Antioxidant Supplements and Cardiovascular Disease in Men

To the Editor: The conclusion of Dr Sesso and colleagues¹ that vitamin C does not affect cardiovascular outcome in male physicians is not surprising because of an experimental design that did not consider human vitamin C physiology and did not include vitamin C measurements. In humans, plasma and tissue vitamin C concentrations are tightly controlled. Plasma concentrations have a steep sigmoidal response in relation to dose, and a similar steep response occurs in tissue.^2- 5 At doses above approximately 100 mg daily, circulating immune cells are saturated, and at doses of 200 mg daily or greater, there are only marginal increases in plasma concentrations.^2- 5 Physicians in the control group, who likely consumed at least 3 servings of fruits or vegetables daily, would have ingested more than 100 mg of vitamin C per day. Even a single glass of orange juice would have provided 90 mg of vitamin C. Those who took an allowed multivitamin would have had further intake of 60 mg daily. Additional intake of 500 mg daily in the treatment group would not affect tissue concentrations at all and would increase plasma concentrations only marginally.