INDEX

Garlic

(Source: SaluGenecists, Inc.)

Summary

Garlic, a cousin to onions, leeks and chives, is arranged in a head, called the \”bulb,\” which is made up of separate tear-drop shaped cloves encased in paper-like sheathes. The cloves themselves are off-white in color and firm in texture, although they can be easily crushed.

The use of garlic in the treatment of a wide variety of conditions has been recorded in the historical documents of virtually every culture. Examples include the medicinal use of garlic being mentioned in Sanskrit texts from approximately 5,000 years ago, Chinese texts from approximately 3,000 years ago and The Codex Ebers, an Egyptian medical papyrus dating to about 1550 BC.

Garlic contains 0.1-0.36% of a volatile oil composed of sulfur-containing compounds, including alliin (S-allyl-L-cysteine sulfoxide), diallyl disulfide, and dialyl trisulfide. Other active constitutents in garlic include alliinase, myrosinase, and peroxidase enzymes; S-methyl-L-cysteine sulfoxide; glucosinolates; vitamins; minerals; and protein.

Diallyl sulfide, dialyl trisulfide and allicin are thought to be responsible for most of garlic’s beneficial pharmacological properties, with the latter being referred to as a thiosulfphanate and being formed from the interaction between alliin and the enzyme alliinase upon the crushing of the garlic bulb. Typical forms used medicinally include fresh garlic cloves or commercial preparations standardized for alliin content.

Garlic exerts a variety of important physiological effects. It has been shown to support immune system function and have broad-spectrum antimicrobial activity. It also has significant anticancer effects and antioxidant activity. Its cardiovascular actions including lipid (cholesterol and triglyceride) lowering, platelet aggregation inhibition, enhancement of fibrinolytic activity, prolongation of bleeding and clotting time, and prevention of LDL oxidation. Additionally, it also possesses anti-inflammatory properties, hypoglycemic actions, digestive effects and cleansing actions. Garlics most important clinical uses are in the areas of infection, cancer prevention, cardiovascular disease, diabetes, asthma and gastrointestinal complaints.

The possible side effects of garlic include a pervasive odor on the breath and skin, gastrointestinal irritation in individuals with infectious/inflammatory gastrointestinal conditions or a lowered Phase II sulfur-detoxification capability (individuals with the latter may also experience headache and nausea), and increased risk of bleeding. Garlic may be contraindicated for individuals who have bleeding disorders, gastrointestinal conditions or diabetes and for those who are taking blood-thinning medications or are having surgery.

Garlic is involved in drug/nutrient/herb interactions with the following: insulin, warfarin, paracetamol, chlorpropamide, saquinavir (Fortovase) and other protease inhibitors, Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), oral contraceptives, chemotherapeutic agents, antifungals, glucocorticoids, cyclosporine, some calcium channel blockers and a few other medications.

Typical dosage varies depending upon the form being used and the health care application for which it is being used.

Key Constituents

Garlic contains 0.1-0.36% of a volatile oil composed of sulfur-containing compounds, including alliin (S-allyl-L-cysteine sulfoxide), diallyl disulfide, and dialyl trisulfide. Other constitutents in garlic include:

  • Enzymes: alliinase, myrosinase, and peroxidase
  • S-methyl-L-cysteine sulfoxide
  • Protein (16.8%, dry weight basis)
  • Glucosinolates
  • Vitamins: vitamin B6, C, thiamin, pantothenic acid
  • Minerals: manganese, selenium, phosphorus, calcium, potassium, copper, iron

Allicin, diallyl sulfide and dialyl trisulfide are thought to be responsible for most of garlic’s beneficial pharmacological properties.

The primary beneficial compounds in garlic, which are called thiosulphanates, are formed when the garlic clove is crushed. Before it is crushed, the potentially active molecules are physically separated from the enzymes that activate them, e.g., alliin is physically separated from the enzyme alliinase. When the garlic clove is crushed, these molecules come together and produce garlics thiosulphanates. Allicin, the predominant thiosulphanate in garlic, comprises 70-80% of the active compounds produced and is mainly responsible for garlics pungent odor. The essential oil of garlic yields approximately 60% of its weight in allicin after exposure to allinase. Within one hour of mashing the garlic, however, garlic’s volatile compounds are destroyed. So, to gain the maximum health benefits of garlic, the clove must be fresh and mashed just prior to consumption. In addition, allinase is inactivated by heat, which is why cooked garlic produces less odor than fresh and not nearly as powerful physiological effects.

Historical Use

Garlic’s usage in the treatment of a wide variety of conditions is documented in the historical documents of virtually every culture. Sanskrit records note the medicinal use of garlic approximately 5,000 years ago; the Chinese have been using garlic medicinally for at least 3,000 years; The Codex Ebers, an Egyptian medical papyrus dating to about 1550 BC, lists garlic as an effective remedy for numerous ailments, including hypertension, headache, bites, worms, and tumors. Among the ancient Greeks, Hippocrates, Aristotle and Pliny cite numerous therapeutic uses for garlic.

Garlic has been used to treat coughs, toothache, earache, dandruff, hypertension, atherosclerosis, hysteria, diarrhea, dysentery, diphtheria, vaginitis, and many other conditions.

In the 1600s, garlic’s powerful therapeutic effects gave rise to the folklore alleging the herb’s ability to ward off vampires. In 1721, four condemned criminals were recruited to bury the dead during a widespread plague in Marseilles. 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.

In 1858, Pasteur noted garlic’s antibiotic activity, and Albert Schweitzer used garlic in Africa to treat amebic dysentery, and as an antiseptic in the prevention of gangrene during the two World Wars.

Physiological Effects

  1. Antimicrobial Activity: antibacterial, anti-fungal, anthelmintic, antiviral
  2. Immune-enhancing Activity
  3. Anti-Cancer Actions
  4. Cardiovascular Actions: lipid (cholesterol and triglyceride) lowering, platelet aggregation inhibition, enhancement of fibrinolytic activity, prolongation of bleeding and clotting time, prevention LDL oxidation
  5. Anti-inflammatory Action
  6. Hypoglycemic Action
  7. Cleansing Actions
  8. Digestive Effects

 

Antimicrobial activity

Garlic has been shown to have broad-spectrum antimicrobial activity against many genera of bacteria, viruses, worms, and fungi. Numerous studies, as far back as 1944 and as recently as 2001, have demonstrated that fresh and vacuum-dried powdered garlic preparations are effective antibiotic agents against a wide range of organisms including:

Bacteria:

  • alpha- and beta-hemolytic Streptococcus
  • Citrobacter sp.
  • Escherichia coli
  • 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

Antibacterial Activity

Many studies have compared garlics antimicrobial effects with and those of commonly used antibiotics, including penicillin, streptomycin, chloramphenicol, erythromycin, and tetracyclines. Not only has garlic demonstrated comparable efficacy, but in these and more recent studies, garlic has been shown to inhibit the growth of some bacteria that have become resistant to one or more antibiotics.

At a recent conference, Dr. Ronald Cutler, a physician at the University of East London, UK, reported his research using a cream containing allicin to successfully eliminate methicillin-resistant Staphylococcus aureus. This drug-resistant strain of Staphylococcus infects hospital patients and is a potential danger for healthcare workers and people with weakened immune systems.

Although these strains of Staph bacteria have developed resistance to commonly used antibiotic drugs, they are unlikely to be able to develop resistance to garlic. Allicin is not effective against every species of bacteria, but those that are susceptible to this compound have never been found to develop resistance to it.

Garlic may also prove helpful against another drug-resistant pathogen, vancomycin-resistant enterococci (VRE). Research presented by Dr. Jaya Prakash of the National University of Health Sciences in Lombard, Illinois, on VRE samples taken from patients with this infection showed that although allicin did not kill the VRE, it did prevent its growth, which suggests that increasing patients consumption of fresh garlic before they enter the hospital might help prevent VRE from establishing itself in their digestive tracts. Dr. Prakah noted that patients sometimes enter the hospital with VREs already in their digestive tracts, or they may contract the infection in the hospital. Once this pathogen takes hold, it can spread to the bladder and to catheters, causing serious and very difficult-to-treat infection.

Garlic administration has also been shown to significantly reduce the number of coliforms and anaerobes in the feces. Garlic is particularly effective against pathogenic bacteria in the colon because up to 20% of the allicin produced when fresh garlic is crushed is not absorbed from the digestive tract, but is excreted in the feces. And, unlike antibiotic drugs, which indiscriminately eliminate all organisms in their path, garlic, while destroying harmful organisms (including E.coli, Staphylococcus aureus, Clostridium perfringens, and Salmonella spp.) does not harm beneficial gut bacteria, such as Lactobacillus acidophilus.

Antifungal Activity

Garlic has demonstrated significant antifungal activity in many in vitro and in vivo studies. Both animal and in vitro studies have shown garlic to be more potent than nystatin, gentian violet, and six other reputed antifungal agents in inhibiting Candida albicans. Aqueous garlic extracts, even at a dilution of 1:100 have been shown in vivo to be very effective against the common Tinea corporis, capitis and cruris fungal skin infections.

In one study at a major Chinese hospital, garlic therapy alone was an effective treatment of cryptococcal meningitis, a potentially deadly fungal infection.

Anthelmintic Activity

Garlic extracts have been shown to have anthelmintic activity against common intestinal parasites, including Ascaris lumbricoides (roundworm) and hookworms.

Antiviral Activity

Garlic has been shown to protect mice from infection with intranasally inoculated influenza virus, and by to enhance neutralizing antibody production when given with influenza vaccine.

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: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. Fresh garlic extract was virucidal against all viruses tested. Virucidal activity of commercial products was dependent upon their preparation processes. Those products producing the highest level of allicin and other thiosulfinates had the best virucidal activity. No antiviral activity was found for alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide.

Immune-Enhancing Activity

A large amount of research has demonstrated garlic’s immune-potentiating actions, most of which are thought to be due to volatile factors released when the enzymes present in garlic combine with its sulfur-containing compounds: allicin, diallyl disulfide, diallyl trisulfide and others. Fresh garlic, commercial products containing allicin, and aged garlic preparations have all shown these properties. Garlic has been shown to enhance the pathogen-attacking activity of T-cells, neutrophils and macrophages, to increase the secretion of interleukin, and to increase natural killer cell activity. In individuals eating the equivalent of two bulbs a day, killer cell activity increased 140%. In those consuming 1,800mg of odorless aged garlic daily, killer cell activity increased 156%.

Anti-Cancer Activity

Hippocrates’ prescription of eating garlic as a treatment for cancer is now being substantiated by animal and human studies. Several components in garlic have displayed significant anti-cancer effects. In animal studies, garlic extracts and allicin have displayed potent antitumor effects. In human studies, garlic has been shown to inhibit the formation of nitrosamines (powerful cancer-causing compounds formed during digestion). Epidemiological studies show an inverse relationship between cancer rates and garlic consumption. In China, a study comparing populations in different regions found that where garlic consumption was high, death from gastric cancers was significantly less than in regions where garlic consumption was low. Recent studies suggest that compounds in garlic or their metabolites may increase the acetylation of core nucleosomal histones and thereby favor cell differentiation.

Cardiovascular Actions

Garlic is protective against heart disease and strokes via its ability to impact the process of atherosclerosis at many steps.

Cholesterol and Triglyceride Lowering Activity

Garlic has been shown to lower blood cholesterol levels while raising HDL cholesterol, even in apparently healthy individuals. Results from numerous double-blind, placebo-controlled studies in patients with initial cholesterol levels greater than 200, show that supplementation with commercial preparations providing a daily dose of at least 10mg alliin or a total allicin potential of 4,000mcg typically lowers lower total serum cholesterol levels by about 1012%; LDL cholesterol by about 15%; and triglyceride levels by 15%. HDL cholesterol levels usually increase by about 10%. The combination of lowering LDL while raising HDL can significantly improve the HDL to LDL ratio, lowering the risk of heart disease and stroke.

Increased dietary intake of garlic and onion has also been shown to lower cholesterol levels. In a 1979 population study, researchers studied three populations of vegetarians in the Jain community in India who consumed differing amounts of garlic and onions. 53 subjects had nearly identical diets, except for the amount of garlic and onions consumed. In the group consuming the highest amount of garlic and onions, numerous favorable effects on blood lipids were noted, including significantly lower cholesterol and triglyceride levels as shown below:

Garlic/onion Cholesterol Triglyceride
None 208 mg/dl 109 mg/dl
10/200 g/week 172 mg/dl 75 mg/dl
50/600 g/week 159 mg/dl

Blood fibrinogen (discussed below) levels were also significantly higher in the group eating no onions or garlic.

In patients with hyperlipidemia, garlic might lower cholesterol levels by the same mechanism as statin drugs, i.e., by acting as an HMG-CoA reductase inhibitor.

Blood Pressure Lowering Activity

In both experimental animal models and humans with hypertension, garlic has demonstrated blood pressure lowering effects. A meta-analysis of eight trials (seven double-blind, one single-blind) with a combined total of 415 subjects

concluded that garlic preparations yielding contain 1.3% alliin at a dosage of 600 to 900mg daily (corresponding to 7.8 and 11.7mg of alliin or the equivalent of approximately 1.82.7g of fresh garlic daily) can lower systolic and diastolic blood pressures over a 1-3 month period. The typical drop from pooled data was 11 mmHg in the systolic and 5.0mmHg in the diastolic. If this degree of blood pressure reduction in hypertensives can be maintained, the risk of stroke may be reduced by 3040% and the risk of heart attack by 2025%.

Garlic is thought to reduce blood pressure by causing smooth muscle relaxation and vasodilation by activating production of endothelium-derived relaxation factor.

Platelet Aggregation Inhibition

Excessive platelet aggregation significantly increases the risk of atherosclerosis, heart disease, and strokes. Garlic preparations standardized for alliin content as well as garlic oil have demonstrated significant inhibition of platelet aggregation. In one study, 120 patients with increased platelet aggregation were given either 900mg/ day of a dried garlic preparation containing 1.3% alliin or a placebo for 4 weeks. In those receiving garlic, spontaneous platelet aggregation disappeared; microcirculation of the skin increased by 47.6%; plasma viscosity decreased by 3.2%; diastolic blood pressure dropped from an average of 74 to 67mmHg; and fasting blood glucose concentration dropped from an average of 90 to 79mg/dl.

Fibrinolytic Activity

Epidemiological studies suggest that excessive fibrinogen formation is a major primary risk factor for cardiovascular disease. Fibrinogen, an acute phase protein involved in the clotting system, also plays many other roles, including several which promote atherosclerosis, such as acting as a cofactor for platelet aggregation, determining the viscosity of blood, and stimulating the migration and proliferation of smooth muscle cells in the intima of the artery walls.

Detailed population studies have supported the link between fibrinogen levels and cardiovascular disease. The first such study, the Northwick Park Heart Study in the UK, involved 1,510 men aged 4064 years who were randomly recruited and tested for a range of clotting factors, including fibrinogen. At 4 years follow-up, a stronger association was found between cardiovascular deaths and fibrinogen levels than for cholesterol. Five additional prospective epidemiological studies have confirmed this association.

Garlic preparations standardized for alliin content as well as garlic oil, and both fried and raw garlic have been shown to significantly increase serum fibrinolytic activity in humans within the first 6 hours after ingestion and continuing for up to 12 hours.

Prevention of LDL Oxidation

Lipoprotein (LDL) oxidation plays a significant role in the development of atherosclerosis since only after LDL has been oxidized does it adhere to the arterial intima initiating the development of arterial plaque. Substances which prevent oxidation of LDL can help prevent or slow down the progression of atherosclerosis. This is considered a primary mechanism of action via which antioxidants such as vitamin E, vitamin C, and beta-carotene provide protection against heart disease.

Garlic is known to exert antioxidant activity, and recent studies confirm its protective effects against LDL oxidation. In one study, healthy human volunteers given 600mg/day of a garlic preparation providing 7.8mg alliin for 2 weeks had a 34% lower susceptibility to lipoprotein oxidation compared with controls. In another study, a placebo-controlled double-blind trial of 23 subjects with coronary artery disease who had one to three major coronary arteries that were at least 75% blocked, subjects were given 300mg of garlic powder or placebo, and their serum was evaluated 2 and 4 hours after a single dose. In the subjects receiving garlic, the atherogenicity of their sera was markedly decreased. Less cholesterol accumulated and lower levels of oxidized LDL were found in human aortic smooth muscle cells cultured with patients sera after treatment compared with those cultured with sera obtained prior to the administration of the garlic. After 3 weeks of therapy at 300mg, three times daily, blood serum atherogenicity had decreased twofold compared with initial levels.

Anti-inflammatory Action

In experimental models of inflammation, garlic extract has demonstrated significant anti-inflammatory activity, most likely due to 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. Allicin and other sulfhydryl compounds in garlic and onions compete with insulin (also a disulfide protein) for insulin-inactivating compounds, thus causing an increase in free insulin. In addition, garlic’s constituents, allylpropyl disulfide and S-allyl cysteine have been shown to stimulate insulin secretion in the pancreas and also to increase hepatic metabolism.

Cleansing Effects

Garlic possesses diuretic, diaphoretic, emmenagogue, and expectorant actions.

Digestive Effects

Garlic is a carminative, anti-spasmodic and digestant, making it useful in cases of flatulence, nausea, vomiting, colic, and indigestion.

Typical Use

Although as noted above, garlic has a wide range of well-documented effects, its most important clinical uses are in the areas of:

  • Infection: effective against a wide range of infections including candidiasis, strep and staph, colds, flu, and Herpes simplex types 1 and 2
  • Cancer prevention: anti-tumor effects, inhibits formation of cancer-promoting compounds, antioxidant effects
  • Cardiovascular disease: cholesterol and blood pressure lowering effects, inhibition of platelet aggregation and fibrinogen formation, antioxidant effects.
  • Diabetes: increases insulin release and the amount of free insulin
  • Asthma: inhibits the formation of inflammatory compounds, antioxidant effects
  • Gastrointestinal complaints: anti-microbial, anti-inflammatory, anti-oxidant effects

Typical Use

  • Fresh garlic cloves
  • Commercial preparations standardized for alliin content providing a daily dose equal to at least 4,000mg of fresh garlic, which translates to at least 10 mg alliin or a total allicin potential of 4,000mcg.

Interactions

  • Insulin: animal studies suggest insulin dose may require adjusting due to hypoglycemic effects of whole garlic (in rats) and its constituent allicin (in rabbits).
  • Warfarin: the anticoagulant activity of warfarin is enhanced due to increased fibrinolytic activity and diminished platelet aggregation caused by garlic components allicin, ajoene, trisulfides, and adenosine. Garlic decreases blood concentrations of warfarin. Theoretically, garlic might enhance effects of other anticoagulant, antiplatelet drugs including aspirin, clopidogrel (Plavix), enoxaparin (Lovenox), and others.
  • Paracetamol: garlic changes pharmacokinetic variables of paracetamol. Chlorpropamide: garlic produces hypoglycaemia when taken with chlorpropamide.
  • Saquinavir (Fortovase): garlic decreases plasma levels of the protease inhibitor saquinavir by up to 54%. Researchers suspect garlic induces cytochrome P450 3A4 metabolism of saquinavir. Prolonged use (10 days) seems necessary for significant induction of CYP3A4. Other protease inhibitors (amprenavir, nelfinavir, ritonavir) may also be affected; patients taking these medications should avoid taking garlic.
  • Other drugs potentially affected by garlic
  • ‘s effects on CYP3A4 include oral contraceptives, some calcium channel blockers (diltiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), glucocorticoids, alfentanil (Alfenta), cisapride (Propulsid), fentanyl (Sublimaze), lidocaine (Xylocaine), losartan (Cozaar), fexofenadine (Allegra), midazolam (Versed), cyclosporine (Neoral, Sandimmune),and others.
  • Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs): Since NNRTIs and protease inhibitors are metabolized through similar routes, garlic could possibly affect NNRTI-type antiretroviral drugs including nevirapine (Viramune), delavirdine (Rescriptor), and efavirenz (Sustiva).

Toxicology

At the dosages recommended, garlic is non-toxic in the vast majority of individuals. In a small percentage of patients, however, it may irritate the digestive tract. Additionally, a small percentage of individuals with a genetically inherited weakness in liver detoxification pathways involving sulfur compounds cannot effectively detoxify allicin or other sulfur-containing compounds. In these individuals, consumption of garlic may cause headache, nausea and gastric irritation.

Prolonged feeding of very large amounts of raw garlic to rats has been found to result in anemic, weight loss and failure to grow.

Contraindications

  • Bleeding disorders: Garlic may increase risk of bleeding and may increase clotting time and is therefore contraindicated in individuals with bleeding disorders.
  • Surgery: Garlic intake should be discontinued 10 days before surgery since garlic may increase blood clotting time.
  • Blood-thinning drugs: Caution should be exercised when prescribing garlic for patients taking blood-thinning medications such as aspirin or warfarin.
  • Gastrointestinal conditions: Caution should be exercised when using garlic in individuals with infectious or inflammatory gastrointestinal conditions as garlic can irritate the gastrointestinal tract.
  • Diabetes: Garlic might, theoretically, cause a reduction in blood sugar levels, thus interfering with blood sugar control, and should therefore be used with caution, particularly in individuals using medications to control blood sugar.