How should we move forwards? The hypothesis behind intervention trials with vitamin E is that lipid peroxidation is a major contributor to atherosclerosis and cardiovascular disease (which I believe1), and that administration of vitamin E will decrease the extent of lipid peroxidation and be protective against cardiovascular disease. What was not shown in CHAOS, GISSI-Prevenzione, or any of the other major intervention trials is that the vitamin E did decrease lipid peroxidation in the patients. Some apparently healthy human beings show higher rates of lipid peroxidation than others (Prof Erik Änggård has called them “the rancids”). Are they at higher risk of cardiovascular disease and would they be the only ones to benefit from extra antioxidants? It seems to me that these questions ought to be tackled before starting more major trials. We do not administer antihypertensive drugs to patients in clinical trials without checking blood pressure, so why should we give antioxidants without checking that they have decreased oxidant status? After all, if vitamin E did not change lipidperoxidation rates significantly in the study population overall, then the hypothesis would predict “no effect”, exactly as seen in the GISSI-Prevenzione study.