Garlic oil is obtained by steamed distillation of the crushed fresh bulbs.¹ These volatile compounds are generally considered responsible for most pharmacologic properties of garlic. Other constituents of garlic include the following^1,²:

Allicin is mainly responsible for garlic’s pungent odor. It is formed by the action of the enzyme alliinase on the compound alliin. The essential oil of garlic yields approximately 60% of its weight in allicin after exposure to alliinase. The enzyme is inactivated by heat, which accounts for the fact that cooked garlic produces neither as strong an odor as raw garlic nor nearly as powerful physiologic effects.¹

History and Folk Use

Garlic has been used throughout history for the treatment of a wide variety of conditions. Its usage predates written history. Sanskrit records document the use of garlic remedies approximately 5000 years ago, whereas the Chinese have been using it for at least 3000 years. The Codex Ebers, an Egyptian medical papyrus dating to about 1550 BC, mentions garlic as an effective remedy for various ailments, including hypertension, headache, bites, worms, and tumors. Hippocrates, Aristotle, and Pliny cited numerous therapeutic uses for garlic. In general, garlic has been used throughout the world to treat coughs, toothache, earache, dandruff, hypertension, atherosclerosis, hysteria, diarrhea, dysentery, diphtheria, vaginitis, and many other conditions.¹^–³

Stories, verse, and folklore (such as its alleged ability to ward off vampires) give historical documentation to garlic’s power. Sir John Harrington, in writing The Englishman’s Doctor in 1609, summarized garlic’s virtues and faults ³:

Garlic then have power to save from death

Bear with it though it maketh unsavory breath,

And scorn not garlic like some that think

It only maketh men wink and drink and stink.

In 1721, during a widespread plague in Marseilles, France, four condemned criminals were recruited to bury the dead. The gravediggers proved to be immune to the disease. Their secret was a concoction they drank consisting of macerated garlic in wine. This became known as vinaigre des quatre voleurs (“four thieves” vinegar), and it is still available in France today.

Garlic’s antibiotic activity was noted by Pasteur in 1858. Garlic was used by Albert Schweitzer in Africa to treat amebic dysentery and as an antiseptic in the prevention of gangrene during World Wars I and II.

Pharmacology

Although garlic has a wide range of well-documented effects, its most important clinical uses are in the areas of infection, cancer prevention, and cardiovascular disease.

Antimicrobial Activity

Garlic has broad-spectrum antimicrobial activity against many genera of bacteria, viruses, worms, and fungi, as summarized in several works.⁴^–⁷ These findings support the historical use of garlic in the treatment of various infectious conditions.

Antimicrobial Effects

Antibacterial Activity

Dating back to 1944, studies demonstrated that both garlic juice and allicin inhibited the growth of Staphylococcus, Streptococcus, Bacillus, Brucella, and Vibrio species at low concentrations.⁷^–⁹ In more recent studies, using serial dilution and filter paper disk techniques, fresh and vacuum-dried powdered garlic preparations were found to be effective antibiotic agents against many bacteria, as listed in Box 63-1.⁴^–⁷ ^,10 ^,11 In these studies, the antimicrobial effects of garlic were compared with commonly used antibiotics, including penicillin, streptomycin, chloramphenicol, erythromycin, and tetracyclines. Besides confirming garlic’s well-known antibacterial effects, the studies demonstrated its efficacy in inhibiting the growth of bacteria that had become resistant to one or more of these antibiotics.⁷

BOX 63-1 Clinical Relevant Microbes Inhibited by Garlic

• Bacteria

• Alpha- and β-hemolytic Streptococcus

• Citrobacter spp.

• Escherichia coli

• Helicobacter pylori

• Klebsiella pneumoniae

• Mycobacteria

• Proteus vulgaris

• Salmonella enteritidis

• Staphylococcus aureus

• Fungi

• Candida albicans

• Cryptococcus neoformans

• Helminths

• Ascaris lumbricoides

• Hookworms

• Viruses

• Herpes simplex types 1 and 2

• Human rhinovirus type 2

• Parainfluenza virus type 3

• Vaccinia virus

• Vesicular stomatitis virus

Data from references 4–7, 10, 11.

Garlic administration has also been shown to significantly reduce the number of coliforms and anaerobes in the feces.¹² One clinical application of garlic’s antibacterial activity may be in the treatment of Helicobacter pylori, because a clinical investigation indicated that garlic intake for long durations (years) was associated with a significantly lower average antibody titer. This suggests an indirect inhibitory effect on the reproduction of H. pylori and possibly progression to more serious peptic ulcer diseases.¹³

Antifungal Activity

Garlic demonstrated significant antifungal activity in many in vitro and in vivo studies.^4,¹⁴^–¹⁹ From a clinical perspective, inhibition of Candida albicans has the most significance, because both animal and in vitro studies showed garlic to be more potent than nystatin, gentian violet, and six other reputed antifungal agents.^4,¹⁵^–¹⁷ Although allicin and the volatile oil fraction are clearly the most potent active anticandida components,^20,²¹ aqueous garlic extracts have been shown in vivo to be effective, even at a dilution of 1:100, against the common tinea corporis, capitis, and cruris fungal skin infections.¹⁵

In one study at a major Chinese hospital, garlic therapy alone was used effectively in the treatment of cryptococcal meningitis, one of the most serious fungal infections imaginable.¹⁸

Anthelmintic Effects

Garlic extracts have anthelmintic activity against common intestinal parasites, including Ascaris lumbricoides (roundworm) and hookworms.^12,²²

Antiviral Effects

Garlic’s antiviral effects have been demonstrated by its protection of mice from infection with intranasally inoculated influenza virus and by its enhancement of neutralizing antibody production when given with influenza vaccine.²³

The in vitro virus-killing effects of fresh garlic, allicin, and other sulfur components of garlic were determined against herpes simplex types 1 and 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity was the following:

ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate

Ajoene was found in oil macerates of garlic but not in fresh garlic extracts. No antiviral activity was found for alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract was virucidal against all viruses tested. Virucidal activity of commercial products was dependent on their preparation processes. Those producing the highest level of allicin and other thiosulfinates had the best virucidal activity.²⁴ The antiviral activity of an allicin-containing garlic supplement was investigated in 146 subjects randomized to receive a placebo or an allicin-containing garlic supplement, one capsule daily, over a 12-week period.²⁵ The garlic-treatment group had significantly fewer colds than the placebo group (24 vs 65 patients). The placebo group, in contrast, recorded significantly more days challenged virally (366 vs 111 patients) and a significantly longer duration of symptoms (5.01 vs 1.52 days). This study indicates that allicin-containing garlic supplements can prevent the common cold virus.

Immune-Enhancing Effects

Extensive research has shown that garlic has many immune-potentiating properties, most of which are thought to be due to volatile factors composed of sulfur-containing compounds: allicin, diallyl disulfide, diallyl trisulfide, and others. For example, in vitro studies with allicin showed that it stimulated enhanced cell-mediated cytotoxicity in human peripheral mononuclear cells. In animal models, multiple administration of allicin elicited marked antitumor effects via immunostimulatory mechanisms.²⁶ Fresh garlic, commercial products containing allicin, and aged garlic preparations have all shown these immune-enhancing properties. Garlic has been shown to enhance the pathogen-attacking activity of T cells, neutrophils, and macrophages, which increase the secretion of interleukin and natural killer (NK) cell activity.²⁷^–³⁰ The increase in killer cell activity was a remarkable 140% in those who ate the equivalent of two bulbs a day and 156% in those who consumed 1800 mg of odorless, aged garlic.

Anticancer Effects

The famous Greek physician Hippocrates prescribed eating garlic as a treatment for cancer. Animal research and some human studies suggest this may have been well-founded advice. It must be kept in mind that much of garlic’s anticancer effect is likely an indirect effect via its impact on the immune system. Nonetheless, several garlic components have displayed significant anticancer effects, including enhancing phase II metabolizing enzymes, antioxidant properties, inhibition of the formation of nitrosamines, direct tumor growth inhibition, and the ability to induce apoptosis.³¹^–⁴⁹ Human studies showing garlic’s anticancer effects are largely based on epidemiologic studies.³¹^–³⁵ These studies typically show an inverse relationship between cancer rates and garlic consumption. Human studies have also shown that garlic inhibits the formation of nitrosamines (powerful cancer-causing compounds formed during digestion).^45,⁴⁶

Cardiovascular Effects

Garlic appears to be an important protective factor against heart disease and strokes via its ability to affect the process of atherosclerosis at many steps. Since there is substantial clinical information on garlic’s beneficial effects on the cardiovascular system, the pharmacology is discussed later in the section on “Clinical Applications”.

Other Effects

Antiinflammatory Effects

Garlic extract has demonstrated significant antiinflammatory activity in experimental models of inflammation.^2,¹² This activity is probably a result of garlic’s inhibition of the formation of inflammatory compounds.

Hypoglycemic Action

Garlic and onions have often been used in the treatment of diabetes. Allicin has been shown to have significant hypoglycemic action. This effect is thought to be due to increased hepatic metabolism, increased release of insulin, and the insulin-sparing effect.⁵⁰ The latter mechanism appears to be the major factor, because allicin and other sulfhydryl compounds in garlic and onions compete with insulin (also a disulfide protein) for insulin-inactivating compounds, which results in an increase in free insulin.

Interestingly, when allicin was administered to groups of rats fed a high-fructose diet, the control group that was fed a diet enriched by fructose alone continued to gain weight, whereas the groups fed allicin did not.⁵¹ This study indicates that garlic may have some practical use in weight control.

Miscellaneous Effects

Garlic possesses diuretic, diaphoretic, emmenagogue, and expectorant action.^1,¹⁰ It is also a carminative, antispasmodic, and digestant, making it useful in cases of flatulence, nausea, vomiting, colic, and indigestion.^12,⁵²

Commercial Preparations

The modern use of garlic primarily features the use of commercial preparations designed to offer the benefits of garlic without the odor. The marketplace is swamped with garlic products, and each manufacturer claims its product is the best. However, there are vital considerations when choosing a garlic product to prescribe. First, if the primary goal is to lower cholesterol or blood pressure, as well as exert immune-enhancing or antimicrobial effect, it is important to ensure that the product provides a sufficient level of allicin. Because allicin is not actually in the product at significant levels, manufacturers often refer to the allicin potential or allicin yield. These terms signify the amount of allicin produced when allinase is activated in the garlic tablet or powder.

The next issue is not so simple to tell from a label. It involves the quality and character of the enteric coating of the tablet. For the allicin to be liberated within the intestinal tract, the tablet must not only be resistant to the stomach’s acid, it must disintegrate rapidly when it reaches the small intestine. According to research conducted by the renowned garlic experts Lawson et al,⁵³ when 24 brands of enteric-coated garlic were analyzed for tablet dissolution using an approved method (U.S. Pharmacopoeia dissolution method 724A), only one brand released the amount of allicin claimed on the label. The second-best brand released only 44% of its label claim, and 75% of the brands released less than 10% of their label claim. Failure to deliver an effective dosage of allicin most assuredly does not lower cholesterol or blood pressure.

Why so many garlic products fail to deliver allicin is basically due to two major problems. First, many of the garlic products contained little alliinase activity. Alliin was plentiful, but because the activity of alliinase was low, the level of allicin formed was also low. Next, many tablets contained excipients (e.g., binders and fillers) that actually inhibit alliinase activity. The alliinase activity in 63% of the brands was less than 10% of the expected activity. The inability to release an effective dose of allicin would explain why so many studies on garlic supplements fail to show benefits in lowering cholesterol or blood pressure.⁵⁴ For example, studies done on one particular garlic supplement before 1993 were mostly positive. The results from these positive studies were the main reason garlic supplements have been allowed to refer to cholesterol-lowering activity in Germany and the United States. However, most studies published since 1995 have failed to show a consistent effect in lowering cholesterol.⁵⁵^–⁵⁷

Although the authors of the negative studies on garlic believed that the underlying reason for the results was a better-designed study, a more likely explanation is that they were due to a poorer quality tablet. Specifically, research conducted by Lawson showed that tablets manufactured before 1993 were twice as resistant to disintegration in acid as tablets manufactured after 1993, and that the older tablets released three times the amount of allicin than the more recently manufactured tablets.⁵³ Examination of package labels shows several changes in tablet excipients between the pre-1993 and post-1993 tablets. Again, these excipients are believed to block allinase activity.

Importantly, most studies that show a positive effect of garlic and garlic preparations in reducing cholesterol and blood pressure are those that use products that deliver a sufficient dosage of allicin, other garlic components such as S-allylcysteine, and garlic extracts (e.g., aged garlic extract [AGE]) that protect against atherosclerosis via additional mechanisms, including protection against low-density lipoprotein (LDL) oxidation and improvement of endothelial cell function.

Kyolic, the AGE manufactured by the Wakunaga Wakunaga Pharmaceutical Co., Ltd. (Osaka, Japan), is a highly standardized AGE produced by extraction and aging of organic fresh garlic, at room temperature, for 20 months. The process increases antioxidant levels and converts allicin to mostly stable water-soluble organosulfur compounds, such as S-allylmercaptocysteine and S-allylcysteine. These compounds have a high bioavailability and considerable antioxidant effects.^58,⁵⁹ AGE has minimal cholesterol-lowering and antimicrobial effects, but based upon good clinical data, it does have antiatherosclerotic, antiaging, and anticancer effects.

The antioxidant effects of AGE have been shown to prevent LDL oxidation ⁹⁶ as well as improve endothelium-dependent vasodilation via increased nitric oxide production and decreased output of inflammatory cytokines. In a double-blind, placebo-controlled, cross over study in 15 men with angiographically proven coronary artery disease, AGE supplementation for 2 weeks significantly improved brachial artery flow-mediated endothelium-dependent dilation by 44%.⁹⁷ In a double-blind study of AGE in normal, healthy individuals, dosages between 2.4 and 7.2 g/day were shown to produce a dose-dependent selective inhibition on platelet aggregation and adhesion.⁶⁰ In a 1-year study, AGE was shown to produce a modest reduction in the calcium score of 7.5, determined by electron beam tomography, whereas the placebo group demonstrated an average increase in calcium scores of 22.2.^61,⁶²

Epidemiologic and animal studies suggest AGE and its organosulfur constituents, such as S-allylcysteine and S-allylmercaptocysteine, have anticarcinogenic effects. Several clinical studies validated an anticancer effect for AGE. In one double-blinded study in patients with colorectal polyps using high-AGE (AGE 2.4 mL/day) and low-AGE (AGE 0.16 mL/day) doses, in 37 patients chosen as efficacy evaluated subjects, 47.4% (9/19 patients) in the high-AGE and 66.7% (12/18 patients) in the low-AGE group had at least one new adenoma for the first and second interval (0 to 12 months after intake). The decrease rate of at least one adenoma was 50.0% (7/14 patients) in the high-AGE group for the second interval (6 to 12 months after intake), whereas there was no decrease in subjects in the low-AGE group.⁶³ The difference from baseline for total size of adenomas increased in the low-AGE group, whereas an increase in the high-AGE group was suppressed for the second interval. The difference from baseline for the total size of adenomas in subjects who had adenomas at baseline increased in the low-AGE group and decreased in the high-AGE group for the second interval. The results of this study suggest the possibility of preventive and therapeutic effects of AGE on colorectal adenomas, although it would be necessary to investigate these results in larger scale and longer term trials.

In a double-blind study in patients with advanced cancer, the primary end point used was a quality of life (QOL) questionnaire based on the Functional Assessment of Cancer Therapy. The sub-end points were changes in the NK cell activity and the salivary cortisol levels before and after administering AGE. The group consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group.⁶⁴

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