- Email: [email protected]
The nutraceutical benefit, part iv: garlic
NUTRITIONAL PHARMACEUTICALS
Editors: Gil Hardy, PhD Eric Newsholme, PhD, DSc
The Nutraceutical Benefit, Part IV: Garlic Tomoi Sato, MD, and Go Miyata, MD, PhD From the Surgical Metabolism and Nutrition Laboratory, Department of Surgery, SUNY Upstate Medical University Hospital, Syracuse, New York, USA INTRODUCTION Garlic, Allium sativum, has been consumed as a spice and also as a medicine for thousands of years all over the world. In ancient Egypt, garlic was consumed to remedy diarrhea. And in ancient Greece, it was consumed to treat intestinal and lung disorders.1 The authors, both raised in rural Japan, remember being given miso-soup with garlic as a remedy for the common cold with headache, fever and sore throat. Garlic has antimicrobial, antineoplastic, anticardiovascular, immuno-stimulatory and hypoglycemic properties. Onion, Allium cepa, which is also a member of the same family Liliaceare, has similar properties to garlic, so in this article we focus primarily on the health effects of garlic. The antimicrobial property of garlic has been known for a long time and reported frequently.1–5 Pasteur reported the antibacterial activity of garlic in 1858.1 Antibacterial property has been tested in many studies. Using serial dilution, in vitro, fresh garlic extract inhibited the growth of 14 species of bacterias (e.g., Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli) even at 128 times dilution.1 A 5% solution of freshly reconstituted dehydrated garlic added to a broth had bactericidal activity on Salmonella typhimurium.2 The antimicrobial activity of fresh garlic extract was diminished with boiling.1 This is attributed to allicin, a key antimicrobial component of garlic and gives it its characteristic odor. Allicin is denatured by boiling.3 In addition, garlic has antifungal property. Timonin and Thexton showed that an aqueous extract of garlic diluted to 1:1615 with a culture medium completely inhibited growth of fungi in soil samples.4 Furthermore, garlic has antibacterial activity to Helicobacter pylori,5 a major cause of dyspepsia, gastric and duodenal ulcer and gastric cancer. Jonkers et al. reported that 2 g/l of garlic extract completely inhibited growth of H. pylori by agar dilution method.5 It may be that the antibacterial effect of
Correspondence to: Tomoi Sato, MD, Department of Surgery, SUNY Upstate Medical University Hospital, 750 East Adams Street, Syracuse, NY 13210, USA. E-mail: [email protected]
H. pylori contributes to prevention of gastric cancer formation. The antineoplastic property of garlic has been shown in human epidemiologic and also in experimental animal studies. Cangshan County of Shandong Province in China has one of the lowest mortality risks of gastric cancer: 13 times lower in individuals consuming 20 g/d of garlic than in those consuming less than 1 g/d.6 In a casecontrol study in Italy, negative correlation between frequency of garlic consumption and gastric cancer risk (relative risk ⫽ 0.8) was observed in 1016 gastric cancer patients and 1159 healthy control people under age 75 y.7 In the Iowa Women’s Health Study, a reduced risk of colon cancer was observed in over 40 000 women who consumed garlic more than once a week (relative risk ⫽ 0.68).8 But not all epidemiologic studies could document garlic’s antineoplastic property.9 While animal studies clearly document the anticancer properties as follows: Pretreatment with diallyl sulfade, one of organosulfur compounds naturally occurring in garlic, at a dose of 200 mg/kg BW inhibited nuclear aberrations and the incidence of esophageal cancer induced by N-nitrosomethylbenzylamine in SpragueDawley rats10 as well as colon cancer in mice, induced by 1,2-dimethylhydrazine.11 Organosulfur compounds (allyl methyl trisulfide, diallyl trisulfide, allyl methyl disulfide, diallyl sulfide) inhibited benzo(a)pyrene-induced forestomach tumors in mice.12 Dietary supplementation of garlic powder significantly reduced the incidence of 7,12-dimethylbenz(a)anthracere (DMBA)-induced mammary tumor (35% versus 85%) and significantly depressed the in vivo binding of DMBA to mammary cell DNA.13 The mechanisms of anticancer property of garlic lie in the stimulatory effect on the glutathione S-transpherase, an enzyme which assists in the detoxification of many carcinogens,12 in inhibitory effect on formation and activation of nitrosamines,6,10,13–15 known naturally occurring powerful carcinogens and immunotoxic agents in nature, and in immunostimulatory activity, described below. But the antineoplastic mechanism remains to be fully determined. Another major nutraceutical effect of garlic is its anticardiovascular property. Consuming garlic has been shown to: 1)
Nutrition 16:787–788, 2000 ©Elsevier Science Inc., 2000. Printed in the United States. All rights reserved.
reduce serum cholesterol levels; 2) have antiplatelet aggregation; and 3) antioxidant property; preventing atherosclerosis and cardiovascular diseases. In a double-blind crossover Canadian study, the consumption of 7.2 g of garlic extract per day for half a year showed a 5.5% reduction in systolic blood pressure, a 7.0% reduction in total serum cholesterol, and a 4.6% reduction in low density lipoprotein cholesterol as compared with placebo administrated to 41 moderately hypercholesterolemic men aged 32– 68 y.16 Also, in rat studies given a cholesterol or lard-fed diet, garlic extract supplementation decreased plasma triacylglycerols and cholesterol as compared to controls.17 Hypocholesterol activity of garlic is due to an inhibition at several enzymatic steps in hepatic cholesterol synthesis18,19 and increases in bile acid and neutral sterol excretion.17 In addition, garlic and its components, allicin, alliin and S-allyl sulfate, have antiplatelet aggregation20,21 and antioxidant effects.22,23 The net effects of these activities result in preventing atherosclerosis and cardiovascular diseases. Garlic also has immuno-stimulatory property. Garlic extract or its components, diallyl trisulfide and diallyl sulfide, stimulates T cell proliferation24,25 and macrophages’ cytotoxicities on tumor cell lines.25 Pretreatment with diallyl sulfide restored suppression of the antibody response, induced by N-nitrosodimethylamine in a dose dependent manner.15 Thus, garlic stimulates both humoral and cellular immunity. Additionally, garlic has known hypoglycemic properties, which have been demonstrated in alloxan induced diabetic rats26,27 and rabbits.28 The extract of garlic28 and its component, S-allylcysteine sulfoxide,26,27 significantly decreased blood glucose concentration. Its activity appears to be in part due to stimulation of insulin secretion from  cell in the pancreas.27 In summary, based on both animal and human data the health benefits of garlic include antimicrobial, antineoplastic, anticardiovascular, immuno-stimulatory, and hypoglycemic properties. Such properties make garlic an attractive compound to be included in the daily diet not only for its unique flavor, but also for its medicinal benefits. 0899-9007/00/$20.00 PII S0899-9007(00)00391-9
788
Sato and Miyata
Nutrition Volume 16, Number 9, 2000
REFERENCES 1. Farbman KS, Barnett ED, Bolduc GR, Klein JO. Antibacterial activity of garlic and onions: a historical perspective. Pediatr Infect Dis J 1993;12:613 2. Johnson MG, Vaughn RH. Death of Salmonella typhimurium and Escherichia coli in the presence of freshly reconstituted dehydrated garlic and onion. Appl Microbiol 1969;17:903 3. Cavallito CJ, Bailey JH. Allicin, the antibacterial principle of Allium sativum. I. Isolation, physical properties and antibacterial action. J Am Chem Soc 1944;66:1950 4. Timonin MI, Thexton RH. The rhizosphere effect of onion and garlic on soil microflora. Soil Sci Soc Am Proc 1950;15:186 5. Jonkers D, van den Broek E, van Dooren I, et al. Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J Antimicrob Chemoth 1999; 43:837 6. Mei X, Wang ML, Xu HX, et al. Garlic and gastric cancer: the effect of garlic on nitrite and nitrate in gastric juice. Acta Nutrimenta Sinca 1982;4:53 7. Buiatti E, Palli D, Decarli A, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer 1989;44:611 8. Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol 1994;139:1 9. Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study on Allium vegetable consumption, garlic supplement use, and the risk of
10.
11.
12.
13.
14.
15.
16.
17.
18.
lung carcinoma in the Netherlands. Cancer Res 1994;54:6148 Wargovich MJ, Woods C, Eng VWS, Stephens LC, Gray K. Chemoprevention of N-nitrosomethylbenzylamine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. Cancer Res 1988;48:6872 Wargovich MJ. Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazineinduced colon cancer. Carcinogenesis 1987;8:487 Sparnins VL, Mott AW, Barany G, Wattenberg LW. Effects of allyl methyl trisulfide on glutathione S-transferase activity and BP-induced neoplasia in the mouse. Nutr Cancer 1986;8:211 Liu J, Lin RI, Milner JA. Inhibition of 7,12dimethylbenz[a]anthracene-induced mammary tumors and DNA adducts by garlic powder. Carcinogenesis 1992;13:1847 Shenoy NR, Choughuley ASU. Inhibitory effect of diet related sulphydryl compounds on the formation of carcinogenic nitrosamines. Cancer Lett 1992;65:227 Jeong HG, Lee YW. Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice. Cancer Lett 1998;134:73 Steiner M, Khan AH, Holbert D, Lin RIS. A doubleblind 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;64:866 Chi MS, Koh ET, Stewart TJ. Effects of garlic on lipid metabolism in rats fed cholesterol or lard. J Nutr 1982;112:241 Qureshi AA, Abuirmeileh N, Din ZZ, Elson CE,
19.
20. 21. 22.
23.
24.
25.
26.
27.
28.
Burger WC. Inhibition of cholesterol and fatty acid biosynthesis in liver enzymes and chicken hepatocytes by polar fractions of garlic. Lipids 1983;18:343 Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids 1993;28:613 Jain RC. Onion and garlic in experimental atherosclerosis. Lancet 1975;1:1240 Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978;30:355 Kourounakis PN, Rekka EA. Effect on active oxygen species of alliin and Allium sativum (garlic) powder. Res Commun Chem Path 1991;74:249 Munday JS, James KA, Fray LM, Kirkwood SW, Thompson KG. Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 1999;143:399 Lau BHS, Yamasaki T, Gridley DS. Garlic compounds modulate macrophage and T-lymphocyte functions. Mol Biother 1991;3:103 Feng ZH, Zhang GM, Hao TL, et al. Effect of diallyl trisulfide on the activation of T cell and macrophage-mediated cytotoxicity. J Tongji Med Univ 1994;14:142 Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356 Augusti KT, Sheela CG. Antiperoxide effect of S-allyl cysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 1996;52:115 Jain RC, Vyas CR. Garlic in alloxan-induced diabetic rabbits. Am J Clin Nutr 1975;28:684
Editors: Gil Hardy, PhD Eric Newsholme, PhD, DSc
The Nutraceutical Benefit, Part IV: Garlic Tomoi Sato, MD, and Go Miyata, MD, PhD From the Surgical Metabolism and Nutrition Laboratory, Department of Surgery, SUNY Upstate Medical University Hospital, Syracuse, New York, USA INTRODUCTION Garlic, Allium sativum, has been consumed as a spice and also as a medicine for thousands of years all over the world. In ancient Egypt, garlic was consumed to remedy diarrhea. And in ancient Greece, it was consumed to treat intestinal and lung disorders.1 The authors, both raised in rural Japan, remember being given miso-soup with garlic as a remedy for the common cold with headache, fever and sore throat. Garlic has antimicrobial, antineoplastic, anticardiovascular, immuno-stimulatory and hypoglycemic properties. Onion, Allium cepa, which is also a member of the same family Liliaceare, has similar properties to garlic, so in this article we focus primarily on the health effects of garlic. The antimicrobial property of garlic has been known for a long time and reported frequently.1–5 Pasteur reported the antibacterial activity of garlic in 1858.1 Antibacterial property has been tested in many studies. Using serial dilution, in vitro, fresh garlic extract inhibited the growth of 14 species of bacterias (e.g., Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli) even at 128 times dilution.1 A 5% solution of freshly reconstituted dehydrated garlic added to a broth had bactericidal activity on Salmonella typhimurium.2 The antimicrobial activity of fresh garlic extract was diminished with boiling.1 This is attributed to allicin, a key antimicrobial component of garlic and gives it its characteristic odor. Allicin is denatured by boiling.3 In addition, garlic has antifungal property. Timonin and Thexton showed that an aqueous extract of garlic diluted to 1:1615 with a culture medium completely inhibited growth of fungi in soil samples.4 Furthermore, garlic has antibacterial activity to Helicobacter pylori,5 a major cause of dyspepsia, gastric and duodenal ulcer and gastric cancer. Jonkers et al. reported that 2 g/l of garlic extract completely inhibited growth of H. pylori by agar dilution method.5 It may be that the antibacterial effect of
Correspondence to: Tomoi Sato, MD, Department of Surgery, SUNY Upstate Medical University Hospital, 750 East Adams Street, Syracuse, NY 13210, USA. E-mail: [email protected]
H. pylori contributes to prevention of gastric cancer formation. The antineoplastic property of garlic has been shown in human epidemiologic and also in experimental animal studies. Cangshan County of Shandong Province in China has one of the lowest mortality risks of gastric cancer: 13 times lower in individuals consuming 20 g/d of garlic than in those consuming less than 1 g/d.6 In a casecontrol study in Italy, negative correlation between frequency of garlic consumption and gastric cancer risk (relative risk ⫽ 0.8) was observed in 1016 gastric cancer patients and 1159 healthy control people under age 75 y.7 In the Iowa Women’s Health Study, a reduced risk of colon cancer was observed in over 40 000 women who consumed garlic more than once a week (relative risk ⫽ 0.68).8 But not all epidemiologic studies could document garlic’s antineoplastic property.9 While animal studies clearly document the anticancer properties as follows: Pretreatment with diallyl sulfade, one of organosulfur compounds naturally occurring in garlic, at a dose of 200 mg/kg BW inhibited nuclear aberrations and the incidence of esophageal cancer induced by N-nitrosomethylbenzylamine in SpragueDawley rats10 as well as colon cancer in mice, induced by 1,2-dimethylhydrazine.11 Organosulfur compounds (allyl methyl trisulfide, diallyl trisulfide, allyl methyl disulfide, diallyl sulfide) inhibited benzo(a)pyrene-induced forestomach tumors in mice.12 Dietary supplementation of garlic powder significantly reduced the incidence of 7,12-dimethylbenz(a)anthracere (DMBA)-induced mammary tumor (35% versus 85%) and significantly depressed the in vivo binding of DMBA to mammary cell DNA.13 The mechanisms of anticancer property of garlic lie in the stimulatory effect on the glutathione S-transpherase, an enzyme which assists in the detoxification of many carcinogens,12 in inhibitory effect on formation and activation of nitrosamines,6,10,13–15 known naturally occurring powerful carcinogens and immunotoxic agents in nature, and in immunostimulatory activity, described below. But the antineoplastic mechanism remains to be fully determined. Another major nutraceutical effect of garlic is its anticardiovascular property. Consuming garlic has been shown to: 1)
Nutrition 16:787–788, 2000 ©Elsevier Science Inc., 2000. Printed in the United States. All rights reserved.
reduce serum cholesterol levels; 2) have antiplatelet aggregation; and 3) antioxidant property; preventing atherosclerosis and cardiovascular diseases. In a double-blind crossover Canadian study, the consumption of 7.2 g of garlic extract per day for half a year showed a 5.5% reduction in systolic blood pressure, a 7.0% reduction in total serum cholesterol, and a 4.6% reduction in low density lipoprotein cholesterol as compared with placebo administrated to 41 moderately hypercholesterolemic men aged 32– 68 y.16 Also, in rat studies given a cholesterol or lard-fed diet, garlic extract supplementation decreased plasma triacylglycerols and cholesterol as compared to controls.17 Hypocholesterol activity of garlic is due to an inhibition at several enzymatic steps in hepatic cholesterol synthesis18,19 and increases in bile acid and neutral sterol excretion.17 In addition, garlic and its components, allicin, alliin and S-allyl sulfate, have antiplatelet aggregation20,21 and antioxidant effects.22,23 The net effects of these activities result in preventing atherosclerosis and cardiovascular diseases. Garlic also has immuno-stimulatory property. Garlic extract or its components, diallyl trisulfide and diallyl sulfide, stimulates T cell proliferation24,25 and macrophages’ cytotoxicities on tumor cell lines.25 Pretreatment with diallyl sulfide restored suppression of the antibody response, induced by N-nitrosodimethylamine in a dose dependent manner.15 Thus, garlic stimulates both humoral and cellular immunity. Additionally, garlic has known hypoglycemic properties, which have been demonstrated in alloxan induced diabetic rats26,27 and rabbits.28 The extract of garlic28 and its component, S-allylcysteine sulfoxide,26,27 significantly decreased blood glucose concentration. Its activity appears to be in part due to stimulation of insulin secretion from  cell in the pancreas.27 In summary, based on both animal and human data the health benefits of garlic include antimicrobial, antineoplastic, anticardiovascular, immuno-stimulatory, and hypoglycemic properties. Such properties make garlic an attractive compound to be included in the daily diet not only for its unique flavor, but also for its medicinal benefits. 0899-9007/00/$20.00 PII S0899-9007(00)00391-9
788
Sato and Miyata
Nutrition Volume 16, Number 9, 2000
REFERENCES 1. Farbman KS, Barnett ED, Bolduc GR, Klein JO. Antibacterial activity of garlic and onions: a historical perspective. Pediatr Infect Dis J 1993;12:613 2. Johnson MG, Vaughn RH. Death of Salmonella typhimurium and Escherichia coli in the presence of freshly reconstituted dehydrated garlic and onion. Appl Microbiol 1969;17:903 3. Cavallito CJ, Bailey JH. Allicin, the antibacterial principle of Allium sativum. I. Isolation, physical properties and antibacterial action. J Am Chem Soc 1944;66:1950 4. Timonin MI, Thexton RH. The rhizosphere effect of onion and garlic on soil microflora. Soil Sci Soc Am Proc 1950;15:186 5. Jonkers D, van den Broek E, van Dooren I, et al. Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J Antimicrob Chemoth 1999; 43:837 6. Mei X, Wang ML, Xu HX, et al. Garlic and gastric cancer: the effect of garlic on nitrite and nitrate in gastric juice. Acta Nutrimenta Sinca 1982;4:53 7. Buiatti E, Palli D, Decarli A, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer 1989;44:611 8. Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol 1994;139:1 9. Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study on Allium vegetable consumption, garlic supplement use, and the risk of
10.
11.
12.
13.
14.
15.
16.
17.
18.
lung carcinoma in the Netherlands. Cancer Res 1994;54:6148 Wargovich MJ, Woods C, Eng VWS, Stephens LC, Gray K. Chemoprevention of N-nitrosomethylbenzylamine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. Cancer Res 1988;48:6872 Wargovich MJ. Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazineinduced colon cancer. Carcinogenesis 1987;8:487 Sparnins VL, Mott AW, Barany G, Wattenberg LW. Effects of allyl methyl trisulfide on glutathione S-transferase activity and BP-induced neoplasia in the mouse. Nutr Cancer 1986;8:211 Liu J, Lin RI, Milner JA. Inhibition of 7,12dimethylbenz[a]anthracene-induced mammary tumors and DNA adducts by garlic powder. Carcinogenesis 1992;13:1847 Shenoy NR, Choughuley ASU. Inhibitory effect of diet related sulphydryl compounds on the formation of carcinogenic nitrosamines. Cancer Lett 1992;65:227 Jeong HG, Lee YW. Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice. Cancer Lett 1998;134:73 Steiner M, Khan AH, Holbert D, Lin RIS. A doubleblind 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;64:866 Chi MS, Koh ET, Stewart TJ. Effects of garlic on lipid metabolism in rats fed cholesterol or lard. J Nutr 1982;112:241 Qureshi AA, Abuirmeileh N, Din ZZ, Elson CE,
19.
20. 21. 22.
23.
24.
25.
26.
27.
28.
Burger WC. Inhibition of cholesterol and fatty acid biosynthesis in liver enzymes and chicken hepatocytes by polar fractions of garlic. Lipids 1983;18:343 Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids 1993;28:613 Jain RC. Onion and garlic in experimental atherosclerosis. Lancet 1975;1:1240 Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978;30:355 Kourounakis PN, Rekka EA. Effect on active oxygen species of alliin and Allium sativum (garlic) powder. Res Commun Chem Path 1991;74:249 Munday JS, James KA, Fray LM, Kirkwood SW, Thompson KG. Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 1999;143:399 Lau BHS, Yamasaki T, Gridley DS. Garlic compounds modulate macrophage and T-lymphocyte functions. Mol Biother 1991;3:103 Feng ZH, Zhang GM, Hao TL, et al. Effect of diallyl trisulfide on the activation of T cell and macrophage-mediated cytotoxicity. J Tongji Med Univ 1994;14:142 Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356 Augusti KT, Sheela CG. Antiperoxide effect of S-allyl cysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 1996;52:115 Jain RC, Vyas CR. Garlic in alloxan-induced diabetic rabbits. Am J Clin Nutr 1975;28:684