title: Ascorbic acid and atherosclerotic cardiovascular disease.
abstract: In this chapter, we have briefly reviewed the current scientific knowledge of the role of vitamin C in the prevention of atherosclerosis and its associated clinical manifestations. There is good evidence from animal studies that vitamin C can slow the progression of experimental atherosclerosis. Most of these studies, however, were done either in guinea pigs, using ascorbic acid depletion, or in cholesterol-fed rabbits, using ascorbic acid supplementation. Both animal models have limitations, as guinea pigs are not a well-established (nor well-studied) model of atherosclerosis, and rabbits develop atherosclerosis at high serum beta-VLDL cholesterol levels, and in addition can synthesize ascorbic acid. In contrast, humans develop atherosclerosis spontaneously and readily at moderately elevated serum LDL cholesterol levels and have lost the ability to synthesize ascorbic acid. Thus, the animal studies discussed, although quite promising and suggestive of an anti-atherogenic effect of ascorbic acid, need to be expanded to primates before more definitive conclusions can be drawn. Similar to the animal data, the current evidence from epidemiological studies on the role of vitamin C in the prevention of CVD is inconclusive, with some studies showing a very strong correlation between increased vitamin C intake and incidence of CVD events and other studies showing no correlation at all. Studies on CVD risk factors indicate that vitamin C may moderately decrease total serum cholesterol levels, increase HDL levels, and exert a hypotensive effect. These findings are particularly intriguing and should be pursued vigorously in basic research studies to elucidate biological mechanisms. In addition, it appears that large placebo-controlled, double-blind, randomized trials of vitamin C supplementation (without simultaneous supplementation with vitamin E) in populations with a wide range of vitamin C body levels are needed in order to confirm or refute a role for vitamin C in the prevention of CVD. Unfortunately, no such trials are currently being conducted. The possible mechanisms by which ascorbic acid may affect the development of atherosclerosis and the onset of acute coronary events include effects on arterial wall integrity related to biosynthesis of collagen and GAGs, altered cholesterol metabolism mediated by vitamin C-dependent conversion of cholesterol to bile acids, and effects on triglyceride levels via modulation of lipoprotein lipase activity. A particularly intriguing possible mechanism for the anti-atherogenic effect of vitamin C is prevention of atherogenic, oxidative modification of LDL. Numerous in vitro studies have demonstrated that ascorbic acid strongly inhibits LDL oxidation by a variety of mechanisms. The potential effects of ascorbic acid on platelet function and EDRF metabolism are particularly intriguing, as they might have widespread consequences for the prevention of atherosclerotic lesion development as well as acute clinical events. Thus, both metabolic and antioxidant functions may contribute to the possible reduction of CVD risk by vitamin C.
authors.affiliation: Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118-2394, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lynch
authors.forename: J M
authors.initials: JM
authors.lastname: Gaziano
authors.forename: B
authors.initials: B
authors.lastname: Frei
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004812:Epidemiologic Methods; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D011817:Rabbits; D012307:Risk Factors
chemical_list: D000975:Antioxidants; D016326:Extracellular Matrix Proteins; D008074:Lipoproteins; D002784:Cholesterol; D001205:Ascorbic Acid