Elsevier

The Lancet

Volume 357, Issue 9257, 3 March 2001, Pages 657-663
The Lancet

Articles
Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study

https://doi.org/10.1016/S0140-6736(00)04128-3Get rights and content

Summary

Background

Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer.

Methods

We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45–79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality.

Findings

Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0·0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 μmol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0·0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women.

Interpretation

Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Introduction

The role of antioxidants in chronic diseases such as cardiovascular disease and cancer is controversial. Evidence from prospective studies suggests that a high dietary intake of antioxidants is protective for cardiovascular disease and cancer, although findings have not been consistent and trial data have not been conclusive.1, 2, 3, 4, 5, 6, 7 Ascorbic acid (vitamin C) plays a part in many biological processes, including free radical scavenging, collagen and hormone synthesis, haemostasis, and protection of lipid membranes which might affect chronic disease risk.8, 9, 10, 11, 12, 13 Investigators in some prospective studies have shown a significant inverse relation between ascorbic acid and cancer or cardiovascular disease, but the protective concentration and the potential size of the relation have varied between these studies. Results of some studies show only increased risk of mortality or cardiovascular disease at very low concentrations,13 but no effect within the usual population range; conversely, those of others indicate only reduced risk in individuals with high concentrations or those who take supplements.12 Findings from trials on the effect of supplementation have shown no change in mortality, but these trials have been generally small and of short duration.14, 15 Most studies have been in men or with data for men and women pooled. Data for women alone are more inconsistent than data on men.13

We present data from a prospective population study examining the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer in men and women.

Section snippets

Participants

The individuals in this analysis were part of EPIC-Norfolk, a prospective population study of 30 466 men and women aged between 45 and 79 years, resident in Norfolk, UK, who completed a baseline questionnaire survey, and of whom 25 663 attended a clinic visit.16 They were recruited from age-sex registers of general practices in Norfolk as part of a nine-country collaborative study (EPIC, European Prospective Investigation into Cancer and Nutrition) designed to investigate dietary and other

Results

Table 1 shows characteristics of the participants according to sex-specific quintile of plasma ascorbic-acid concentration. Ascorbic acid was inversely related to cardiovascular risk factors, including systolic blood pressure and body mass index, and positively to HDL cholesterol. The proportion of individuals who smoked and had a history of diabetes fell as the quintile of ascorbic acid increased. By contrast, the proportion of those who took any supplements rose as the quintile increased.

Discussion

In this population of men and women aged between 45 and 79 years, increasing plasma ascorbic acid concentration was strongly and independently associated with reduction in risk of mortality from all causes, cardiovascular disease, and ischaemic heart disease, with a dose-response relation across the whole population distribution. Although plasma ascorbic acid was measured once only for each individual, the relation with mortality was strong. The assumption is that one value would indicate the

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