Garlic

Plant Part Used

Bulb

Active Constituents

Primarily sulfur containing compounds (alliin – converted to allicin in vivo, diallylsulfides, S-allyl-cysteine, ajoenes among others), enzymes (including alliinase), glucosinolates, vitamins A, B, and C.(1),(65) Garlic is reported to contain about 1% alliin, which converts to allicin in the presence of the enzyme alliinase.

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Garlic has been used as a medicine for over 5000 years by more cultures than perhaps any other plant. Garlic originated in central Asia, but it is now found in Europe, North Africa, Asia, and North America. Traditionally garlic has been a remedy for abnormal growths, bronchitis, pneumonia, digestive problems, intestinal infections, tuberculosis, dysentery, earaches and infections, vascular disorders of many kinds, and poor circulation. Today, garlic extracts are used mainly for cardiovascular protection and immune effects.

Common garlic dietary supplements include garlic powder (or dehydrated garlic), aged garlic extract, and garlic oil extract (macerated or heat-distilled). However, garlic supplements differ widely in their properties and contents, hence variances in clinical study outcomes.  Many positive clinical studies have been reported using a proprietary aged garlic extract (AGE), enteric coated products and timed release products.

Ethnocultural studies have shown that cultures with a high garlic intake have an inverse relationship to their cultures’ cancer rates.(3)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

600-900mg daily of enteric coated garlic in three divided doses, standardized to 1.3/0.6% alliin/allicin-yield

Aged garlic extract, 300-1200mg tablets daily in divided doses; or ¼-½ teaspoon (300-600mg); or 30-60 drops with a meal twice daily.

Time-release garlic, 650mg daily.

Most Common Dosage

600mg daily of garlic in three divided doses, standardized to 1.3% 1.3/0.6% alliin/allicin-yield

Aged garlic extract (Kyolic), 600mg tablets daily in divided doses; or ¼ teaspoon (300mg); or 30 drops with a meal twice daily.

Time-release garlic, 650mg daily.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 1.3.0.6% alliin/allicin yield; aged garlic products should be standardized to contain 1mg/gm S-allyl cysteine (SAC) content.

Uses

Frequently Reported Uses

  • Cardiovascular protection; may lower blood pressure, cholesterol levels and homocysteine
  • Cancer proctection
  • Immune support
  • Antioxidant
  • Inhibits H. pylori

Other Reported Uses

  • Stress and fatigue
  • Protects against diabetes associated risks
  • Vascular support
  • Neuroprotective
  • Hepatoprotective

Toxicities & Precautions

General

No toxicity is reported in recommended dosages.(4) It is recommended that very large doses of garlic not be ingested over a long period of time.(5)

Side Effects

Some individuals may experience GI distress or irritation when beginning use.(6)

Odorless garlic products are available for those requiring less residual smell from the garlic bulb.

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Cardiovascular

Garlic’s benefits on the cardiovascular system are one of the main reasons this supplement is so popular around the world. Garlic has been reported to lower total cholesterol, LDL cholesterol and triglycerides, and increases HDL cholesterol in laboratory studies and human trials, although results have been controversial.(10),(12),(13),(14),(15), Garlic may be of benefit in the prevention of heart disease and atherosclerosis.(16),(17) Garlic has been reported in laboratory studies to  inhibit platelet aggregation and influence blood viscosity through its fibrinolytic activity.(18),(19),(20),(21) This activity leads to the use of garlic in the supportive treatment of cardiovascular disease (CVD) and CVD risk factors.(22),(23),(24) A human study of 13 normolipidemic patients reported that aged garlic extract significantly inhibited both the total percentage and initial rate of platelet aggregation.(25)

A meta-analysis of randomized, double-blind, placebo-controlled trials of garlic’s utility in hypercholestrolemia was reported in 2000.(26) In the 13 trials included in the report, the garlic supplements reduced total cholesterol level from the baseline significantly more than placebo, with a conclusion that the available data suggests that garlic is superior to placebo in reducing total cholesterol levels. The authors concluded, however, that the size of the effect is modest, and the robustness of the effect is debatable, and the use of garlic for hypercholesterolemia may be of questionable value.

Reports of garlic products having no effect on serum lipids has been seen in various studies, and remains a controversial issue.(6),(27),(28),(29),(30) Another analysis in 2009 Looked at MEDLINE, CINAHL and the Cochrane Database from the earliest published date through to November 2007 in order to identify randomized, placebo-controlled trials of garlic that reported effects on total cholesterol (TC), triglyceride (TG) concentrations, LDL or HDL. Twenty-nine trials were included garlic was found to significantly reduce TC and TG but exhibited no significant effect on LDL or HDL.(68) The authors concluded that future studies should be conducted evaluating the impact of adjunctive garlic therapy with fibrates or statins on TG concentrations.

Several studies used garlic oil to treat hypercholesterolemia, which is processed by heating to extreme temperatures. Changes can occur in the active constituents when exposed to cooking or other processing which can render the garlic product virtually ineffective.(31) Cooking is known to denature proteins and, therefore, may inactivate the enzyme (allinase) that is necessary in converting alliin into allicin, the major bio-active constituent in garlic. Powdered garlic supplements can lose bioactivity due to organosulfur compounds and not be effective.(69) It is imperative to use standardized supplements, including timed release, enteric coated and aged garlic. Aged garlic extracts (AGE) have laboratory and human studies that have antioxidant activity by increasing superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibiting lipid peroxidation and inflammatory prostaglandins. AGE has been reported to have cardiovascular benefits by reducing cholesterol synthesis through ihibition of 3-hydroxy-3-methylglutaryl-CoA reductase (may have an additive effect with statins in its action,), inhibition of cholesterol, LDL oxidation, and platelet aggregation, inhibition of arterial plaque formation, decreasing homocysteine, lowering blood pressure, and increasing microcirculation, also important in diabetes related complications. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemia- or reperfusion-related neuronal death and improving learning and memory retention. More studies in humans are warranted.(70)

Garlic use has been reported to be beneficial in hypertension in laboratory animals and human subjects.(32),(33),(34) A meta-analysis in 1994 found that garlic supplements were clinically useful in treating mild hypertension, although the authors stated that further research should be performed in this area.(35) A 2008 systematic review and meta-analysis of randomized controlled trials reviewed the literature of using garlic for hypertension.(71) The conclusion of the analysis was that garlic was superior to placebo in reducing systolic and diastolic blood pressure. A recent study reported that individuals whose blood pressures are on the lower side are more likely to consume more garlic in their diets.(36) Studies have reported that garlic’s ability to lower blood pressure may in part be due to the decreased production of nitric oxide by the activation of inducible nitric oxide synthase.(37),(38) However, current laboratory animal data has reported that pulmonary vasodilator responses to allicin are independent of the synthesis of nitric oxide, ATP-sensitive K+ channels, activation of cyclo-oxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed.(39) Other methods attributing to garlic’s hypotensive qualities may include its anti-thrombotic activity.(40)

A comprehensive meta-analysis in 2001 assessed the impact of garlic supplementation on cardiovascular risk factors. Forty-five randomized trials and 73 additional studies reporting adverse events were identified and assessed. Trials evaluating lipid outcomes were adjusted for any differences that existed in baseline characteristics. Compared with placebo, the effect on total cholesterol, low-density lipoprotein levels, and triglyceride levels of garlic preparations may lead to small improvements at 1 and 3 months. When evaluated at 6 months no improvements were noted. Also the evaluators noted no statistically significant changes in high-density lipoproteins. Significant reductions in platelet aggregation were reported, the effects on blood pressure outcomes were "mixed" and concerning glycemic-related outcomes, no effects were noted. The authors stated that the clinical significance of the trials evaluated was limited by the quality of the studies, the short duration of the studies and the lack of information regarding the garlic preparations used in the studies.(41)

Several clinical studies out of Russia using a timed-released product found positive effects on hypertension (both systolic and diastolic and to lower total cholesterol levels and also raise HDL. (72),(73)

Immune support/Cancer

Garlic has been found to improve immunity in both laboratory and clinical studies. Aged garlic has been reported in a clinical study to improve immunity of patients with advanced cancer (including colorectal, liver and pancreatic) by improving NK cell numbers and activity, thereby helping to improve the quality of life in these patients.(74) Garlic is also reported to stimulate macrophage and LAK cell activity, and to increase the production of IL-2, TNF, and interferon-gamma.(75) The organosulfur components of garlic are reported to be responsible for the immune modulation.(76)

Garlic is reported in laboratory studies to detoxify chemical carcinogens and prevent carcinogenesis, along with directly inhibiting the growth of cancer cells.(42),(43) Garlic is reported to inhibit nitrosamine formation, which has lead to it being studied in cancer therapy.(3) Garlic and its components have been reported active against various cancers in vitro, including cancerous cell lines from the human bladder,(44) certain hepatic cells lines,(45) some breast cancer cell lines,(46),(47) prostate,(48) and some colorectal and stomach cancers(49),(50),(51),(77) among others.

Organosulfur compounds originating from garlic have been found in laboratory studies to inhibit carcinogen activation, boost phase 2 detoxifying processes, cause cell cycle arrest mostly in G2/M phase, stimulate the mitochondrial apoptotic pathway and increase acetylation of histones.(78) Garlic-derived sulfur compounds influence also gap-junctional intercellular communication and participate in the development of multidrug resistance.

Several population studies show an association between increased intake of garlic and reduced risk of certain cancers, including cancers of the stomach, colon, esophagus, pancreas,(79),(80) and breast. An analysis of data from seven population studies showed that the higher the amount of raw and cooked garlic consumed, the lower the risk of stomach and colorectal cancer.

A 2009 literature search using the Medline and EMBASE databases for the period 1955-2007 found there was no credible evidence to support a relation between garlic intake and a reduced risk of gastric, breast, lung, or endometrial cancer, and there is very limited evidence supported a relation between garlic consumption and reduced risk of colon, prostate, esophageal, larynx, oral, ovary, or renal cell cancers.(81)

A Cochrane Database search in 2009 of randomized, controlled trials using garlic in preventing and treating the common cold.(82) Although the number of days of illness was lower in the garlic group compared with the placebo group, the number of days to recovery was similar in both groups. The authors concluded there is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold.

Other Uses

Garlic has been reported in laboratory and clinical studies to have antioxidant activity, A small clinical trial found that garlic significantly lowered plasma and erythrocyte pro-oxidant levels and to increased activities of some antioxidant enzymes, including glutathione peroxidase and superoxide dismutase.(83) Garlic’s antioxidant activity contributes to its positive health effects, including for cardiovascular disease, liver health, anti-cancer effects, sickle cell anemia, BPH, and others.(84),(85),(86),(87)

Garlic supplements have been used for centuries for blood sugar regulation. Laboratory and clinical studies support the use of garlic in blood sugar regulation, including aged garlic and timed release supplements. Evidence suggests that garlic's anti-oxidative, anti-inflammatory, and anti-glycative properties are responsible for garlic's role in preventing diabetes progression and the development of diabetes-related complications.(88) A small clinical study found that timed release garlic helps lower fasting blood sugar levels in patients with type 2 diabetes.(89) An in vitro study found that aged garlic inhibits formation of advanced glycation endproducts (AGEs), potentially decreasing AGEs associated diabetic complications.(90) Further clinical studies need to be performed using garlic preparations for diabetes related health problems.

Allicin and alliin are reported to have anti-infective effects against bacteria and fungi.(7),(8),(9) It is thought that garlic either helps in increasing the release of insulin or has insulin-sparing properties.(10) Garlic also has reported antigiardial activity in vitro.(11)

Garlic has been reported in laboratory studies to inhibit Helicobacter pylori, a causative agent in peptic ulceration.(58),(59) A small clinical study found garlic oil to be effective in treating dyspeptic patients with H. pylori infection.(91) A study reported no activity against H. pylori, but freshly chopped garlic was used in the study, which can destroy necessary enzymes unless preserved appropriately.(60) Research has reported that the enzyme allinase may be irreversibly inhibited by stomach acid and may fail to form adequate amounts of allicin or other thiosulfinates below pH 3.6.(61),(62) Recommending a quality garlic supplement is essential, and enteric coating may be advantageous.

An aged garlic product has been reported to have hepatoprotective properties.(53) It is suggested that the hepatoprotective effects of the garlic product are due primarily to the reduced glutathione-sparing properties of its constituents, most probably its organosulphur compounds. Diallyl sulfide compounds extracted from garlic were reported useful in combination with doxorubicin to protect the liver from oxidative injuries due to the chemotherapy drug and to improve the clinical efficacy of doxorubicin.(54) Also, S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur compounds in ethanol extracts of garlic was reported to protect laboratory animals against acetaminophen-induced liver injury.(55) The diallyl disulfides in garlic are reported to increase tissue activities of the phase II detoxification enzymes quinone reductase and glutathione transferase in laboratory animals.(56) A recent laboratory animal study reported that the use of a garlic extract in chemical induced hepatocarcinogenesis significantly reduced the number and area of positive foci compared with placebo, suggesting strong supportive evidence for the anticarcinogenic activity of garlic.(57) Of further note, as reported in a few laboratory animal studies, there is the potential for very large amounts of allicin to damage liver tissue if absorbed(63),(64) However, there are positive studies while using high quality garlic preparations standardized to allicin potential without reported adverse effects.

Garlic may also help in the detoxification of heavy metals from the body, including lead.(52) The mechanism of action appears to be that garlic protects the membranes of red blood cells against heavy metal ions by chelating the metal ions, allowing them to be excreted from the body.

A Cochrane database review in 2006 found that there was insufficient evidence to recommend increased garlic intake for preventing pre-eclampsia and its complications.(92)

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