Vitamin C Levels in Plasma May Predict Stroke Risk

Susan Jeffrey
January 17, 2008 — A new analysis from a prospective cohort study suggests that higher plasma levels of vitamin C are associated with a reduced risk for stroke. Researchers report that those in the highest quartile for plasma vitamin C had a 42% reduced risk for stroke compared with those in the lowest quartile.
The results, from the prospective European Prospective Investigation into Cancer (EPIC)–Norfolk study, are published in the January 1 issue of the American Journal of Clinical Nutrition.
Whether the causal link between plasma vitamin C and stroke can be identified, plasma vitamin C concentrations may nevertheless be a good predictive indicator of stroke risk, lead author Phyo Kyaw Myint, MRCP, from the clinical gerontology unit at Addenbrooke's University Hospital in Cambridge, United Kingdom, told Medscape Neurology and Neurosurgery.
"Vitamin C is a biomarker of fruit and vegetable consumption, which have many nutrients which may be biologically active and protective for stroke; high fruit and vegetable consumption has been reported in previous studies to be protective for stroke," he said. "Measuring plasma vitamin C levels may identify those who will most benefit from established risk factor management such as blood pressure control."
Trials Negative to Date
Because of its antioxidant activity, higher levels of ascorbic acid are thought to be associated with reduced cardiovascular disease risk, the authors write. However, randomized trials of supplementation with antioxidant vitamins including beta-carotene, vitamin E and vitamin C, including the Heart Outcomes Prevention Evaluation (HOPE) study and the Finnish Alpha-Tocopherol, Beta Carotene Cancer Prevention Study, have shown no effect in reducing cardiovascular risk.
Previous prospective studies have shown that high fruit and vegetable intakes, for which plasma vitamin C is a good biomarker, are associated with lower stroke risk. However, few studies have examined the relationship between plasma vitamin C concentrations and stroke risk, and those that have were limited in their ability to account for potential confounding factors, Dr. Myint and colleagues write. "We explored the relation between baseline plasma vitamin C concentrations and future stroke risk in British participants in the European Prospective Investigation into Cancer (EPIC)–Norfolk," study, a population-based prospective study.
The study included 20,649 men and women aged 40 to 79 years, who were free of prevalent stroke at baseline. Participants completed a health questionnaire and attended a clinic between 1993 and 1997, when baseline measurements of plasma vitamin C were taken. They were then followed up for incident strokes through March of 2005.
For 196,713 person-years of follow-up and average follow-up of 9.5 years, 448 incident strokes occurred.
In a Cox proportional hazards model, those in the highest quartile for plasma vitamin C concentrations had a 42% lower risk for stroke (P = .001) compared with those in the lowest quartile. The association was independent of confounding factors, including age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use.
The results were not substantially different after exclusion of those with illnesses, those taking supplements containing ascorbic acid, and those with a history of early stroke during the first 2 years of follow-up, they note.
Their study does have limitations, they note, including that the vitamin C levels were taken in a single measurement at baseline.
"We believe that these findings are of interest for several reasons," Dr. Myint and colleagues conclude. "First, the strong inverse association between plasma vitamin C and stroke suggests that plasma vitamin C is likely to be a good biomarker of whatever causal factors affect stroke risk, most plausibly the dietary intake of plant foods," although they add that identification of the relevant factors may lead to better stroke prevention.
"Second, irrespective of any causal associations, plasma vitamin C appears to be a good predictive risk indicator of stroke, independent of known risk factors such as age, BP [blood pressure], smoking, lipids, diabetes and BMI [body mass index]," they conclude. "Given that about half of the risk of stroke is unexplained by conventional cardiovascular disease risk factors, and that the predictive validity of traditional cardiovascular disease risk factors appears to diminish with age, risk markers that may help identify those persons at greatest risk of stroke for targeted preventive interventions with established therapies, such as BP (blood pressure) reduction, may be of interest."
The Message? Eat Your Fruit and Veg
In an editorial accompanying the article, Sebastian J. Padayatty, MRCP, PhD, and Mark Levine, MD, from the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, call the study by Myint and colleagues, "refreshing in that its findings are both clear and not overstated."
"On the basis of the evidence presented, the investigators did not advocate an increased intake of vitamin C to prevent stroke," they note. "Such strict interpretation of the data avoids a confusing correlation with causation and allows improved hypothesis generation, but is not sufficient grounds to advocate unfounded and possibly useless treatments."
What can be said to patients and the public at this point is that high intakes of fruits and vegetables are associated with many health benefits, including a reduction in stroke, they conclude. "Because we do not know why or how the benefit occurs or what fruit and vegetables are effective, it is prudent to consume a wide variety. The optimum intake for reduction of stroke and cardiovascular disease is unknown, but an intake of 5 - 9 servings daily is associated with benefit, and the public should aim toward the higher intakes."
The EPIC-Norfolk study is supported by research program grant funding from Cancer Research UK and the Medical Research Council, with additional support from the Stroke Association, British Heart Foundation, Research Into Ageing, Academy of Medical Sciences, and Wellcome Trust. The authors and editorialists have disclosed no relevant financial relationships.
Am J Clin Nutr. 2008;87:5-7, 64-69.