Vitamin C in Cardiovascular Disease

Vitamin C deficiency is associated with an increased risk of atherosclerosis, but there is little evidence of protective effects at intakes greater than needed to meet requirements (Jacob, 1998). A systematic review (Ness et al., 1996) found limited evidence of benefits of high intakes of vitamin C in reducing the incidence of stroke, but inconsistent evidence with respect to coronary heart disease. 

Scorbutic guinea pigs develop hypercholesterolemia, which may lead to the development of cholesterol-rich gallstones. This is largely the result of impaired activity of cholesterol 7-hydroxylase, which is an ascorbate-dependent enzyme (Section 13.3.8), resulting in reduced oxidation of cholesterol to bUe acids. There is no evidence that increased intakes of vitamin C above requirements result in increased cholesterol catabolism. 

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Tfcble 8 Some of the most important clinical/epidemiological studies using vitamin C in cardiovascular disease... 

I 56 Lee D, Folson AR, Harnak L, et al, Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes Am J Clin Nutr 2004 80 1 I 94-1200. 

Photo 42 Linus Pauling with Mrs. Dorothy B. Munro (center) and Dr. Matthias Rath (right) at a celebration of Pauling s 90th birthday, on February 28, 1991, in San Francisco. Dorothy Munro was for twenty years his devoted secretary. Matthias Rath co-authored several papers on the beneficial effects of vitamin C on cardiovascular disease, of which SP 143 is representative. 

Oxidative stress is an imbalance in ROS levels. It has been implicated in some forms of cancer, in cardiovascular disease, and in Alzheimer s and Parkinson s diseases. One way that living systems respond to oxidative stress is by lowering ROS concentrations by scavenging free radicals with the aid of antioxidants, such as vitamins E and C. 

Interestingly, excess histamine concentrations have been noted in heart disease and cancers, and the amine has been implicated in the progression of these diseases. Enstrom et al. (1992) demonstrated an inverse relationship between vitamin C supplementation and mortality in a cohort of over 11,000 people from the NHANES I database. The SMR (number of observed deaths divided by number of expected deaths) was 0.82 (0.60-1.09, 95% Cl) and 0.66 (0.53-0.82, 95% Cl) for all cancers and all cardiovascular diseases, respectively. The antioxidant potential of ascorbic acid is often cited as playing a role in the protective effects of supplemental vitamin C. In addition to its antioxidant properties, the antihistamine property of supplemental vitamin C may prove efficacious and warrants further study. 

BLUM, S., VARDI, M., BROWN, J. B., RUSSELL, A., MILMAN, U., SHAPIRA, C., LEVY, N. S., MILLER-LOTAN, R., ASLEH, R. LEVY, A. P. 2010. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics, 11, 675-84. 

Vitamin E can also act as an antioxidant (qv) in animals and humans alone or in combination with vitamin C (qv). Both are good free-radical scavengers with the vitamin C acting to preserve the levels of vitamin E (35). Vitamin E in turn can preserve the levels of vitamin A in animals (13). It has been shown that vitamin E reduces the incidence of cardiovascular disease (36—39). This most likely results from the antioxidant property of the vitamin which inhibits the oxidation of low density Hpoproteins (LDLs) (40—42). The formation of the oxidized LDLs is considered important in decreasing the incidence of cardiovascular disease (43). 

The role of the antioxidant properties of vitamins C, E, and p-carotene in the prevention of cardiovascular disease has been the focus of several recent studies. Antioxidants reduce the oxidation of low-density lipoproteins, which may play a role in the prevention of atherosclerosis. However, an inverse relationship between the intake or plasma levels of these vitamins and the incidence of coronary heart disease has been found in only a few epidemiological studies. One study showed that antioxidants lowered the level of high-density lipoprotein 2 and interfered with the effects of lipid-altering therapies given at the same time. While many groups recommend a varied diet rich in fruits and vegetables for the prevention of coronary artery disease, empirical data do not exist to recommend antioxidant supplementation for the prevention of coronary disease. 

Because the potential benefits outweigh the possibilities of harm, many experts recommend a daily multivitamin that does not exceed the RDA of it component vitamins. Multivitamins ensure an adequate intake for those vitamins—folic acid, vitamin B6, vitamin B12, and vitamin D—that are most likely to be deficient. However, the the evidence is insufficient to recommend for or against the use of supplements of vitamins A, C, or E multivitamins with folic acid or antioxidant combinations for the pre vention of cancer or cardiovascular disease. Most experts recommend against the use of p-carotene supplements, either alone or in combina Don, for the prevention of cancer or cardiovascular disease. 

When present in excess methionine is toxic and must be removed. Transamination to the corresponding 2-oxoacid (Fig. 24-16, step c) occurs in both animals and plants. Oxidative decarboxylation of this oxoacid initiates a major catabolic pathway,305 which probably involves (3 oxidation of the resulting acyl-CoA. In bacteria another catabolic reaction of methionine is y-elimination of methanethiol and deamination to 2-oxobutyrate (reaction d, Fig. 24-16 Fig. 14-7).306 Conversion to homocysteine, via the transmethylation pathway, is also a major catabolic route which is especially important because of the toxicity of excess homocysteine. A hereditary deficiency of cystathionine (3-synthase is associated with greatly elevated homocysteine concentrations in blood and urine and often disastrous early cardiovascular disease.299,307 309b About 5-7% of the general population has an increased level of homocysteine and is also at increased risk of artery disease. An adequate intake of vitamin B6 and especially of folic acid, which is needed for recycling of homocysteine to methionine, is helpful. However, if methionine is in excess it must be removed via the previously discussed transsulfuration pathway (Fig. 24-16, steps h and z ).310 The products are cysteine and 2-oxobutyrate. The latter can be oxidatively decarboxylated to propionyl-CoA and further metabolized, or it can be converted into leucine (Fig. 24-17) and cysteine may be converted to glutathione.2993... 

ACE drinks, containing beta-carotene (vitamin A precursor) and vitamins C and E. These materials are antioxidants and there is evidence that eliminating free radicals in the body will protect against cancer and cardiovascular diseases, particularly in older people. Suggested levels to... 

In case LDL oxidation is considered as an important risk factor, the dosage of vitamin E may be important to determine a clinical effect. However, with respect to inhibition of protein kinase-C and the release of proinflammatory cytokines the intracellular transfer of RRRT (natural vitamin E) by the tocopherol-associated protein may be a crucial point. Consequently, natural vitamin E is considered more effective than the synthetic one. Since the activity on LDL oxidation was pointed out as important for the prevention of cardiovascular disease, most of the long-term trials with vitamin E were conducted at dosages >200 mg/day (about 200 lU/d). In a recent meta-analysis the association of plasma levels and mortality was studied in 1168 elderly European men and women (25). No association was found between the plasma concentration and all-cause or cause-specific mortality. 

Rotterdam 6 yr 5395 M-F High intakes of vitamin E and C are associated with a lower risk of Alzheimer disease activity is more evident in smokers high intakes of /3-carotene may protect against cardiovascular disease (201,202)... 

A rich source of iron and vitamins C and A, parsley also yields fatty acids and an essential or volatile oil. The essential oil of the leaves is considered superior to that from the seeds and is used in condiments and seasonings. Parsley seed oil is used in fragrances for perfumes, soaps and creams. Parsley has a very high content of vitamins (/i-carotene, thiamin, riboflavin and vitamins C and E) and is a rich source of calcium, iron and folate (Athar et al., 1999). A high proportion of the carotene is 9-cis-P-carotene, which is considered effective against cancer and cardiovascular disease (Ben-Amotz and Fishier, 1998). 

As discussed in Section 13.3.5, ascorbate enhances the intestinal absorption of inorganic iron, and therefore it is frequently prescribed together with iron supplements. It is also used when it is desired to acidify the urine (e.g., in conjunction with some antibiotics). Supplements of vitamin C (often of the order of grams per day) are widely consumed to protect against cancer, cardiovascular disease, and viral infections, although (as discussed below) the evidence of efficacy is poor. 

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