Allium sativum

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

Adler AJ, Holub BJ. Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men [see comments] Am J Clin Nutr 1997 Feb;65(2):445-450 Comment in: Am J Clin Nutr 1997 Feb;65(2):561-562.
Abstract: This study examined the effects of garlic and fish-oil supplementation (alone and in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects. After an initial run-in phase, 50 male subjects with moderate hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1) 900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic/d + 12 g oil placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n-3 fatty acids/d; and 4) 900 mg garlic/d + 12 g fish oil/d. In the placebo group, mean serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and triacylglycerols were not significantly changed in relation to baseline. Mean group total cholesterol concentrations were significantly lower with garlic+fish oil (-12.2%) and with garlic (- 11.5%) after 12 wk but not with fish oil alone. Mean LDL-C concentrations were reduced with garlic+fish oil (-9.5%) and with garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol concentrations were reduced with garlic+fish oil (- 34.3%) and fish oil alone (-37.3%). The garlic groups (with and without fish oil) had significantly lower ratios of total cholesterol to high- density-lipoprotein cholesterol (HDL-C) and LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men. The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol, LDL-C, and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to HDL-C.

Bergner P. The Healing Power of Garlic. Rocklin CA: Prima Publishing, 1996.

Berthold HK, Sudhop T, von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: a randomized controlled trial. JAMA 1998 Jun 17;279(23):1900-1902.
Abstract: CONTEXT: Garlic-containing drugs have been used in the treatment of hypercholesterolemia even though their efficacy is not generally established. Little is known about the mechanisms of action of the possible effects on cholesterol in humans. OBJECTIVE: To estimate the hypocholesterolemic effect of garlic oil and to investigate the possible mechanism of action. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Outpatient lipid clinic. PATIENTS: We investigated 25 patients (mean age, 58 years) with moderate hypercholesterolemia. INTERVENTION: Steam-distilled garlic oil preparation (5 mg twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. MAIN OUTCOME MEASURES: Serum lipoprotein concentrations, cholesterol absorption, and cholesterol synthesis. RESULTS: Baseline lipoprotein profiles were (mean [SD]): total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/ dL). Lipoprotein levels were virtually unchanged at the end of both treatment periods (mean difference [95% confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [-7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to 9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9] mg/dL), P=.20; triglycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to 12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%0], P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] microg/d, P=.78), and changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs 10.6% [21.1%], P=.62) were not different in garlic and placebo treatment. CONCLUSIONS: The commercial garlic oil preparation investigated had no influence on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic therapy for treatment of hypercholesterolemia cannot be recommended on the basis of this study.

Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, MA: Integrative Medicine Communications, 1998.

Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998 Apr;58(4):257-263.
Abstract: Thirty patients with coronary artery disease (CAD) were administered garlic (study group) while another 30 patients received the placebo (control group). Various risk parameters were determined at 1.5 and 3 months of garlic administration. Garlic, administered in a daily dose of 2 x 2 capsules (each capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic), reduced significantly total serum cholesterol and triglycerides, and increased significantly HDL-cholesterol and fibrinolytic activity. There was no effect on the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet aggregation (PAg) and eicosanoid metabolism were examined; it inhibited Pag induced by several platelet agonists, and also platelet thromboxane formation. Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl trisulphide (DATS) - derived from garlic and are usual constituents of garlic oil, showed antiplatelet activity, and also inhibited platelet thromboxane formation. In this respect DATS was more potent than DADS. The nature of inhibition of PAg by DATS was found to be reversible.

Burnham BE, Garlic as a Possible Risk for Postoperative Bleeding. Plastic and Reconstructive Surgery 1995; 95: 213.

D'Arcy PF. Adverse reactions and interactions with herbal medicines, part 1, adverse reactions. Adverse Drug Reactions and Toxicological Review 10 (Winter 1991) 189-208.

Demott K. St. John’s wort tied to serotonin syndrome. Clinical Psychiatry News 1998;26:28.
McLeskey CH, Meyer TA, Baisden CE, Gloyna DF, Roberson CR. The incidence of herbal and selected nutraceutical use in surgical patients. Annual Meeting of American Society of Anesthesiologists (ASA) October 1999.
Abstract: An estimated 60 million American adults are reported to use herbal products. Consumers assume, because these products are natural, they are harmless. However, reports of allergic reactions, adverse effects and drug-herb interactions are surfacing. Following IRB approval, a questionnaire was given to 979 presurgical patients. Subjects were asked to indicate the amount and duration of products taken. Age and surgical procedure were noted. 170 surgical patients (17.4%) reported taking such products. Median age of herb users and non-users was 62 years. Of the patients taking these agents, 55% took only one product, 45% took multiple products. In decreasing order, the most commonly utilized herbs among this group were: gingko biloba (32.4%), garlic (26.5%), ginger (26.5%), ginseng and St. John's Wort (14%). Nutraceuticals most widely used were glucosamine (17%), chromium picolinate (17%) and chondroitin (12%). Over 40 herbs were listed as occasionally taken. Females represented 63% of herbal users and 54% of non-users (p=0.05). 19.3% of female patients took one or more of these products vs. 14.5% of male patients. Neurosurgical, gynecologic and orthopedic surgical patients' use of herbals was slightly higher than other surgical groups at 21%, 21% and 20%. Recently one-third of the American public has been identified as users of herbal products. Our lower incidence may result from reluctance of patients to admit taking such products or lack of understanding among patients regarding drug intake and contents of these products. Anesthesia providers, surgeons, and patients should be aware that these medications may not be harmless and are in increasing use. Adverse effects and drug-herbal interactions may suggest alterations in an anesthetic plan.

Dirsch VM,Gerbes AL,Vollmar AM. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB. Mol Pharmacol 1998 Mar;53(3):402-407.
Abstract: The pharmacological role of garlic in prevention and treatment of cancer has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors. The effect was dose and time dependent. Apoptosis was judged by three criteria, morphology of cells, quantification of subdiploid DNA content by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the production of intracellular peroxide in a dose- and time-dependent fashion, which could be partially blocked by preincubation of the human leukemic cells with the antioxidant N-acetylcysteine. Interestingly, N- acetylcysteine-treated cells showed a 50% loss of ajoene-induced apoptosis. Moreover, ajoene was demonstrated to activate nuclear translocation of the transcription factor nuclear factor kappaB, an effect that was abrogated in N-acetylcysteine-loaded cells. These results suggested that ajoene might induce apoptosis in human leukemic cells via stimulation of peroxide production and activation of nuclear factor kappaB. This is a novel aspect in the biological profile of this garlic compound and an important step in elucidating the underlying molecular mechanisms of its antitumor action.

Dorant E, van den Brandt PA, Goldbohm RA, Hermus RJ,Sturmans F. Garlic and its significance for the prevention of cancer in humans: a critical view. Br J Cancer 1993 Mar;67(3):424-429.
Abstract: Recently published results of epidemiologic case-control studies in China and Italy on gastric carcinoma in relation to diet suggest that consuming garlic may reduce the risk of gastric cancer. Chemical constituents of garlic have been tested for their inhibiting effect on carcinogenesis, using in vitro and in vivo models. In most experiments inhibition of tumour growth was established using fresh garlic extract, garlic compounds or synthetically prepared analogs. In this review the strengths and weaknesses of the experiments are discussed and the outcomes are evaluated to assess the possible significance of garlic or garlic compounds for the prevention of cancer in humans. It is concluded that evidence from laboratory experiments and epidemiologic studies is presently not conclusive as to the preventive activity of garlic. However, the available evidence warrants further research into the possible role of garlic in the prevention of cancer in humans.

Fukushima S, Takada N, Hori T, Wanibuchi H. Cancer prevention by organosulfur compounds from garlic and onion. J Cell Biochem Suppl 1997;27:100-105.
Abstract: Environmental compounds are known to be involved in both the generation and prevention of many human cancers. It is important to discover naturally occurring or synthetic compounds which can block the process of carcinogenesis. We have focused attention on several organosulfur compounds (OSCs) in garlic and onion, and analyzed their potential for chemoprevention in the post-initiation stage in a liver medium-term bioassay (Ito test) and a multi-organ carcinogenesis bioassay. In the ITO test, rats were given diethylnitrosamine (DEN), 200 mg/kg b.w., i.p.; starting 2 weeks later they were treated with test chemicals for 6 weeks and then killed. All rats were subjected to 2/3 hepatectomy 1 week after the start of test chemical treatment. Inhibitory effects of a number of compounds could be identified in terms of reduced numbers and areas of liver glutathione S-transferase placental (GST-P) positive foci. In the multi-organ carcinogenesis bioassay, rats were given DEN, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N'- dimethylhydrazine, and dihydroxy-dipropylnitrosamine during the first 4 weeks, followed by test chemicals for 24 weeks. Various organs were examined. As a result, oil-soluble OSCs such as methyl propyl disulfide and propylene sulfide demonstrated inhibitory effects on the development of GST-P positive foci. Moreover, water-soluble OSCs such as S-methylcysteine and cysteine similarly decreased GST-P focus formation. In contrast, OSCs such as diallyl sulfide, diallyl trisulfide, and allyl methyl trisulfide enhanced formation of such altered hepatocellular foci. Inhibitory potential for colon and renal carcinogenesis was observed in rats treated with diallyl disulfide. Thus, the results indicate that some OSCs exert chemopreventive effects on chemical carcinogenesis. It must, however, be borne in mind that they may also demonstrate promotion potential, depending on the organ examined.

Ip C,Lisk DJ, Thompson HJ. Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis. Carcinogenesis 1996 Sep;17(9):1979-1982.
Abstract: Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. Additionally, supplementation of Se-garlic inhibited the post-initiation phase of mammary carcinogenesis when it was given continuously to the animals. In this report, experiments were carried out in which treatment with the Se-garlic was started after carcinogen dosing (DMBA or MNU) but was restricted to either the early or late stage of neoplastic progression. The results from these two models showed that a short-term exposure to the Se-garlic for 1 month immediately following carcinogen administration was just as effective in cancer prevention as the continuous exposure regimen (5 months), suggesting that the Se-garlic may irreversibly alter the process of clonal expansion and/or selection of transformed cells during their early stage of development. Plasma and mammary tissue selenium levels essentially returned to basal levels at 1 month after withdrawal of supplementation. These observations imply that the outcome of cancer protection by short-term Se-garlic intervention was not due to a slow turnover, and therefore a lingering presence, of selenium in the target organ or in the circulation. The above finding was in contrast to that of a second study in which Se-garlic was supplemented starting at 13 weeks after carcinogen treatment. With this protocol, the number of new tumors and the number of new tumor-bearing rats found during the intervention period (weeks 13 to 22) were not statistically different between the control and supplemented groups, suggesting that Se-garlic had a minimal effect on the later stages of mammary carcinogenesis.

Isaacsohn JL, Moser M, Stein EA, Dudley K, Davey JA, Liskov E, Black HR. Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial. Arch Intern Med 1998 Jun 8;158(11):1189-1194
Abstract: BACKGROUND: Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However, much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled. OBJECTIVE: To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia. METHODS: This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low- density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical- looking tablet, also given 3 times per day with meals. The main outcome measures included levels of total cholesterol, triglycerides, low- density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment. RESULTS: Twenty-eight patients (43% male; mean +/- SD age, 58 +/- 14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57 +/- 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients. CONCLUSION: Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia.

Jain AK,Vargas R; Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993 Jun;94(6):632-635.
Abstract: PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p - 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p - 0.05). There were no significant changes in high- density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.

Jung EM,Jung F, Mrowietz C, Kiesewetter H, Pindur G, Wenzel E. Influence of garlic powder on cutaneous microcirculation. A randomized placebo-controlled double-blind cross-over study in apparently healthy subjects. Arzneimittelforschung 1991 Jun;41(6):626-630.
Abstract: In a randomized placebo-controlled double-blind cross-over study it could be shown that 5 h after the administration of garlic powder (Kwai, Sapec; total dose of 900 mg garlic powder) a significant increase in capillary skin perfusion by 55% occurs in the healthy volunteers. Placebo did not cause any changes. The difference between the two study phases is also significant. The increased erythrocyte velocity results from vasodilation of precapillary arterioles which increases diameter of erythrocyte column by an average of 8.6%. Simultaneously inflow of interstitial fluidity accompanied by a significant decrease in haematocrit and plasma viscosity occurs (rheoregulation).

Keeler RF, Tu AT. Handbook of Natural Toxins. New York: Marcel Dekker, Inc.,1983.

Koch HP, Lawson LD. (eds.). Garlic: The Science and Therapeutic Application of Allium sativum L. and Related Species. 2nd ed. Baltimore: Williams and Wilkins, 1996.

Lau BH, Yamasaki T, Gridley DS. Garlic compounds modulate macrophage and T-lymphocyte functions. Mol Biother 1991 Jun;3(2):103-107.
Abstract: Organosulfur compounds of garlic have been shown to inhibit growth of animal tumors and to modulate the activity of diverse chemical carcinogens. There is also evidence that garlic may modulate antitumor immunity. In this study, we determined the effects of an aqueous garlic extract and a protein fraction isolated from the extract on the chemiluminescent oxidative burst of the murine J774 macrophage cell line and thioglycollate-elicited peritoneal macrophages obtained from BALB/c mice. T-lymphocyte activity was determined using mouse splenocytes incubated with phytohemagglutinin, labeled with [3H]- thymidine and assayed for lymphoproliferation. Significant dose-related augmentation of oxidative burst was observed with garlic extract and the protein fraction. The protein fraction also enhanced the T- lymphocyte blastogenesis. The data suggest that garlic compounds may serve as biological response modifiers by augmenting macrophage and T- lymphocyte functions.

Lawson D L, 1998. Letter, JAMA, 1998,280(18):1568 (Reproduced in Herbalgram,1999:24).

Lawson LD. Garlic: a review of its medicinal effects, and indicated active compounds. In : Lawson LD, Bauer, R (eds) Phytomedicines of Europe: Chemistry and Biological Activity. Washington DC:American Chemical Society, 1998:176-209.ACS Symposium Series 691.

Leung A. Encyclopedia of Common natural Ingredients used in Food, Drugs and Cosmetics. John WIley and Sons, NY, NY 1980, 176-178.
.
Milner JA, 1996. Garlic: its anticarcinogenic and antitumorigenic properties. Nutr Rev 1996 Nov;54(11 Pt 2):S82-86.
Abstract: Overall, several investigations indicate that garlic and its organic allyl sulfur components inhibit the cancer process. Furthermore, these studies reveal that the benefits of garlic are not limited to a specific species, a particular tissue, or a specific carcinogen. Finally, odor is not a prerequisite for the protection provided by garlic against the initiation of chemical carcinogenesis. Although the water-soluble compound S-allyl cysteine is effective in reducing the risk of chemically induced tumors in experimental animals, it has no effect on established tumors. However, oil-soluble compounds such as diallyl disulfide are effective in reducing the proliferation of neoplasms. Although the evidence supports the benefits of garlic, additional evidence is needed to determine the quantity needed by humans to minimize cancer risk.

McGuffin M, et al. (eds.). American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.

Muenscher, WC. Poisonous Plants of the United States. New York: The MacMillan Company, 1951.

Murphy JM. Preoperative considerations with herbal medicines. AORN J.1999 Jan;69(1):173-5, 177-178, 180-183.

Newall, CA, Anderson, LA, and Phillipson, JD. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press, 1996.

Parish RA, McIntire S, Heimbach DM. Garlic burns: a naturopathic remedy gone awry. Pediatr Emerg Care 1987 Dec;3(4):258-260.
ABSTRACT: We report the case of a child who sustained partial thickness burns from a garlic-petroleum jelly plaster, which had been applied at the direction of a naturopathic physician. A review of the literature reveals that "garlic burns" have not previously been reported, although medicinal properties of garlic have been investigated by physicians and biochemists. The pediatrician caring for children in an area where naturopathic medicine is routinely practiced should be aware of the potential side effects of plasters, poultices, and other "natural" remedies in children.

Pedraza-Chaverri J, Tapia E, Medina-Campos ON, de los Angeles Granados M;, Franco M. Garlic prevents hypertension induced by chronic inhibition of nitric oxide synthesis. Life Sci 1998;62(6):PL 71-77.
Abstract: It has been reported that garlic activates nitric oxide synthase in vitro and that chronic inhibition of nitric oxide (NO) synthesis by N omega-nitro-L-arginine-methyl-ester (L-NAME) induces arterial hypertension in rats. In this work, we studied the effect of oral administration of L-NAME for 4 weeks on control and garlic-fed rats. Basal systolic blood pressure was recorded 4 weeks after garlic supplementation, and on weeks 1, 2, 3, and 4 after L-NAME treatment. At the end of the study, the in vivo NO production was evaluated indirectly by measuring the urinary excretion of the stable end products of NO metabolism, nitrite (NO2-) and nitrate (NO3-). It was found that L-NAME induced arterial hypertension on weeks 1-4 in control rats but not in garlic-fed rats, whose blood pressure remained essentially as the basal values. Also, during this time period, blood pressure remained unchanged in garlic-fed rats without L-NAME treatment. Urinary excretion of NO2-/NO3- decreased in L-NAME-treated rats, increased in garlic-fed rats, and remained unchanged in garlic- fed rats treated with L-NAME. It was concluded that garlic blocks the L- NAME-induced hypertension by antagonizing in vivo the inhibitory effect of L-NAME on NO production.

Phelps S; Harris WS, 1993. Garlic supplementation and lipoprotein oxidation susceptibility. Lipids 1993 May;28(5):475-477.
Abstract: Interventions which make serum lipoproteins less susceptible to oxidation may be antiatherogenic. The antioxidant properties of garlic which have been demonstrated in vitro led us to investigate the effects of garlic supplements on lipoprotein oxidation susceptibility in humans. Ten healthy volunteers were given 600 mg/d of garlic powder (6 tablets of Kwai) for two weeks in a placebo-controlled, randomized, double-blind crossover trial. We found that although serum lipid and lipoprotein levels were not lowered in this short time period, the ex vivo susceptibility of apolipoprotein B-containing lipoproteins to oxidation was significantly decreased (-34%). Because garlic has been reported to beneficially affect serum lipid levels, platelet function, fibrinolysis and blood pressure, this additional effect of retarding lipoprotein oxidation may contribute to the potential antiatherosclerotic effect of garlic.

Pinto JT, Qiao C, Xing J,Rivlin RS, Protomastro ML, Weissler ML, Tao Y, Thaler H, Heston WD. Effects of garlic thioallyl derivatives on growth, glutathione concentration, and polyamine formation of human prostate carcinoma cells in culture [see comments] Am J Clin Nutr 1997 Aug;66(2):398-405 Comment in: Am J Clin Nutr 1997 Aug;66(2):425-6
Abstract: This study investigated whether naturally occurring garlic derivatives and synthetic S-cysteinyl compounds that resemble garlic constituents have antiproliferative effects on human prostate carcinoma (LNCaP) cells. Studies also examined whether S-allylmercaptocysteine and S- allylcysteine affect two important molecular targets, namely reduced glutathione and polyamines. Results showed that S-allylmercaptocysteine (50 mg/L) diminished LNCaP cell growth whereas the antiproliferative effect of S-allylcysteine was not as pronounced. Studies using synthetic S-cysteinyl analogues revealed that growth inhibition was most effective with compounds containing a disulfide or an active diallyl moiety. Marginal to no inhibitory effect was observed with monosulfinic analogues. Both S-allylmercaptocysteine and S- allylcysteine caused an increase in LNCaP cell reduced glutathione concentrations. Putrescine and spermine concentrations decreased and spermidine increased 3 d after S-allylmercaptocysteine treatment. At 5 d after S-allylmercaptocysteine treatment, polyamine concentrations were similar to those of saline-treated controls. Diminished cell growth and altered polyamine concentrations suggest that S- allylmercaptocysteine may impede the polyamine synthesizing enzyme, ornithine decarboxylase, either by enhancing the formation of reduced glutathione, a known inhibitor of ornithine decarboxylase, or by reacting directly with ornithine decarboxylase at its nucleophilic thiol moiety. Because S-allylcysteine also increases reduced glutathione formation but does not significantly inhibit growth, the latter mechanism may be more likely for this compound. These data provide further evidence that nonessential nutrients derived from garlic may modulate tumor growth. Further research is required on effects of garlic derivatives in vivo before information from the present studies can be used to assist in the development of effective nutritional strategies for preventing progression of prostate cancer.

Pizzorno J, Murray M. A Textbook of Natural Medicine. Seattle, Bastyr, 1995

Reicks MM, Crankshaw DL. Modulation of rat hepatic cytochrome P-450 activity by garlic organosulfur compounds. Nutr Cancer 1996; 25(3):241-248.
Abstract: Garlic organosulfur compounds exert chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens, possibly by inhibiting carcinogen activation via cytochrome P-450- mediated oxidative metabolism. It has been suggested that the variability in potency of tumor inhibition by garlic sulfur compounds is due to structural differences, such as the number of allyl and sulfur groups. In this study, diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS) were administered to acetone- treated adult male Sprague-Dawley rats by gastric gavage at a dose of 1.75 mmol/kg in cottonseed oil. After 15 hours, hepatic microsomal cytochrome P-450 activity and content were examined. The activity of p- nitrophenol (pNP) hydroxylase (E.C. 1.14.13.29) was significantly decreased by all garlic compounds, whereas benzphetamine N-demethylase and ethoxyresorufin O-deethylase activities were not changed. The activity of pNP hydroxylase was decreased to 31%, 54%, and 65% of control activity, and immunodetectable CYP2E1 protein levels were decreased in a similar manner by DAS, DADS, and AMS, respectively. Additional acetone-treated rats were given 4-methyl pyrazole, a ligand specific for CYP2E1, intraperitoneally five hours after garlic compound administration. Ten hours later, pNP hydroxylase activity was decreased to 73%, 78%, and 67% of control levels by DAS, DADS, and AMS, respectively. Further studies are needed to determine whether the variable potency of inhibition of CYP2E1 enzyme activity is related to chemopreventive efficacy of garlic sulfur compounds.

Rose KD, et al. Spontaneous Spinal Epidural Hematoma with Associated Platelet Dysfunction from Excessive Garlic Ingestion: A Case Report. Neurosurgery 1990; 26: 880-882.

Schaffer EM, et al. 1996. Garlic and associated allyl sulfur components inhibit N-methyl-N- nitrosourea induced rat mammary carcinogenesis. Cancer Lett 1996 Apr 19;102(1-2):199-204
Abstract: Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water- soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N- nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU- induced mammary carcinogenesis.

Silagy CA, Neil HAA. Meta-analysis of the effect of garlic on blood pressure. J Hypertens 1994 Apr;12(4):463-8
Abstract: Ojective: To undertake a systematic review, including meta-analysis, of published and unpublished randomized controlled trials of garlic preparations to determine the effect of garlic on blood pressure relative to placebo and other antihypertensive agents. Data identification: Studies were identified by a search of Medline and the Alternative Medicine electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. STUDY SELECTION: Only randomized controlled trials of garlic preparations that were at least 4 weeks in duration were deemed eligible for inclusion in the review. DATA EXTRACTION: Data were extracted from the published reports by the two authors independently, with disagreements resolved by discussion. RESULTS: Eight trials were identified (all using the same dried garlic powder preparation (Kwai) with data from 415 subjects included in the analyses. Only three of the trials were specifically conducted in hypertensive subjects, and many had other methodological shortcomings. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diastolic blood pressure (DBP). The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic then in those treated with placebo. For DBP the corresponding reduction in the garlic- treated subjects was slightly smaller. CONCLUSIONS: The results suggest that this garlic powder preparation may be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects. More-rigorously designed and analysed trials are needed.

Steiner M, Lin RS. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J Cardiovasc Pharmacol 1998 Jun;31(6):904-908.
Abstract: Garlic and some of its organosulfur components have been found to be potent inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in vivo, however, especially when administered over extended periods, is sparse. We recently performed a 10-month study comparing the effect of aged garlic extract (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men. In the course of the intervention trial, we examined platelet functions and susceptibility of lipoproteins to oxidation in a subgroup of this study population. Study subjects supplemented with 7.2 AGE per day showed a significant reduction of epinephrine- and, to a lesser degree, collagen-induced platelet aggregation but failed to demonstrate an inhibition of adenosine diphosphate (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar flow chamber at moderately high shear rate, was reduced by approximately 30% in subjects taking AGE compared with placebo supplement. A trend toward decreased susceptibility of lipoproteins to oxidation also was noted during AGE administration compared with the placebo period. We conclude that the beneficial effect of garlic preparations on lipids and blood pressure extends also to platelet function, thus providing a wider potential protection of the cardiovascular system.

Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr 1996 Dec;64(6):866-870.
Abstract: A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [cholesterol concentrations 5.7-7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet, they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo, then switched to the other supplement for an additional 4 mo. Blood lipids, blood counts, thyroid and liver function measures, body weight, and blood pressure were followed over the entire study period. The major findings were a maximal reduction in total serum cholesterol of 6.1% or 7.0% in comparison with the average concentration during the placebo administration or baseline evaluation period, respectively. Low-density-lipoprotein cholesterol was also decreased by aged garlic extract, 4% when compared with average baseline values and 4.6% in comparison with placebo period concentrations. In addition, there was a 5.5% decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract. We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.

Sumiyoshi H, 1997 [New pharmacological activities of garlic and its constituents] Nippon Yakurigaku Zasshi 1997 Oct;110 Suppl 1:93P-97P.
Abstract: According to the recent pharmacological findings, garlic is a preventive rather than therapeutic. Epidemiological studies in China, Italy and USA showed the inverse relationship between stomach and colon cancer incidences and dietary garlic intake. Anti-carcinogenic activities of garlic and its constituents including sulfides and S- allyl cysteine, have been demonstrated using several animal models. Garlic preparations has been also shown to lower serum cholesterol and triglyceride levels, which are major risk factors of cardiovascular diseases, through inhibition of their bio-synthesis in the liver, and to inhibit oxidation of low density lipoprotein. Furthermore, in vitro and in vivo studies have revealed that aged garlic extract stimulated immune functions, such as proliferation of lymphocyte, cytokine release, NK activity and phagocytosis. More recently, aged garlic extract has been demonstrated to prolong life span of senescence accelerated mice and prevent brain atrophy. Manufacturing processes significantly affect chemical constituents in garlic preparations. Different forms contain different phytochemicals and may have different effects and toxicities. For example, aged garlic extract inhibited t- BuOOH-induced oxidation, whereas raw garlic stimulated the oxidation. Although garlic has been used as a condiment and folklore for a long time, it has been noted to cause adverse reactions, such as stomach ulcer and anemia. Among the garlic preparations, only aged garlic extract has been proven to be safe through toxicological studies. Thus, aged garlic extract could be the most promising garlic preparation for disease prevention.

Voelker R. Herbs and Anesthesia. JAMA, 281(20).May 26, 1999:1882.

Warshafsky S, Kramer RS, Sivak SL. Effect of Garlic on Total Serum Cholesterol. Annals Int. Med. 1993.119: 599-605

Yoshida H, Iwata N, Katsuzaki H, Naganawa R, Ishikawa K, Fukuda H, Fujino T, Suzuki A. Antimicrobial activity of a compound isolated from an oil-macerated garlic extract. Biosci Biotechnol Biochem 1998 May; 62(5):1014-1017.
Abstract: A compound showing antimicrobial activity was isolated from an oil-macerated garlic extract by silica gel column chromatography and preparative TLC. On basis of the results of NMR and MS analyses, it was identified as Z-4,5,9-trithiadeca-1,6-diene-9-oxide (Z-10-devinylajoene; Z-10-DA). Z-10-DA exhibited a broad spectrum of antimicrobial activity against such microorganisms as gram-positive and gram-negative bacteria and yeasts. The antimicrobial activity of Z-10-DA was comparable to that of Z-ajoene, but was superior to that of E-ajoene. Z-10-DA and Z-ajoene are different in respect of substitution of the allyl group by the methyl group flanking a sulfinyl group. This result suggests that substitution by the methyl group would also be effective for the inhibition of microbial growth.
on of microbial growth.