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 princi pal antioxidant micronutrients are hitherto underrated risk factors fo r cardiovascular diseases. Complementary observational data consistent ly suggest optimal, i.e., potentially protective plasma levels of appr oximately >50 mu mol/L of vitamin C, >30 mu mol/L of lipid-standardize d 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 multiplicat ively. 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 c ardiovascular diseases was substantially reduced by daily intake of >1 30 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-carote ne, but only in smokers-in comparison with a suboptimal intake that ve ry probably permits only suboptimal plasma levels. Antioxidant deficit s can be avoided by ''prudent diets'' rich in fruits/vegetables, and n et 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 p rotective diets but other, presumably synergistic constituents await e valuation, e.g., carotenoids other than beta-carotene, phenols/bioflav onoids, minerals such as potassium and selenium, fibers, mono- and n-3 polyenic fatty acids, and oxygen-sensitive B vitamins such as folate.