4.7.1 Functions of Sulfur-Containing Compounds in Garlic in Medicine, Nutrition, and Pest Control
22.214.171.124 Natural History and Association with Humanity15 27 28
Garlic, Allium sativum (Liliaceae or lily family) has an ancient association with humans. It is so ancient that garlic is not found in nature and its exact origins are unknown. The earliest documented occurrence of garlic's use by humans is the fine clay sculptures of garlic cloves found at El Mahasna, Egypt which have been dated to 3750 BC, almost 6000 years ago. Its use by humans certainly predates even this artifact. While the exact origin of garlic is unknown, the best determination for its origin is the Eurasian continent north of Afghanistan and northwest of Tibet. This is an area rich in Allium species, most of which are found growing in narrow gorges. A. longicuspis bears a close similarity to A. sativum and may be its progenitor.
Alliums are usually classed as members of the lily family (Liliaceae). The genus contains about 450 species including several cultivated species such as A. cepa (onion), A. porrum (leeks), A. schoenoprasum (chives), and at least one species cultivated as an ornamental, A. gigantium. A bulb of garlic is derived from leaf tissue, with each bulb divided into sections or "cloves". Roots develop below the bulb. Bulbs are the food storage organs for the plant and contain rich reserves of carbohydrates (including fructans, see Chapter 3) and proteins. As the food storage organs of the plant, the bulbs would be ideal targets for predation by numerous animal species. Alliums, garlic in particular, have evolved powerful antiherbivory compounds as an adaptation for protection against predation. It is these compounds which yield garlic's second great benefit to humans — effective medical drugs.
* This section of Chapter 4 on garlic has been prepared by James E. Hoyt, Department of Biology, University of Michigan.
As a valuable food and medical species, garlic has been introduced by humans to all temperate climates throughout the world, although it prefers hot, dry climates. It is unable to thrive in moist tropical and arctic habitats. As mentioned above, the known use of garlic by humanity extends back for 6000 years, and its use before that time can reasonably be inferred. In addition to ancient Egypt, we have visual images of garlic being dispensed in Sumeria. Written records are found in Egypt, with 22 garlic preparations cited as being used for the treatment of heart problems, headache, animal bites, worms, and tumors. People of Greece and Rome used garlic extensively. Pliny the Elder gives 61 remedies using garlic for rheumatism, hemorrhoids, ulcers, and loss of appetite. Rome gave garlic to its legions to boost endurance and to be used as a prophylactic against disease. In China the 5th century text, Ch'i-min-yao-shu (essential arts for people) lists garlic as a prominent medicinal. The Indian text, Charaka-Samhita, dates from the 1st century but is based on an older text. In it, garlic is offered as a diuretic, gastrointestinal tonic, for the treatment of eye ailments, as a heart stimulant, and as an antiheumatic. Ayurvedic, Unani, and Tibbi medical systems list garlic as a prophylactic and as a cure for colic, cholera, dyspepsia, typhoid, dysentery, arteriosclerosis, gastric and laryngeal tuberculosis, lupus, duodenal ulcers, lung gangrene, whooping cough, pulmonary phthisis, and bronchestasis. Garlic is constantly mentioned in western medicine. Hildegard von Bingen writes of its use, as does Culpepper. Louis Pasteur in 1858 provides the first modern scientific report of garlic's action as an antibacterial while tons of garlic were used in World Wars I and II as field dressings for wounds. Current literature searches on "garlic" yield almost 1000 papers since 1985 on all aspects of garlic agriculture and biological actions.
Garlic bulbs are a rich source of carbohydrates and proteins. Analysis of garlic indicates it contains 61 to 64% moisture, 31% carbohydrate, 5 to 6% protein, and only 0.2% fat. Significant levels of phosphorous (3.9 to 4.6 mgg-1), potassium (1.0 to 1.2 mgg-1) and calcium (0.5 to 0.9 mgg-1) are present.
Garlic produces a variety of sulfur-based compounds which are effective as insect repellents and insecticides, antiherbivory compounds and probable anti-fungal agents. All Allium species produce volatile chemicals which act as repellents to many insects. Planting alliums, especially garlic, with other agricultural or ornamental species will often protect those species against insect predation. Garlic has additional protection for those insects and animals not deterred by its volatile metabolites. Sequestered in vacuoles within the plant's cells is an odorless, sulfur-based compound, (+)S-allyl-l cysteine sulfoxide or alliin, (Figure 4.22). Alliin comprises approximately 0.24% of the fresh weight of the bulb, or about 3.7 mgg-1. In the cytosol, normally separate from alliin, is an enzyme, allinase. Allinase is found in all alliums and is capable of acting
on several different substrates. When the cells are disrupted, e.g., an animal eating the bulb, the cell's vacuoles are broken and alliin (substrate) mixes with allinase (enzyme). The result is a chemical change in which alliin is converted to sulfenic acid (Figure 4.23) and ammonia. Two molecules of sulfenic acid
FIGURE 4.23 Chemical structure of sulfenic acid from garlic, Allium sativum. (Chemical structure by James E. Hoyt.)
then combine to form one molecule of water and one of allyl-2-propenethio-sulfinate or allicin15 (Figure 4.24), a strong smelling and fiery tasting chemical that repels almost every animal except most humans. Usually one taste is sufficient to deter further predation and the plant survives. Allicin soon breaks down into diallyl disulfide (Figure 4.25) which is another strong smelling copound and has been shown to be a powerful insecticide. Further transformations occur with time resulting in a variety of sulfite compounds. Commercial insecticide/repellent preparations are now available to farmers and home users (Garlic Barrier AG, EPA #66352-2 from Allium Associates) and are certified for use against mites, nematodes, and mosquito larvae on a wide variety of crops. It is further used as a fungicide and as an antibiotic for poultry, cattle, and aquaculture shellfish.
FIGURE 4.25 Chemical structure of diallyl disulfide from garlic, Allium sativum. (Chemical structure by James E. Hoyt.)
126.96.36.199 Garlic as Medicine
188.8.131.52.1 Antibiotic Action (Bactericide, Fungicide, Parisiticide)
The significant antibiotic compound of garlic is allicin. It has been shown to be effective against a broad range of bacteria species at dilutions of 1:10.5 Bacteria shown to be susceptible include some of the most dangerous to human health, such as tuberculosis (Mybacterium tuberculosis), staph (Staphylococcus aureus and S. faecalis), and salmonella (Salmonella typhimurium). Antibiotics such as penicillin are generally stronger then allicin. However, drug resistance is an increasing danger to human health. For instance, there are now strains of tuberculosis which are fully or partially resistant to every class of antibiotic currently available. Allicin could prove to be a life-saving alternative therapy and a model for the development of drug families.
One underlying mechanism of action for garlic's antibiotic (and anticancer) action is the stimulation of the immune system, both systemically and locally. Lymphocytes and macrophages are attracted to the sites where garlic is injected.29 Therefore, injections near the sites of localized disease can mobilize the body's immune system to that site. Ingestion of garlic stimulates a general systemic increase in the immune system.
Fresh garlic extracts have been found to inhibit many fungal species and have been used to protect plants and stored foods as well as in medicine. Another pathogen that has been developing resistance to conventional antibiotics is Candida albicans. Garlic has been shown to be effective in suppressing candida infections. Indeed, it is as effective as conventional drugs such as amphotericin and nystatin, acting faster but without the difficulties in administration or the side effects those drugs produce. A similar result was found for ringworm.
Fresh garlic has been found to be effective against amebic dysentery, hookworm, and pinworm. Garlic has been a traditional remedy for tapeworm, lice, and other parasites.
184.108.40.206.2 Antitoxin (Heavy Metals and Biotic Toxins)
Garlic has been shown to be a strong antioxidant. It reduces damage to liver cells by inhibiting the formation of free radicals and preventing the oxidation of lipid peroxides. This can protect the liver from chemicals such as carbon tetrachloride. It has also been shown to prevent lysis of blood cells in vitro due to toxic levels of metals such as lead, aluminum, mercury, and copper.
Garlic can lower blood lipid levels. Evidence indicates three possible means by which this can occur. First, garlic reduces or inhibits lipogenesis (the formation of fats in the liver and adipose tissue). Second, garlic accelerates the breakdown and excretion of lipids. Finally, garlic enhances the transfer of lipids from storage in adipose tissue to the bloodstream.29 This last is an interesting effect. People who are on a garlic regime will show an increase in blood lipid levels during the first few months as fat is recruited from storage and transferred to the blood stream. As fat reserves are reduced, however, the other two activities of garlic, reduced lipogenesis and enhanced breakdown and excretion, act to reduce serum lipid levels. In addition to lowering overall serum lipid levels, garlic shifts the ratio of low- and high-density lipoproteins, increasing the amount of high-density lipo-proteins, the so-called "good" lipoproteins.
Garlic is used as a treatment for atherosclerosis in Germany where it has been shown to reduce serum cholesterol levels by 10%. When combined with reduced cholesterol diet, serum cholesterol levels decline 20%.
Cancer can be seen as a failure of the cell's regulatory mechanism caused by mutation in specific regulatory genes called protooncogenes. Mutations can occur from exposure to chemical mutagens, radiation, and viruses. As noted above, garlic contains compounds which are antioxidants and can protect the liver from mutagenic chemicals such as carbon tetrachloride. Some fractions from garlic have been shown to protect cells grown in vitro from radiation. However, fresh garlic proved fatal.29 Garlic also appears to have some antiviral properties. Whether this is caused by direct action on the virus or through stimulation of the immune system is not known. Taken together, the indications are that garlic should be effective in preventing cancer. When cancer is already present, studies indicate that garlic stimulates the immune system, especially when applied directly to the tumor. Another possible means by which garlic compounds may act is by directly inhibiting guanylate cyclase activity31 which would interfere with tumor metabolism.
Garlic has been shown to reduce platelet aggregation. Together with its effects on sero-lipids and cholesterol, this can have a tremendous impact on heart disease and is an official treatment for hypertension in Japan. It has also been shown to reduce blood glucose levels and to increase blood insulin levels. Traditionally, garlic has been used as a treatment for diabetes though its effects are small. It appears to lower the levels of "stress hormones" and to increase stamina, two effects with which the Roman legions were apparently familiar.
The most apparent problem with using garlic in human medicine is its strong odor. This is a problem of social esthetics. A problem of clinical importance is that some people are allergic to sulfur-based compounds. In most such cases, garlic would be unsuitable as either a food or a medical preparation. Garlic appears to suppress spermatogenesis. This is related to its effect on cholesterol and glucose metabolism. Perhaps the most difficult problem with widespread use of garlic compounds is the development of resistant strains of pathogens. The dimensions of this problem are unknown; on the one hand garlic has been used successfully against pathogens for millennia, apparently without the evolution of resistance. On the other, we have ample general evidence of the evolution of drug resistance by pathogens (bear in mind that most of these drugs are derived from naturally occurring compounds themselves). Alliums themselves are subject to pathogenic attack; Sclerotium cepivorum is a fungus specialized to infect alliums. So the evidence is clear that pathogens can evolve defenses to these drugs.
It is critically important for us to understand the mechanisms of action of garlic compounds on the cellular and molecular level, both to develop new antibiotic and immune-boosting agents, and to protect the efficacy of what we currently have available.30,31
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