Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study.
ABSTRACT The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population.
The objective was to examine the relation between baseline plasma vitamin C concentrations and risk of incident stroke in a British population.
A population-based prospective study was conducted in 20,649 men and women aged 40-79 y without prevalent stroke at baseline and participating in the European Prospective Investigation into Cancer-Norfolk prospective population study. The participants completed a health questionnaire and attended a clinic during 1993-1997 and were followed up for incident strokes through March 2005.
Over 196,713 total person-years (average follow-up: 9.5 y), 448 incident strokes occurred. In a Cox proportional hazards model, persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of 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. Similar results were obtained after exclusion of persons with illnesses, users of ascorbic acid-containing supplements, and persons with a history of early strokes during the initial 2 y of follow-up.
Plasma vitamin C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke.
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ABSTRACT: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid-outcome associations. A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (-0.13-SD change; 95% CI: -0.20-, -0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10(-6)) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.American Journal of Clinical Nutrition 01/2015; 101(1):202-9. · 6.50 Impact Factor
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ABSTRACT: Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice-independent of dietary vitC-are able to modulate their vitC homeostasis during high-fat (HF) feeding. Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates. HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P < 0.05). Hepatic de novo biosynthesis of vitC was upregulated (P < 0.05) as measured by GLO capacity, and liver vitC was reduced (P < 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT (P < 0.05). Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.European Journal of Nutrition 04/2014; · 3.84 Impact Factor
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ABSTRACT: Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.Nutrients 09/2014; 6(9):3818-3846. · 3.15 Impact Factor