SUMMARY This book gathers together for the first time all the world's known and vast scientific research of the past 100 years on the possible medicinal benefits of garlic and garlic preparations and reviews the thousands of years of historical medicinal uses of garlic. It also contains the world's scientific literature on the composition of garlic and the chemical changes that take place when garlic is processed by a large variety of common methods. It contains methods on how to analyze these compounds -- a knowledge of which is essential to identifying the active compounds of garlic and to understanding how to conduct well-designed and repeatable clinical trials as well as to evaluating the quality of the many types of commercial garlic products. The book presents comprehensive tables of the large number of clinical trials that have been conducted on the cardiovascular effects of garlic -- e.g., serum cholesterol and triglyceride levels, blood pressure, and fibrinolysis -- with generally very positive results. The many anticancer and antioxidant studies are critically reviewed. The results of nine epidemiological studies from around the world are summarized, all of which give great encouragement that garlic may be able to significantly reduce the incidence of intestinal cancers. Considerable emphasis is placed on reviewing the evidence for identifying the active compounds for each particular effect of garlic. The book also reviews what harmful effects garlic may have when consumed in large amounts or used in improper ways and explores what little is known about the metabolism of garlic's compounds in the body. The book strongly attempts to help remove much of the confusion that is found in the minds of the public about g arlic by critically reviewing what is really known about the compounds of garlic and garlic products and their effects on the body when consumed at reasonable levels. HIGHLIGHTS This is the first book written on garlic in English by garlic scientists and is by far the largest and most comprehensive book ever written on garlic. It is the first book to gather together and critically evaluate the abundant scientific evidences for the health benefits of garlic and to compare the composition of the many types of commercial garlic products. The book also contains much new data that is being published for the first time. Chapter 1 (History -- pp. 1-24; 64 references). A thorough review of the historical and legendary medicinal and non-medicinal uses of garlic over the past 4,000 years. Chapter 2 (Botany -- pp. 25-36; 180 references). A botanical description of the garlic plant, where it is grown, and a commentary on the varieties of garlic and other Allium species. Chapter 3 (Composition and Chemistry -- pp. 37-108; 795 references). 1. Composition. The identity and amounts of all the known compounds of garlic are given and divided into sulfur (Section 3.2 and Table 3.3, p. 42) and non-sulfur (Section 3.3 and Table 3.1, p. 38) compounds. 2. Alliinase. Alliinase, the enzyme which forms allicin upon crushing garlic, is shown to be the most abundant single protein in garlic (pp. 49, 79-80). The separate cellular locations for alliin and alliinase are illustrated (cover, p. 51). 3. Variation. The variation in content of sulfur compounds (alliin, glutamylcysteines, etc.) among 69 strains of garlic is given (Fig. 3.3, Table 3.5, Fig. 3.5, pp. 45, 46, 49). 4. Allicin. The physical properties, reactions and stability of allicin under a variety of conditions are given (pp. 53-68). In water or garlic juice, allicin is much more stable than has been commonly described (p. 58). 5. Odor and cooking. The composition of garlic odor and garlic breath are given (pp. 65-67) and the effects of cooking on garlic's sulfur compounds are described (pp. 68-69). 6. Garlic products. Commercial garlic products -- powders, oils, and extracts -- are discussed in good detail with respect to their composition, brand to brand variation, and stability (pp. 92-107). A comparison of 28 unnamed brands of garlic powder tablets after being exposed to simulated gastric and intestinal fluids under standardized conditions reveals a large amount of variation in allicin yield and particularly the effective allicin yield, underscoring the need for powder tablets to be adequately protected from stomach acid and to be standardized for effective allicin yield (Table 3.19, p. 96). 7. Aged extracts. The compositional changes that take place when garlic extracts are aged over many months are described and quantified to determine what levels of compounds should be expected from an aged extract (Table 3.25, p. 104). Analysis of presently available commercial aged extract products revealed only 10% of expected values (p. 104). The effects of aging garlic in vinegar are also shown (p. 106). 8. Nutrients and minerals. A comparison of the content of the nutrients and minerals in garlic to their dietary needs is given (Table 3.16, p. 87), which reveals that these components do not significantly contribute to garlic's health benefits. The common belief that the germanium content of garlic is important is dispelled since one clove can only provide 0.01% of the typical dietary intake. The selenium content of normal garlic is also shown to be much too small to be of benefit, although it can be increased greatly when grown in selenium-enriched soil. Chapter 4 (Analytical Methods -- pp. 109-134; 305 references). Early and modern methods for the analysis of the sulfur compounds in garlic cloves and commercial garlic products are described. For all classes of sulfur compounds associated with garlic, analysis by high performance liquid chromatography (HPLC) is shown to be superior to other methods because it is the least damaging method. Methods are described for the standardization of allicin and other compounds released from garlic or garlic products (pp. 56, 121-122, 132-134). Chapter 5. (Medicinal Effects -- pp. 135-212; 1264 references) 1. Serum cholesterol and triglycerides (pp. 136-148). To date, 40 clinical trials have been conducted on the lipid lowering effects of fresh garlic and garlic products, with an average decrease in serum cholesterol of 9.9% and in serum triglyceride of 13.4% in 8 to 16 weeks (Tables 5.1 and 5.2, pp. 142-143). Seven trials (not placebo-controlled) with 3-10 g of fresh garlic gave a 16% decrease in cholesterol and a 30% decrease in triglycerides. Twenty-three studies (13 placebo-controlled) with 4600 persons using allicin-standardized (3600-5400 mcg), acid-protected garlic powder tablets at a dose (0.6-0.9 g powder) equal to 1.8-2.7 g of fresh garlic, resulted in an average decrease in serum cholesterol of 12.6%, with a decrease of 10.3% for the placebo-controlled studies. Of the nine studies that measured lipoproteins, seven reported a significant decrease in LDL cholesterol (average 16% decrease). Allicin-derived garlic oils were also found to decrease serum lipids to a similar or greater extent. Considerable evidence (not yet absolutely proven) from both human and animal studies indicate that allicin is responsible for most of the serum-lipid lowering effects observed at low doses in 4 to 12 weeks (pp. 147-148). 2. Blood pressure (pp. 148-154). In 14 human studies (10 placebo-controlled) with allicin-standardized garlic powder tablets (0.6-0.9 g powder), systolic and diastolic blood pressures decreased by 6.7% and 7.9%, respectively, in 1-6 months (Table 5.3, p. 152). While allicin appears not be involved in the effect, the responsible compounds are not yet known (p. 153). 3. Antithrombotic effects (pp. 156-162). The ability of garlic to prevent blood platelets from aggregating (thus reducing the risk of blocked arteries) is well established in vitro, and allicin has been clearly shown to be responsible for most of the effect. Several animal and human studies have also shown that garlic at low to moderate doses can prevent platelet aggregation and thrombus formation in vivo. Since allicin-derived garlic oils, garlic cloves, and garlic powder tablets have similar effects in vivo at similar levels of allicin equivalence, it appears that allicin is also responsible for most of the in vivo antithrombotic effects (p. 162). 4. Antibiotic effects (pp. 162-176). As one of the most common historical and modem uses of crushed garlic, the numerous antibacterial and antifungal studies as well as the fewer number of antiviral and antiprotozoal studies are reviewed. While positive antimicrobial effects on the intestinal tract and skin have been clearly established, studies on the blood-born microorganisms have been few, but encouraging. Furthermore, there is evidence that crushed garlic is more effective against toxic bacteria than against normal flora. Allicin and related thiosulfinates have been repeatedly shown to be responsible for all of the antimicrobial effects of garlic. Allicin-derived compounds present in garlic oils also have antimicrobial activity, although less than for allicin (Table 5.7, p. 163). 5. Anticancer effects (pp. 176-187). The results of nine epidemiological studies from seven countries are given, which demonstrate a consistent correlation between garlic consumption and decreased risk of gastrointestinal cancers (Table 5.8, p. 177). A 5-year study in the U.S. which monitored the intake of 127 foods by 41,400 Iowa women showed that consumption of one or more weekly servings of garlic was associated with more decreased risk (35% lower) of colon cancer than was consumption of any other food. A large number of animal and in vitro anticancer studies have been conducted with garlic and allicin-derived compounds, most of which show very positive effects at generally high concentrations. Since cooked garlic is associated with decreased cancer risk, both allicin-derived compounds as well as other unidentified compounds appear to be about equally responsible for the anticancer effects of garlic (pp. 186-187). 6. Antioxidant effects (pp. 187-191). Numerous in vitro studies plus 11 animal studies have consistently shown that garlic, allicin, and allicin-derived garlic oils possess good antioxidant activity as demonstrated by decreased lipid peroxidation, increased free radical scavenging (decreased hydroxyl radicals), and increased glutathione. Only two human studies have been conducted, with conflicting results (p. 190). At low concentrations, allicin and allicin-derived sulfides appear to be responsible for most of the in vivo and in vitro activity; however, at much higher concentrations, alliin, the glutamylcysteines, and S-allylcysteine also have activity (pp. 190-191). 7. Immune effects (pp. 191-192). A small number of human (3), animal (6), and in vitro (5) studies indicate that low doses of garlic can stimulate the immune system as shown by increased numbers of lymphocytes, increased phagocytosis, increased natural killer cell activity, and increased antibody titers. Several compounds appear to be responsible for the effects, since both allicin-derived oils and allicin-depleted garlic extracts have activity. 8. Hypoglycemic effects (pp. 193-196). Both animal and human studies indicate that garlic can modestly reduce blood glucose levels. Although most studies have used large doses for a single day, one recent controlled clinical trial found significant reduction with the equivalent of 2.5 grains fresh garlic taken for four weeks. Allicin appears to be responsible for the effect since the activity is found in the ether-extract and is absent when alliin is removed (p. 194). Chapter 6 (Metabolism -- pp. 213-220; 55 references). The results of the comparatively few studies on the rates of absorption, metabolic fate, and rates of elimination of garlic's sulfur compounds are presented. Although these compounds are well-absorbed, their distribution among tissues and metabolic fate has not been well-studied. Consequently, the specific mechanisms and sites of action for these compounds are not yet understood. Allicin and several allicin-derived compounds are rapidly converted by blood cells and liver to allyl mercaptan, although the metabolic fate of allyl mercaptan is still unknown (pp. 213-4). Liver can also at least partially metabolize alliin to diallyl disulfide (p.216). Chapter 7 (Toxicology -- pp. 221-228; 211 references). This chapter discusses the studies that have been conducted which show the safe levels of garlic consumption as well as its potentially adverse effects when consumed in unusually large amounts. Several human studies have shown that up to 15-20 grams per day of uncooked garlic cloves can be eaten without adverse effects as long as it is consumed with a meal (Table 7.1, p. 221). It is recommended that 10 grams per day represents a safe level, which well encompasses the often recommended dose of one clove (3-5 grams) per day. Since cooking prevents allicin formation, considerably more cooked garlic can be safely consumed. When fresh garlic is consumed alone on an empty stomach, the allicin causes considerable abdominal irritation. Several cases of skin burns have also been reported when crushed garlic remains in contact with skin for several hours (p. 225). There have also been many reports of localized skin allergies to garli c in persons who frequently handle or cut cloves (Table 7.2, p. 227). Article copyright American Botanical Council. ~~~~~~~~ By Larry Lawson, Heinrich P. Koch and Larry D. Lawson, editors. 1996. Williams & Wilkins Publishing Company, Baltimore, MD. 340 pages, 2,580 references.