Handbook of Vitamin C Research

Vitamin C: Dietary Requirements, Dietary Sources, and Adverse Effects 133between higher vitamin C intake and lower blood pressure [106]. Furthermore, vitamin Calso appears to improve the endothelium-dependent vasomotor capacity of coronary arteriesin patients with hypertension and ischemic heart disease [107].Congestive Heart FailurePatients with congestive heart failure (CHF) demonstrate systemic vasoconstriction andreduced peripheral perfusion. Although an increased sympathetic tone and an activated reninangiotensinsystem have been proposed to be involved in the reduced vasodilator capacity inheart failure, clinical studies have documented that endothelial dysfunction of peripheralresistance arteries and an impaired flow-dependent, endothelium-mediated dilation of conduitarteries appear to be commonplace in patients with CHF [108]. An important functionalconsequence of endothelial dysfunction is the inability of a vessel to dilate in response toendothelium-derived NO after physiological stimuli [109, 110]. It has been hypothesized thatthis is caused by reduced synthesis of NO possibly due to a reduced NO-synthase geneexpression [111], although other mechanisms such as reduced availability of L-arginine orenhanced inactivation of NO by free radicals may be involved as well [112]. Vitamin C hasbeen shown to improve endothelial dysfunction in patients with CHF by increasing theavailability of nitric oxide [113]. This finding suggests that endothelial dysfunction inpatients with CHF may be due to accelerated degradation of nitric oxide by free radicals.Coronary Heart DiseaseUntil recently, the results of most prospective studies indicated that low or deficientintakes of vitamin C were associated with an increased risk of cardiovascular diseases andthat modest dietary intakes of about 100 mg/day were sufficient to reduce cardiovasculardisease risk among nonsmoking men and women [26]. Other studies, however, failed to findsignificant reductions in the risk of coronary heart disease (CHD) among vitamin Csupplement users in well-nourished populations [114, 115]. One of the notable exceptions tothe above-mentioned findings was reported in the First National Health and NutritionExamination Survey (NHANES I) Epidemiologic Follow-up Study. This study found that therisk of death from cardiovascular diseases was 42% lower in men and 25% lower in womenwho consumed more than 50 mg/day of dietary vitamin C and who regularly took vitamin Csupplements, corresponding to a total vitamin C intake of about 300 mg/day [116]. Anotherexception comes from a 16-year follow-up study of more than 85,000 women, in whichhigher vitamin C intakes were shown to be cardioprotective [117]. The study showed thatvitamin C intake of more than 359 mg/day from diet plus supplements or supplement useitself was associated with a 28% reduction in risk for CHD. In women who did not takevitamin C supplements, however, dietary vitamin C intake was not significantly associatedwith CHD risk. More recently, a pooled analysis of 9 prospective cohort studies, includingmore than 290,000 adults who were free of CHD at baseline and followed for an average of10 years, found that those who took more than 700 mg/day of supplemental vitamin C had a