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Garlic: Health Benefits and Actions BioMedicine 2 (2012) 17e29 Available online at www.sciencedirect.com www.biomed-online.com Review article Garlic: Health benefits and actions Chia-Wen Tsai a, Haw-Wen Chen a, Le-Yen Sheen b, Chong-Kuei Lii a,* a Department of Nutrition, China Medical University, Taichung, Taiwan b Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan article info abstract Article history: Recent years have seen an increasing emphasis on foods and food components in disease Received 24 October 2011 prevention. Garlic (Allium sativum L.), one of the best-researched herbal remedies, holds Received in revised form a unique position in history, traditionally employed to treat infection, colds, diabetes, heart 21 November 2011 disease, and a host of other disorders. Clinically, it has been evaluated for lowering blood Accepted 11 December 2011 pressure, cholesterol, and glucose concentration, as well as for the prevention of arterio- Available online 31 January 2012 sclerosis and cancer. Epidemiologically, garlic consumption inversely correlates with the risk of oral, stomach, esophageal, colon, and prostate cancers. In addition, the biological Keywords: activities of garlic, including antibacterial, antithrombotic, antioxidant, immunomodula- cancer tory, and antidiabetic actions and modulation of drug metabolism, have been extensively cardiovascular disease investigated. Here, we briefly summarize the recent findings on garlic and its sulfur- drug metabolism containing compounds in preventing cardiovascular diseases and cancer, along with its foodedrug interaction modulation of drug-metabolizing enzymes and membrane transporter activities. Finally, garlic garlic safety and drug interaction are discussed. Copyright ª 2012, China Medical University. Published by Elsevier Taiwan LLC. All rights reserved. 1. Chemicals and bioactive components of appropriate conditions, allicin can be transformed into other garlic lipid-soluble products such as ajoene and vinyldithiin. Ajoene is identified as a principal product in garlic extract prepared by The unique flavor and health-promoting functions of garlic using ether as a solvent [3]. are generally attributed to its rich content of sulfur-containing In contrast to the processes stated above, alternative compounds, i.e., alliin, g-glutamylcysteine, and their deriva- pathways occur in case of different means of garlic storage. An tives. Processing a fresh and intact garlic bulb by crushing, aging process caused by immersing intact or sliced raw garlic grinding, or cutting induces the release of the vacuolar in alcohol or vinegar for several months results in sulfur- enzyme alliinase, which very quickly catalyzes alliin to allicin containing compounds in this aged product dramatically [1,2]. Allicin is, however, a very unstable compound, soon different from those found in garlic oil. This aging process rearranged and transformed into numerous lipid-soluble is supposed to cause considerable loss of allicin. Meanwhile, sulfur-containing byproducts, mostly diallyl disulfide (DADS) with the action of g-glutamyltranspeptidase, the other but also diallyl sulfide (DAS), diallyl trisulfide (DATS), sulfur-containing precursor g-glutamylcysteine is trans- allylmethyl trisulfide, and diallyl tetrasulfide [1]. These formed into water-soluble S-allylcysteine (SAC) and subse- compounds emit strong odors and are kept in garlic oil. Under quent metabolites, including S-allylmercaptocysteine (SAMC) * Corresponding author. Department of Nutrition, China Medical University, Taichung, Taiwan. E-mail address: [email protected] (C.-K. Lii). 2211-8020/$ e see front matter Copyright ª 2012, China Medical University. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.biomed.2011.12.002 18 BioMedicine 2 (2012) 17e29 and S-methylcysteine. Unlike the oily sulfur compounds, increase in oxidative damage, and smoking as well- these water-soluble compounds are odorless but have a more demonstrated risk factors [11]. delicate and less characteristic flavor [4]. Due to the accompanying inflammation in the plaque, In addition to sulfur-containing compounds as stated cardiovascular disorders are regarded as chronic above, garlic is also rich in trace elements. In raw garlic, the inflammation-related diseases [11]. The increased production amounts of zinc, manganese, copper, selenium, and iodine in and release of inflammatory mediators, such as reactive 100 g fresh weight of garlic are 556.1, 446.9, 143.3, 5.5 and oxygen species (ROSs), tumor necrosis factor alpha (TNF-a), 2.5 mg, respectively [5]. The protein content of raw garlic interleukin 6 (IL-6), arachidonic acid metabolites, and nitric ranges from 2.6% to 3.0%, depending on the variety of garlic. oxide is noted in the atherosclerotic lesion [12]. This results in The average content of free amino acids is 2.13%. Concentra- a greater expression of adhesion molecules, including P- tions of dietary fiber and total tocopherols in raw garlic are selectin, E-selectin, vascular cell adhesion molecule (VCAM), 2310 and 103.1 mg/100 g fresh weight, respectively. Ascorbic intercellular adhesion molecule (ICAM), and monocyte and total polyphenols levels are 73.6 and 1.9 mg in 100 g dry chemotactic protein-1 on the cell surfaces of monocytes, weight [6]. Over 70 fatty acids have been determined, with leukocytes and vascular endothelial cells, which accelerates linoleic (46e53%), palmitic (20e23%), oleic (4e13%), and a- the adherence of monocytes and leukocytes to the vascular linolenic (3e7%) acids being most abundant, accounting for endothelium and their subsequent transmigration into the 80% of the total lipids [7]. subendothelial space. Within the intima, activated macrophages release ROSs, scavenge oxidized low-density lipoprotein (oxLDL), become 2. Garlic preparations and supplements foam cells, and lead to the development of the fatty streak in the early stage of atherosclerosis [13,14]. This explains why Because of the complex chemistry of garlic, variations in phytochemicals with anti-chronic inflammation, hypolipi- processing methods can yield quite different preparations. demic, and antioxidative properties are thought to be capable Raw garlic homogenate, the major preparation of garlic, is the of decreasing the incidence of atherosclerosis. most common form of garlic consumed, and allicin the main Garlic has been regarded as a potent antiatherogenic food compound present in fresh raw garlic homogenate. There are [15]. Its lowering of blood cholesterol is believed largely due to currently many garlic supplements on the market, garlic oil, a reduction in LDL-cholesterol [16,17], which may be due to powder, and aged extract being the most popular. inhibition of hepatic hydroxymethylglutaryl-CoA reductase Garlic oil is mostly obtained by steam distillation, with activity by alliin and allicin [18]. Over the past decade, several a yield around 2.5e3.0 g/kg fresh garlic. In garlic oil, DAS, intervention studies and systemic meta-analytic reviews have DADS, and DATS, differing in their number of sulfur atoms, investigated the effectiveness and properties of garlic in pre- and allylmethyl sulfide are the four most abundant volatile venting cardiovascular disease (Table 1). allyl sulfides [8]. Garlic power is generated from garlic cloves A double-blind placebo-controlled randomized study that have been dehydrated and pulverized into powder. Due to including 51 patients with coronary conditions indicated that deactivation of alliinase by heat during dehydration, the 12 months’ treatment with 300 mg/d garlic powder signifi- major active constituents of garlic powder are alliin and cantly decreased the total cholesterol and LDL-cholesterol a small amount of oil-soluble sulfur compounds. levels [19]. A reduction of 32.9 and 27.3 mg/dL in LDL- To overcome the strong and irritant odor and the possible cholesterol resulting from the garlic was observed in men side effects of raw garlic and garlic oil, including growth and women, respectively. retardation and destruction of gut microflora, an “aging” A similar reduction in total cholesterol and LDL- process has been applied to garlic. Aged garlic is prepared by cholesterol, along with an increase in high-density lipopro- soaking whole or sliced garlic cloves in alcohol or vinegar tein-cholesterol, were also reported in hypercholesterolemic solution for 6e20 months, which removes the several irritant adults who were administered 10 g/d garlic extract for 4 sulfur-containing compounds and also stabilizes some months, 5 g/d raw garlic for 6 weeks, or 600 mg/d garlic unstable compounds such as allicin [4,9]. The water-soluble powder for 12 weeks [20e22]. Oily macerate of garlic (1620 mg/ compounds SAC and SAMC are the most abundant sulfur- day for 30 days) was found to significantly lower the levels of containing components, and trace amounts of oil-soluble total cholesterol, LDL-cholesterol, and triacylglycerides in 70 allyl sulfides exist in aged garlic. In contrast to odoriferous hypertensive adults [23]. However, Burggraaf and colleagues garlic oil and raw garlic, garlic powder and odorless aged garlic reported that 12 weeks of 2.1 g/d garlic powder administration product are currently the most popular garlic supplements on did not change the lipid profiles in overweight subjects with the market. normal blood lipid levels [24]. A meta-analysis including 29 trials recently revealed that garlic supplementation markedly reduced blood total choles- 3. Garlic and cardiovascular disorders terol levels (e0.19 mmol/L; 95% CI e0.33
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