New insights into the physiology and pharmacology of vitamin C.

US government work, not subject to copyright Pharmacokinetic data are now available for the absorption, plasma concentrations and renal excretion of vitamin C. With these new insights, it is worth reconsidering the clinical role of vitamin C in scurvy and subclinical deficiency, the amount of vitamin C required for good health and, in particular, the speculative use of high doses of vitamin C to treat cancer. Scurvy, the dread of sailors past, conjures up images of perilous sea voyages and rough tattooed men laid low by ignorance of a vital amine, later designated vitamin C (which, as it happens, is not an amine). While scurvy devastated seafarers, it was endemic in the landbound, occurring widely wherever fruit and vegetables were in short supply. Military campaigns from the Crusades to the Napoleonic Wars, the American Civil War, and even World War I were stymied by widespread and often fatal scurvy among the troops. The antiscorbutic principle, identified and named ascorbic acid (vitamin C) in 1932, is a simple watersoluble sugar-like molecule. Early experiments, though perhaps flawed, showed that the consumption of as little as 10 mg of vitamin C a day would prevent signs of clinical scurvy. Although minute amounts will forestall death, the optimum requirements for good health are not known. Vitamin C is concentrated in many tissues, but these tissue stores are easily depleted. James Lind’s Treatise on Scurvy, first published in 1753, reported the onset of the disease in sailors after a month and a half at sea and described lassitude as its early and invariable symptom. Depletion– repletion studies in volunteers using a diet free of vitamin C have shown that plasma vitamin C falls below 10 μmol/L in less than a month. At these concentrations, fatigue is invariably present, and physical signs appear soon after. A person who has been consuming 100 mg of vitamin C daily will not develop scurvy for a month, even if the intake of vitamin C is stopped altogether. Recently, on the advice of the Food and Nutrition Board of the US National Academy of Sciences, US and Canadian recommended dietary allowances were increased from 60 mg per day to 75 mg per day for women and 90 mg per day for men. Vitamin C intake is less than 60 mg in 20%–30% of US adults. It is even lower among many population subgroups, including children. Subclinical vitamin C deficiency is much more common than is generally recognized, especially because the first symptom of deficiency is fatigue, a nonspecific and common complaint. As an electron donor, vitamin C acts as a cofactor for 8 enzymes involved in collagen hydroxylation, biosynthesis of carnitine and norepinephrine, tyrosine metabolism and amidation of peptide hormones. Vitamin C also has many nonenzymatic actions. It is a powerful water-soluble antioxiNew insights into the physiology and pharmacology of vitamin C