Design for a study to determine optimal dosage of ascorbic acid and alpha-tocopherol in humans.

Some clinical trials of vitamins C and E have neglected important design features. Our objective was to demonstrate a detailed design that includes essential elements for an effective study of these vitamins in vivo. While taking 400 IU (international units) of vitamin E, subjects took different dosages of vitamin C during three distinct periods. Dosages were 200 mg in food, 500 mg as supplements twice a day (500 × 2), and 1,000 mg as supplements twice a day (1000 × 2). Ten participants spent 3 weeks at each dosage before plasma was drawn on two consecutive days. Final samples were taken after a week with no supplementation. Selected by investigators at four institutions, endpoints were protein carbonyls, TBARs (thiobarbituric reactive substances), and Heinz body formation in RBCs (red blood cells). TBARs and protein carbonyls did not change significantly with dosage. However, Heinz body formation increased at either higher or lower intakes of vitamin C. Even with daily vitamin E, Heinz bodies were significantly fewer at 500 × 2. Results indicate that even with 400 IU vitamin E daily, it is possible to distinguish the effect of different levels of vitamin C with Heinz bodies. This effect may be due to pro-oxidant action of vitamin C or to prolonged survival of RBCs.