Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease.

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Epidemiological studies show that a high intake of anti-oxidant-rich foods is inversely related to cancer risk. While animal and cell cultures confirm the anticancer effects of antioxidants, intervention trials to determine their ability to reduce cancer risk have been inconclusive, although selenium and vitamin E reduced the risk of some forms of cancer, including prostate and colon cancer, and carotenoids have been shown to help reduce breast cancer risk. Cancer treatment by radiation and anticancer drugs reduces inherent antioxidants and induces oxidative stress, which increases with disease progression. Vitamins E and C have been shown to ameliorate adverse side effects associated with free radical damage to normal cells in cancer therapy, such as mucositis and fibrosis, and to reduce the recurrence of breast cancer. While clinical studies on the effect of anti-oxidants in modulating cancer treatment are limited in number and size, experimental studies show that antioxidant vitamins and some phytochemicals selectively induce apoptosis in cancer cells but not in normal cells and prevent angiogenesis and metastatic spread, suggesting a potential role for antioxidants as adjuvants in cancer therapy.

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Risk factors for cardiovascular disease, including high cholesterol, high homocysteine, hypertension and inflammation, increase the risk of dementia, including its most common form, Alzheimer's disease (AD). High cholesterol is also associated with elevated beta-amyloid (Abeta), the hallmark of AD. Oxidative damage is a major factor in cardiovascular disease and dementia, diseases whose risk increases with age. Garlic, extracted and aged to form antioxidant-rich aged garlic extract (AGE or Kyolic), may help reduce the risk of these diseases. AGE scavenges oxidants, increases superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibits lipid peroxidation and inflammatory prostaglandins. AGE reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase and is additive with statins in its action. Inhibition of cholesterol, LDL oxidation, and platelet aggregation by AGE, inhibits arterial plaque formation; AGE decreases homocysteine, lowers blood pressure, and increases microcirculation, which is important in diabetes, where microvascular changes increase heart disease and dementia risks. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemia- or reperfusion-related neuronal death and improving learning and memory retention. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE in helping prevent cardiovascular and cerebrovascular diseases and lowering the risk of dementia and AD.