The new trial, published in the Archives of Internal Medicine , investigated the effects of garlic, both raw and from supplements, on the cholesterol levels of 192 adults with slightly elevated cholesterol levels (hypercholesterolaemia).
After six months of garlic intervention, no significant changes in LDL-cholesterol levels were observed.
"The garlic products, all extensively characterised chemically, had neither a statistically detectable effect nor clinically relevant effect on plasma lipid concentrations in adults with moderate hypercholesterolaemia," wrote lead author Christopher Gardner from Stanford University Medical School.
High cholesterol levels have a long association with many diseases, particularly cardiovascular disease (CVD), the cause of almost 50 per cent of deaths in Europe, and reported to cost the EU economy an estimated €169bn ($202bn) per year.
"Garlic supplements, many of which seek to package the benefits of raw garlic in more palatable forms, are promoted as cholesterol-lowering agents and are among the top-selling herbal supplements," explained Gardner and collaborators from the University of Albany and Plant Bioactives Research Institute in Utah.
Crushing garlic is said to trigger the formation of allicin, a compound shown to prevent the formation of cholesterol in laboratory studies.
Despite these positive results from the lab, however, clinical trials in humans have reported mixed results.
The new study followed 192 adults (average age 50) with moderately elevated LDL levels (150 milligrams per decilitre) and randomly assigned them to receive raw garlic (49 subjects), a powdered garlic supplement (47 subjects, Garlicin, Nature's Way Products), an aged garlic supplement (48 subjects, Kyolic-100, Wakunaga of America) or placebo (48 subjects) fro six months.
Each garlic intervention provided the equivalent of an average-sized garlic clove each day, six days per week.
One hundred and sixty-nine adults completed the study, and the researchers report that no statistically significant changes in LDL-levels were observed in any of the groups.
Levels of other types of cholesterol-including high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol-high density lipoprotein cholesterol ratio, also remained the same.
"The results of this trial should not be generalized to other populations or health effects.
Garlic might lower LDL in specific subpopulations, such as those with higher LDL concentrations, or may have other beneficial health effects," wrote the authors.
"Also, we studied only one dosage level, and effects might emerge at higher doses, if tolerated."
No serious adverse events were reported, although bad body and breath odour were reported to occur often in 57 per cent of the raw garlic group.
The researchers note that the major garlic components were stable throughout the duration of the trial in all three garlic groups.
"Based on our results and those of other recent trials, physicians can advice patients with moderately elevated LDL cholesterol concentrations that garlic supplements or dietary garlic in reasonable doses are unlikely to produce lipid benefits," they concluded.
In an accompanying editorial, Mary Charlson and Marcus McFerren from Weill Cornell Medical College, New York said that, although the study authors "convincingly demonstrate that raw garlic and two popularly used supplements do not reduce LDL cholesterol more than 10 milligrams per decilitre when used for six months vs. placebo for six months, the results do not demonstrate that garlic has no usefulness in the prevention of cardiovascular disease."
The editorial notes that the study focussed only on allicin as the active ingredient, but note that a host of other bioactive compounds may have cardiovascular benefits "The selection of a single compound for the purpose of standardisation when exact mechanisms of action are unknown continues to hinder our ability to evaluate the health effects of natural products," wrote Charlson and McFerren.
"Innovation is require to move away from the single active principal method," they said.
"Garlic is one of the top-selling dietary supplements in the United States, in part because familiarity with garlic as a food gives consumers confidence that garlic supplements are safe.
In general, they probably are," concluded Charlson and McFerren.
"Do they prevent cardiovascular disease?
The jury is still out."
Consumer awareness of the health benefits of garlic, mostly in terms of cardiovascular and immune system health, has benefited the supplements industry, particularly since consumers seek the benefits of garlic without the odours that accompany the fresh bulb.
Garlic supplements are worth more than $100m (€79.5m) in the US and are also one of the biggest sellers in the UK market.
According to a 1998 survey by Hartman and New Hope, garlic supplements are used twice as much as other herbal supplements.
Source: Archives of Internal Medicine Volume 167, Pages 346-353, "Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia " Authors: C.D. Gardner, L.D. Lawson, E. Block, L.M. Chatterjee, A. Kiazand, R.R. Balise, H.C. Kraemer Editorial: Archives of Internal Medicine Volume 167, Pages 325-326, "Garlic: What we know and what we don't know" Authors: M. Charlson, M. McFerren