Plasma ascorbic acid and risk of heart disease and cancer

Abstract

Sir—Kay-Tee Khaw and colleagues (March 3, p 657) report an inverse association between plasma ascorbic acid concentrations and mortality in men and women. They suggest that increased ascorbic acid intake might lessen risk of coronary heart disease and cancers. However, we think that the investigators have overinterpreted their results, since although adjustment was made for several risk factors, the potential major confounding of the chronic low-grade inflammatory response was not taken into account. This omission is highly pertinent since evidence suggests that serum antioxidant concentrations (carotenoids, ascorbic acid) correlate strongly and inversely with markers of inflammation in illness and in apparently healthy individuals, and abundant data suggest that markers of low-grade inflammation predict vascular disease independently of traditional risk factors. Indeed, Khaw and Woodhouse have previously reported a significant inverse relation between markers of the acute-phase response (C-reactive protein and fibrinogen) and serum ascorbic acid concentrations in 96 men and women. Moreover, available evidence from studies in ill patients suggests that the observed low ascorbic acid concentrations do not alter with extra supplementation of this substance but rather by resolution of the inflammatory response. The above observations could also explain the largely disappointing results of supplementation trials. Thus, we urge Khaw and colleagues to reanalyse their data with correction for a marker of the inflammatory response such as C-reactive protein (with a sensitive assay) or fibrinogen. Only with such analyses can we start to dissect the relevance of diet compared with inflammation in determining ascorbic acid concentrations and, by extrapolation, risk of vascular disease and cancers.