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Garlic & Cancer
Laboratory Studies
Laboratory experiments have found that garlic has significant anti-carcinogenic properties. In vitro studies have found that garlic and various components of garlic protect against cancers of the colon [1-3] and prostate, [4] whilst animal experiments have found significant anti-carcinogenic effects of garlic and its components in cancers of the stomach, [5-6] lungs, [5, 7] liver [5, 8] skin, [9, 10] bladder, [11] breast, [12-16] cervix [17] and peritoneum. [18]
Chemoprotective Mechanisms
There are several mechanisms thought to be responsible for garlic's chemo-protective effects including its ability to protect against DNA and chromosomal damage, its potent antioxidant activity as well as the ability to detoxify or deactivate carcinogens (cancer-causing substances) by acting on certain enzymes involved with their metabolism. In laboratory experiments, various components of garlic have been shown to protect against peroxy radicals and hydroxyl radicals as well as improving levels of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathioneS-transferase (GST), and catalase. [19] Substances capable of increasing the activity of GST are particularly protective against carcinogens as it is an enzyme capable detoxifying cancer-causing chemicals. [20-22] Animal studies have shown that consumption of a phytochemical found in garlic called allyl methyl trisulfide (AMT), increases GST activity and results in a 70% reduction in the number of stomach tumours. [23]
Another possible mechanism involves a phytochemical in garlic called diallyl sulphide (DAS), which can inhibit an enzyme involved in the activation of various carcinogens and other toxic chemicals known as cytochrome P450 2E1. [24] Additionally, garlic extracts have been shown to prevent chromosomal damage. [25] Moreover, DAS specifically has been shown to assist in the repair of DNA. [26, 27]
Epidemiology
The results from epidemiological studies have found that consumption of garlic is strongly associated with a decrease in the risk of various cancers. One cohort study in the Netherlands found that garlic had no significant protection against lung, [28] colon [29] stomach [30] or breast cancer [31], however case-control studies from around the world have found that higher intakes of garlic decrease the risk of cancers of the breast [32,33], prostate [34] esophagus, [35,36] larynx [37] and nasal passage [38]
Perhaps garlic's most significantly protective effect is against colorectal cancer and stomach cancer [39-43] Higher garlic intakes have been found to decrease the risk of colon cancer in case-control studies [44-47] as well as cohort studies, including the Iowa women's study [48] which found a 32% reduced risk among over 35,000 women, and the U.S. Male health professionals study [49] which found a 37% reduced risk among 50,000 men.
In 2000, Dr Lenore Arab, Professor of Nutrition and Epidemiology at the University of North Carolina and colleagues published a meta-analysis of 22 epidemiological studies which have looked at the relationship between garlic consumption and the incidence of cancer. The average higher intake was approximately equivalent to about 5 cloves per week. The pooled results found that higher intakes of garlic were associated with a 35% reduction in the risk of all cancers, a 30% reduction in the risk of colorectal cancers and a 45% reduction in the risk of stomach cancer. [50]
Garlic and Cardiovascular Disease (CVD)
Garlic possesses a range of cardio-protective actions including the ability to improve serum cholesterol and triglyceride levels, lower blood pressure and thin the blood by inhibiting platelet aggregation and improving fibrinolytic activity .
Atherosclerosis
Perhaps the most significant evidence for garlic's cardio-protective ability comes from a series of animal experiments which all showed that long-term feeding of garlic (~2% of diet) could significantly inhibit the formation of atherosclerosis [51-56] (atherosclerosis is the hardening and narrowing of the arteries which leads to coronary heart disease and ischemic stroke). For example, in a study with rabbits, both garlic and onion oil not only inhibited the rise in serum cholesterol levels and fibrinolytic activity caused by high cholesterol feeding, it reduced atherosclerotic development by approximately 50%. [57] It is thought that the component responsible for this anti- atherogenic affect is an important phytochemical found in garlic called allicin , as atherosclerosis was significantly inhibited in cholesterol-fed rats when given allicin [58]
Cholesterol
Animal experiments have demonstrated that garlic consumption can significantly reduce serum total cholesterol , LDL cholesterol and triglycerides; [59-72] all known indicators predicting heart disease risk. In 2000, Professor Edzard Ernst and his colleagues at the University of Exeter published a meta-analysis of 13 randomized, placebo-controlled crossover trials which examined the effect of garlic supplementation on serum cholesterol levels involving 796 hypercholesterolaemic people. Overall, garlic supplementation reduced total cholesterol levels by an average of 2 0.41 mmol/L ( 2 15.7mg/dL ), which was a reduction of approximately 5%. [73] The results of similar meta-analyses have found a greater improvement (9% & 12%), [74,75] however included studies with poorer methodologies. These improvements are considered statistically significant however they are less effective than the effect of statin cholesterol-lowering drugs (approx 17-32%). [76,77]
It is thought that the mechanisms by which garlic decreases cholesterol levels is by interfering with it's synthesis in the liver. Results from animal experiments have shown that garlic consumption reduces the activities of cholesterol producing enzymes in the liver such as malic enzyme, fatty acid synthase, glucose-6 phosphate dehydrogenase and HMG-CoA reductase [78-80]
Although elevated LDL cholesterol levels increase the risk of heart disease, their damage appears to occur when they become oxidized. [81] Aged garlic extract has been shown to reduce the oxidation of LDL cholesterol in vitro, [82] an effect which has also been demonstrated in a few small human trials. [83,84]
Hypertension
Another reported benefit of garlic is its relaxing effect on the blood vessels, [85] an action which was discovered over a century ago, when it was noticed that feeding garlic to soldiers in high altitudes appeared to counter the constricting effect that low oxygen levels had on the blood vessels of lungs ( hypoxic pulmonary vasoconstriction ), [86] an effect which has been replicated in animals given garlic as well. [87] It was thought that this effect may be explained by garlic's ability to activate the enzyme which is involved in the production of endothelial nitric oxide ; (a substance which relaxes blood vessels) when it was noticed that the vascular relaxation in the lungs of rats exposed to hypoxic conditions was dependant on nitric-oxide. [88] In another study, garlic administration stopped the action of a drug used to inhibit endothelial nitric oxidase in rats [89] thus preventing the hypertension (high blood pressure)that the drug would have otherwise caused.
Further studies suggest that the allicin present in garlic is responsible for this effect. [90] In fact, allicin alone has been shown to lower blood pressure when fed to hypertensive rats. [91,92] Additional investigations have found numerous mechanisms to explain why garlic may have a hypotensive effect, including a reduction in the synthesis of various substances involved in blood vessel constriction known as prostanoids , [93] a reduction in the activity of angiotensin converting enzyme (ACE), [94] a reduction in the renin-angiotensin system (RAS) [95] and the ability to affect the transport of certain electrolytes across cell membranes in the muscles of blood vessels. [96]
Regardless of the mechanisms involved, garlic has been shown to decrease or prevent hypertension and normalize blood pressure in rodents [97-103] and dogs [104,105] as well as prolonging the lifespan of animals with hypertension. [106]
In humans studies, preliminary findings suggest that people who eat the most garlic are likely to have lower blood pressure levels; [107] suggesting that regular garlic consumption may help in maintaining healthy blood pressure. A pilot study in 1993 at the New Orleans Clinical Research Centre found that a popular garlic preparation containing 1.3% allicin at a large dose (2400 mg) significantly decreased blood pressure in hypertensive patients without any side effects. [108]
A meta-analysis of 8 randomized controlled trials (involving 415 subjects) which examined the effect of garlic supplementation on blood pressure found that three trials showed a significant reduction in systolic blood pressure and four in diastolic blood pressure. [109] The authors concluded that:
The results suggest that this garlic powder preparation may be of some clinical use in subjects with mild hypertension.
Since then, a further 3 trials have demonstrated the hypotensive action of garlic using garlic tablets, [110] aged garlic extract, [111] and dietary consumption of garlic. [112]
Fibrinolytic Activity
Another risk factor for coronary heart disease is low fibrinolytic activity [113-115] that is, the action of certain enzymes which are capable of dissolving fibrin ; an insoluble protein formed during blood coagulation /clotting. Low fibrinolytic activity may result in abnormal clotting which can cause ischemia (blockages of blood vessels which occur in heart disease and ischemic stroke ). Garlic has been shown to significantly improve fibrinolytic activity in animal studies [116-119] and in human subjects; garlic oil increased fibrinolytic activity by between 36% to 130% in both heart disease patients [120,121] and healthy subjects. [122] Moreover, both raw and fried garlic have been shown to significantly enhanced fibrinolytic activity [123] whilst dried garlic powder has shown mixed results. [124-126]
Platelet Aggregation
Another way in which garlic inhibits abnormal blood clotting is by reducing the activation of platelets , an effect presumably due to a compound in garlic called ajoene (a product formed by the decomposition of allicin) which has an anti- thrombotic effect (blood thinning) comparable to that of aspirin. [127] Platelets are small fragments in the blood which aggregate / clump together to form a blood clot. When clots superimpose over an atherosclerotic plaque , the blood vessel can narrow or become blocked. Platelet activation is also a significant factor in the process of atherosclerotic development. [128]
Both in vitro experiments and animal studies have shown that garlic is capable of preventing acute platelet thrombus formation in coronary arteries , [129] reducing platelet aggregation in many different species of animals, [130-132] as well as acting on factors which promote platelet aggregation, such as inhibiting thromboxane-B2 (TXB2) synthesis [133] , inhibiting biosynthesis of prostacyclin [134] as well as inhibiting cyclooxygenase activity and collagen-induced platelet aggregation [135,136] Both single doses [137-139] and long-term intake [140-146] of various forms of garlic (including raw garlic, garlic oil and garlic extracts) have demonstrated the ability to inhibit platelet aggregation in human studies as well.
There are various mechanisms thought to be responsible for garlic's anti-platelet effect, including the ability to lower platelet calcium concentrations, [147] inhibiting the synthesis of thromboxane A2 and 12-HETE (chemicals involved in platelet aggregation) by interfering with the cyclooxygenase and lipoxygenase pathways in arachidonic acid metabolism [148,149]
Garlic Phytochemicals
As well as those mentioned thus far such as AMT, DAS and allicin, there are many other potentially beneficial phytochemicals present in garlic, most notably organosulphur compounds . For example, S-allyl cysteine (SAC), founding aged garlic and diallyl-di-sulfide (DADS), present in garlic oil have been shown to be able to inhibit cholesterol synthesis in the liver. [150,151] Ethyl acetate from crushed raw garlic increases fibrinolytic activity whilst decreasing LDL cholesterol and triglyceride levels. [152] Adenosine and polysulfides have been identified has having anti-platelet activity. [153] Ajoene (a product of allicin decomposition ) inhibits the activity of phorbol myristate acetate (PMA) a chemical used to promote tumours. [154] Other organosulphides found in garlic which may contribute towards its favourable health effects include diallyl disulphide, dimethyl-, methyl alIyI sulphides, dimethyl-, dipropyl- allyl propyl- and methyl allyl disulphides, dimethyl-, diallyl- and methylallyl trisulfides, methyl propyl trisulphide, diallyl thi-sulphinate, and sulphur dioxide. [155,156]
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