Botanical Substances: Garlic (Allium Sativum)

GARLIC (ALLIUM SATIVUM)

Chemistry

The pharmacologic activity of garlic involves a variety of organo-sulfur compounds. Dried and powdered formulations contain many of the organosulfur compounds found in raw garlic and will likely be standardized to allicin or alliin content. Allicin is respon-sible for the characteristic odor of garlic, and alliin is its chemical precursor. Dried powdered formulations are often enteric-coated to protect the enzyme allinase (the enzyme that converts alliin to allicin) from degradation by stomach acid. Aged garlic extract has also been studied in clinical trials, but to a lesser degree than dried, powdered garlic. Aged garlic extract contains no alliin or allicin and is odor-free. Its primary constituents are water-soluble organosulfur compounds, and packages may carry a standardiza-tion to the compound S-allylcysteine.

Pharmacologic Effects

A. Cardiovascular Effects

In vitro, allicin and related compounds inhibit HMG-CoA reductase, which is involved in cholesterol biosynthesis , and exhibit antioxidant properties. Several clinical trials have investigated the lipid-lowering potential of garlic. The most recent meta-analysis involved 29 randomized, double-blind, placebo-controlled trials and found a small but significant reduc-tion in both total cholesterol (−0.19 mmol/L) and triglycerides (−0.011 mmol/L), but no effect on low- or high-density lipopro-teins. These results echoed another review in patients with baseline hypercholesterolemia (total cholesterol > 200 mg/dL) that found a significant reduction in total cholesterol of 5.8% using garlic for2–6 months. The effect of garlic became insignificant, however, when dietary controls were in place. Results of a study by the National Center of Complementary and Alternative Medicine (NCCAM) evaluating three different sources of garlic (fresh, pow-dered, and aged garlic extract) in adults with moderately elevated cholesterol contradicted the findings of these reviews and found no effect of any formulation of garlic versus placebo on LDL choles-terol. Cumulatively, these data indicate that garlic is unlikely to be effective in reducing cholesterol to a clinically significant extent. Clinical trials report antiplatelet effects (possibly through inhibi-tion of thromboxane synthesis or stimulation of nitric oxide syn-thesis) following garlic ingestion. A majority of human studies also suggest enhancement of fibrinolytic activity. These effects in com-bination with antioxidant effects (eg, increased resistance to low-density lipoprotein oxidation) and reductions in total cholesterol might be beneficial in patients with atherosclerosis. A randomized, controlled trial among persons with advanced coronary artery disease who consumed dried powdered garlic for 4 years showed significant reductions in secondary markers (plaque accumulation in the carotid and femoral arteries) as compared with placebo, but primary endpoints (death, stroke, myocardial infarction) were not assessed.

Garlic constituents may affect blood vessel elasticity and blood pressure. A variety of mechanisms have been proposed. There have been a limited number of randomized, controlled trials in humans for this indication. Ten trials were included in a system-atic review and meta-analysis that found no effect on systolic or diastolic pressure in patients without elevated systolic blood pres-sure but a significant reduction in systolic and diastolic pressure among the three trials involving patients with elevated systolic blood pressure.

B. Endocrine Effects

The effect of garlic on glucose homeostasis does not appear to be significant in persons with diabetes. Certain organosulfur con-stituents in garlic, however, have demonstrated hypoglycemic effects in nondiabetic animal models.

C. Antimicrobial Effects

The antimicrobial effect of garlic has not been extensively studied in clinical trials. Allicin has been reported to have in vitro activity against some gram-positive and gram-negative bacteria as well as fungi (Candida albicans), protozoa (Entamoeba histolytica), and certain viruses. The primary mechanism involves the inhibition of thiol-containing enzymes needed by these microbes. Given the availability of safe and effective prescription antimicrobials, the usefulness of garlic in this area appears limited. 

D. Antineoplastic Effects

In rodent studies, garlic inhibits procarcinogens for colon, esopha-geal, lung, breast, and stomach cancer, possibly by detoxification of carcinogens and reduced carcinogen activation. Several epide-miologic case-control studies demonstrate a reduced incidence of stomach, esophageal, and colorectal cancers in persons with high dietary garlic consumption.

Adverse Effects

Following oral ingestion, adverse effects may include nausea (6%), hypotension (1.3%), allergy (1.1%), and bleeding (rare). Breath and body odor have been reported with an incidence of 20–40% at recom-mended doses using enteric-coated powdered garlic formulations. Contact dermatitis may occur with the handling of raw garlic.

Drug Interactions & Precautions

Because of reported antiplatelet effects, patients using anticlotting medications (eg, warfarin, aspirin, ibuprofen) should use garlic cautiously. Additional monitoring of blood pressure and signs and symptoms of bleeding is warranted. Garlic may reduce the bioavailability of saquinavir, an antiviral protease inhibitor, but it does not appear to affect the bioavailability of ritonavir.

Dosage

Dried, powdered garlic products should be standardized to con-tain 1.3% alliin (the allicin precursor) or have an allicin-generating potential of 0.6%. Enteric-coated formulations are recommended to minimize degradation of the active substances. A daily dose of 600–900 mg/d of powdered garlic is most common. This is equivalent to one clove of raw garlic (2–4 g) per day.