Garlic
Allium sativum L. Family: Liliaceae (lilies)
Garlic , allium , stinking rose , rustic treacle , nectar of the gods , camphor of the poor , poor man's treacle 1
 
Clinical Overview
Uses
Evidence suggests that garlic may produce modest but not clinically significant effects in the treatment of dyslipidemia and hypertension. Traditionally, it has been used for its antiseptic and antibacterial properties, as well as for treating the common cold, upper respiratory tract infections, mild bronchitis, and rhinitis, and to relieve cough and congestion. Other potential uses include treatment of atherosclerosis, benign prostatic hyperplasia, diabetes, gastrointestinal (GI) disorders, and stomach and colon cancer; however, evidence is lacking.

Dosing
The following doses are recommended: 2 to 5 g of fresh raw garlic; 0.4 to 1.2 g of dried garlic powder; 2 to 5 mg garlic oil; 300 to 1,000 mg of garlic extract (as solid material). Other preparations should correspond to 4 to 12 mg of alliin or approximately 2 to 5 mg of allicin, an active constituent of garlic. However, dosage is complicated by the volatility and instability of important constituents in various products (eg, aged extracts, deodorized garlic, distilled oils). Administer garlic preparations with food to minimize GI upset. Because garlic is widely consumed, dosage will remain a matter of personal tolerance.

Contraindications
Contraindicated if known allergy to garlic and its constituents.

Pregnancy/Lactation
Garlic may be used safely in pregnancy and breast-feeding. However, consumption by breast-feeding mothers may impact the infant's behavior during breast-feeding, causing prolonged attachment to the breast and increased sucking. There have been documented emmenagogue effects.

Interactions
Garlic may reduce saquinavir plasma concentrations. Caution patients taking saquinavir to limit ingestion of garlic and to avoid taking garlic supplements without consulting their health care provider. Based on available reports, no special precautions are necessary in patients eating garlic and taking warfarin. However, because warfarin has a narrow therapeutic index, caution patients against use of alternative medicines without consulting their health care provider and to report any signs of bleeding. Based on an initial study, garlic does not appear to interact with alprazolam, dextromethorphan, docetaxel, or ritonavir.

Adverse Reactions
Body odor and malodorous breath are the most common complaints after ingesting garlic preparations. Mild GI adverse reactions (eg, bloating, flatulence, nausea) have been commonly reported with use. Ingestion of a single 25 mL dose of fresh garlic extract has caused burning of the mouth, esophagus, and stomach; nausea; sweating; and light-headedness. The safety of repeated doses of this amount has not been defined. Alterations in coagulation have also been reported. Ingestion of large amounts may increase the risk of postoperative and spontaneous bleeding. Ingestion as a food or supplement or topical use may cause allergic reactions (contact dermatitis, anaphylaxis, angioedema, generalized urticaria, pemphigus, and photoallergy). Topical exposure to crushed, uncooked garlic cloves for 3 to 5 minutes has resulted in toxic contact dermatitis. Repeated exposure to garlic dust can induce asthmatic reactions.

Toxicology
Research reveals little or no information regarding the toxicology of garlic.

 
Botany
Garlic is a perennial bulb with a tall, erect flowering stem that grows up to 1 m. The leaf blade is flat, linear, solid, and approximately 1.25 to 2.5 cm wide, with an acute apex. The plant may produce pink to purple flowers that bloom from July to September in the Northern Hemisphere. The bulb is odiferous and contains outer layers of thin sheathing leaves surrounding an inner sheath that encloses the clove. Often the bulb contains 10 to 20 cloves that are asymmetrical in shape, except for those closest to the center. 2
 
History
Allium comes from the Celtic word for burning or smarting. Garlic was valued as an exchange medium in ancient Egypt; its virtues were described in inscriptions on the Great Pyramid of Cheops. Folk uses of garlic have ranged from the treatment of leprosy in humans to managing clotting disorders in horses. During the Middle Ages, physicians prescribed the herb to cure deafness. American Indians used garlic as a remedy for earaches, flatulence, and scurvy.
 
Chemistry
Fresh garlic is a source of numerous vitamins, minerals, and trace elements, although most are only found in minute quantities. Garlic contains the highest sulfur content of any member of the genus Allium . Two trace elements, germanium and selenium, have detectable quantities and have been postulated to play a role in the herb's antitumor effect.
Garlic contains approximately 0.5% of a volatile oil composed of sulfur-containing compounds (diallyldisulfide, diallyltrisulfide, methylallyltrisulfide). 3,  The bulbs contain an odorless, colorless, sulfur-containing amino acid called alliin (S-allyl-L-cysteine sulfoxide), which has no pharmacologic activity. 4 When the bulb is ground, the enzyme allinase is released, resulting in the conversion of alliin to 2-propenesulfenic acid, which dimerizes to form allicin. Allicin gives the pungent characteristic odor to crushed garlic and is believed to be responsible for some of the pharmacologic activity of the plant.
 
Uses and Pharmacology
Antiseptic/Antibacterial properties   The antiseptic and antibacterial properties of garlic have been known for centuries. As recently as World War II, garlic extracts were used to disinfect wounds. During the 1800s, physicians routinely prescribed garlic inhalation for the treatment of tuberculosis. Preparations containing garlic extracts are used widely in Russia and Japan.
Garlic juice and essential garlic oil, water, and ethanol extracts inhibit the in vitro growth of Aspergillus niger , Bacillus species, Candida species, Cryptococcus species, Erwinia carotovora , Escherichia coli , Mycobacterium tuberculosis , Pasteurella multocida , Proteus species, Pseudomonas aeruginosa , Rhodotorula rubra , Shigella sonnei , Staphylococcus aureus , Streptococcus faecalis , Toruloposis species, and Trichosporon pullulans . 2,  , 5 Both gram-positive and gram-negative organisms are inhibited in vitro by garlic extracts. Garlic extracts inhibit the growth of numerous strains of Mycobacterium , but at concentrations that may be difficult to achieve in human tissues. Garlic extracts have shown antifungal activity when tested in vitro and their use has been suggested in the treatment of oral and vaginal candidiasis. This activity is attributed to allicin; however, it may not have antimicrobial activity in vivo because it is a relatively unstable and highly reactive compound. The potency of garlic is such that 1 mg is equivalent to 15 Oxford units of penicillin, making garlic about 1% as active as penicillin. 5
Animal data   Research reveals no animal data regarding the use of garlic for antiseptic/antibacterial properties.
Clinical data   In an attempt to quantitate the in vivo activity of garlic extracts, researchers orally administered 25 mL of fresh garlic extract to volunteers. 6 Serum and urine samples were tested for antifungal activity against 15 species of fungal pathogens. While serum exhibited anticandidal and anticryptococcal activity within 30 minutes after ingestion, no biological activity was found in urine. The findings suggest that while garlic extracts may exhibit some antifungal activity in vivo, they are probably of limited use in the treatment of systemic infections.
Antithrombotic effects   Studies on the effects of platelet aggregation have produced inconsistent results, possibly related to variations in study design and in the garlic preparation used. The proposed mechanism for garlic oil inhibition of platelet function is via interference with thromboxane synthesis. 7,  Researchers isolated a component of garlic oil that inhibits platelet aggregation and identified it as methylallyltrisulphide. Methylallyltrisulphide is present in natural oil in a concentration of 4% to 10%. The purified compound inhibits adenosine diphosphate-induced platelet aggregation at a concentration of less than 10 mcmol/L in plasma. 3
Further studies indicated that the most potent antithrombotic compound in garlic is 4,5,9, trithiadodeca-1,6,11-triene 9-oxide, also known as ajoene. This compound is formed by an acid-catalyzed reaction of 2 allicin molecules, followed by rearrangement. The compound can be synthesized commercially. Scientists demonstrated the effect of ajoene in preventing clot formation caused by vascular damage. The experiment was designed to mimic the conditions of blood flow in small- and medium-sized arteries by varying the velocity of the blood; the compound proved to be effective in both conditions. The authors suggested that the compound may be useful in situations in which emergency treatment is needed to prevent clot formation produced by vascular damage. 8
Clinical data   The platelets from healthy subjects who had eaten garlic cloves (100 to 150 mg/kg) showed complete inhibition to aggregation induced by 5-hydroxytryptamine. 9,  Other studies have shown that ingestion of aged garlic extract can produce an inhibition of some of the platelet functions important for initiating thromboembolic events in arterial circulation. 10,  However, the ingestion of 4.2 g of raw garlic over 1 week did not impair platelet function in a small study of 18 patients. 11,  The effects of garlic on platelet aggregation may be dependent on the garlic preparation used. Differences appear to be mostly dependent on their content of organo-sulfur compounds, many of which are unstable or capable of interconversion during processing. 12
Blood glucose effects   Garlic has been suggested to reduce blood glucose levels, 4,  increase serum insulin, and improve liver glycogen storage. 5
Animal data   Oral administration of garlic ethanol extract increased insulin levels and decreased serum glucose, as well as total cholesterol, triglycerides, creatinine, urea, uric acid, and transaminase levels in streptozotocin-induced diabetic rats. 13,  However, one review suggests that the antiglycative, as well as anti-inflammatory and antioxidative effects warrant further investigation because of inconsistent results. 14
Clinical data   A review of the literature demonstrated that glucose levels decreased from 89 to 9 mg/dL in healthy volunteers given garlic (800 mg dried powder for 35 days) compared with a placebo group. 15,  However, other reviews have shown that garlic has no effect on glucose levels. 16 Garlic administration should not be recommended for this indication because of the lack of randomized, well-controlled trials.
Dyslipidemia   A number of trials have examined the effects of garlic on lipoproteins and hypercholesterolemia. The exact mechanism for this action is uncertain, but it is thought that the organic disulfides present in garlic oil can reduce the activity of the thiol group found in many enzymes and can oxidize nicotinamide adenine dinucleotide phosphate (NADPH). These compounds can inactivate thiol enzymes, such as coenzyme A and HMG-CoA reductase, and can oxidize NADPH, all of which are factors normally required for lipid synthesis.
Clinical data   Individual randomized, controlled trials comparing garlic with placebo have provided disparate results. Some studies have suggested that garlic has no effect in adults with mild to moderate hypercholesterolemia. 17,  , 18,  , 19,  , 20,  , 21,  , 22,  Evidence also demonstrated no effect on cardiovascular risk factors in children with familial hyperlipidemia. 23,  However, other studies specifically examining moderate hypercholesterolemia in men have shown beneficial effects on lipid profiles by reducing total cholesterol and low-density lipoprotein cholesterol (LDL-C). 24,  , 25,  Adult patients (N = 192) with moderate hypercholesterolemia (LDL-C of 130 to 190 mg/dL or 3.36 to 4.91 mmol/L) randomized to receive garlic at an approximate dose of 4 g clove/day as raw garlic, powdered garlic supplement, aged garlic extract supplement, or placebo taken 6 days/week over 6 months produced no statistically or clinically significant effects on fasting plasma lipid concentrations, including LDL-C. 22
One meta-analysis on the use of garlic for hypercholesterolemia specifically reviewed randomized, controlled trials comparing garlic with placebo. 26,  The inclusion criteria were mean total cholesterol levels of 200 mg/dL (5.17 mmol/L). Pooling data from 13 trials (including 796 patients) suggested that garlic is superior to placebo in reducing cholesterol levels. However, the effect was modest (6% reduction in total cholesterol). Another meta-analysis of 16 randomized, controlled trials (including 1,365 patients) also showed a modest reduction in serum lipids. Overall, a 12% greater reduction was observed with garlic therapy compared with placebo. This meta-analysis, however, consisted of small, randomized studies of poor quality, and not all patients were hyperlipidemic. 27
Other data reveals a possible role for garlic as add-on therapy to traditional medicines (eg, reducing the dose of HMG-CoA reductase inhibitors). 28,  Additional trials have demonstrated that allicin, the presumed active ingredient of garlic, may reduce total cholesterol and LDL-C in adults with moderate hypercholesterolemia. 29,  A placebo-controlled, double-blind, randomized pilot study in 19 high-risk patients receiving an HMG-CoA reductase inhibitor and aspirin for atherosclerotic disease demonstrated that 4 mL of aged garlic extract (1,200 mg) slowed the accumulation of coronary artery calcification, as detected by electron beam tomography after 1 year. However, larger studies are required to validate this cardiovascular benefit. 30 Overall, these effects are generally short-term, and whether they are sustainable beyond 6 months is unclear. The evidence for lowering LDL-C and total cholesterol is still questionable and may not be clinically meaningful.
GI effects   The effect of garlic on the GI system has been the topic of some debate.
Animal data   Oral administration of garlic oil (0.1 mL per 10 g) in mice reduced the gastric transit time of a charcoal meal by 75% and prevented castor oil-induced diarrhea for up to 3 hours. 31 The investigators concluded that garlic oil can be investigated for its effectiveness in the management of hypermotile intestinal disorders. An additional role proposed in the literature is the use of garlic in the treatment of Helicobacter pylori infection; however, the evidence does not support this. 32
Clinical data   One study demonstrated that 2 tablets daily of dried garlic preparation (approximately 1 g/day) relieved abdominal and epigastric distress, belching, flatulence, nausea, and colic compared with placebo. 33
Hypertension
Animal data   Research reveals no animal data regarding the use of garlic for blood pressure control.
Clinical data   Strong evidence for the effect of garlic on blood pressure is lacking. The results of a meta-analysis suggest that garlic supplements of 600 to 900 mg/day for 1 to 3 months are associated with a clinically important reduction in blood pressure. 34,  The meta-analysis included 8 trials consisting of 415 patients. However, the trials were of generally poor to moderate quality and not all patients were hypertensive. A review of the literature suggested that the effects of garlic on blood pressure were insignificant. 16 No firm conclusions can be drawn from these trials.
Immunology   Garlic contains the trace elements germanium and selenium, which have been thought to play a role in improving host immunity.
Animal data   One study found that 2 oil-soluble compounds from garlic, diallyl sulfide and diallyl disulfide, when applied topically, succeeded in protecting mice against carcinogen-induced skin tumors as well as increasing survival rate. 8
Clinical data   Research reveals no clinical data regarding the use of garlic in immunology.
Oncology
Animal data   The antineoplastic activity of garlic has been studied in mice injected with cancer cells pretreated with a garlic extract. No deaths occurred in this treatment group for up to 6 months, while mice injected with untreated cancer cells died within 16 days. 5 It is believed that the reaction of allicin with sulfhydryl groups (the concentration of which increases rapidly in dividing cells) may contribute to this inhibitory effect.
Clinical data   Scant data, primarily from case-control studies, suggest that dietary garlic consumption is associated with decreased odds of laryngeal, gastric, colorectal, and endometrial cancers, as well as adenomatous colorectal polyps. 35
The protective effect of garlic against colorectal and gastric cancers was addressed in meta-analyses of 18 studies. 36 It was concluded that high intake of garlic may offer protection. These results should be interpreted with caution because of the heterogeneity of trials included in the meta-analyses.
Garlic supplementation of 2 capsules twice a day (mixture of 200 mg aged garlic and 1 mg steam-distilled garlic oil per capsule) for 7.3 years had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence in 3,365 randomized adults who were seropositive or seronegative for H. pylori . 37,  , 38
A systematic review of case-controlled and cohort studies of patients receiving garlic demonstrated an inverse relationship between garlic intake and colorectal cancer risk. However, the minimum intake of garlic among the studies was heterogeneous, and firm conclusions cannot be drawn. 39
Other uses   Researchers demonstrated that allicin increased the levels of 2 important antioxidant enzymes in the blood, catalase and glutathione peroxidase. This discovery confirmed the antioxidant and free-radical scavenging potential of allicin. In vivo and in vitro ischemia reperfusion studies demonstrated that aqueous garlic administered prior to ischemia reperfusion inhibited lipid peroxidation and prevented glutathione depletion, thereby protecting the function and structure of different organs against injury because of oxidative damage and neutrophil infiltration. 40,  However, the clinical utility of antioxidant activity is not clear to researchers, and further clinical studies are required. Other researchers studied the sulfur compounds in aged garlic extract and found 5 sulfur compounds that inhibited lipid peroxidation in the liver, preventing a reaction considered to be one of the main features of aging in liver cells. According to the findings, the sulfur compounds “appear to be approximately 1,000 times more potent in antioxidant activity than the crude, aged garlic extract.” 8
A relationship between an increase in allium food consumption (onion and garlic) and the decreased incidence of benign prostatic hyperplasia was demonstrated in a case-controlled study of 1,369 patients with benign prostatic hyperplasia and 1,451 matched controls. However, precise allium intake (ie, type or variety of allium vegetable, intake of other allium vegetables, means of preparation) or long-term dietary patterns were difficult to assess. 41
 
Administration & Dosage
Garlic dosage is complicated by the volatility and instability of important constituents and by products such as deodorized garlic, aged extracts (a popular deodorized form of garlic), and distilled oils. The World Health Organization recommends the following doses: 2 to 5 g of fresh raw garlic; 0.4 to 1.2 g of dried garlic powder; 2 to 5 mg garlic oil; 300 to 1,000 mg of garlic extract (as solid material). Other preparations should correspond to 4 to 12 mg of alliin or approximately 2 to 5 mg of allicin. Administer with food to prevent GI adverse reactions. 2,  Because garlic is widely consumed, dosage will remain a matter of personal tolerance. 23,  , 26,  , 42,  , 43
 
Pregnancy/Lactation
Garlic may be used safely in pregnant and breast-feeding mothers. 2,  Apparent garlic odor in breast milk peaked after 2 hours of garlic ingestion and decreased thereafter in 8 breast-feeding mothers. Breast milk that smelled of garlic prolonged infant attachment to the breast and increased sucking. 44,  There have been documented emmenagogue effects. 45
A Cochrane review identified only 1 trial (100 women) showing no clear difference between garlic and placebo ingestion in the risk of developing preeclampsia and gestational hypertension or in incidences of caesarean section and perinatal mortality. 46 Further evidence is required to draw firm conclusions.
 
Interactions
Alprazolam   Based on available data, garlic does not appear to interact with alprazolam. In 14 healthy subjects, pretreatment with garlic extract 1,800 mg twice daily for 14 days did not alter the pharmacokinetics of a single oral dose of alprazolam 2 mg. 47
Dextromethorphan   Based on available data, garlic does not appear to interact with dextromethorphan. In 14 healthy subjects, pretreatment with garlic extract 1,800 mg twice daily for 14 days did not alter the pharmacokinetics of a single dose of dextromethorphan. 47
Docetaxel   In 10 women with metastatic breast cancer treated with docetaxel 30 mg/m2 weekly for 3 of 4 weeks, garlic (600 mg twice daily for 12 consecutive days, beginning on day 5 of the docetaxel dosage) did not affect docetaxel's pharmacokinetics. 48
Ritonavir   Based on available data, garlic does not appear to interact with ritonavir. In 10 healthy subjects, garlic (7 doses of 10 mg) did not alter the pharmacokinetics of ritonavir administered as a single 10 mg oral dose. 49
Saquinavir   In 10 healthy subjects, ingestion of garlic supplements reduced saquinavir plasma concentrations. 50 Compared with administration of saquinavir alone, coadministration of garlic supplements (dose not specified) decreased the saquinavir area under the plasma concentration-time curve 51%, decreased the trough levels (8 hours after saquinavir administration) 49%, and decreased the peak concentration 54%. The mechanism of this interaction is unknown.
Warfarin   There is no report of an interaction occurring with administration of warfarin and ingestion of garlic. However, there are reports of inhibition of platelet aggregation in individuals ingesting garlic that may increase the risk of bleeding. 51,  , 52,  , 53,  Case reports have associated spontaneous spinal epidural hematoma, prolonged clotting time with increased bleeding, and hemorrhaging with garlic ingestion. 53,  , 54,  , 55,  In contrast, in a double-blind, placebo-controlled study of 14 men, garlic did not affect platelet aggregation. 56,  A double-blind, placebo-controlled trial that randomized 48 patients receiving warfarin therapy to aged garlic extract or placebo 5 mL twice a day for 12 weeks demonstrated no bleeding and no difference in the incidence of minor adverse reactions (eg, colds, dizziness, fatigue, headache). 57
No studies evaluate the effect of garlic and its extracts in patients requiring stringent blood glucose control, but potential for serious interactions exists.
 
Adverse Reactions
Although garlic is used extensively for culinary purposes with essentially no ill effects, the safety of long-term use of concentrated extracts is unclear.
Controlled clinical trials and observational studies have consistently documented that body odor and malodorous breath are the most common complaints after ingestion of garlic preparations. 58
A single 25 mL dose of fresh garlic extract has caused burning of the mouth, esophagus, and stomach; nausea; sweating; and light-headedness. The safety of repeated doses of this amount has not been defined. Rarely, ingestion may also cause anaphylaxis. 59
Topical exposure to crushed, uncooked garlic cloves for 3 to 5 minutes has resulted in toxic contact dermatitis. 60,  Additionally, repeated exposure to garlic dust can induce asthmatic reactions. 58,  Garlic dust allergy, presenting as coughing, wheezing, chest tightness, difficulty breathing, blocked or runny nose, sneezing, and running or itching eyes is relatively rare. However, an IgE-mediated hypersensitivity reaction has been reported to affect mainly young atopic subjects. Cross-sensitivity to other members of the Liliaceae family may be observed. 61,  The degree of cross-reactivity appears to vary among individuals. 62
Case reports have documented excessive dietary intake of garlic or garlic tablets leading to alterations in coagulation (ie, spinal epidural hematoma, increased clotting time, postoperative bleeding, retrobulbar hemorrhage). 58,  , 63,  Ingestion of large amounts, as reported in case studies, may increase the risk of postoperative and spontaneous bleeding. However, platelet function does not seem to be affected. 2,  , 11,  , 63
Randomized clinical trials and observational studies of garlic-coated tablets have reported mild GI adverse reactions (eg, nausea, bloating, flatulence). Small intestinal obstruction, epigastric and esophageal pain, hematemesis, and hematochezia have been reported in single-case reports. 58,  Hypotensive effects, Ménière disease, and myocardial infarction have also been documented. 58
 
Toxicology
Research reveals little or no information regarding the toxicology of garlic.
 
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