Garlic and Allicin and Other Sulfur-Containing Compounds as Anticancer Agents

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Garlic and Allicin and Other Sulfur-Containing Compounds as Anticancer Agents

Garlic and its compounds are of renewed interest due to anticancer, antibiotic, and heart-beneficial properties. Of prime significance is the fact that the sulfur compound called allicin is formed from the vegetable garlic by the action between the compound alliin and the enzyme allinase, both naturally present in garlic, and allicin has been listed as an inhibitor for lactate dehydrogenase, the main distinguishing enzyme for cancer cell metabolism (e.g., E.J. Hoffman, "Enzyme Inhibitors for Cancer Cell Metabolism" in Townsend Letter for Doctors & Patients, May, 1997). And garlic itself is a folkloric treatment against cancer. A few brands of garlic tablets claim an allicin content, e.g., "Garlicin," "Garlique," and "Garlinase." The allicin is formed after ingestion, since the tablets contain a dry, powdered mixture of alliin and allinase, and are sealed away from moisture until the time of usage.

In further substantiation, the subject has been covered by Michael J. Wargovich, Hiromichi Sumiyoshi, and Allan Baier in a chapter on "Chemoprevention of Gastrointestinal Cancer in Animals by Naturally Occurring Organosulfur Compounds in Allium Vegetables," which appeared in Vitamins and Minerals in the Prevention and Treatment of Cancer, Maryce M. Jacobs Ed. (CRC Press, Boca Raton Florida, 1991, pp. 69-75.) The cancer-inhibiting effects of garlic and garlic-derived agents, particularly diallyl sulfide (DAS) and S-allyl-cysteine (SAC), and also garlic oil, were of special concern. Allicin, however, was not discussed as such. (As a further comment, the eye-watering property of onions is due to a gaseous compound named thiopropanal S-oxide. This sulfur compound is formed and released when onion cells are disturbed, causing a particular enzyme to contact an indigenous sulfur compound, yielding thiopropanal S-oxide. It may further be asked, are any or all of these onion-derived co mpounds anticancer?)

In the same volume, in a chapter by Carmia G. Borek, the antioxidant role of selenium and vitamin E, and vitamin C, is discussed, a fact which is now common knowledge. A chapter by Richard F. Branda on the effect of folic acid deficiency indicates that low levels are found in cancer patients, but, contrarily, increasing folic acid intake may accelerate tumor growth. Accordingly, research is ongoing on folic acid antagonists as chemotherapeutic agents, as folate deficiency may influence the spread of cancer. Altogether, a mixed bag. In a chapter on potassium vs. cancer by Maryce M. Jacobs and Roman J. Pienta, epidemiological and follow-up studies have shown that increased potassium intake decreases cancer risk, whereas increased sodium increases cancer risk. Even more important than levels is the potassium/sodium ratio -- the higher the better. Also noted is that potassium levels are higher in normal tissues than in cancerous tissues, with the possible exception for leukemic bon e marrow. It was concluded, however, that potassium-rich diets appear of questionable merit in curing malignancies.

For more about the medical aspects of garlic, there is the volume Garlic: The Science and Therapeutic Applications of Allium Sativum L. and Related Species, Second Edition, edited by Heinrich P. Koch (Williams & Wilkins, Baltimore Maryland, 1996). A list of 2,580 references is appended, 2,240 of which deal with garlic. A chapter on The Composition of Garlic Cloves and Processed Garlic, by Larry D. Lawson, contains tables listing the general breakdown for the composition of garlic cloves, and provides a bar chart illustrating that garlic has many times the sulfur content of other vegetables, and nearly four times that of onions, broccoli, and cauliflower. Interestingly, apricots have about as much sulfur as the latter three.

There are nearly 40 organic chemical compounds in garlic, known or anticipated, and not including vitamins and minerals. Probably the most significant is alliin and its conversion to allicin by the action of the enzyme allinase (or alliinase), and compounds called the ???-glutamylcysteines which are precursors for alliin. Alliin itself has no antibiotic activity unless converted to allicin, and it is further noted that allicin is the parent compound for the diallyl sulfides; the characteristic odor-producing compounds. Allicin belongs to a class called thiosulfinates (THS). Its precursor alliin is formed from still other compounds, as indicated, and there are complex pathways for the biogenesis of garlic's indigenous sulfur compounds, starting initially with the sulfate ion (Lawson, in Garlic, pp. 72-75). The precursors for alliin in mature plants are concentrated in the bulbs, but in premature plants most may be found in the leaves and stems.

Dried garlic has a sulfur content of 1.0 percent of its dry weight, and the dried product is about 35% of its fresh weight (Lawson, in Garlic, p. 41). About 72% of the sulfur compounds consist of alliin, allicin, and the two principal ???-glutamylcysteines. The known sulfur compounds in garlic comprise about 86% of the sulfur content.

Of prime interest are the thiosulfinates, which include allicin, or diallyl thiosulfinate, with the formula CH2=CHCH2-SS(=O)-CH2CH=CH2 for which several optional scientific names exist (Lawson, in Garlic, p. 40-42). The stability of allicin depends upon the temperature and solvent and is generally longer than the half-life of a few hours sometimes reported. At room temperature, pure allicin has a half-life of 16 hours, and in water a half-life of 30-40 days. At a temperature of -70øC, allicin in water had no change in 2 years, but the pure compound had a half-life of only 25 days at the same temperature.

Cooking affects garlic's sulfur compounds in that heat inactivates enzymes (Lawson, in Garlic, pp. 68-69). Thus allinase (or alliinase) becomes inactivated by cooking so as to prevent the formation of allicin and other thiosulfinates. Boiling unpeeled whole garlic cloves for 15 minutes completely inactivates aliinase, although there is a small amount of alliin due to the cloves bumping into each during heating. The small allicin content is in turn converted to diallyl trisulfide for the most part, with smaller amounts of the di- and trisulfides also produced -- and thus even boiled garlic can produce garlic breath.

The thiosulfinates (e.g., allicin) are very reactive, combining with reducing agents and undergoing spontaneous reactions in various solvents and media (Lawson, in Garlic, pp. 59-65). The reaction products are more stable than the thiosulfinates but still contain the thioallyl groups (S-allyl) or thiomethyl groups, and are active components in garlic oils.

At room temperature the thiosulfinates (e.g., allicin) in crushed garlic slowly convert to various diallyl and allyl sulfides, etc., a conversion accelerated by heating, as in steam-distillations to produce garlic oil. Pure allicin itself is an oily liquid, but is unstable, and has been noted to disappear in less than 20 hours at room temperature (which corresponds to a half-life of a few hours as sometimes reported). The decomposition products are various allyl sulfides, and may include what are called the vinyldithiins and ajoene. In organic solvents, the conversion products are different than in water, and also include the vinyldithiins and ajoene. At acidic conditions the thiosulfinates are relatively stable, but under basic conditions undergo rapid hydrolysis to form disulfides. Allicin reacts rapidly with the amino acid cysteine.

Allicin inhibits a large number of enzymes in vitro which contain cysteine at the active sites, but inhibits very few othenvise (Lawson, in Garlic, p. 65). The same kind of inhibition reaction occurs with glycylcysteine, N-acetylcysteine, and protein-cysteine.

The reference further makes the following statement, that "many of the explanations given for the biological effects of garlic focus on the ability of allicin to react with sulfhydril enzymes." Additionally, "allicin reacts with the sulfhydril group of acetyl-CoASH, the building block of cholesterol and triglyceride synthesis." In further comment, it is not known whether lactate dehydrogenase contains cysteine at the active sites. In any event, allicin inhibits this particular enzyme, as per Zollner's Handbook of Enzyme Inhibitors (VCH Verlagsgellschaft mbH., Weinheim, FRG, 1989,1993).

In the aforecited volume on Garlic, in a chapter on Therapeutic Effects and Applications of Garlic and Its Preparations, by Hans D. Reuter, Heinrich P. Koch, and Larry D. Lawson, there is a section on Anticancer Effects. The role of garlic in treating cancer is traced from ancient times, and more recent epidemiological studies indicate that there is indeed a beneficial anticancer effect. Statistical studies in fact furnish evidence that cancer occurs least in countries where garlic and onions are a significant part of the diet. Examples include the French Provence, Italy, the Netherlands, the Balkans, Egypt, India, and China. A specific citation (1936) refers to the connection between diet and cancer, whereby there is cancer-inhibiting noted for leek or Allium plants, although the reasons were not known. Very possibly the stimulation of gastric secretions and the restoration of intestinal flora, along with the inhibition of gastrointestinal autointoxication, work against cance r formation. The notation is added that the use of black or green tea along with garlic can be correlated with the prevention of tumorigenesis.

As to clinical trials where garlic has been used against advanced cancer, only one study is apparently known (Reuter, Koch and Lawson, in Garlic, p. 176). Conducted in Russia with the results published in 1962, a garlic juice preparation was introduced either intravenously or intramuscularly. The former was administered in 0.2-2 milliliter daily doses, the latter in 1-5 milliliter daily doses, over a period of 37 days. The 35 patients tested had cancers variously of the lung, cervix, stomach, lower lip, mammary gland, larynx, and also leukemia. It is stated that 26 showed positive results in varying degree, but none experienced complete healing.

Another case cited, however, was of a man whose pituitary shrunk by 50% over a 5-month period is which he ate 5-7 grams of fresh garlic daily. This was noted to be the first case in which this particular kind of cancer regressed without the use of chemotherapy or surgery. The results were reported in 1993 in the journal Neurochirurgia.

In comment, the intravenous or intramuscular dosages of garlic juice administered, above, were only over a very short period. If administered over a period of months -- as with conventional chemotherapy -- the results could have been dramatically more positive. Furthermore, no figures on allicin content were given. Presumably alicin, the most active ingredient derived from garlic, would have been present if the juice was extracted by crushing the garlic. There is also the matter of freshness, in that allicin gradually decomposes, and rather rapidly under some conditions.

As to the man's daily consumption of fresh garlic, an amount of garlic weighing 5-7 grams is relatively minuscule, being only about 0.2 to 0.3 of an ounce. (Fresh garlic weighs about one gram per clove, so that 5-7 grams amounts to circa 5-7 cloves per day.) As a point of reference, a garlic tablet of one of the several brands which produce allicin from a powdered mixture of alliin and allinase, will yield an announced 5,000 micrograms of allicin, or 5 milligrams of allicin -- albeit some may yield up to 14 mg/g (Lawson, in Garlic, p. 95). Fresh crushed garlic will yield about 3-7 milligrams of allicin per gram of garlic, depending upon the variety and strain (Lawson, in Garlic, p. 46). Using an average of 5 mg/g for convenience, in terms of allicin one tablet would be equivalent to one gram or one clove of fresh garlic. (Thus 5-7 grams per day of fresh garlic could be supplied by 5-7 tablets per day. The recommended usage is ordinarily one tablet per day.)

The reference further states that epidemiological studies support the fact that garlic consumption correlates with a reduced risk for cancer, especially of the gastrointestinal tract (Reuter, Koch and Lawson, in Garlic, pp. 176-178). In what was called the "Iowa Women's Health Study," which involved the intake of 127 different foods including 44 vegetables and fruits, it was found that garlic was the only food which showed a significant statistical reduction in cancer risk. While the foregoing study did not include onions, other studies have shown that onions and other Allium species correlate to a reduced gastrointestinal cancer risk. Another study conducted in the Netherlands, however, showed no correlation between the consumption of garlic supplements (tablets) and a reduced risk for stomach, colon, rectum, lung, or breast cancers. The reference notes that garlic supplements vary widely in composition according to type and brand.

Early in vivo experiments (1913) showed that garlic and its compounds, notably diallyl sulfide, inhibited tumors in mice, and similar results were subsequently obtained by others, both in vivo and in vitro (Reuter, Koch and Lawson, in Garlic, pp. 178-186). For instance, for mice fed garlic or garlic juice, tumor growth could be inhibited. In experiments reported in 1949, alliin freshly isolated from garlic bulbs was directly injected into rat sarcomas, resulting in reduction and dissipation. Parallel results were obtained by intramuscular injections. On the other hand, others subsequently could not find any alliin activity against transplanted and induced tumors. Ehrlich ascites tumor cells were deactivated by fresh garlic extract containing allicin, and cells of Yoshida sarcoma (a mammary tumor) were deactivated by allicin. Similar experiments and results are described, with the perspective that cancer cell virulence can be neutralized by fresh garlic, and at the same time an a ntibody response continues intact such that the animals become immune to untreated tumor cells.

A further discovery is that garlic contains a polypeptide of unknown structure that is an inhibitor for guanylate cyclase (Reuter, Koch and Lawson, in Garlic, p. 179, Lawson, in Garlic, p. 79). Found in several other vegetable plants, this substance has a tumor-inhibiting property. Skin cancers were inhibited by topical applications of garlic oil, which contain allyl and diallyl sulfides (Reuter, Koch and Lawson, in Garlic, p. 180)

The anticancer action of garlic has been explained in several ways. Thus there is the opinion that the antibiotic substance (thiosulfinates, of which allicin is the main example) inhibit proteolytic enzymes (e.g., cathepsin) in human malignancies (Reuter, Koch and Lawson, in Garlic, p. 181). Another finding is that garlic extract inhibits pyruvate dehydrogenase, thereby interrupting cellular respiration. (Pyruvate dehydrogenase is involved in the formation of pyruvic acid or pyruvate.) "Enzyme inhibition may thus be generally considered as the mechanism whereby the active components in garlic exert their tumor-inhibiting effect."

With regard to the inhibiting action of garlic oil, onion oil, and diallyl sulfide on skin cancers, it has been found that these substances enhance the activity of glutathione peroxidase in epidermis cells, which is ordinarily suppressed by the presence of the tumor promoter TPA.

As for stomach cancer, the thiosulfinates in garlic have an antimicrobial effect, inhibiting the growth of Fusarium moniliforme in the gut, at the same time reducing the concentrations of carcinogenic nitrate, and preventing the formation of carcinogenic dimethylnitrosamine and other nitrosamines. Further information is as follows:

- The Ames test has been used to demonstrate that garlic has antimutagenic properties.

- Garlic has been found to interfere with cell division or mitosis.

- The selenium and germanium compounds present in garlic may have an anticancer effect, although it is suspected that the concentrations are too small.

Increasingly complicated mechanisms for the anticancer action of garlic and its sulfur-containing compounds are presented in the reference. An exception is the presence of another remarkable substance in Allium bakeri, a steroid called laxogen (Reuter, Koch and Lawson, in Garlic, p. 186). An additional anticancer compound of interest, found in stressed garlic, is allixin, a sulfur-free compound.

Another interesting item is that the volatiles from garlic can repress the germination of pollen from flowers, with the effect similar to that of irradiation by gamma rays.

The section concludes with the observation that the agents in garlic responsible for its anticancer properties are allicin, allicin-derived compounds, and other as yet-unidentified compounds. Further specifics are provided as follows:

1. With regard to epidemiological studies correlating garlic consumption with a decreased risk of colon cancer, the garlic was for the most part cooked. Since allicin is destroyed by cooking, the inference is that allicin is not necessary for reduced cancer risk. (We may, however, distinguish "risk" from "cure.")
2. With regard to gastric cancer, where large-amounts of fresh garlic are eaten, the antibiotic effects of garlic may predominate, whereby the nitrate-reducing bacteria in the gut are affected. Garlic and its thiosulfinates (allicin) act against these bacteria and thereby reduce the amount of carcinogenic nitrosamines It is concluded that allicin does not have a direct effect against gastric cancer.
3. Animal studies indicate that allicin from fresh garlic greatly decreases breast cancer incidence in mice. Moreover, volatile sulfur compounds from garlic and from garlic oil both decreased liver tumor incidence in toads. (Presumably allicin per se was not a factor.)
4. Animal studies using diallyl sulfide and diallyl disulfide (as derived from allicin) showed positive effects against carcinogen-induced cancers. (Allicin itself was not tested.)
5. There is evidence from animal studies that garlic compounds other than allicin play an important anticancer role. Thus commercial aged garlic (which contains little alliin and no active alliiinase, nor allicin-derived compounds) showed a consistent decrease in carcinogen-induced tumors and DNA adducts or modifications. The reference adds that future studies should include clinical trials with humans.

Regarding the medicinal use of garlic -- even consumptive uses -- it has been found that there are acute, subacute, and chronic toxicities (Koch, in Garlic, pp. 221-224). While absorptive poisoning by the plant itself is not suspect, the use of plant extracts, active components, or oils in highly concentrated form can be expected to have toxic effects. Thus allicin is strongly hepatotoxic when administered in large doses over a long period. The dosage levels tested were 100 mg/kg of body weight, equivalent to a human eating 1750 grams or 500 cloves of raw garlic every day. Oral consumption of garlic off at levels of from 10 to 200 milligrams per day does not affect the erythrocytes (red blood corpuscles or cells) in humans, but does so in cats, causing serious anemia. Leukocytes (white blood corpuscles or cells) are also noted to be changed by allicin, increasing the germicidal activity.

Diallyl sulfide administered intravenously (in alcohol) at high dosages would produce heart stoppages in frogs. Rabbits suffered myosis (contraction of the pupil of the eye), blood-pressure drop, and increasing heart rate.

The liver and liver enzymes are adversely affected by the ingestion of Allium plants in large amounts. Thus garlic and onions can be hepatotoxic, as well as extracts of garlic.

Aqueous garlic extracts given to rats intraperitoneally, increased lactate dehydrogenase activity in liver.

Diphenylamine is found in onions but not garlic. Considered responsible for a blood sugar-lowering effect, it is nevertheless questionable because of nephrotoxic (kidney-toxic) properties. An aqueous garlic extract administered to mice adversely affected weight growth and other properties, and in rats was found to elevate lactate dehydrogenase activities. Garlic oil was lethal to fasted rats but not to fed rats. No mutagenic effects were observed in other tests on hamsters and mice.

Appropriately, in the introduction to the aforecited chapter on Toxicity, Side Effects, and Unwanted Effects of Garlic, the reference comments that a better term for side-effects would be adverse-effects (Koch, in Garlic, p. 221)

There have been many other books written about garlic, quite a few of which are still in print, with considerable of these concerned with culinary uses. About garlic's medicinal properties, in addition to John Heinerman's The Healing Benefits of Garlic: From Pharaohs to Pharmacists (Keats, New Canaan CT, 1994), a volume for the general reader is Stephen Fulder's The Garlic Book: Nature's Powerful Healer (Avery Publishing Group, Garden City Park, New York, 1997). There is a section on garlic as a protective against cancer which describes some of the studies where garlic or allicin has been tried.

Specifically mentioned are the investigations of Dr. A.S. Weissberger of Case Western University, Cleveland, who in 1953 advanced the idea allicin might act against cancer cells. In experiments with mice, those injected with cancer cells and allicin lived for 6-months as compared to a control group which lived only sixteen days.

Fulder further describes the work of Professor Sydney Belman of the New York Medical Center who, in working with mice, found that onion and garlic oil acted against cancer from chemical carcinogens. More recently, Professor Michael Wargovich of the Department of Medical Oncology at the M.D. Anderson Hospital in Houston Texas, found that diallyl sulfide, one of the several sulfides found in garlic oil, acted against chemically-induced tumors in mice.

Fulder's book, published in 1997, further mentions that over 100 studies have now been carried out variously with cells, animals, and tissues which indicate that garlic, garlic oil, allicin, the sulfides and other garlic compounds are protection against cancer. At the same time, these substances protect against genetic changes in the DNA. It is nevertheless reminded that garlic is a preventive, not a cure.

The medical folklore of Third World countries regards garlic as a cancer preventive. In China both garlic and green tea are thought to protect against stomach and lung cancer. Fulder cites the "designer foods" research program sponsored by the National Cancer Institute, whose aim is to determine whether specific food components act against cancer. Among the food items selected for study are garlic, rosemary, and licorice.

If garlic has not been clinically demonstrated to be a cancer preventive in humans, nonetheless epidemiological statistics show that garlic-eating people have fewer cancers. For example, in comparing neighboring counties in China, the people in one county eat about six cloves a day, in the other, none. The stomach cancer incidence of the first county was about 3.5 per 100,000 population, in the latter about 40 per 100,000, which is over 10 times greater. Also mentioned are the results of the Iowa Women's Health Study, published by Dr. K. Steinmetz and colleagues in 1994, in which, for the 127 foods consumed by 41,387 women, only garlic correlated with a reduced colon cancer risk.

Fulder adds the well-known fact that garlic's sulfur groups react with toxic heavy metals in the body. Thus cysteine is a conventional treatment to remove lead. A Bulgarian garlic preparation called Satal counteracts lead poisoning. Garlic in fact combines in equal weights with both lead and mercury. Garlic provides a way to cleanse the body of food additives and solvents, and before chemical antibiotics, functioned as a natural antibiotic against both bacteria and fungi.

As to safety, Fulder states that garlic is extremely safe, as evidenced by its daily consumption by millions of people worldwide. For instance, the people of Gangshan County in Shandong Province, China take on average 20 grams or seven cloves of garlic per day. In studies on cholesterol reduction by garlic, carried out over a three-month period, the consumption level reached 20 cloves per day with no ill effects. Garlic oil in the amount of 200 milligrams, which is equivalent to 70 cloves of garlic, is noted to have no toxic side-effects.

Such toxic effects as may occur are with impossibly high doses. For rats, toxicity occurred with doses of 5 grams of fresh garlic juice per kilogram of body weight, which is equivalent to a person sitting down and eating 300 mashed cloves of garlic. At such levels, garlic pungency will injure the stomach, as it would be the case, say, with red peppers. At very high doses allicin is noted to be toxic to the stomach and liver, as found in animal studies which were equivalent to a person consuming 500 cloves of garlic. Garlic pungency is noted to irritate the skin or mouth tissues, and some people are extra-allergic. Also noted is that garlic reduces blood-clotting times.

Another interesting reference, more concise, is by Eric Block of the State University of New York, Albany, which appeared in the Scientific American, in the March, 1985 issue. Titled "The Chemistry of Garlic and Onions," it contains many of the same things as noted in the previous references, observing that extracts from both garlic and onions are antibacterial and antifungal as well as being antithrombotic - that is, they inhibit the aggregation of blood platelets into thrombi, a process which also involves fibrin. Their therapeutic value can be traced back to the Codex Ebers, an Egyptian source dating back to circa 1550 BC, which gives over 800 medicinal formulas, including 33 citations for garlic against numerous ailments including headache, heart problems, worms, bites, and tumors. Mentioned also is the concoction known as Four Thieves Vinegar, consisting of garlic macerated in wine, which was supposed to have made gravediggers immune to an outbreak of plague in 1721. Better known as vinaigre des quatre voleurs, it is still available in France.

Brock gives attention to the chemistry of the onion as well as garlic, and there is a relationship. Thus onions contain what is named trans(+)-S-(l-propenyl)-L-cysteine sulfoxide, which is a postional isomer of alliin. The stoichiometric formulas are the same, differing in only the position of a double bond. The compound named above is the lacrimatory precursor, or LP. It is converted by the enzyme allinase (or alliinase) into the lacrimatory factor, or LF, the substance which brings tears to a person slicing onions.

The stoichiometric formula for LF is C3H6SO, and it is now agreed that the structural formula can be represented as C2H5CH=SO, with the name propanethial S-oxide. There are two structural isomers, designated syn- and anti-, with the former predominating, whereby the ethyl group (C2H5-) is nearer to the oxygen atom at the end of the chain.

This is compared with allicin, the corresponding product obtained from garlic, and whose stoichiometric formula can be written as C6H10SSO or as (C3H5)2SSO, and whose structural formula is CH2=CHCH2-SS(=O)CH2CH=CH2 as indicated previously, but which can also be written as C3H5SSOC3H5. There is a kind of symmetry between LF and allicin, as if the latter was sort of a dimer of the former, doing a bit of rearranging in the hydrocarbon group taking away an oxygen atom.

And if allicin is bioactive, say against cancer -- then so may be the lacrimatory factor LF. It is in fact noted that LF is highly reactive, as is allicin.

A number of sulfur-containing byproducts may also result from the action of allinase (or alliinase) enzymes. These include pyruvate and ammonia. There is also the indication that another reactant or cofactor is involved, namely pyridoxal phosphate, which serves to activate the principal reactant or substrate.

With regard to blood clotting times or coagulation disorders, these can be correlated to cancer formation and angiogenesis, as indicated by John Boik in Cancer & Natural Medicine: A Textbook of Basic Science and Clinical Research (Oregon Medical Press, Princeton, Minnesota, 1995, p. 25). By angiogenesis is meant the formation of a vascular support system, the network of arteries, veins, and capillaries which are necessary for tumor growth. These coagulation disorders may involve the blood-clotting protein fibrin and the processes of fibrinolysis, or still other factors such as the presence or absence of heparin or other natural agents. The same reference cites clinical tests in China using garlic preparations (Boik, Cancer & Natural Medicine, p. 29). Of 57 patients with advanced carcinomas, a marked improvement occurred in 13%, with some improvement in 50%. The criteria and results, however, were subject to interpretation. Possible modes of action may involve a reduced angiogene sis, reduced platelet aggregation, and increased fibrinolysis.

Correspondence:

E.J. Hoffman

P.O. Box 1352

Laramie, Wyoming 82070 USA

307-742-3458

Bibliography

Block, Eric, The Chemistry of Garlic and Onions, Scientific American, 252(3), 114-119 (March, 1985).

Boik, John, Cancer & Natural Medicine: A Textbook of Basic Science and Clinical Research, Oregon Medical Press, Princeton MN, 1995, p. 25.

Fulder, Stephen, The Garlic Book: Nature's Powerful Healer, Avery Publishing Group, Garden City Park, NY, 1997.

Garlic: The Science and Therapeutic Applications of Allium Sativum L. and Related Species, 2nd Edition, Heinrich P. Koch wad Larry D. Lawson Eds., Williams & Wilkins, Baltimore MD, 1996.

Heinerman, John, The Healing Benefits of Garlic: From Pharaohs to Pharmacists, Keats, New Canaan CT, 1994.

Hoffman, E.J., Enzyme Inhibitors for Cancer Cell Metabolism, Townsend Letter for Doctors & Patients, May, 1997.

Vitamins and Minerals in the Prevention and Treatment of Cancer, edited by Maryce M. Jacobs, CRC Press, Boca Raton FL, 1991.

Wargovich, Michael J., Hiromichi Sumiyoshi and Allan Baler, Chemoprevention of Gastrointestinal Cancer in Animals by Naturally Occurring Organosulfur Compounds in Allium Vegetables, in Vitamins and Minerals in the Prevention and Treatment of Cancer, Maryce M. Jacobs Ed., CRC Press, Boca Raton FL, 1991, pp. 69-75.

Zollner, Helmward, Handbook of Enzyme Inhibitors, VCH Verlagsgellschaft mbH., Weinheim, FRG, 1989. VCH Publishers, New York.

Zollner, Helmward, Handbook of Enzyme Inhibitors, 2nd edition revised and enlarged, in 2 volumes, VCH Verlagsgellschaft mbH., Weinheim, FRG, 1993. VCH Publishers, New York.

Townsend Letter for Doctors & Patients.

~~~~~~~~

By E.J. Hoffman

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