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ANTIOXIDANTS: Vitamins A, E and C
There are several proposed mechanisms by which increased intake and plasma concentrations of the antioxidants (A, E and C) may positively impact the development of diseases such as certain cancers, cardiovascular disease, retinal damage and dementia. They slow the mutation action of free radicals produced during oxidative reactions; formation of free radicals are a step in the formation of cancer cells, cause damage to cells in the eye, lead to heart disease. They affect the bacterial in the intestines and their ability to produce chemicals that promote mutation as well. They inhibit the oxidative modification of LDL-C, the first step in formation of placque in the coronary arteries and elsewhere. In the prostate antioxidants inhibit malignant changes in dividing cells. Vitamin E intake has been associated with enhanced glucose tolerance and insulin action in diabetes. Vitamins A, E and C also help support the immune system, platelet function, and in formation and repair of collagen and muscle. A recent study revealed that a significant portion of the US population has low serum levels of vitamin E, which may increase their risk for chronic diseases in which low dietary intake or blood concentration have been implicated.
The protective roles of A, C and E have been shown to be variably effective in the prevention of certain cancers. Vitamins A and E have been shown to decrease the incidence of prostate cancer, and stomach cancer in certain patients who smoke or have reflux disease. They have been shown to decrease the incidence of formation of new benign colon polyps. There have been variable reports in their efficacy in the prevention of breast, colon, cervical and lung cancer. A word of caution, however: B-carotene, one form of vitamin A frequently found in some multivitamins and other supplements, was shown in one study to increase the incidence of lung cancer in male smokers. Studies to further clarify potential benefits and complications are ongoing.
Supplementation with vitamins C and E may be of benefit in the prevention of pre-eclampsia in women at increased risk of the disease.
Vitamin A has been shown to decrease the risk of stroke. Vitamin E has been shown to be variably effective in the prevention and treatment of coronary artery disease. One study, however, showed a negative effect on mortality in people who had suffered a first myocardial infarction. Studies are ongoing. In type-2 diabetics high-dose vitamin E reduces levels of C-reacitve protein (CRP), a marker of inflammation and a predictor of cardiovascular disease. Increased vitamin E intake has also been associated with enhanced glucose tolerance and insulin action. In postmenopausal women there was an inverse association between natural vitamin E intake and stroke.
Vitamins A, E and C have been shown to provide protection to the retina from macular degeneration and possibly cataract formation. Five studies are ongoing to confirm results.
Studies suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in elderly men. Increased oxidation is an important feature of Alzheimer's disease (AD) and low concentrations of C and E have been observed in the cerebrospinal fluid (CSF) and plasma of AD patients. Supplementation with C and E raise levels in both, suggesting a possible mechanism of benefit.
Cosmetics vontaining vitamins A and C can provide some relief from the signs of skin aging while preventing further damage.
Several words of caution are in order. Excessive amounts of vitamin A are toxic and may be lethal (see Appendix C). In the Nurses' Health Study those who had the highest intake of vitamin A had higher rates of nontraumatic hip fracture than women with the lowest intake. Also, in patients with known coronary artery disease and low levels of HDL, the good news was that for patients taking antioxidants the restenosis rate was 1.8% vs 3.9% in the placebo group, but the restenosis rate was 0.7% for the niacin and statin group, while those on niacin and statin alone stenosis regressed by 0.7%. This was a small study with several limitations, but emphasizes the need to make decisions for choice of nutirional supplements within the context of overall health.
Ford ES, et al. Serum Alpha-ocopherol status in the United States Population: findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 1999 Aug 1;150(3):290-300.
Albanes D et al. Effects of alpha-tocopherol and b-carotene supplements on cancer incidence in the Alpha-tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995 Dec;62(6S):1427S-1430S.
Knecht P et al. Dietary flavenoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 1997;145:223-30.
Gey KF. Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 1998;7(1-2):113-74.
Faure H et al. Carotenoids: 2. Diseases and supplementation studies. Ann Biol Clin (Paris) 1999 May;57(3):273-82.
Prasaad KN et al. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr 1999 Feb;18(1):13-25.
Morrisey PA et al. Optimal nutrition: vitamin E. Proc Nutr Soc 1999 May;58(2):459-68.
Watkins ML et al. Multivitamin use and mortality in a large prospective study. Am J Epidemiol 2000 Jul 15;152(2):149-62.
Evans WJ. Vitamin E, vitamin C and exercise. Am J Clin Nutr 2000 Aug;72(2S):647S-52S.
Giovannucci E et al. Intake of carotenoids and retinal in relation of risk to prostate cancer. J Nat Cancer Inst 1995;87:1767-76.
Heinonen OP et al. Prostate cancer and supplementation with alpha-tocopherol and betcarotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998 Mar 18;90(6):440-6.
Hartman TJ et al. The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev 1998 Apr;7(4):335-40.
Christen WG et al. Design of Physicians' Health Study 11-a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in the prevention of cancer, cardiovascular disease, and eye disease, and a review of results of completed trials. Ann Epidemiol 2000 Feb;10(2):125-34.
Gunawardena K et al. Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. Prostate 2000 Sep;44(4):287-95.
Stone WL et al. Tocopherols and etiology of colon cancer. J Natl Cancer Inst 1997 Jul 16;89(14):1006-14.
Cascinu S et al. Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer. Cancer Invest 2000;18(5):411-6.
Ekstrom AM et al. Dietary antioxidant intake and the risk of carida cancer and noncardia cancer of the intestine and diffuse types: a population-based case-control study in Sweden. Int J Cancer 2000 Jul 1;87(1):133-40.
Terry P et al. Antioxidants and cancers of the esophagus and gastric cardia. Int J Cancer 2000 Sep 1;87(5):750-4.
Cancer of breast, cervix, and lung
Kimmick, GC et al. Vitamin E and breast cancer: a review. Nutr Cancer 1997;27(2):109-17.
Woodson K et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst 1999 Oct 20;91(20):1738-43.
Ahmed MI et al. Lipid peroxidation and antioxidant status in human cervical carcinoma. Dis markers 1999 Dec;15(4):283-91/
Stefani ED et al. Doetary antioxidants and lung cancer risk: a case-control study in Uruguay. Nutr Cancer 1999;34(1):100-10.
Chappell LC, et al. Effect of anti-oxidants on the occurance of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999;354:810-816.
Cardiovascular Disease and Stroke
Stephens, NG et al. Randomizes, controlled trial of Vitamin E in patients with coronary disease: Cambridge Heart Association Study (CHAOS). Lancet 1996;347:781-6.
Rapola JM et al. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997 Jun 14;349(9067):1715-20.
Hercberg S et al. The potential role of antioxidant vitamins in preventing cardiovascular diseases and cancers. Nutrition 1998 Jun;14(6):513-20.
Marchioli R. Antioxidant vitamins and prevention of cardiovascular disease: Laboratory, epidemiological and clinical trial data. Pharm Res 1999 Sep;40(3):227-38.
Hirvonen T et al. Intake of flaveniods, carotenoids, vitamins C and E, and risk of stroke in male smokers.
Jialal I, et al. High-dose vitamin E reduces serum levels of C-reactive protein in daibetes. Free Radic Biol Med 2000;8:790-792.
Yochum LA, et al. Intake of antioxidant vitamins and risk of death from stroke in postmenopausal women. Am J Clin Nutr 2000;72:476-483.
Evans WJ. Vitamin E, vitamin C and exercise. Am J Clin Nutr 2000;72:647s-52s.
Brown B, et al. Simvastatin and Niacin, antioxidant vitamins, or the combination for the prevention of coronary artery disease. NEJM 2001 Nov;345(22):1583-1591.
Macular degeneration and Cataracts
The Age-Related Eye Disease Study Research Group. A randomized, Placebo-Controlled, Clinical Trial of Hogh-Dose Supplementation with vitamins C and E, Beta-Carotene and Zinc for Age-Related Macular Degeneration and vision loss. Arch Ophthalmol. 2001;119:1417-1436.
Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Nutr 1995 Dec;62(^S):1448S-1461S.
Delcourt C et al. Associations of antioxidant enzymes with cataract and age-related macular degeneration. The POLA study. Ophthomology 1999 Feb;106(2):215-22.
Delcourt, C et al. Age-related macular degeneration and antioxidant status in the POLA study. Arch Ophthamology 1999 Oct;117(10):1384-90.
Evans JR. Antioxidant vitamin and mineral supplements for age-related macular degeneration. Cochrane Database Syst Rev 2000;(2):CD000254.
Masaki KH et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000 Mar 28;54(6):1265-72.
Kontush a, et al. Inlfuence of Vtiamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease. Free Radic Biol Med. 2001;31:345-354.
Bourdel-Marchasson I, et al. Antioxidant defenses and oxidative stress markes in erythrocytes and plasma from normally nourished elderly Alzheimer's patients. Age Ageing.2001;30:235-241.
Alschuler M, et al. Cosmeceuticals with vitamins A and C for aging skin. Altern Med Alert 2000;3:S1-S2.
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