Allium Organosulfur Compounds

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Allium organosulfur compounds may be phyotchemi-cals of importance to human health by acting as antioxidants, thus protecting against free radical-mediated damage to important cellular targets such as DNA and membranes implicated in cancer and neurodegenerative diseases and aging. Protection against oxidative damage to LDL and cellular membranes could also protect against cardiovascular disease. Aged garlic extract (AGE) inhibits lipid peroxidation and the oxidative modification of LDL, reduces ischemic/reperfusion injury, and enhances the activity of the cellular antioxidant enzymes superoxide dismutase, catalase, and glu-tathione peroxidase. AGE also inhibits the activation of the oxidant-induced transcription factor NF-kB. Investigation of the major organosulfur compounds in AGE identified highly bioavailable water-soluble organosulfur compounds with antioxidant activity, such as S-allylcysteine and S-allylmeracptocysteine.

Organosulfur compounds such as diallyl sulfide may also protect against cancer by modulation of carcinogen metabolism, and this may involve altered ratios of phase 1 and phase 2 drug-metabolizing enzymes. Various garlic preparations including aged garlic extract have been shown to inhibit the formation of nitrosamine-type carcinogens in the stomach, enhance the excretion of carcinogen metabolites, and inhibit the activation of polyarene carcinogens. Inhibitory effects of organosulfur compounds on the growth of cancer cells in vitro, including human breast cancer cells and melanoma cells, have been observed. Modulation of cancer cell surface antigens, associated with cancer cell invasiveness, has been observed, and in some cases cancer cell differentiation can be induced. AGE can reduce the appearance of mammary tumors in rats treated with the powerful carcinogen dimethyl benz(a)anthracene (DMBA), which is activated by oxidation by cytochromes P450 to form the DNA binding form of DMBA diol epoxide, resulting in DNA legions and cancer initiation. The antibacterial activity of these allium compounds may also prevent bacterial conversion of nitrate to nitrite in the stomach. This may reduce the amount of nitrite available for reacting with secondary amines to form the nitrosamines likely to be carcinogenic particularly in the stomach.

Allium organosulfur compounds appear to possess a range of potentially cardioprotective effects. In one study, 432 cardiac patients were divided into a control group (210) and a garlic-supplemented group (222), and garlic feeding was found to reduce mortality by 50% in the second year and by approximately 66% in the third year. Furthermore, the rate of reinfarction was reduced by 30 and 60% in the second and third year, respectively. It should be noted that only a small number of patients in both groups experienced the end event of death or myocardial infarction, and a much larger scale study is needed. AGE lowers cholesterol and triglycerides in laboratory animals and can reduce blood clotting tendencies. It has been suggested that garlic supplementation at a level of 10-15 g of cooked garlic daily could lower serum cholesterol by 5-8% in hypercholestro-lemic individuals. However, there may be more important cardioprotective effects of garlic. In animal studies, AGE suppressed the levels of plasma throm-boxane B2 and platelet factor levels, which are important factors in platelet aggregation and thrombosis. In rats, frequent low doses (50mg/kg) of aqueous extracts of garlic or onions (onion was less potent) produced significant antithromotic activity (lowering of thromboxane B2) without toxic side effects.

Aqueous extracts of raw garlic also inhibited cyclooxygenase activity in rabbit platelets, again contributing to an antithrombotic effect. In addition, AGE and S-allyl cysteine and S-allyl mercapto-cysteine have antiplatelet adhesion effects. Platelet adhesion to the endothelial surface is involved in atherosclerosis initiation. Furthermore, S-allyl mer-captocysteine inhibits the proliferation of rat aortal smooth muscle cells, another important atherosclerotic process. Indeed, this antiproliferative effect on smooth muscle cells may be indicative of a possible antiangiogenic ability in relation to prevention of tumor growth and metastasis.

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