Garlic (Allium sativum) as the cure and cancer therapy – anticancer plant
Research studies about Garlic – Allium sativum as the biological and cancer therapy. Is Garlic anticancer plant or not?
Garlic (Allium sativum)
From INTERNET: Herbal Therapies for Cancer, by Vivekan Don Flint and Michael Lerner, Research Assistance: Melanie Smith, October 1997.
There is no data in the National Toxicity Program on garlic (1074), but the ancient Chinese classified garlic as a moderately toxic herb because high doses can lead to stomach upset and intestinal gas (1075). In 1983, Caporaso reported that the maximum tolerable dose of fresh aqueous garlic extract was 25 ml and that greater amounts caused severe burning sensations in the esophagus and stomach, as well as vomiting (1076).
In a review of the research on garlic by Judith Dausch and Daniel Nixon in a 1990 issue of Preventive Medicine, they note that there have been hundreds of animal and human studies since the 1930s on the potential benefits of garlic or its active ingredients. Since the 1970s, most research has focused on its antibacterial activity, lipid-lowering effects, antiplatelet aggregation effects, drug metabolizing properties and its anti-carcinogenic actions. They conclude that „evidence suggests a potential role for garlic or its components in several areas including prevention or control of cardiovascular disorders, treatment of viral and fungal conditions and prevention and treatment of certain cancers.“(1075). According to a 1995 survey, garlic is the second most popular segment of the over the counter market for herbs (1077).
As of September 1996, the Office of Alternative Medicine (OAM) had identified 250 citations in the medical literature for garlic, of which 171 pertained to cancer. Of the 89 studies they reviewed, ten were carried out with human subjects, 61 were animal studies and ten were in vitro studies. All of the human studies the OAM evaluated were studies of garlic as preventive for cancer and showed mixed results, with Chinese studies generally showing positive results for the cancers examined and Western studies showing no association.
It was first believed by researchers that the single beneficial element in garlic was allicin, the compound formed when the bulb is crushed. Allicin is an unstable compound that is strongly antibacterial and mainly responsible for garlic’s characteristic odor. But in addition to allicin, researchers have discovered 32 other sulfur compounds in garlic, along with 17 amino acids, Germanium, Calcium, Selenium, Copper, Iron, Potassium, Magnesium, Zinc, and small amounts of vitamins A, B1 and C. The main active components in garlic seem to be the various sulfur compounds, including Allicin, Allixin, diallyl Disulfide, diallyl Trisulfide and thioallyl amino acids, as well as other compounds formed during cooking and food preparation.(1075)
Dausch and Nixon report that, with regards to cancer research, the majority of human studies have been epidemiological in nature. Others have been in vitro or animals studies of the possible role of garlic in the prevention of cancer. According to Dausch and Nixon:
One possible beneficial effect of garlic or its components may be their ability to enhance the body’s mechanism for eliminating exogenous substances including carcinogens. In some studies garlic has been shown to have a stimulating effect on certain enzymes that are known to be involved in removing toxic substances. Antihepatotoxic [liver detoxifying] activity of garlic sulfur components have been described in vitro and vivo (1074).
This capacity to enhance liver detoxification could potentially be of great interest to cancer patients who are undergoing chemotherapy for cancer, since the it is the liver that functions to eliminate the toxic chemotherapy from the body.
Li and colleagues at the Strang-Cornell Cancer Research Laboratory describe the research on garlic in a 1995 article in Oncology Reports:
…Based on experimental and epidemiological evidences garlic could be classified as an anticarcinogen. The specific phase(s) of the carcinogenic process, i.e., initiation, promotion, or progression at which garlic or its constituents may exert its biological effect, however, remains to be determined in many cases…
Sources and mode of extraction of specific constituents from garlic showed an inhibitory effect on the production of DNA adducts initiated by chemical carcinogens on mammary cell DNA. Postulates to explain the anti-carcinogenic effect of garlic constituents have been proposed and these range from bio-inactivation of carcinogens, induction of free radical scavenging mechanisms, enhanced detoxification involving the glutathione pathway, and more recently, it has been suggested the cancer cells may be growth arrested in the G1-G0 phase of the cell cycle…(1078)
Describing their 1991 research on one of the active components of garlic, Maurya and Singh conclude:
Diallyl sulfide [DAS], an organosulfur compound identified as the flavor component in garlic, has been shown to inhibit chemically-induced neoplasia of forestomach and lung in mice. Even though the exact mechanism(s) of anti-neoplastic activity of DAS is not known, several independent studies suggest that this effect may, at least in part, be due to the elevation of glutathione-S-transferase [detoxification] activity (1079).
Although most research with garlic and cancer has focused on prevention, intriguing evidence exists concerning the potential for garlic as an adjunct to therapy for existing cancers. According to Boik, „theoretically, garlic may inhibit cancer by a variety of mechanisms, including reduced
angiogenesis, reduced platelet aggregation, and increased fibrinolysis (discussed below)“ (1180).
Dutch researchers found that compounds in garlic inhibit endothelial umbilical cell proliferation in vivo, an indication that they might also inhibit tumor angiogenic activity, which also involves the rapid proliferation of endothelial cells.
The antiangiogenic effect of thiols, compounds found in garlic, may be related to their ability to inhibit free-radical production by macrophages. Macrophages are found in great numbers in solid tumors, and can comprise 10 to 30 percent of the cells in a tumor. Under the low-oxygen conditions found in the interiors of solid tumors, macrophages secrete large amounts of angiogenesis factors, perhaps because of the stimuli are similar to those found in situations where wound healing is required (1182). According to Koch: We showed previously that thiol-containing compounds inhibited the production of macrophagemediated angiogenic activity. Since thiol containing compounds may act on macrophages by affecting activation and inhibiting the production of oxygen free-radicals, we studied the effects of oxygen free-radical scavengers on production of angiogenic activity…We conclude that oxygen free-radical scavengers are potent inhibitors of the production of macrophage-mediated angiogenic activity (1083).
Compounds found in garlic might also influence angiogenesis through their effects on the process of fibrinolysis, or the breaking down of fibrin. Fibrin is the protein material that comprises the essential portion of blood clots and is formed as a result of the process of inflammation. The area around tumors is commonly inflamed and a provisional stroma, or support structure, composed of fibrin forms around the tumor. According to Boik, the formation of this fibrin stroma may be the most important single precondition for tumor angiogenesis to occur. Boik cites research showing that the removal of this fibrin through the process of fibrinolysis terminates angiogenesis. He also speculates that by increasing fibrinolysis, the periphery of the tumor may be exposed to greater immune attack (1084).
A number of human studies have been carried out on the fibrinolytic properties of garlic that might have a bearing on some forms of cardiovascular disease. Some of these studies also indicate potential benefit to people with cancer.
Italian researcher Legnani and colleagues found the following responses to garlic ingestion (900 mg daily of dried powder) in a study of 12 healthy subjects in a randomized, double-blind, placebo controlled study on fibrinolysis and platelet aggregation: Total euglobulin fibrinolytic activity…[was] significantly higher 4 and 6 hours after garlic…ingestion, and no differences were recorded between treatments. After 14 days of treatment, t-PA [tissue plasminogen activator, the principle mediator of fibrinolysis] activity was significantly higher after garlic…Platelet aggregation…was significantly inhibited 2 and 4 hours after garlic ingestion; platelet aggregation values were also significantly lower after 7 and 14 days of garlic treatment (1085).
Arora also assessed the fibrinolysis-enhancing properties of garlic in patients with ischemic heart disease and in healthy control subjects. Though blood fibrinolytic activity was enhanced, the peak activity occurred at the 4th week of garlic therapy but was not sustained despite its continuous use and returned to about the pre-garlic values at the 12th week. Garlic withdrawal did not cause any further change in blood fibrinolytic activity (1086).
Another study in humans, this one a placebo-controlled double-blind study by Kiesewetter and colleagues, demonstrated a significant decrease in thrombocyte aggregation through the administration of 800 mg of garlic daily powder over a period of four weeks. Plasma viscosity was also shown to decrease (1087). Both effects lessen the likelihood of tumor cell arrest at potential metastatic sites.
Feng and colleagues found that diallyl trisulfide (DATS) at high levels had an inhibitory effect on T cell activation, but at appropriate concentrations augmented the activation of T lymphocytes, immune cells that might play a role in the immune response to cancer. In addition: DATS can antagonize the inhibition of tumor-derived immunosuppressive factors produced by S180 cells and Ehrlich ascitic cancer cells on the activation of T cells, and reduce the inhibitory rate significantly…When macrophages were pretreated with DATS for 24 hours, the cytotoxicity of macrophages to three tumor cell lines was significantly higher than that in corresponding control group…These results indicate that DATS can augment the activation of T cells and enhance the antitumor function of macrophages, suggesting that DATS may be potentially useful in tumor therapy (1088).
Evidence also exists of a direct anticancer effect with garlic. An in vitro study by Xie examined the effect of garlic oil on the DNA content of the cancer cell cycle using flow cytometric analysis: This technique may measure DNA content of 5000 cells per second and traces the dynamic changes in the cell proliferation cycle and offers a hint for designing clinical treatment protocol, monitor prognosis and elucidate the mechanisms of antitumor drugs. The authors’ previous studies showed significant effect of garlic oil on prolongation of life expectancy and inhibition of tumor growth in mice. Using FCM [flow cytometric analysis] the authors analyzed the effect of garlic oil on cell cycle in S180 tumor cells, 2-6 hours after single administration or multiple administration. The number of cells in S phase rapidly decreased, in G1 phase increased. This suggests garlic oil may blockade cells…progress from G1 phase to S phase and result in accumulation of cells in G1 phase and directly inhibit the synthesis of DNA and the cell cycle (1089).
A second study by Xie and colleagues on the effect of Kang ai-bao II on cancer cells using confocal laser scanning microscopy found that this garlic preparation had a destructive effect on DNA and RNA of cancer cells (1090).
Dausch and Nixon describe a 1985 Chinese study by Xiyu that compared the cytoxic effects of fresh garlic, diallyl trisulfide, 5-FU, mitomycin and cis-DDP on human gastric cancer cells in vitro. Mitomycin exerted the strongest effect, but fresh garlic also had a marked killing effect. Diallyl trisulfide was stronger than 5-FU against this gastric cell line (1091).
Li and colleagues also demonstrated an antiproliferative effect with aged garlic (AGE) and two of its allyl constituents in a human breast carcinoma model. They determined that „aged garlic extract demonstrated substantial inhibitory effect on the cancer cell lines; these AGE treated cells had substantially lowered growth rate than that of the cells treated with each compound alone“(1092).
In a 1993 study published in Oncology, Hiromitsu Takeyama and colleagues examined the effect of an amino acid compound derived from garlic, S allyl cysteine, or SAC on nine human melanoma cell line in vitro. They found that growth was inhibited in all melanoma cell lines, while it was not inhibited in three lymphoblastoid cell lines. The researchers also found that morphological changes were induced in the melanoma cells by SAC and that the cells appeared more differentiated and possibly had reverted to a less malignant state (1093).
In another study examining the effect of garlic constituents on a melanoma cell line in culture, David Hoon and colleagues at the UCLA Medical Center found that an extract of aged garlic significantly inhibited the growth a the melanoma cells and „appeared to be a more potent or an equivalent inducer of differentiation of melanoma compared to some known cytokines and agents…The modulatory effect on cell growth and differentiation by [garlic extract] may have potential benefit for prevention and control of melanoma progression in humans (1094).
Similarly, in a 1993 study using canine mammary tumor cells in vitro, Sundaram and Milner found that three water soluble constituents of garlic did not significantly inhibit cell growth, while two oilsoluble compounds, diallyl sulfide and diallyl disulfide, did significantly inhibit growth and a third, diallyl trisulfide, resulted in cell death (1095).
Dausch and Nixon also summarize numerous in vivo studies with mice demonstrating immunomodulatory and anticancer effects:
* In a 1964 study, Kimura and Yamamoto described the effects of garlic extracts on a transplanted ascites sarcoma in rats. When injected interperitoneally, the extract inhibited tumor cell proliferation by producing irregularities in chromosomes during cell division (1096);
* In a 1967 study, Fujiwara and Natata found that when mice were injected twice at a seven-day interval with a suspension of Ehrlich ascites tumor cells pretreated with garlic extract, they developed a strong immunity to the same type of tumor cells. They attributed this acquired immunity to the interaction of allicin with tumor cell proteins (1097).
* In a 1973 study, Nakata treated a variety of tumor cell types in mice with fresh garlic extract. Tumor development was found to be reversed in mice injected with Ehrlich ascites tumor and Yoshida sarcoma cells that were preincubated with garlic solution (1098)
* In a 1981 study, Cheng and Tung tested numerous compounds in Sarcoma 180 tumor-bearing mice and found that multiple intratumoral injections of allicin or allithiamine resulted in significant tumor inhibition (1099);
* In a 1981 study, Dhillon found a substance purified from garlic effective in inhibiting the growth of two Morris hepatomas in rats (1100);
* In a 1982 study, Criss compared the effectiveness in inhibiting Morris hepatoma 3924A in rats by dietary administration versus subcutaneous injection of garlic extract. Subcutaneous injection lowered tumor growth by 30-50 percent compared to 10 to 25 percent by dietary administration (1101) ;
* In a 1983 study, Choy found a 42 to 59 percent inhibitory effect by the oral administration of a garlic suspension on the growth of Ehrlich ascites tumors in the peritoneal cavities of tumorinoculated mice. Survival time was increased significantly by the administration of garlic (1102);
* In a 1986 study, Lau and Marsh studied the immunotherapy effects of garlic extract and other agents on transplanted transitional cell carcinoma in mice. Intralesional administration was found to be much more effective in inhibiting growth than the intraperitoneal route. Also, five intralesional treatments of garlic extract to the bladders of mice with transplanted transitional cell carcinoma resulted in inhibition of tumor growth as well as the production of macrophages and lymphocytes, leading to the destruction of tumor cells. It was theorized the result was due to enhanced production of lymphokines, such as tumor necrosis factor, that could result in increased natural killer cell activity (1103).
In a follow-up study, Marsh confirmed that garlic administered intravesically (into the bladder) was a more effective immunotherapy for transitional cell carcinoma than was BCG: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), keyhole limpet hemocyanin (KLH), and an extract of Allium sativum (AS) was studied in mice transplanted intravesically with mouse bladder tumor cells (MBT-2)…Immunotherapy with BCG (2 X 10(6) CFU), CP (250 micrograms), KLH (50 micrograms), or AS (25 mg) was administered directly into the bladder via urethral catheter on day 1, day 6, or days 1 and 6. On day 21 the bladders and spleens were excised and weighed, and the bladders were examined macroscopically and microscopically for evidence of tumor. The results of the study showed that two treatments given one and six days after tumor transplant yielded the lowest tumor incidence and that CP and AS appeared equally effective or even slightly more effective than BCG in this model. These results suggest that clinical evaluation of CP or AS may be worthwhile (1104).
The efficacy of garlic with bladder cancer in vivo was also evaluated by Donald Lamm at West Virginia University using an extract of aged garlic. The researchers ranomized 72 mice into six groups and inoculated each with a transitional cell carcinoma line: Tumor incidence was significantly reduced in the groups which received AGE [aged garlic extract]…relative to Saline controls. All doses of AGE significantly reduced tumor volume when compared to the Saline control. There was no statistical difference between the group receiving…garlic extract and the BCG control group. The highly beneficial reduction in tumor growth with AGE immunotherapy suggests that AGE will prove to be a highly effective form of immunotherapy for the treatment of transitional cell carcinoma of the bladder (1105).
In an Indian study, Unnikrishnan and Kuttan examined the antitumor activity of extracts of eight commonly used spices in India in mice transplanted intraperitoneally with Ehrlich ascites tumor: Oral administration of extracts of black pepper, asafoetida, pippali and garlic could increase the percentage of life span in these mice by 64.7%, 52.9%, 47% and 41.1%, respectively… Garlic extract and asafoetida extracts also inhibited two stage chemical carcinogenesis induced by 7,12 dimethyl benzanthracene and croton oil on mice skin with significant reduction in papilloma formation. These results indicate the potential use of spices as anti-cancer agents as well as antitumor promoters (1106).
Several studies indicate that garlic enhance the effectiveness of some chemotherapies or inhibit the mutagenic effect of chemotherapeutic drugs on normal cells. Pan and colleagues in 1988 examined the cytotoxic effects of allyl trisulfide when combined with three chemotherapeutic agents on a moderately differentiated human gastric adenocarcinoma cell line: The inhibitory effects of [allyl trisulfide], MMC [mitomycin] alone or combined on MGC [human gastric adenocarcinoma] tumor in nude mice were observed…The in vitro test of combinations of two drugs showed that [allyl trisulfide] plus MMC or 5 FU plus DDP had markedly synergistic effect on MGC cells…The inhibition test on the growth of MGC tumor in nude mice indicated that the inhibition rates of [allyl trisulfide], MMC alone or combined were 58.3%, 86.3% and 84.3%.
The systemic toxic effect of MMC alone was severe, whereas [allyl trisulfide] alone or MMC plus [allyl trisulfide] showed mild toxicity. For this reason, [allyl trisulfide] plus MMC is recommended for clinical trials on poorly differentiated gastric cancer (1107).
Using a thioallyl derived from garlic, Yellin and his colleagues examined the relationship between glutathione metabolism and sensitivity to chemotherapeutic agents such as cisplatin. They used a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas: An inverse relationship between GSH [glutathione] levels and cisplatin sensitivity was identified…Cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum)…Pretreatment with SAC to lower cellular glutathione levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth (1108).
In this study, while the garlic derivative used demonstrated no anticancer activity itself, it did enhance the effects of cisplatin. Another intriguing implication of this study was that the presence of the antioxidant glutathione in some way inhibited the sensitivity to cisplatin, evidence that antioxidant supplementation might not be useful for patients using some chemotherapies. In another study indicating garlic’s potential usefulness as an adjunct to chemotherapies, Chinese researchers Zhao and Huang screened vegetables for possible inhibition of mutagenicity caused by antineoplastic drugs: We found that 7 out of 11 kinds of commonly eaten vegetables had the ability to inhibit mutagenicity caused by chemical drugs such as Mitomycin C, Bleomycinia, Fluorouracil, Cis-Diaminodichloroplatinum, Arabinosylcytosin and mustargen. They were garlic, green Chinese onion, onion, garlic bulb, tomato, cucumber and water radish…We believe that our results can be helpful in the preparation of cancer patients’ diet, who are receiving chemotherapy and in the prevention of cancer (1109).
Dausch and Nixon cite several studies that examine the mutagenic potential of garlic. Substances that are mutagenic promote mutations, or permanent changes in the DNA in the body’s cells. Some mutations can potentially lead to cancer. Garlic has been reported to be mutagenic in several species of bacteria, but two studies with mice demonstrated no mutagenic effects. In fact, another study with mice cited by Dausch and Nixon showed that diallyl sulfide was among the most effective agents in inhibiting chemically-induced nuclear aberrations.
However, a more recent study by M. Takada published in the Japanese Journal of Cancer Research shows a possible cancer-promoting effect by some organosulfur compounds found in garlic and onions: Four organosulfur compounds from garlic and onions were examined for modifying effects…on neoplasia of the liver in male F344 rats…Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and allyl mercapton (AM) exerted enhancing effects on their development, while dimethyl trisulfide also tended to increase them…These results suggest that IAIE, DPT, and AM promote rat hepatocarcinogenesis and their promoting effect might be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus appropriate to consider not only a possible protective role of garlic and onions, but also enhancing effects (1110).
The research with garlic seems to indicate it may have promise as an adjunctive therapy for cancer because of direct anticancer effect, immune stimulation and also possible inhibition of metastases.
However, research is unclear on how a patient might best use garlic.
Garlic researcher Robert Lin, Ph.D. advises consumers to beware that manufacturers wishing to give the impression that allicin is the main active component in garlic may fortify their products with this readily made compound. According to Lin: Allicin is a transient and highly unstable compound which is produced when garlic’s cellular structures are ruptured due to cutting and crushing…Once allicin is formed, it decomposes rapidly and is mostly lost within one day. Since allicin has a germicidal power when added to cultured micro-organisms, some garlic products have been promoted as drugs for treating infectious diseases. The truth is that almost all cooked garlic and garlic products (including so-called garlic supplements) contain insignificant amounts of allicin. Further, there is no compelling evidence showing that allicin is the active compound in the body (1111).
Sundaram and Milner concluded in their study which showed diallyl disulfide inhibited proliferation of canine mammary tumor cells:
Essential oils of garlic are known to contain approximately 60% DADS …It is impossible at this point to extrapolate the quantity of garlic or its oil that would need to be consumed by human beings to potentially reduce the growth of neoplastic tissue. Nevertheless, intakes of 20 grams per day have been reported in some areas of the world. This intake has been correlated with a reduction in the incidence of stomach cancers (1112).
And Legnani found significant effects on fibrinolysis and platelet aggregation the following responses to garlic ingestion in humans at a level of 900 mg daily of dried powder and Kiesewetter found a clinical effect in humans at a level of 800 mg per day.
Studies have also employed various garlic derivatives, both oil soluble and water soluble, and, in animal studies, used both oral administration and injection. These studies seem to indicate that injection is a more effective route of administration, though at least three studies did show life extension in animals given garlic orally. Further, studies by Marsh and Lamm seem to indicate that garlic extracts given intravesically in mice may be significantly more useful as an immunotherapy for transitional cell carcinoma of the bladder than BCG, while the studies by Takeyama and Hoon indicate the potential for garlic to inhibit the growth of melanoma.
A caveat for cancer patients interested in the use of garlic as an adjunct to therapy is research by Pruthi showing that, due to the instability of numerous sulfur compounds, the application of heat above 60 degrees centigrade can cause not only the pungency, but possibly also the medicinal properties of garlic to be lost (1113). However, a cold-aged extract from Japanese whole-clove garlic has been developed that allows for the conversion of some of the active components to be converted in less irritating compounds which also have less odor (1114).
Richard Grossman, a New York-based authority on herbal medicine, recommends Kyolic brand garlic for patients interested in an aged garlic product which is less pungent than fresh whole garlic.
Source: The book Thousand Plants against Cancer without Chemo-Therapy, author Giuseppe Nacci, M.D.