By Dónal P. O’Mathúna, PhD
Cardiovascular disease is a complex group of heart-related conditions that is by far the leading cause of death in women.1 About 500,000 women die each year in the United States from cardiovascular disease. That is almost one death per minute and is more than the next seven leading causes of death combined. One in five U.S. women have some form of cardiovascular disease, and almost two-thirds of those who die suddenly from coronary heart disease had no previous symptoms. The risk of heart disease is two to three times higher after menopause than among women of the same age before menopause, and the risks among African American and Mexican American women are higher than among white women. Anything that can reduce the incidence of or damage from cardiovascular disease will have a significant impact on women’s health.
Cardiovascular disease can arise from interactions between a number of factors, including high serum cholesterol and triglyceride levels, elevated blood pressure, increased platelet aggregation, and reduced fibrinolysis (the process by which blood clots are broken down). All of these conditions are impacted by lifestyle factors such as smoking, stress, and obesity. Related to the latter is the recognition that dietary factors play an important role in the development of cardiovascular disease.
For centuries, garlic has been recommended for cardiovascular health. Many cultures have long viewed garlic as an important dietary supplement with beneficial health effects. Ayurvedic medicine in ancient India refers to the beneficial effects of garlic for blood flow and strengthening the heart.2 The Egyptian Codex Ebers (1500 BC) recommended garlic for treating heart disease and also for tumors, worms, bites, and many other conditions. The ancient Greek physician Hippocrates (400 BC) and the Roman authority Pliny the Elder (77 AD) similarly recommended garlic for the cardiovascular system. During the ancient Olympics, athletes were encouraged to consume copious quantities of garlic to increase their stamina.3
Clinical work as early as 1926 found garlic to have beneficial effects on cardiovascular disease. These effects had to be rediscovered in the 1960s and 1970s when a number of studies noted reductions in serum cholesterol and triglycerides levels.2 However, all these early studies were conducted with raw garlic administered at very high doses: between seven and 28 cloves per day. This amount of raw garlic has serious social ramifications, regardless of any health benefits.
Mechanism of Action
A number of mechanisms are believed to be involved in garlic’s cardiovascular effects reflecting the biological activity of several of the sulfur compounds. Some of these inhibit liver enzymes involved in making cholesterol, including HMG-CoA reductase (the enzyme inhibited by the statin drugs). Garlic also contains antioxidants that reduce the oxidation of LDL cholesterol, thus giving rise to beneficial effects that can counteract the development of atherosclerosis. Other constituents in garlic cause smooth muscle relaxation that can lead to reduced hypertension. Some garlic preparations have antiplatelet properties and other effects that counteract blood-clotting mechanisms.
Because of the odor problem, much work has been conducted to find more palatable and less odorous formulations of garlic. However, this generates further problems in attempting to review the effectiveness of garlic. Garlic’s cardiovascular effects are believed to be caused by sulfur-containing compounds.4 An intact clove of garlic contains almost all its sulfur in one storage compound called alliin (a name coming from garlic’s botanical name, Allium sativum). Raw garlic also contains an enzyme called alliinase, which rapidly converts alliin to allicin. The distinctive aroma and taste of garlic is due to allicin, but this is very volatile and unstable, breaking down either in a few hours at room temperature or after 20 minutes of cooking. Raw garlic can be consumed as whole cloves, but usually it is crushed or cut into slivers, and more commonly, it is cooked. However, depending on whether it is cooked in water, oil, or alcohol, different sets of compounds are formed.
As allicin decomposes, dozens of other more stable sulphur compounds are formed. Many of these are biologically active. To complicate matters even further, garlic supplements are prepared in different ways, resulting in different ingredients. The two most common powered formulations are dried garlic powder and aged garlic extract (AGE). During the aging process, the volatile components are lost, thus leading to AGE being called odorless garlic.4 Garlic oil also is available, with three different methods commonly used to make these preparations, again each containing different mixtures of sulfur compounds. The most commonly used dosage form in clinical trials is a standardized garlic powder extract called Kwai (200-400 mg tid).
This raises an important issue for clinical studies: Different preparations contain different compounds in different ratios, which may impact the effects the garlic preparations have on people.
Although garlic’s biological activities have been demonstrated in laboratory and animal tests, controversy continues over their clinical significance.5 Results of trials have been contradictory. Another problem has been that while earlier studies often found beneficial effects, more recent trials have not. Often, the more recent trials were larger, longer, and of higher methodological quality.
Cholesterol and lipid levels. Two meta-analyses published in 1993 and 1996 generated much interest in garlic because they reported 9% and 12% reductions in total cholesterol levels, respectively.4 Two additional randomized, controlled trials (RCTs) at around the same time reported reduced cholesterol levels (though only 6%), although with no changes in triglyceride levels. Since then, six more RCTs have found no significant reductions in cholesterol or triglyceride levels compared to placebo. A 2002 review noted that in spite of earlier beneficial results, "in the last five years, no randomized, double-blind, placebo-controlled study could be found in which the results indicated a clear beneficial effect of a garlic preparation alone on blood lipids."4 Additionally, although benefits were found after one and three months, no trials lasting six months or longer showed significant reductions in cholesterol levels.6 There seems to be no debate over the finding that garlic does not impact HDL-cholesterol levels.
Antioxidant effects. Although many of garlic’s components have demonstrated an antioxidant effect, very few studies have been conducted on the clinical significance of this effect. The results of studies measuring serum antioxidant capacity for those taking garlic have been variable. The particular garlic preparation used here is significant. AGE products are made by soaking garlic slivers in alcohol for 20 months, which removes almost all allicin, but leaves other compounds with greater antioxidant capacity.3
Blood-clotting effects. In contrast to the unclear effects above, almost all trials examining garlic’s impact on fibrinolysis have had positive effects. Fibrinolysis leads to the breakdown of blood clots and its impairment increases the risk of cardiovascular disease. Fibrinolytic activity, acute and chronic, has been increased with all types of garlic preparations in most of the studies examining this factor.3 Another aspect of blood clotting, platelet aggregation, also is effected by garlic. Again, most studies here have found beneficial effects. However, a review published in 2000 by the Agency for Healthcare Research and Quality concluded that these results must be taken as preliminary.6 While positive, all the studies found for this review were very small and of limited duration, and some had serious methodological flaws.
Antihypertensive effects. Several studies have examined the role of garlic preparations in lowering blood pressure. A 2002 review located almost 30 studies, though most were small, of short duration, and not conducted to the highest methodological standards.4 Of these, almost three-quarters found the garlic preparations of no greater benefit that placebo.
Garlic is well-known for its adverse breath and body odor after oral ingestion. Eating raw garlic and high doses of supplements also can cause mouth and gastrointestinal irritation and burning, heartburn, nausea, vomiting, and diarrhea.7 Some people also are susceptible to allergic reactions to garlic. The effects of garlic on platelet aggregation and fibrinolysis may increase the risk of bleeding, especially when combined with warfarin or other anticoagulants. Case reports of postoperative bleeding and spontaneous epidural hematoma point to the importance of informing patients about this increased risk.8 There also is some evidence that allicin may stimulate the activity of a cytochrome P450 enzyme involved in the metabolism of many drugs.7 Some of the more common drugs whose effectiveness thus may be reduced include oral contraceptives, calcium channel blockers, HIV protease inhibitors, and cyclosporine. Formulations containing alliin or alliinase are not believed to cause this type of drug interaction.
Overall, garlic preparations appear to be of some limited value as a complementary strategy to reducing some risk factors associated with cardiovascular disease. The evidence as this stage points to limited beneficial effects for garlic as an anticoagulant and in lowering cholesterol levels slightly for short periods of time. For example, when taken for up to six months, garlic lowers cholesterol levels 4-12%, which must be contrasted with statin drugs that typically reduce cholesterol levels by 17-55%.7 Although garlic also has been recommended as having other cardiovascular benefits, larger, more rigorous studies must be conducted before recommending garlic as a routine therapy or instead of conventional therapy.
Given the many associations between garlic and cardiovascular health, and the preliminary research results now available, use of garlic in the diet can be encouraged as part of an overall heart-healthy diet. Whether garlic supplements will provide significant cardiovascular benefits remains to be seen.
Dr. O’Mathúna, Lecturer in Health Care Ethics, School of Nursing, Dublin City University, Ireland, is on the Editorial Advisory Board of Alternative Therapies in Women’s Health.
1. American Heart Association. General heart disease and stroke facts about women. Available at: www.americanheart.org/downloadable/heartsmart/1082152512419GRFWWomensFacts.doc. Accessed Jan. 5, 2005.
2. Rahman K. Historical perspective on garlic and cardiovascular disease. J Nutr 2001;131:977S-979S.
3. Banerjee SK, Maulik SK. Effect of garlic on cardiovascular disorders: A review. Nutr J 2002;1:4-18.
4. Brace LD. Cardiovascular benefits of garlic (Allium sativum L). J Cardiovasc Nurs 2002;16:33-49.
5. Jakubowski H. On the health benefits of Allium sp. Nutrition 2003;19:167-168.
6. Mulrow C, et al. Garlic: Effects on cardiovascular risks and disease, protective effects against cancer, and clinical adverse effects. Rockville, MD: Agency for Healthcare Research and Quality; 2000. AHRQ publication 01-E023. Available at: www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.28361. Accessed Nov. 20, 2004.
7. Garlic. Natural Medicines Comprehensive Database. Available at: www.naturaldatabase.com. Accessed Nov. 19, 2004.
8. Awang D, Fugh-Berman A. Herbal interactions with cardiovascular drugs. J Cardiovasc Nurs 2002;16:64-70.