Since 1981, 52 randomized controlled trials of at least four weeks duration have been published on the ability of a variety of garlic supplements to affect serum lipids.(1
) However, the results have been inconsistent. Although most of the earlier trials reported positive effects, 10 of the 13 trials published since 1995 have found no effect on serum cholesterol or serum triglyceride.(2
) Systematic reviews (meta-analyses) of these trials have concluded that most of the positive studies had significant design problems.(1
) The authors of most of the meta-analyses and of the trials that showed no effect have concluded that “garlic,” rather than the particular supplement used in the trials, has little, if any, effect on serum lipids. However, this conclusion assumes that garlic supplements contain similar amounts of compounds as garlic itself and that they are as effective as crushed fresh garlic in delivering active compounds to the body, assumptions that have long been suspected as doubtful,(6
) but which has been given little attention in prior trials.
Although several forms of garlic supplements have been used in clinical trials, the most common form has been garlic powder (dried garlic) supplements.(1
) In fact, most garlic powder supplements claim to lower serum cholesterol and to be standardized on allicin (diallyl thiosulfinate) yield, including those used in clinical trials. Considerable evidence has indicated that allicin is responsible for most of the effects of garlic on serum lipids.(10
) However, it has been known since 1944 that allicin is absent from garlic and garlic powders until the enzyme, alliinase, has been activated, by the crushing of cloves or the wetting of powder, allowing the transformation of the amino acid, alliin, to allicin and other allyl thiosulfinates ().(6
) When fresh garlic is crushed or blended, allicin formation is complete in approximately six seconds, well before consumption.(74
) With supplements the opportunity for allicin formation does not occur until after consumption, when the tablets dissolve. However, because the activity of alliinase is dramatically affected by the gastrointestinal environment (gastric acid, intestinal proteases) and by supplement processing procedures,(7
) the amount of allicin produced in the body from supplements, and, hence, confidence in extrapolating clinical trial results to fresh garlic, can be highly questionable.
Structures and formation of compounds analyzed
We have determined that upon subjecting garlic powder tablets to the simulated gastrointestinal dissolution conditions defined in the U.S. Pharmacopeia/National 4 Formulary,(14
) that the allicin released from the tablet brand used in most of the clinical trials from 1994–2000 varied from 14% to 18% (compared to 100% upon adding crushed tablets to water).(2
) The same evaluation of 24 brands of acid-protected (enteric-coated) tablets revealed an allicin release of 3–94%, with an average of 13%, clearly demonstrating the difficulty of allicin formation from supplements under gastrointestinal conditions and the need to establish allicin release in vivo.(13
) Indeed, allicin bioavailability, measured as exhaled allyl methyl sulfide, has been demonstrated to be complete (>95%) for the brand that gave a dissolution allicin release of 94%, while tablets of the same alliin content, but lower alliinase activity, gave allicin bioavailability values as low as 5%.(13
) Hence, confidence in the ability of a garlic powder supplement to represent crushed fresh garlic in a clinical trial can only be established based on bioavailability studies, although some confidence can be obtained by subjecting the tablets to simulated conditions. To date, no clinical trial has been conducted with a garlic supplement of known allicin bioavailability, and only one trial has reported the dissolution allicin release.(17
) Therefore, the results of past clinical trials on serum lipids can only be applied to the particular product used in the trial and cannot be considered valid for crushed fresh garlic.
The authors have undertaken a large-scale clinical trial to address this issue (June 2002–June 2005). This trial will test the effects of blended raw garlic, an enteric-coated powdered garlic supplement of known high allicin bioavailability, and a dried aged garlic extract supplement on plasma LDL-cholesterol concentrations among approximately 200 moderately hypercholesterolemic adults. A major focus of the current clinical trial is not only that of high methodological design quality but also to more thoroughly define the quality of the garlic products being consumed than has been done in the past, particularly with respect to (1) composition of the unique sulfur compounds of garlic, (2) stability of suspected active compounds under the lengthy storage and particular usage conditions of the clinical trial, and (3) bioavailability of suspected active compounds when bioavailability is in question. The intent of the results to be presented here is to address issues of composition, stability, and bioavailability, separate from and preceding the trial results.