Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies

J Nutr. 2001 Mar;131(3s):989S-93S. doi: 10.1093/jn/131.3.989S.


The medicinal use of garlic dates back thousands of years, but there was little scientific support of its therapeutic and pharmacologic properties until recently. In the past decade, the cancer-protective effects of garlic have been well established by epidemiologic studies and animal experiments. However, the cardiovascular-protective properties of garlic are less well understood. In particular, despite the reported hypocholesterolemic effect of garlic, the mechanism of the effect is unclear. In a recent randomized, double-blind, placebo-controlled intervention study, we showed that aged garlic extract (AGE) supplementation was effective in lowering plasma concentration of total cholesterol by 7% and LDL cholesterol by 10% in hypercholesterolemic men compared with subjects consuming a placebo. Supplementation of AGE in animal diets similarly reduced plasma concentrations of total cholesterol and triacylglycerol by 15 and 30%, respectively. In subsequent experiments using cultured rat hepatocytes, we found 44--87% inhibition of cholesterol synthesis by the water-extractable fraction (WEF), methanol-extractable fraction (MEF) and petroleum ether-extractable fraction (PEF) of fresh garlic, and Kyolic (liquid form of AGE). These observations suggested that hydrophilic and hydrophobic compounds of garlic are inhibitory to cholesterol synthesis. Because S-allylcysteine (SAC) alone was less potent than Kyolic, which contains SAC and other sulfur compounds, a maximal inhibition appears to require a concerted action of multiple compounds of garlic. In a series of experiments, we further characterized the inhibitory potency of individual water-soluble and lipid-soluble compounds of garlic. Among water-soluble compounds, SAC, S-ethylcysteine (SEC), and S-propylcysteine (SPC) inhibited cholesterol synthesis by 40--60% compared with 20--35% by gamma-glutamyl-S-allylcysteine (GSAC), gamma-glutamyl-S-methylcysteine (GSMC) and gamma-glutamyl-S-propylcysteine (GSPC). Lipid-soluble sulfur compounds (i.e., diallyl sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl trisulfide) at low concentrations (0.05--0.5 mol/L) slightly (10--15%) inhibited cholesterol synthesis but became highly cytotoxic at high concentrations (1.0--4.0 mol/L). All water-soluble compounds, except S-allylmercaptocysteine, were not cytotoxic, judging from the release of cellular lactate dehydrogenase into the culture medium. Taken together, the results of our studies indicate that the cholesterol-lowering effects of garlic extract, such as AGE, stem in part from inhibition of hepatic cholesterol synthesis by water-soluble sulfur compounds, especially SAC.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Anticholesteremic Agents / therapeutic use
  • Cholesterol / biosynthesis
  • Cholesterol / blood
  • Cysteine / analogs & derivatives*
  • Garlic / chemistry
  • Garlic / therapeutic use*
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Liver / drug effects
  • Liver / metabolism*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Plants, Medicinal*
  • Randomized Controlled Trials as Topic
  • Rats
  • Solubility
  • Sulfur Compounds / pharmacology
  • Toxicity Tests


  • Anticholesteremic Agents
  • Plant Extracts
  • Sulfur Compounds
  • S-allylcysteine
  • Cholesterol
  • Cysteine