Raw garlic or garlic supplements lack beneficial effects on LDL-cholesterol

While spending so much time last week on the issue of conscientious objection by pharmacists, I overlooked the 26 February publication in Archives of Internal Medicine of a very well-designed clinical trial to test the hypothesis that garlic/garlic supplements lower LDL-cholesterol. The trial, conducted at Stanford University Medical School, was notable in that several of the authors are well-recognized experts in the chemistry and preclinical pharmacology of garlic and paid particular detail to the bioavailability of the sulfur-containing amino acids thought to exert garlic’s beneficial effects in previous animal studies.
Unfortunately, neither raw garlic or either one of two well-characterized supplements had any effect on LDL-cholesterol levels over a 6-month period. The two supplements tested were Garlicin (Nature’s Way Products Inc, Springville, Utah) and Kyolic-100 (Wakunaga of America Co, Mission Viejo, Calif). The use of raw garlic in one arm was also a major strength in that supplements are often criticized for lacking the enzymatic activity necessary for conversion of the precursor compound (alliin) to the purported active compound (allicin). The methods section also includes details on how the “study sandwiches” were prepared for the raw garlic group.


The study was well-justified as noted in the text:

The plausibility of a cholesterol-lowering effect of garlic in human beings is supported by significant positive effects in approximately 85% of more than 110 animal studies that examined the effects of allicin-derived garlic oils, crushed raw garlic, and garlic powder on serum lipid concentration. Furthermore, clinical trials conducted before 1995 with garlic powder tablets at doses of 0.6 to 1.2 g suggested a modest beneficial effect of garlic on lipid concentration in adults with substantial hypercholesterolemia, but these trials were criticized for serious design and conduct limitations. Trials conducted after 1995 with similar doses consistently reported no significant effects on plasma lipid concentrations in similar populations. Notably, almost all commercial garlic supplements, especially those used in post-1995 trials, yield unexpectedly low amounts of the putative garlic active agent allicin under physiologically relevant dissolution conditions. Therefore, the effectiveness of garlic and garlic supplements has remained ambiguous.

The authors also paid tremendous detail to the chemical composition, consistency, and stability of the study agents used:

Before study initiation and at 3, 6, 12, 18, and 24 months during the study, 14 sulfur and 2 nonsulfur compounds were measured in all 3 garlic products, as described elsewhere. The content and potential of allyl thiosulfinates (mainly allicin) for raw garlic and Garlicin, respectively, were nearly identical. Substantial qualitative and quantitative differences were found between Kyolic aged extract tablets and raw garlic and Garlicin, as a result of the aging and extraction procedures. Raw garlic thiosulfinate content was stable at 4°C for 3 days when mixed with condiments used in study sandwiches. Allyl thiosulfinate content in raw garlic stored at -80°C and the ability of Garlicin tablets stored at 4°C to produce thiosulfinates on hydration were unchanged after 2 years. S-Allylcysteine content in Kyolic tablets stored at room temperature was stable for 1 year but declined by 12% at 2 years; the storage temperature was, therefore, changed to 4°C. Dissolution formation and release of allicin from Garlicin tablets, under simulated gastrointestinal tract conditions defined by the United States Pharmacopeia, were found to be equal to their potential to produce allicin in water. Complete in vivo formation of allicin from Garlicin tablets was verified by finding a similar area under the curve for the exhaled allicin metabolite allyl methyl sulfide, in comparison with consuming raw garlic, in which allicin is fully present before consumption.

Nevertheless, none of the three garlic treatment arms had effects on LDL-cholesterol. However, the authors note that other effects of garlic components may contribute to improved cardiovascular health independent from LDL-cholesterol. Most notably, garlic compounds inhibit platelet aggregation and, in fact, large amounts of garlic are contraindicated in patients on anticoagulant therapy. Therefore, it is surprising that the authors did not monitor other common clinical parameters of hemostasis that might have provided more information on the action of garlic in human volunteers.
The not-for-profit American Botanical Council published a detailed press release on 26 February that is very much worth reading as it includes key interviews with the principal investigators.

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