PLASMA VITAMIN C FOR PREDICTING CARDIOVASCULAR DISEASE: MORE THAN A NUTRITIONAL BIOMARKER

Intervention trials with specifi c nutrients have been performed in an attempt to reduce cardiovascular disease (CVD). However, over-all results so far have not been very convincing (1). Nevertheless, the health benefi t (reduction in CVD) of fruit and vegetable consumption is generally assumed. Investigators have attributed benefi ts to specifi c nutrients measured in blood, such as vitamin C. Given these assumptions, it has been proposed that plasma vitamin C concentrations can predict risk of CVD events (2,3). This was recently confi rmed in the EPIC-Norfolk population study (4), wherein the top quartile of baseline plasma vitamin C was associated with 42% lower risk of stroke compared to the bottom quartile, independently of use of ascorbic acid-containing supplements, smoking, and stroke risk factors (4). Given the limited accuracy of the measurement of fruit and vegetable intake with food-frequency questionnaire, plasma vitamin C has been proposed as a candidate biomarker of fruit and vegetable consumption because these foods are the primary sources of dietary vitamin C (5). Humans cannot effi ciently synthesize the chemically instable ascorbic acid (the antioxidant vitamin C). On average, the human body loses ± 3% of its vitamin C content per day. Although plasma vitamin C status is generally regarded as a nutritional biomarker, correlation between vitamin C intake and vitamin C concentration is rather weak: only about 17% of the variance of plasma vitamin C concentration can be explained by vitamin C intake (6). Vitamin C status in humans is not only determined by dietary vitamin C content, but also by environmental and lifestyle factors (e.g., smoking), biological factors (e.g., infl ammation, iron excess), and pathological conditions (e.g., malabsorption, chronic haemolysis) (Table 1). Here we further wish to point towards potential confounding by infl ammation, iron status, and iron-related genetic polymorphisms as important determinants of plasma vitamin C (7).