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Garlic and Organosulfur Compounds


Summary

  • Garlic (Allium sativum L.) is a particularly rich source of organosulfur compounds, which are currently under investigation for their potential to prevent and treat disease. (More Information)
  • Crushing or chopping garlic releases an enzyme called alliinase that catalyzes the formation of allicin. Allicin rapidly breaks down to form a variety of organosulfur compounds. (More Information)
  • Since cooking can inactivate alliinase, some scientists recommend letting garlic stand for ten minutes after chopping or crushing before cooking it. (More Information)
  • Several different types of garlic supplements are available commercially, and each type provides a different profile of organosulfur compounds depending on how it was processed. (More Information)
  • The results of randomized controlled trials suggest that garlic supplementation inhibits platelet aggregation, but it is not known whether garlic supplementation can prevent cardiovascular disease. (More Information)
  • The results of a few epidemiological studies suggest that high intakes of garlic and other Allium vegetables (e.g., onions and leeks) may help protect against gastric and colorectal cancer, but it is not known whether garlic-derived organosulfur compounds are effective in preventing or treating human cancers. (More Information)

Introduction

Garlic (Allium sativum L.) has been used for culinary and medicinal purposes by many cultures for centuries (1). Garlic is a particularly rich source of organosulfur compounds, which are thought to be responsible for its flavor and aroma, as well as its potential health benefits (2). Consumer interest in the health benefits of garlic is strong enough to place it among the best-selling herbal supplements in the United States (3). Scientists are interested in the potential for organosulfur compounds derived from garlic to prevent and treat chronic diseases, such as cancer and cardiovascular disease (4).

Organosulfur Compounds from Garlic

Two classes of organosulfur compounds are found in whole garlic cloves: (1) gamma-glutamylcysteines, and (2) cysteine sulfoxides. Allylcysteine sulfoxide (alliin) accounts for approximately 80% of the cysteine sulfoxides in garlic (1). When raw garlic cloves are crushed, chopped, or chewed, an enzyme known as alliinase is released. Alliinase catalyzes the formation of sulfenic acids from cysteine sulfoxides (figure 1). Sulfenic acids spontaneously react with each other to form unstable compounds called thiosulfinates. In the case of alliin, the resulting sulfenic acids react with each other to form a thiosulfinate known as allicin (half-life in crushed garlic at 23°C is 2.5 days). The formation of thiosulfinates is very rapid and has been found to be complete within 10-60 seconds of crushing garlic. Allicin breaks down in vitro to form a variety of fat-soluble organosulfur compounds (figure 2), including diallyl trisulfide (DATS), diallyl disulfide (DADS), and diallyl sulfide (DAS), or in the presence of oil or organic solvents, ajoene and vinyldithiins (2). Crushing garlic does not change its gamma-glutamylcysteine content. Water-soluble organosulfur compounds, such as S-allylcysteine, are formed from gamma-glutamylcysteines during long-term incubation of crushed garlic in aqueous solutions, as in the manufacture of aged garlic extracts (see Sources below). 

Bioavailability and Metabolism

Allicin-derived Compounds

The absorption and metabolism of allicin and allicin-derived compounds are only partially understood (5). Although a number of biological activities have been attributed to various allicin-derived compounds, it is not yet clear which of these compounds or metabolites actually reach target tissues (1). Animal studies using radiolabeled compounds indicate that allicin or its breakdown products are absorbed intestinally (6, 7). However, allicin and allicin-derived compounds, including diallylsufides, ajoene, and vinyldithiins, have never been detected in human blood, urine, or stool, even after the consumption of up to 25 g of fresh garlic or 60 mg of pure allicin (1). These findings suggest that allicin and allicin-derived compounds are rapidly metabolized. The concentration of allyl methyl sulfide in the breath has been proposed as an indicator of the bioavailability of allicin and allicin-derived compounds (5). Human consumption of crushed garlic and equivalent amounts of allicin, DATS, DADS, ajoene, and allyl methyl sulfide resulted in similar increases in breath concentrations of allyl methyl sulfide, suggesting that allicin and allicin-derived compounds are metabolized to allyl methyl sulfide, a volatile compound that can be measured in exhaled air.

Gamma-Glutamylcysteines and S-Allylcysteine

Gamma-glutamylcysteines are thought to be absorbed intact and hydrolyzed to S-allylcysteine and S-1-propenylcysteine, since metabolites of these compounds have been measured in human urine after garlic consumption (8, 9). The consumption of aged garlic extract, a commercial garlic preparation that contains S-allylcysteine, has been found to increase plasma S-allylcysteine concentrations in humans (10, 11).

Biological Activities

Related to Cardiovascular Disease Prevention

Inhibition of Cholesterol Synthesis

Garlic and garlic-derived organosulfur compounds have been found to decrease the synthesis of cholesterol by hepatocytes (liver cells) (12). Several garlic-derived organosulfur compounds, including S-allylcysteine and ajoene, have been found to inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), a critical enzyme in the cholesterol biosynthesis pathway (13, 14). Garlic-derived compounds may also inhibit other enzymes in this pathway, including sterol 4-alpha-methyl oxidase (15).

Inhibition of Platelet Aggregation

A variety of garlic-derived organosulfur compounds have been found to inhibit platelet aggregation in the test tube (16, 17).

Anti-inflammatory Activity

Inflammation appears to play an important role in the pathology of cardiovascular disease (18). Garlic-derived organosulfur compounds have been found to inhibit the activity of the inflammatory enzymes, cyclooxygenase and lipoxygenase, in vitro [reviewed in (19)] and to decrease the expression of inducible nitric oxide synthase (iNOS) in inflammatory white blood cells (macrophages) (20, 21). More recently, organosulfur compounds have been found to decrease the production of inflammatory signaling molecules in cultured macrophages (22) and human whole blood (23).

Inhibition of Arterial Smooth Muscle Proliferation

The proliferation and migration of normally quiescent arterial smooth muscle cells are central features of vascular diseases, including atherosclerosis and coronary restenosis (24). Although the significance of these findings for human cardiovascular disease is not yet clear, limited cell culture research suggests that organosulfur compounds from garlic may inhibit the proliferation and migration of vascular smooth muscle cells (13, 25, 26).

Antioxidant Activity

A number of organosulfur compounds have been found to have antioxidant activity in the test tube, and there is some evidence that organosulfur compounds can stimulate the synthesis of glutathione, an important intracellular antioxidant (27). Although garlic oil supplementation in hypertensive adults was reported to decrease a biomarker of in vivo lipid (fat) oxidation in a small uncontrolled trial (28), it is not yet clear whether garlic-derived organosulfur compounds have clinically important antioxidant effects in vivo.

Hydrogen Sulfide-Mediated Vasodilatory Activity

The preservation of normal arterial function plays an important role in cardiovascular disease prevention. Hydrogen sulfide, a gaseous signaling molecule produced by some cells within the body, acts as a vasodilator (relaxes blood vessels) and thus may have cardioprotective properties (29, 30). A recent study found that garlic-derived compounds are converted to hydrogen sulfide by red blood cells in vitro (31). However, human consumption of a high dose of raw garlic does not increase breath hydrogen sulfide levels, suggesting that significant metabolism of garlic compounds to hydrogen sulfide does not occur in vivo (32).

Biological Activities Related to Cancer

Effects on Carcinogen Metabolism

Inhibition of Phase I biotransformation enzymes: Some chemical carcinogens do not become active carcinogens until they have been metabolized by phase I biotransformation enzymes, such as those belonging to the cytochrome P450 (CYP) family. Inhibition of specific CYP enzymes involved in carcinogen activation inhibits the development of cancer in some animal models (33). In particular, DAS and its metabolites have been found to inhibit CYP2E1 activity in vitro (34) and when administered orally at high doses to animals (35, 36). Oral administration of garlic oil and DAS to humans has also resulted in evidence of decreased CYP2E1 activity (37, 38).

Induction of Phase II biotransformation enzymes: Reactions catalyzed by phase II biotransformation enzymes generally promote the elimination of drugs, toxins, and carcinogens from the body. Consequently, increasing the activity of phase II enzymes, such as glutathione S-transferase and quinone reductase, may help prevent cancer by enhancing the elimination of potential carcinogens (39). In animal studies, oral administration of garlic preparations and organosulfur compounds increases the activity of phase II enzymes in a variety of tissues (40-42). The genes for a number of phase II enzymes contain a specific sequence of DNA called an antioxidant response element (ARE). Recent research suggests that allyl sulfides, particularly DATS, promote the translocation of a transcription factor known as Nrf2 to the nucleus where it binds ARE and increases the transcription of ARE-containing genes (43, 44). Although very high doses of organosulfur compounds were administered in most animal studies, at least one study found that quinone reductase activity increased in the gastrointestinal tracts of mice given a dose of DADS that might be achieved by human intake (45).

Enhanced cellular glutathione synthesis: Glutathione is an important intracellular antioxidant and is also required for some phase II biotransformation reactions. There is some evidence from cell culture and animal studies that garlic-derived organosulfur compounds increase intracellular glutathione concentrations (43, 46). Like the genes for many phase II enzymes, the gene for a critical enzyme in glutathione synthesis also contains an ARE. Thus, organosulfur compounds may increase cellular glutathione synthesis by promoting the nuclear translocation and binding of the Nrf2 transcription factor to genes containing AREs (see Induction of Phase II enzymes above).

Induction of cell cycle arrest

Unregulated cell division is a hallmark of human cancers (47). In normal cells, the cell cycle is tightly regulated to ensure faithful DNA replication and chromosomal segregation prior to cell division. Following DNA damage, the cell cycle can be transiently arrested to allow for DNA repair or activation of pathways leading to cell death (apoptosis). Organosulfur compounds, including DATS, DADS, ajoene, and S-allylmercaptocysteine (SAMC), have been found to induce cell cycle arrest when added to cancer cells in cell culture experiments (48-50).

Induction of apoptosis

Apoptosis is a normal physiological process for the self-destruction of cells that are genetically damaged or no longer necessary. Precancerous and cancerous cells are resistant to signals that induce apoptosis (51). Garlic-derived organosulfur compounds, including allicin, ajoene, DAS, DADS, DATS, and SAMC, have been found to induce apoptosis when added to various cancer cell lines grown in culture [reviewed in (48, 51)]. Oral administration of aqueous garlic extract and S-allylcysteine has been reported to enhance apoptosis in an animal model of oral cancer (52, 53).

Antimicrobial Activity

Garlic extracts have been found to have antibacterial and antifungal properties (54, 55). Thiosulfinates, particularly allicin, are thought to play an important role in the antimicrobial activity of garlic (55-57). Allicin-derived compounds, including DATS and ajoene, also have some antimicrobial activity in vitro, although generally less than allicin (1). To date, randomized controlled trials have not provided strong evidence that oral garlic preparations have significant antibacterial activity in humans (58-60); however, clinical trials using allicin-rich garlic preparations (raw or cooked garlic) have not been conducted. A small randomized controlled trial found that application of 1% ajoene cream to the skin twice daily was as effective in treating tinea pedis (athlete’s foot) as 1% terbinafine (Lamisil) cream (61).

Disease Prevention

Cardiovascular Disease

Interest in garlic and its potential to prevent cardiovascular disease began with observations that people living near the Mediterranean had lower mortality from cardiovascular disease (62). Garlic is a common ingredient in Mediterranean cuisine, but a number of characteristics of the “Mediterranean diet” have been proposed to explain its cardioprotective effects. Although few epidemiological studies have examined associations between garlic consumption and cardiovascular disease risk, numerous intervention trials have explored the effects of garlic supplementation on cardiovascular disease risk factors.

Serum Lipid Profiles

More than 40 randomized controlled trials have examined the effects of supplementation with various garlic preparations on serum lipid profiles in individuals with elevated and normal serum cholesterol levels (63). Although many of these trials had methodological limitations, the results of several meta-analyses indicate that garlic supplementation results in modest (6-11%) reductions in serum total cholesterol, LDL cholesterol, and triglyceride levels compared to placebo (63-65). The most comprehensive meta-analysis to date found that the modest reductions in serum cholesterol levels, which were evident up to three months after starting supplementation, were no longer statistically significant after six months of supplementation (63). Several recent clinical trials have not found that the use of garlic supplements results in statistically or clinically significant improvements in serum lipid profiles when compared to a placebo (66-74). The most recent and largest trial included high doses of raw garlic and a garlic supplement with high allicin bioavailability. However, neither supplement had a significant effect on serum lipids after six months in individuals with moderate hypercholesterolemia (74). Hence, garlic consumption strongly appears to have no effect on serum lipids, except possibly in individuals with very high levels of LDL cholesterol.

Platelet Aggregation

Platelet aggregation is one of the first steps in the formation of blood clots that can occlude coronary or cerebral arteries, leading to myocardial infarction (heart attack) or ischemic stroke, respectively. Most randomized controlled trials have found that garlic supplementation results in significant reductions in measures of ex vivo platelet aggregation. Four out of five trials found that supplementation with dehydrated garlic or garlic oil macerates significantly decreased spontaneous platelet aggregation compared to placebo [reviewed in (63)]. More recently, supplementation with aged garlic extract inhibited ex vivo platelet aggregation induced by physiological activators in two separate trials (11, 75).

Blood Pressure

The majority of controlled clinical trials have not found that garlic supplementation significantly reduces systolic or diastolic blood pressure in people with normal or high blood pressure (63, 76). Only three out of 23 randomized controlled trials identified in a systematic review (63) reported statistically significant reductions in diastolic blood pressure (77-79), and only one reported a statistically significant reduction in systolic blood pressure (77). At present, there is little evidence to support the use of garlic supplementation to prevent or treat hypertension.

Garlic and Atherosclerosis

Two studies have attempted to assess the effect of garlic supplementation on the progression of atherosclerosis in humans. One study in Germany used ultrasound imaging to assess the effect of 900 mg/day of dehydrated garlic on the progression of atherosclerotic plaque in the carotid and femoral arteries (80). After four years, the increase in plaque volume was significantly greater in women taking the placebo than in women taking the garlic supplement, but there was no significant difference between men taking garlic or placebo (81). In a smaller pilot study, investigators measured coronary artery calcium using electron beam tomography to assess the effect of supplementation with aged garlic extract on the progression of atherosclerosis in 19 adults already taking HMG-CoA reductase inhibitors (statins) (82). After one year, increases in coronary calcium were significantly lower in those taking aged garlic extract (4 ml/day) than in those taking a placebo. Although coronary calcium scores are correlated with the severity of coronary atherosclerosis, the predictive value of this technique is still under investigation (83). Both studies were funded by companies that market garlic supplements.

Summary: Cardiovascular Disease

In summary, the results of randomized controlled trials suggest that garlic supplementation inhibits platelet aggregation and modestly improves serum lipid profiles when taken for three months. It is not yet known whether garlic supplementation can reduce atherosclerosis or prevent cardiovascular events, such as myocardial infarction or stroke.

Cancer

Gastric Cancer

In an area of China associated with low mortality from gastric (stomach) cancer, 82% of men and 74% of women reportedly consumed garlic at least three times weekly. In contrast, in an area of China known for its high mortality from gastric cancer, only 1% of men and women consumed garlic at least three times weekly (84). Three out of four case-control studies in Europe and Asia found that past garlic consumption was significantly lower in people diagnosed with gastric cancer than in cancer-free control groups (85-87). A meta-analysis that combined the results of case-control studies found that those with the highest garlic intakes had a risk of gastric cancer that was about 50% lower than those with low garlic intakes (88). In contrast, a prospective cohort study in the Netherlands found no association between the use of garlic supplements and gastric cancer risk (89). However, it is important to note that one study reported that the composition of sulfur compounds in various commercially available garlic supplements sold in Europe varied by more than 12-fold (90). More recently, a randomized, double-blind, placebo-controlled intervention study in China found that supplementation with aged garlic extract and steam-distilled garlic oil for 7.3 years did not reduce the prevalence of precancerous gastric lesions or the incidence of gastric cancer (60). The amount of garlic compounds consumed as supplements is probably considerably lower than the amount consumed in garlic food. Thus, regular consumption of garlic food may be needed to observe any anti-cancer effects.

Helicobacter pylori infection and gastric cancer: Infection with some strains of H. pylori bacteria markedly increases the risk of gastric cancer. Although garlic preparations and organosulfur compounds have been found to inhibit the growth of H. pylori in the laboratory, there is little evidence that high garlic intakes or garlic supplementation can prevent or eradicate H. pylori infection in humans (91, 92). Higher intakes of garlic were not associated with a significantly lower prevalence of H. pylori infection in China or Turkey (93, 94). Moreover, clinical trials using garlic cloves (95), aged garlic extract (59), steam-distilled garlic oil (59, 96), garlic oil macerate (97), or garlic powder (98) have not found garlic supplementation to be effective in eradicating H. pylori infection in humans.

Colorectal Cancer

Three out of four case-control studies found that garlic intake was significantly lower in people diagnosed with colorectal cancer than in cancer-free control groups (99-101). In contrast, three prospective cohort studies found no association between garlic consumption and colorectal cancer risk (102-104). However, garlic consumption was generally low in these cohorts, and one study assessed only garlic supplement use (102). A meta-analysis that combined the results of case-control and prospective studies found that the risk of colorectal cancer was about 30% lower in those with the highest garlic intakes compared to those with the lowest intakes (88). An analysis of data from case-control studies conducted in Italy and Switzerland found a similar 26% reduction in risk for those with the highest garlic intake compared to the lowest (105). Colorectal adenomas (polyps) are precancerous lesions. One case-control study of adults undergoing sigmoidoscopy found that those with colorectal adenomas consumed significantly less garlic than those in whom no colorectal adenomas were found (106). A small preliminary intervention trial in 37 patients with colorectal adenomas examined whether supplementation with aged garlic extract for 12 months affected adenoma size and recurrence. Both the number and size of adenomas were significantly reduced in patients given a high dose of aged garlic extract (2.4 ml/day) compared to those given a much lower dose (0.16 ml/day) (107, 108). Larger randomized controlled trials are needed to determine whether garlic or garlic extracts can substantially reduce adenoma recurrence.

Summary: Cancer

The results of epidemiological studies in human populations suggest that high intakes of garlic and other Allium vegetables may help protect against gastric and colorectal cancer, but evidence that high intakes of garlic can reduce the risk of other types of cancer in humans is limited and inconsistent (88, 109). Although garlic and organosulfur compounds have been found to inhibit the development of chemically-induced cancers in animal models of oral, esophageal, gastric, colon, uterine, breast, prostate (110) and skin cancer (51), it is not known whether garlic-derived organosulfur compounds can prevent or slow the development of cancer in humans.

Sources

Food Sources

Allium vegetables, including garlic and onions, are the richest sources of organosulfur compounds in the human diet (109). To date, the majority of scientific research relating to the health effects of organosulfur compounds has focused on those derived from garlic. Fresh garlic cloves contain about 2-6 mg/g of gamma-glutamyl-S-allylcysteine (0.2-0.6% fresh weight) and 6-14 mg/g of alliin (0.6-1.4% fresh weight). Garlic cloves yield about 2,500-4,500 mcg of allicin per gram of fresh weight when crushed. One fresh garlic clove weighs 2-4 g (1).

Effects of cooking

The enzyme alliinase can be inactivated by heat. In one study, microwave cooking of unpeeled, uncrushed garlic totally destroyed alliinase enzyme activity (111). An in vitro study found that prolonged oven heating or boiling (i.e., 6 minutes or longer) suppressed the inhibitory effect of uncrushed and crushed garlic on platelet aggregation, but crushed garlic retained more antiaggregatory activity compared to uncrushed garlic (112). Administering raw garlic to rats significantly decreased the amount of DNA damage caused by a chemical carcinogen, but heating uncrushed garlic cloves for 60 seconds in a microwave oven or 45 minutes in a convection oven prior to administration blocked the protective effect of garlic (113). The protective effect of garlic against DNA damage can be partially conserved by crushing garlic and allowing it to stand for ten minutes prior to microwave heating for 60 seconds or by cutting the tops off garlic cloves and allowing them to stand for ten minutes before heating in a convection oven. Because organosulfur compounds derived from alliinase-catalyzed reactions appear to play a role in some of the biological effects of garlic, some scientists recommend that crushed or chopped garlic be allowed to “stand” for at least ten minutes prior to cooking (111).

Supplements

Several different types of garlic preparations are available commercially, and each type provides a different profile of organosulfur compounds depending on how it was processed (see the table below). Not all garlic preparations are standardized, and even standardized brands may vary with respect to the amount and the bioavailability of the organosulfur compounds they provide (1).

Powdered (Dehydrated) Garlic

Powdered or dehydrated garlic is made from garlic cloves that are usually sliced and dried at a low temperature to prevent alliinase inactivation (114). The dried garlic is pulverized and often made into tablets. To meet United States Pharmacopeia (USP) standards, powdered garlic supplements must contain no less than 0.1% gamma-glutamyl-S-allylcysteine and no less than 0.3% alliin (dry weight) (115). Although powdered garlic supplements do not actually contain allicin, the manufacturer may provide a value for the “allicin potential” or “allicin yield” of a supplement on the label. These values represent the maximum achievable allicin yield of a supplement (116). It is determined by dissolving powdered garlic in water at room temperature and measuring the allicin content after 30 minutes (115). Because alliinase is inactivated at the acid pH of the stomach, most powdered garlic tablets are enteric-coated to keep them from dissolving before they reach the neutral pH of the intestine. It has been argued that it is more appropriate to measure “allicin release” using a USP method for assessing drug release from enteric-coated tablets under conditions that mimic those of the stomach and intestine (115). Allicin release by this method has been shown to parallel true bioavailability (116). Most tablet brands have been found to produce little allicin under these conditions, due mainly to low alliinase activity and prolonged disintegration times (116, 117). Many manufacturers provide information on the “allicin potential” of their powdered garlic supplements, but few provide information on the “allicin release.” A number of controlled clinical trials have examined the effect of powdered or dehydrated garlic supplements on cardiovascular risk factors (see Cardiovascular Disease above). The most commonly used doses ranged from of 600-900 mg/day and provided 3,600-5,400 mcg/day of potential allicin (63).

Garlic Fluid Extracts (Aged Garlic Extract™)

When garlic cloves are incubated in a solution of ethanol and water for up to 20 months, allicin is mainly converted to allyl sulfides, which are lost by evaporation or converted to other compounds (114). The resulting extract contains primarily water-soluble organosulfur compounds, such as SAC and SAMC (118). Garlic fluid extracts, including aged garlic extracts, are standardized to their S-allylcysteine content. In controlled clinical trials, aged garlic extract at doses of 2.4-7.2 g/day resulted in short-term reductions in ex vivo platelet aggregation (11) and reductions in serum cholesterol levels up to 12 weeks (119).

Steam-Distilled Garlic Oil

Steam distillation of crushed garlic cloves results in a product that contains mainly allyl sulfides, including DATS, DADS, and DAS (114). These fat-soluble steam distillation products are usually dissolved in vegetable oil.

Garlic Oil Macerates

Incubation of crushed garlic cloves in oil at room temperature results in the formation of vinyldithiins and ajoene from allicin, in addition to allyl sulfides, such as DADS and DATS (1). Ether extracts are similar in composition to garlic oil macerates, but more concentrated (76).

Principal Organosulfur Compounds in Commercial Garlic Preparations

Product Principal Organosulfur Compounds Delivers allicin-derived compounds?
Fresh garlic cloves

Cysteine sulfoxides (Alliin)
Gamma-glutamylcysteines

Yes, when chopped, crushed, or chewed raw.
Minimal, when garlic cloves are cooked before crushing or chopping.
Powdered garlic (tablets) Cysteine sulfoxides (Alliin)
Gamma-glutamylcysteines
Varies greatly among commercial products.
Enteric-coated tablets that pass the USP allicin release test are likely to provide the most.
Steam distilled garlic oil (capsules) Diallyl disulfide
Diallyl trisulfide
Allyl methyl trisulfide
Yes
Garlic oil macerate (capsules) Vinyldithiins
Ajoene
Diallyl trisulfide
Yes
Aged garlic extract™
(tablets or capsules)
S-Allylcysteine
S-Allylmercaptocysteine
S-1-Propenylcysteine
Minimal

 

Safety

Adverse Effects

The most commonly reported adverse effects of oral ingestion of garlic and garlic supplements are breath and body odor (63, 120). Gastrointestinal symptoms have also been reported, including heartburn, abdominal pain, nausea, vomiting, flatulence, and diarrhea (121). The most serious adverse effects associated with oral garlic supplementation are related to uncontrolled bleeding. Several cases of serious postoperative or spontaneous bleeding associated with garlic supplementation have been reported in the medical literature (122-125). Garlic may trigger allergic responses in some individuals, including asthma in people with occupational exposure to garlic powder or dust (126). Exposure of the skin to garlic has been reported to cause contact dermatitis in some individuals (120, 127). More serious skin lesions, including blisters and burns, have also been reported with topical exposure to garlic for six or more hours.

Pregnancy and Lactation

No adverse effects on pregnancy outcomes have been reported when garlic is consumed in the diet. Although no adverse pregnancy outcomes were reported in a study of Iranian women who took dehydrated garlic tablets (800 mg/day) for two months during the third trimester of pregnancy (128), the safety of garlic supplements in pregnancy has not been established. There is some evidence that garlic consumption alters the odor and possibly the flavor of breast milk. In a controlled cross-over trial, oral consumption of 1.5 g of garlic extract by lactating women increased the perceived intensity of breast milk odor (129). Infants spent more time breast-feeding after their mothers consumed the garlic extract compared to a placebo, but the amount of milk consumed and number of feedings was not significantly different. Additionally, it is not known if topical use of garlic is safe during pregnancy or lactation.

Drug Interactions

Anticoagulant medications

Garlic may enhance the anticoagulant effects of warfarin (Coumadin). There have been two case reports in which prothrombin time (INR) increased in patients who started taking garlic tablets or garlic oil without changing their warfarin dose or other habits (130). However, a recent study in closely monitored patients on warfarin therapy found that garlic fluid extracts (aged garlic extract) did not increase hemorrhagic risk (131). Since garlic supplements have been found to inhibit platelet aggregation (63), there is a potential for additive effects when garlic supplements are taken together with other medications or supplements that inhibit platelet aggregation, such as high-dose fish oil or vitamin E (132). More research is needed to determine whether garlic supplements are safe for people on anticoagulatory therapy.

HIV Protease Inhibitors

Supplementation of healthy volunteers with garlic caplets twice daily (allicin yield, 7,200 mcg/day) for three weeks resulted in a 50% decrease in the bioavailability of the protease inhibitor, saquinavir (Fortovase) (133). Although saquinavir undergoes significant metabolism by CYP3A4, supplementation with garlic extract for two weeks did not significantly alter a measure of CYP3A4 activity in healthy volunteers (134). Garlic extract supplementation (10 mg/day) for four days did not significantly alter single-dose pharmacokinetics of the protease inhibitor, ritonavir (Norvir), but further research is needed to determine steady-state interactions between well-characterized garlic supplements and ritonavir (135).

References


Written in July 2005 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in July 2008 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in July 2008 by:
Larry D. Lawson, Ph.D.
Research Director, Silliker, Inc.
Orem, Utah

Copyright 2005-2014  Linus Pauling Institute


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