Garlic: Is the "Stinking Rose" Good for the Cholesterol Count?
September 1, 1998
Garlic: Is the "Stinking Rose" Good for the Cholesterol Count?
September 1998; Volume 1: 97-99
By Matthew Sorrentino, MD
Garlic has long been thought to be effective in the prevention of heart disease by lowering cholesterol and acting as an anticoagulant.
History
Garlic (Allium sativum) has been advocated for centuries as a medicinal agent. Chinese medicine uses garlic as a treatment to lower blood pressure. The Egyptians believed that garlic increased physical strength. Garlic was thought to prevent bubonic plague in Europe. Garlic was administered as an antiseptic poultice during wartime. Is this common aromatic the miracle drug that advocates say it is? We will review the strongest evidence suggesting that garlic has a cholesterol-lowering effect.
Pharmacology
The common garlic is a member of the allium plant family, which includes onions, shallots, and leeks. These plants contain sulfur-rich derivatives of the amino acid cysteine which are thought to have medicinal benefits. More than 18 different sulfur compounds have been identified in garlic.
When raw garlic is cut or crushed, the enzyme allinase interacts with the cysteine compound alliin to produce allicin. Allicin gives garlic its typical aroma and taste but is fairly volatile and usually breaks down in a few hours at room temperature or after 20 minutes of cooking. More stable compounds such as ajoene and dithiins are formed when garlic is macerated with oil. These compounds may be stable for more than a year.
Allicin is also thought to be one of the most important medicinal substances in garlic, although little or no allicin is present in the intact garlic clove. The garlic plant produces allicin as a natural defense against bacteria and other organisms. Allicin is highly irritating and has been shown to be bactericidal in in vitro studies.
The instability of allicin makes it difficult to study the clinical effects of this compound and its derivatives. Numerous investigators are studying allicin's thrombotic activity, antibacterial or antifungal properties, and antioxidant potential. Early investigations indicate some in vitro activity, but it is unclear if allicin compounds are active clinically. Most clinical studies have used dried garlic powder tablets, and that is the preparation that will be discussed here.
Mechanism of Action
Animal studies evaluating the long-term effects of feeding garlic to atherogenic animals have shown a reduction in atherosclerotic lesions. Inhibition of atherosclerosis by the sulfur-containing compounds is the presumed mechanism.1 Studies in isolated hepatocytes indicate that key enzymes in cholesterol biosynthesis, including HMG-CoA reductase, may be inhibited by the sulfur-containing substances in garlic.2
Clinical Trials
Many small clinical trials have reported that garlic lowers cholesterol. A meta-analysis of five selected trials published in 1993 included a total of 410 individuals.3 Treatments in the trials varied; three trials used garlic powder tablets, one trial used spray-dried garlic powder, and the fifth trial used an aqueous garlic extract. Overall results indicated a 9% reduction in cholesterol levels in the garlic-treated subjects. The dose of garlic was equivalent to approximately one-half to one clove of garlic per day.
Many criticisms of meta-analyses apply to the garlic studies. Poorly designed studies have been published. Comparison among trials is complicated because of the different garlic preparations used, populations studied (hypercholesterolemic vs individuals with normal cholesterol levels), methods (the use of low-cholesterol diets, control groups, randomization, and blinding), and duration of treatment. In addition, very few negative garlic studies had been published at the time of the meta-analysis, suggesting a publication bias toward positive studies.
Since the publication of the meta-analysis, further studies have been reported, with conflicting results. Jain et al showed an 11% reduction in LDL-cholesterol in 42 hypercholesterolemic men and women with total cholesterol levels greater than 220 mg/dL who were treated with garlic.4 Four additional studies, however, have failed to show any significant cholesterol-lowering benefit.5-8
Simons et al, using a crossover design, administered Kwai garlic powder to 28 hypercholesterolemic individuals.5 There was no effect of garlic ingestion on any lipid parameters.
Neil et al performed a double-blind randomized trial using 900 mg/d of garlic powder in 115 hypercholesterolemic subjects following a six-week diet.6 There was no significant difference in lipid values between the active treatment and control groups.
Isaacsohn et al studied individuals with LDL cholesterol levels of less than 160 mg/dL following eight weeks of diet.7 The addition of Kwai garlic powder had no significant lipid-lowering effect. The cholesterol levels upon entrance into this study, however, are lower than studies that show benefit, suggesting that garlic may only bring about significant cholesterol lowering in hypercholesterolemic individuals.
The final negative study, by Berthold et al, used a garlic oil preparation that has been generally thought to be less effective in lowering cholesterol levels than allicin-containing garlic powder.8
The discrepant results among studies may also be explained by manufacturing differences among the garlic preparations. Fresh garlic may be the only preparation that achieves a significant amount of allicin in the diet. The odor and stomach upset that may be caused by chewing raw garlic, however, make it a poor choice for a cholesterol-lowering agent. Cooked garlic may be better tolerated, but prolonged cooking will also inactivate the sulfur-containing compounds thought to be beneficial. No well-designed long-term studies using raw or cooked garlic are available.
Dosage/Formulation
Current market products portray allicin content or allicin potential as a description of their potency. There are significant technical difficulties in the commercial preparation of garlic supplements, however, because of the rapid breakdown of the volatile sulfur compounds.
Garlic powder tablets (Kwai), typically in a dosage of 300 mg tablets taken two or three times a day with meals, are coated and contain freeze-dried fresh garlic. Once ingested, the surface coating of the tablet is digested, allowing the enzyme allinase to convert alliin to the active allicin. The tablet is odorless because no allicin in present until digestion. Digestion of the capsule is supposed to occur sufficiently far along in the digestive tract to avoid a garlic odor, although studies using these preparations do report that some individuals have an undesirable garlic taste and odor when taking these tablets.
Manufacturers have devised methods to attempt to preserve allicin. One method uses rapid drying of cut garlic, presumably before allicin is produced. The rapid degradation of these compounds following drying minimizes the allicin content in standard garlic powder.
Another includes inactivating allinase and adding the enzyme back to the final dried product. Unfortunately, allinase is easily denatured by stomach acid.
Finally, some products, especially deodorized preparations, do not contain any allicin.
Adverse Effects
Garlic is generally considered safe. The most common problems are an undesirable garlic taste and smell, something that can also occur with the so-called "odorless" preparations on the market. Raw garlic can cause stomach upset, reflux, and gas symptoms and may also be caustic to the skin. Garlic may have some anti-thrombotic activity, so it is not recommended for patients taking anticoagulants.1 There are no known drug interactions.
Conclusions
Evidence from a number of studies suggests that garlic may have a mild hypocholesterolemic effect at a dose of about one raw clove per day. This effect seems to be more evident in individuals with elevated cholesterol levels. A number of well-designed trials, however, have failed to show any significant benefit from garlic supplements. The varying quality of garlic preparations may account for some of the different results among studies.
I recommend the use of fresh garlic as a component of a plant-centered diet and as part of an overall strategy of lifestyle modification to lower cholesterol levels. The equivalent of one clove per day is sufficient. The powdered garlic products may be used as well; however, there are concerns about limited shelf life for these products, as well as a lack of knowledge about consistency in the manufacturing process. The garlic may be lightly cooked to avoid the side effects of raw cloves, but too much cooking will deactivate the sulfur-containing compounds that may be the active agents.
For patients with hypercholesterolemia, the cholesterol-lowering effect of garlic is modest and should not substitute for medical drug therapy if greater reductions in cholesterol are desired.
References
1. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy, 3rd ed. Berlin Heidelberg: Springer-Verlag; 1998:112.
2. Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids 1993;28:613-619.
3. Warshafsky S, Kamer RS, Sivak SL. Effect of garlic on total serum cholesterol. A meta-analysis. Ann Intern Med 1993;119:599-605.
4. Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993;94:632-635.
5. Simons LA, Balasubramanian S, von Konigsmark M, et al. On the effect of garlic on plasma lipids and lipoproteins in mild hypercholesterolemia. Atherosclerosis 1995;113:219-225.
6. Neil HA, Silagy CA. Lancaster T, et al. Garlic powder in the treatment of moderate hyperlipidemia: A controlled trial and meta-analysis. J Royal Coll Phys London 1996;30:329-334.
7. Isaacsohn JL, Moser M, Stein EA, et al. Garlic powder and plasma lipids and lipoproteins. A multicenter, randomized, placebo-controlled trial. Arch Intern Med 1998;158:1189-1194.
8. Berthold HK, Sudhop T, von Bergmann K. Effects of a garlic oil preparation on serum lipoproteins and cholesterol metabolism. A randomized controlled trial. JAMA 1998;279:1900-1902.
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