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Garlic

Scientific Name(s): Allium sativum L.
Common Name(s): allium, camphor of the poor, da-suan, Garlic, la-suan, nectar of the gods, poor man's treacle, rustic treacle, stinking rose

Clinical Overview

See also: Orencia

Use

Despite the widespread use of garlic for purposes including cardiovascular health and prevention of the common cold, evidence to support these therapeutic uses is lacking. Garlic does not appear to lower blood glucose, cholesterol, or blood pressure by a clinically significant degree. Extracts of garlic or its chemical constituents may have a role in the prevention of certain cancers; however, adequate clinical evidence is lacking.

Dosing

The following doses have been suggested: 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); 2,400 mg/day of aged garlic extract (liquid). Take with food. Clinical trials have evaluated 180 mg of allicin daily for prevention of the common cold, and at least 5.5 g of raw garlic for the prevention of prostate cancer. Doses of garlic powder used in antihypertensive trials have ranged from 300 to 2,400 mg/day for up to 24 weeks.

Contraindications

Known allergy to garlic and its constituents exists.

Pregnancy/Lactation

Garlic may be used safely in pregnancy and breast-feeding at usual doses. However, consumption by breast-feeding mothers may impact the infant's behavior during breast-feeding, causing prolonged attachment to the breast and increased sucking. Use as an emmenagogue has been documented.

Interactions

See Drug Interactions section.

Adverse Reactions

Body odor and malodorous breath are the most common complaints after garlic ingestion. Mild GI adverse reactions (eg, bloating, flatulence, nausea) have been commonly reported with use. Garlic burns have been documented with topical use. Ingestion of large amounts may increase the risk of postoperative and spontaneous bleeding. Allergy, asthma, pneumonia, contact dermatitis, and anaphylaxis have been reported.

Toxicology

There is little information regarding the toxicology of garlic. Crude garlic fed to rats for 30 days resulted in decreased testosterone levels and altered spermatogenesis.

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 asymmetric in shape, except for those closest to the center. 1, 2, 3

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 by 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. In World War II, garlic extracts were used to disinfect wounds. During the 1800s, physicians routinely prescribed garlic inhalation for the treatment of tuberculosis, and raw garlic applied as a poultice continues to be used by naturopaths today.2, 3, 4

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. The 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), vinyldithiins, and ajoenes. The bulbs contain an odorless, colorless, sulfur-containing amino acid named alliin (S-allyl-L-cysteine sulfoxide), which has no pharmacologic activity of its own. 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, and which further decomposes to diallyl sulfide, -disulfide, -trisulfide, and sulfur dioxide. Allicin gives the pungent characteristic odor to crushed garlic and is believed to be responsible for some of the pharmacologic activity of the plant.2, 3

Uses and Pharmacology

Antifungal

A double-blind, randomized controlled trial in 63 menstruating women found a positive trend but no statistically significant difference in cases of vulvovaginal candidiasis in women treated for 14 days with 2.1 g/day garlic powder (19.2 g/day allicin) compared with placebo. More side effects, mostly GI symptoms such as gastric pain and nausea, were reported in the garlic group (P < 0.01).102

Antimicrobial

Garlic juice and essential garlic oil, water, and ethanol extracts exhibit inhibitory effects in vitro on gram-positive and gram-negative bacteria, as well as fungal pathogens.2, 5

Animal data

Garlic inhibited Helicobacter pylori in in vitro studies and in rodents.6, 7 Garlic has been shown to inhibit Pseudomonas aeruginosa in vitro and in animal models.8

Clinical data

In the an intervention trial conducted in Shandong Province, China, inhibition of H. pylori was described.6, 9 A Cochrane review found few quality trials to evaluate for garlic in the prevention of the common cold. Only 1 trial out of 5 met quality standards (adequate randomization and concealment), finding that 180 mg of allicin daily for 12 weeks resulted in a lower incidence of colds versus placebo.10 Limited clinical studies have evaluated garlic in cystic fibrosis and have found no effect on Pseudomonas aeruginosa infection or on pulmonary function.8, 10, 11

Antioxidant properties

Antioxidant properties have been described, but aside from a role in cancer and hepatoprotection against chemical insult, clinical applications are lacking.25, 63, 64, 65, 66

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 methylallyltrisulfide interference with thromboxane synthesis. Ajoene may also contribute to the observed effects.12, 13, 14, 15

Animal data

Research reveals no relevant animal data regarding the use of garlic as an antithrombotic agent.

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.15 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.16 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,17 and in a double-blind, placebo-controlled study of 14 men, garlic did not affect platelet aggregation.18 In this regard, case studies of a direct causal relationship between garlic consumption and warfarin-related bleeding are lacking. However, there are reports of inhibition of platelet aggregation and increased bleeding times in individuals ingesting garlic. 19, 20, 21, 22

Cancer

Animal data

Animal studies have been conducted with various garlic chemical constituents, as well as with whole garlic.42, 43, 44 Cancers evaluated include esophageal, stomach, colon, renal, prostate, liver, and skin papilloma among others.45, 46, 47, 48

Clinical data

Epidemiological case-control studies suggest an inverse correlation between garlic intake and incidence of colon and gastric cancers, as well as prostate cancer.49, 50, 51, 52, 53, 54 One recent US study did not find benefit for garlic consumption for prevention of colorectal cancer.94 Some studies suggest a similar relationship with breast cancer, esophageal squamous cell cancer, and endometrial cancer.45, 55, 56 Other reviews, including data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, have found no credible evidence for prevention of gastric, breast, lung, and endometrial cancers, and very limited and weak evidence for colon, prostate, esophageal/larynx, ovarian, or renal cancers.54, 57, 58, 59, 60, 61 However, a 2014 meta-analysis reported consumption of garlic was associated with a reduced risk of gastric cancer with "high" intake showing the most significant result (odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38 to 0.62). While heterogeneity of studies was low, the definition of "high intake" varied greatly among studies, ranging from every meal or every day to a few times a month.105 A Chinese case-control study found that consumption of raw garlic reduced the risk for lung cancer.95

A relationship between an increase in allium food consumption (onion and garlic) may exist with a decreased incidence of benign prostatic hyperplasia.62

Colds (ie, upper respiratory infections)

A Cochrane systematic review of data found only one 12-week study (n = 146) that showed significantly fewer cold episodes and days of illness with garlic compared with placebo but similar recovery times between the 2 groups. The reviewers concluded that it was difficult to draw firm conclusions based on evidence from one study.99

Diabetes

Animal data

Results are equivocal, and may be due to a lack of standardization of preparations tested.23, 24, 25 A meta-analysis of animal studies did not find any effect of garlic on glucose levels, but suggested the studies with individual chemical constituents extracted from garlic may affect glucose levels.26

Clinical data

Limited clinical studies have produced equivocal results, and garlic cannot be recommended for routine use in type 2 diabetes.27, 28, 29

Dyslipidemia

Animal data

Garlic is considered relatively nontoxic and the availability of human data makes studies in animals with dyslipidemia irrelevant.

Clinical data

Individual, randomized, controlled trials comparing garlic with placebo have provided disparate results, including those that show no difference versus placebo.30 Heterogeneity exists among trials and poor methodology and a lack of standardization of preparations impedes meta-analysis.31, 32 A meta-analysis pooled data from 39 studies (n = 2,298 adults) of at least a 2-week duration with placebo controls, baseline total serum cholesterol levels greater than 200 mg/dL, and garlic as the sole active treatment. The results were a significant reduction of 17 ±6 mg/dL in total serum cholesterol and an insignificant reduction of 9 ±6 mg/dL in the low-density lipoprotein (LDL) level. Prior systematic reviews and meta-analyses also found only modest reductions in total cholesterol, and no effect on LDL or high-density lipoprotein (HDL) cholesterol. A meta-analysis of 29 trials through November 2007 found a statistically significant decrease in total cholesterol of 0.19 mmol/L or 7.34 mg/dl (95% confidence interval [CI], -0.33 to –0.06 mmol/L) and no effect on LDL or HDL,33 while another meta-analysis of 13 trials through 2008 found no benefit over placebo.34 Garlic cannot be recommended for the management of hyperlipidemia at this stage.30, 33, 34, 35, 36 When contemplating varying results, one must be mindful of factors that might influence outcomes such as differences in the preparations and patient populations. No significant changes were seen in serum triglyceride or high-density lipoprotein levels.91 As an adjunct to conventional medical treatment, the effect of garlic powder supplementation on plasma lipids, lipoproteins, and carotid intima-media thickness (CIMT) was measured to determine cardiovascular risk and progression of atherosclerosis in patients with coronary artery disease. Of the 56 patients who completed the 3-month, randomized, placebo-controlled, single-blind study, those randomized to receive garlic powder tablets (1,200 mcg allicin per tablet twice daily) experienced minor reductions in CIMT from baseline (0.009 ± 0.007 mm), whereas CIMT in the placebo group increased 0.04 ± 0.01 mm. The 3-month mean CIMT difference from baseline was significantly different between the 2 groups (P < 0.001). No significant changes were noted between groups for plasma lipids or lipoproteins.106 Administration of aged garlic extract (2,400 mg/day) for 1 year significantly reduced low-attenuation plaque (LAP) in the coronary arteries of adults with metabolic syndrome compared to placebo in a double-blind, randomized controlled trial (n = 55). Total plaque volume, dense calcium, and noncalcified plaque were not significantly affected.110

A systematic review and meta-analysis of randomized controlled trials investigating the effect of garlic preparations on lipoprotein(a), Lp(a), was conducted in trials published through March 10, 2015. A total of 6 trials met inclusion criteria for the meta-analysis (N = 286). The mean age of patients in all but 1 study ranged from 53 to 60 years who were mildly hypercholesterolemic and/or at moderate to high risk for coronary artery disease; 1 study enrolled patients 8 to 18 years of age with a positive family history. A dosage of 300 mg 3 times daily was administered from 8 weeks to 12 months. Although the meta-analysis did not show a significant change in plasma Lp(a) levels after garlic consumption, subanalysis of trials based on duration of therapy identified a significant improvement in Lp(a) in trials lasting longer than 12 weeks (P < 0.001). This result was supported by meta-regression analysis. The lipid indices that showed significant improvement with garlic supplementation were HDL cholesterol (P = 0.003) and plasma triacylglycerols (P = 0.021). No serious side effects were reported with garlic treatment in any of the trials.114

Hypertension

Animal data

A case report of hypertension and hemolytic anemia in a dog that consumed baked garlic exists.37

Clinical data

Strong evidence for the effect of garlic on blood pressure is lacking. Heterogeneity exists among trials, as well as poor methodology and a lack of standardization of preparations. Systematic reviews and meta-analyses suggest only modest reductions in systolic blood pressure (SBP) where the inclusion criterion was an SBP of at least 140 mm HG. A meta-analysis of 5 trials of adequate quality found no effect.38 Another pooling data from 10 trials found a decrease in SBP of 16 mm Hg (95% CI, −26 to −6) only when participants had a baseline SBP of more than 140 mm Hg39; and a further meta-analysis of 11 trials found a mean decrease in SBP of 10 mm Hg in hypertensive participants.40 A systematic review and meta-analysis of 7 randomized clinical trials from 1988 to 2013 found similar effects on SBP for garlic in hypertensive patients (weighted mean difference [WMD], −6.71 mm Hg) as well as diastolic blood pressure (DBP) (WMD, −4.79 mm Hg); however, overall quality of studies could not be assessed due to insufficient reporting of methodology in some of the trials.107 No effect was demonstrated among normotensive individuals.39, 40 A Cochrane review of garlic’s benefit for reduction of cardiovascular morbidity and mortality concluded there was insufficient outcomes data to determine if garlic was effective.92 Another systematic review and meta-analysis of randomized clinical trials (9 studies; N = 482 hypertensive patients) published through March 2014 found similar results of modest improvements in both SBP and DBP; this review included small study sizes with high heterogeneity.108 A controlled trial randomized elderly patients with systolic hypertension to daily doses of 1, 2, or 4 aged garlic extract capsules, or placebo. None of the garlic groups had a significant reduction in SBP, with the 2-capsule group having a greater reduction than the 4-capsule group. The investigators cited poor compliance in the 4-capsule group as a potential explanation for superior result with 2 capsules.93 Garlic cannot be recommended for the management of hypertension at this stage.38, 39, 40, 41 A meta-analysis, however, investigated the effects of garlic on blood pressure from data of 18 randomized controlled trials published between January 1946 and November 2013 and found a statistically significant improvement in systolic and DBP of 3.75 mm Hg and 3.39 mm Hg (P < 0.001 each) compared to controls, with subgroup analysis favoring benefit in hypertensive patients. Clinical significance of less than a 4 mm Hg reduction is questionable. Doses of garlic powder ranged from 300 to 2,400 mg/day for 2 to 24 weeks.109

The AGE at Heart Trial investigated the effect of aged garlic extract supplementation on blood pressure and other important risk factors of cardiovascular disease, including central blood pressure and arterial stiffness. The double-blind, randomized, placebo-controlled study was conducted in 88 participants with uncontrolled hypertension who were administered 2 capsules daily of Kyolic aged garlic extract (1.2 g aged garlic extract powder and 1.2 mg S-allylcysteine per capsule) or placebo for 12 weeks. Statistically significant reductions from baseline were observed in SBP (mean difference −5 mm Hg; P = 0.016) but not DBP. Subgroup analysis of a proportion of patients (50% to 60%) who were observed to respond to treatment over time revealed statistically and clinically significant average reductions of 11.5 mm Hg SBP and 6.3 mm Hg DBP compared to placebo (P < 0.001). Trends toward improvement in central hemodynamic measures and lipid levels (ie, total cholesterol, LDL cholesterol) were noted. Aged garlic extract was well tolerated.113

Ischemic heart disease

The clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons regarding management of stable ischemic heart disease (2012) recommend that treatment with garlic, coenzyme Q10 (CoQ10), selenium, or chromium should not be used with the intent of reducing cardiovascular risk or improving outcomes in patients with stable ischemic heart disease (strong recommendation; low-quality evidence).90

A randomized, placebo-controlled trial (n = 65) of aged garlic extract plus CoQ10 showed significant improvements in vascular elasticity (pulse-wave velocity) and endothelial function (digital thermal monitor area under the temperature curve) compared with placebo after treatment for 1 year. C-reactive protein levels compared with baseline were reduced in the treatment group, and higher than baseline in the placebo group. No hard outcomes data from the study period were reported.96

Liver disease

In South Korean patients with mild hepatic dysfunction and an elevated gamma-glutamyl transpeptidase (GGT), administration of fermented garlic extract (1.5 g/day) for 12 weeks provided a significant decrease in GGT compared to controls but only in the subgroup of patients who consumed alcohol in the 6 weeks prior to the study (P=0.015). Additionally, ALT, global fatigue severity, and situation-specific fatigue were significantly improved with fermented garlic extract compared to controls (P=0.014, P=0.018, and P=0.011, respectively). Of the 80 participants enrolled in this double-blind, randomized, placebo-controlled study, data from 75 were included in the efficacy analysis. The intervention was well tolerated with no significant difference in adverse events observed between groups. The most frequent side effects reported with the garlic extract was dyspepsia and gastritis.116

Osteoarthritis (OA) prevention

A cross-sectional study of dietary intake of twins found that those consuming diets high in fruits and vegetables had a lower incidence of hip OA. Non-citrus fruits and alliums had the highest protective effects.98

Peripheral vascular disease

A Cochrane systematic review found little data on the benefit of garlic in peripheral arterial occlusive disease. The reviewers found one 12-week study (n = 78) that showed no significant difference between garlic and placebo for pain-free walking distance improvement, SBP and DBP, heart rate, or brachial or ankle pressures.97

Prenatal

A Norwegian cohort study evaluated dietary factors associated with reduced risk for spontaneous pre-term delivery (PTD), and found significantly lower PTD risk for those who consumed dried fruits and alliums, The strongest risk reduction was seen with garlic.100

Tinnitus

The American Association of Otolaryngology – Head and Neck Surgery clinical practice guidelines for tinnitus (2014) recommend against the use of garlic or other dietary supplements for treating patients with persistent, bothersome tinnitus (moderate-quality aggregate evidence).104

Dosing

Garlic dosage is complicated by the volatility and instability of important constituents and by the availability of multiple products, such as deodorized garlic, aged extracts (a popular deodorized form of garlic), and distilled oils. Time-release garlic powder capsules are also being used in clinical studies.67

One resource suggests 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); and 2,400 mg/day aged garlic extract (liquid).2, 110

Clinical trials have evaluated 180 mg of allicin daily for prevention for the common cold,11 and at least 5.5 g of raw garlic for the prevention of prostate cancer.49

Administer with food to prevent GI adverse reactions.2

Pregnancy / Lactation

Garlic may be used safely in pregnancy and lactation.2 In 8 breast-feeding mothers, garlic odor in breast milk peaked after 2 hours of ingestion and decreased thereafter. Breast milk that smells of garlic may prolong infant attachment to the breast and increase sucking.68 A Cochrane review identified only 1 trial (100 women) showing no clear difference between garlic and placebo ingestion in preeclampsia and gestational hypertension risk, or in incidences of cesarean delivery and perinatal mortality.69 Use of garlic as an emmenagogue has been documented.70

Interactions

Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.71, 72, 73, 74

Anticoagulants: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur. Consider therapy modification.71, 72, 73, 74

Herbs (anticoagulant/antiplatelet properties): May enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.71, 72, 73, 74

Hypoglycemic agents: Herbs (hypoglycemic properties) may enhance the hypoglycemic effect of hypoglycemic-associated agents. Monitor therapy.75

Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.71, 72, 73, 74

Protease inhibitors: Garlic may decrease the serum concentration of protease inhibitors. Consider therapy modification.76, 77, 78, 79

Salicylates: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur. Consider therapy modification.71, 72, 73, 74

Thrombolytic agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur. Consider therapy modification.71, 72, 73, 74

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. Randomized clinical trials and observational studies of garlic-coated tablets have reported mild GI adverse reactions, including nausea, bloating, and flatulence. Obstruction of the small intestine, epigastric and esophageal pain, dysphagia, hematemesis, and hematochezia have been reported in single case reports.80, 101

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.80 The consumption of milk prior to garlic ingestion may reduce bad breath.81

Ingestion may rarely cause anaphylaxis.59, 111 Asthma and immunoglobulin E-mediated hypersensitivity, including dermatitis, have been documented. Current drug therapy with omeprazole may facilitate sensitization to food allergens.111 Cross-sensitivity to other members of the Liliaceae family, Amaryllis family (Amaryllidaceae), and asparagus may be observed.80, 82, 83, 84, 85, 111 A case of black-garlic-induced pneumonia was documented in a 77-year-old female who presented with dyspnea and coughing. Drug-induced lymphocyte stimulation test results for both black and raw garlic were positive. Symptoms improved over the next 9 months of a tapered prednisolone regimen and cessation of garlic.115

Case reports of garlic burns following the application of raw garlic poultices exist,4, 86, 87 including an unusually severe case that developed when a garlic and salt paste was covered for 3 hours with an occlusive dressing.103

Case reports have documented alterations in coagulation, spinal epidural hematoma, increased clotting time, postoperative bleeding, and retrobulbar hemorrhage after excessive dietary intake of garlic or garlic tablets. However, platelet function does not seem to be affected.17, 21, 71, 80, 88 Hypotensive effects, Ménière disease, and myocardial infarction have also been documented.80

Based on observed pharmacologic activity, garlic should be used with caution in individuals at risk of hypotension39, 40 and hypoglycemia.27, 28, 29

In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, garlic has been recognized as a product with antiplatelet activity which may increase bleeding risk when used with anticoagulants. The guidance noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].112

Toxicology

Information regarding the toxicology of garlic is limited. Crude garlic fed to rats for 30 days resulted in decreased testosterone secretion and altered spermatogenesis.89 A case report documents severe anemia and hypertension from toxic erythrocyte hemolysis in a dog that ingested baked garlic.37

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