Before 2000, Recommended Dietary Allowances (RDAs) for vitamin C (ascorbic acid) had a simple premise: prevention of frank vitamin C deficiency (scurvy) with an additional margin of safety. For many iterations, the central criterion for all RDAs was ‘‘the amount of nutrient required to prevent the appearance of signs and symptoms caused by a lack of the nutrient’’(italics in original citation) on the basis of nutrient intakes from foods (1). This approach was faulted by chemist and 2-time Nobel Laureate Linus Pauling. Pauling contended that optimum concentrations of some nutrients could be larger than amounts provided by diet alone (2). Pauling’s hypothesis was based on bacterial kinetics data for normal and mutant bacterial enzymes and, by inference, extended to humans who could similarly have mutated enzyme properties that require extra substrate or cofactor. With the use of vitamin C as a model, it was independently proposed that kinetics principles could be applied in situ to derive optimal nutrient recommendations for healthy humans, without reliance on pharmacologic nutrient amounts (3). More recently, Ames (4) has expanded and amplified enzyme kinetics models for vitamins. At the core of all of these proposals are concentration-function relations. Graphically, the proposals have vitamin concentration on the x-axis and vitamin function on the y-axis (Figure 1A). On such a graph, prevention of scurvy, or any other vitamin deficiency for that matter, is simply one curve whose midpoint (ie, Km) occurs at a relatively low, or left-sided, vitamin concentration. Other vitamin concentration-function relations are postulated to exist in addition to, and to differ from, those for overt deficiency, and each would have a curve whose midpoint (ie, Km) would occur farther to the right, at higher vitamin concentrations. These principles about concentrationfunction relations are not simply abstractions, and they have been integrated into the principles underlying Dietary Reference Intakes. Dietary Reference Intakes expand RDAs with 3 other reference values and were published for vitamin C in 2000 (5). In this issue of the Journal, 2 articles address one component of concentration-function relations for vitamin C by focusing on the x-axis, namely vitamin C concentrations found in humans in relation to ingestion of foods and supplements. Schleicher et al (6) describe findings for vitamin C from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004 and compare the findings to NHANES III, which was conducted in 1988–1994. Since 1999, NHANES has become a continuous annual survey conducted by the National

Center for Health Statistics and the Centers for Disease Control and Prevention. The data reported in this issue are the first representative US data for vitamin C since NHANES III. These are valuable data because they represent a snapshot of vitamin C concentrations in the US population and allow assessment of vitamin C status. Assessment benchmarks are set at concentrations of vitamin C, 11.4 and. 11.4 lM. Subjects whose vitamin C concentrations were reported as 0.2 mg/dL, or 11.4 lM, had findings of frank scurvy as previously described (7). How are we doing nationally for vitamin C? The overall prevalence of deficiency decreased to’7%, and mean concentrations for all subjects were close to those expected from intake of the RDA. However, concentrations for women in nearly all age groups were higher than those for men, and smokers had substantially lower concentrations than those in nonsmokers. Mean serum vitamin C concentrations generally were lower as body mass index (BMI) increased, but they were not so low as …