono- and n-3 polyenic fatty acids, and oxygen-sensitive B vitamins such as folate.