2013

NFSC 345 Antoinette Kruger

APPENDIX

Garlic (Allium sativum L.)

0

Abstract
The role of food being a preventive and curing aspect to ones health has been recognized since the beginning of recorded human history. Among these functional foods, garlic has one of the longest histories as a medicinal spice with its roots in antiquity. Ancients prescribed garlic for a variety of conditions ranging from enhancing work productivity to a treatment for respiratory and circulatory aliments. The World Health Organization reported that in 2011 seven and a quarter million people died from cardiovascular disease (CVD) (WHO, 2011). Being the leading cause of death in the world, it is becoming crucial to understand this multifaceted disorder and ways to prevent and treat the sequelae of the disease. The highest proportion of deaths by CVD is by atherosclerotic disease. Atherosclerosis is characterized by the hardening and narrowing of arterial blood vessels with a chronic inflammatory response in the walls of arteries caused by the formation of multiple plaques within the arteries. Unstable plaques can rupture and expose thrombogenic material, such as collagen, to the circulation and eventually induce plateletplatelet aggregation and thrombus formation in the lumen. This activity is the leading cause of atherosclerosis and thus it is imperative to prescribe and treat atherosclerotic patients with antiplatelet drugs. Unfortunately, many of these drugs have adverse side effects and have limitations in long term use. In search of a long term natural remedy, Allium sativum (garlic) has been investigated due to its extensive medicinal history with purported benefits in treatment of CVD and pulmonary functions. Various epidemiological studies show a strong inverse correlation between the consumption of garlic and incidence CVD. Clinical trials have various results, yet give great insight in the needs of future research and standardizations. Garlic shows strong promise in being a preventative and relatively safe dietary supplement for prevention and treatment of mild CVD by inhibition of platelet-platelet aggregation.

A Historical Introduction
Allium sativum, commonly known as garlic, is a species in the onion family. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Garlic is native to central Asia and there are many varieties, some which grow wild across Asia and Europe. Allium sativum is a bulbous plant. It grows up to two feet tall with a hardiness measuring at USDA Zone 8. It

produces hermaphrodite flowers (Figure 1). The main country of cultivation in the world is China (Wikipedia, 2013). Garlic has been used for over seven centuries for culinary and medicinal uses. The flavor profile of garlic is amazing and has a unique spice that has been consistently used in all cuisines from Thai to European to the Americas for centuries. With its abundant historical use in culinary, it is not surprising that it has also had medicinal applications in ancient cultures with its origin in antiquity described in Rivlins (2001) extensive historical review (Table 1). Garlic is one of the earliest documented plants used for treatment of disease and maintenance of health and mention of garlic is found in ancient Egyptian, Chinese, Indian, Greek, and Roman texts. This becomes of particular interest when studying the potential benefits of garlic because these ancient cultures developed the same conclusions about garlics action and efficacy while having no direct contact with one another. The earliest written documentation of garlic is from ancient Egyptian texts. It was a part of their daily diet especially in the labor class. A reoccurring theme throughout early records was giving garlic to the working classes to increase their strength and endurance to be more productive. The 1922 excavation of King Tutankhamens tomb, dating approximately 1500 BC, was able to clearly identify garlic cloves. The significance of the cloves is unknown, but it is clear evidence that the vegetable was in use at that time. Furthermore, the medicinal text of the time, the Codex Ebers, c. 1550 BC, has several prescribed treatments of garlic and is the first written documentation of medicinal garlic. The Codex authorized the use of garlic for abnormal growths (most likely malignancies), circulatory ailments, general malaise, and infestations with insects and parasites. The Jewish slaves in Egypt were fed garlic to promote productivity just as the laborers of the indigenous Egyptians. The Bible references their fondness for the plant. It most likely did not have any religious significance to the ancient Jews, but this cannot be entirely omitted. For example, a 2nd century AD religious text, the Talmud, suggests the intake of garlic to treat infections involving parasites or other disorders and to enhance relations between married couples to promote procreation.

The excavations of ancient Greek temples and the palace of Knossos in Crete, dating back to 1400-1800 BC, unearthed well-preserved garlic, which is further proof of its role in ancient times. Ancient Greeks perceived garlic as a promoter of strength and endurance and used it as one of the first performance enhancing agents for competitive athletes. Olympic athletes were fed garlic prior to competing. Moreover, garlic was an important aspect of the military diet especially when they were at war. The father of medicine, Hippocrates, proclaimed garlic to have cleansing or purgative properties and prescribed it for pulmonary complaints and abdominal growths, particularly uterine. As Rome became the leading power, Greeks medicine and traditions were gradually absorbed by Roman sailors and military that used garlic to promote strength and endurance. Also, the five volume medicinal text of the era, the Historica Naturalis lists twenty-three uses for garlic as a therapy for a variety of disorders, such as significant protection against toxins and infections, a finding corroborated by contemporary investigations of the effects of garlic as an antioxidant. By or before 2000 BC, garlic was a part of the daily diet in China. Ancient Chinese medicinal tonics used garlic as a healer for a wide range of aliments: fatigue, headache, insomnia, respiration disorders, diarrhea, worm infestation, and to enhance male potency. Also, records from this time period discuss garlics use as a food preservative. Approximately two thousand years ago, garlic was introduced to Japan and ancient India is also from approximately two thousand years ago. Their medical texts utilize garlic to cure heart disease, arthritis, fatigue, parasites, digestive disease, and leprosy. In Hinduism and Buddhism, garlic is considered to increase ones desires. The Hindus refrain from using it in religious ceremonies. Buddhists consider it one of the five pungent spices and is thought to arouse sexuality and aggressive drives which is detrimental to their meditation practices. Garlic wasnt introduced to Europe till 800 AD with Roman legions moving north. The monks were the dominate preservation of the knowledge of therapeutic plants including garlic. The leading physician, Abbess of Rupertsberg, of the 12th century claimed raw garlic was more therapeutic than cooked forms. Interestingly enough modern studies have found the same results. The influential medical school of Salerno taught mostly dietetic therapies with a prominent use of garlic. It was taught that it was a hot food that should be consumed during the winter months to reduce the risk of pulmonary infections. Later in the middle ages, garlic functioned as

treatment for the Great Plague. At this time, the general consensus in Europe was that garlic acted as a cleansing agent warding off demons, vampires, and werewolves. Up until the Renaissance, garlic was reserved for the working and lower class citizens. Society perceived garlic as being effective for labor productivity. The upper classes did not see it fit for their consumption. In the 16th century, there was a great interest in the use of medicinal plants. Many universities grew physic gardens to study plants pharmaceutical properties. Many leading physicians continued to prescribe garlic for digestive disorders, infestations with worms and renal disorders, as well as to help mothers during difficult childbirth. With the increased attention on medicinal plants benefits, garlic slowly became acceptable for consumption by the upper classes in Europe. It is said that King Henry IV of France was baptized in water containing garlic to protect him from evil spirits and disease. Yet, in England it still remained food of the working class. The wealthy only consumed garlic for therapeutic purposes, including garlic in their medicine chests. It was used for toothaches, constipation, dropsy, and plague. With the discovery of the Americas, garlic was brought over by Portuguese and Spanish explorers. It should be noted that before the Native Americans used similar bulb plants as a medicinal tea. By the 19th century, garlics perceived therapeutic benefits were widely accepted by the general public. The 1878 Home Book of Health heavily featured garlic with the suggested use as a diuretic, for treatment of infections, as a general tonic, and treatment for asthma or other pulmonary disorders. Its perceived remedy of pulmonary disorders continued into the early 20th century with recommendation written in Health Remedies, a Complete Medical Work and Family Guide. These ancient antidotes become relevant because of the fascinating similarities among cultures and civilizations conclusions that never came in contact with one another. By employing modern science and technology, we can hope to understand the action and mechanism behind the conclusions of our predecessors. Today garlic is thought to be a preventative and a curing agent in treating cancer and cardiovascular disease. Currently consumers interest in garlics health benefits and numerous purported benefits (Table 2) has made it one of the top supplement sellers in the United States. Whole garlic is still

used widely throughout various diets and cuisines. Garlics amazing flavor is thought to be the result of its high content of organosulfur compounds. As Hippocrates predicted, organosulfur compounds have been found to be strong antioxidants. Furthermore, garlic contains bioflavonoids (quercetin and cyanidin, allistatin I and allistatin II) and vitamins (C, E and A) which also protect against oxidative agents and free radicals in the body. Whole garlic cloves contain two classes of organosulur compounds: gamma-glutamylcysteines and cysteine sulfoxides. Allylcysteine sulfoxide (allicin) has the highest concentration making up approximately 80% of all the cysteine sulfoxides in garlic. The absorption and metabolism of allicin, allicin-derived, and organosulfur compounds activity are thought to have the potential to treat and prevent chronic diseases, especially cardiovascular disease and cancer. The dosage needed and the mechanism of these actions is not clearly understood. Each tiny clove has the potential to produce over 200 chemicals which can interact with each other in numerous ways. To complicate the situation more, garlic can be processed in numerous ways which yield different preparations with different components at different levels. Besides whole garlic, commercial forms come in powered garlic tablets, steam distilled garlic oil capsules, garlic oil macerate capsules, and aged garlic oil extract capsules. Each provides different organosulfur compounds and bioavailability. Refer to Table 3 for the common commercial supplements, their compound profile, and bioavailability. It is likely that the health benefits of garlic are the result of the complex chemistry between a wide variety of components, possibly working synergistically together. (Linus Pauling Institute, 2005- 2013) The extensive and fascinating history of garlic, along with the vast consumer interest, and ever increasing chronic disease rate has stimulated abundant research on the different proposed therapeutic effects of this plant. This paper will focus on garlics action and efficacy of preventing cardiovascular disease specifically through inhibition of platelet aggregation and the safety concerns associated with this treatment.

Discussion
Purported Cardiovascular Benefits

Cardiovascular disease (CVD) is the culprit of 7.25 million deaths a year and is the number one cause of death worldwide (WHO, 2011). Among all CVD related deaths,

atherosclerotic disease accounts for the largest proportion of these deaths in both men and women (Chan, Yuen, Chan, & Chan, 2012). Atherosclerosis pathogenesis is characterized by the narrowing of the lumen of blood vessels, hardening of blood vessels, increased platelet aggregation, vascular injury, reduced fibrolytic activity, elevated LDL cholesterol, and decreased HDL cholesterol. Additionally CVDs have been linked to hypertension, diabetes mellitus, high total cholesterol, and obesity metabolic risk factors. Among these contributors, platelet aggregation and insufficient fibrolytic activity are the most responsible in the manifestation of atherosclerosis. (Sobenin and others, 2012). Thus, it is necessary to prevent thrombosis and thromboembolism with the implementation of anti-platelet drugs in the therapy of atherosclerotic patients. Unfortunately, many of these drugs have adverse side effects and have limitations in long term use. In the search of natural herbal remedies, garlic has been studied extensively for its cardioprotective properties. The various epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease (Rahman & Lowe, 2008). Garlic shows much promise as a preventative and curative botanical therapy in CVD with purported benefits including: cholesterol and lipid lowering effects, antithrombotic and antiplatelet aggregratory effects, increased fibrolysis, induction of vasorelaxation, increased endogenous antioxidant defenses, prevention of cardiac hypertrophy, prevention of angiogenesis, and prevention of hyperglycemia (Chan and others 2012; Rahman & Lowe, 2008; Zeng T, 2012).
Evidence Based Efficacy, Proposed Mechanisms, and Conflicting Research

Platelet aggregation starts with platelet adhesion to the walls of blood vessels. This occurs when there is damage to the endothelium and the supportive, underlying collagen is exposed. Nearby endothelial cells well produce Van Willbrands Factor (VWF) which will attract passing platelets to the damaged part of the vessel. The platelet will adhere to VWF by its membrane glycoprotein GpIb/Ia complex. This adhesion will create conformational changes that release aggregratory agents which bind to specific platelet membrane proteins and act via a receptor- mediated transduction pathway to stimulate aggregation of other platelets. The aggregation leads to the formation of a fibrin/fibrinogen-rich thrombus, this action narrows blood vessels and could eventually lead to a blood clot. (Allisona, Loweb, & Rahma, 2012)

Once the platelet is adhered to the vessel wall, it secretes and releases effector molecules that are essential for platelet plug formation at the site of vascular injury. For example, the aggregating agent ADP is released which stimulates intracellular signaling creating conformational changes in nearby platelets resulting in platelet- platelet aggregation at the site of adhesion. This intracellular cascade is started by the stimulation of a platelet by ADP followed by intracellular G-proteins coupled with adenylyl cyclase (AC) which produce a second messenger creating an increase in intracellular calcium and diacyclglycerol (DAG). The culmination of this cellular signaling produces a shape change in the platelet exposing GpIIb/IIIa receptors on the platelet surface. Now that GpIIb/IIIa is exposed on the platelet surface it will bind with adhesive agonists such as fibrinogen which will promote platelet- platelet aggregation. There is a cascade effect of each platelet, which will attract more and more platelets as a thrombus forms. (Allisona and others, 2012) Allisona et al (2012) found that aged garlic extract (AGE) acts on this transduction pathway in a preventative and disaggregatory method. The affinity of GpIIb/IIIa binding to adhesive molecules which stimulate aggregation is closely regulated by the sulfhydryls versus disulfide bond balance found in its active site. This balance is affected by sulfhdryl- reactive agents. The many organosulfur compounds and other chemical compounds in garlic can participate in this chemistry. Allisona et al proposed with their supportive findings that AGE prevents platelet aggregation by blocking many of the sulfhydryls in the active site preventing many disulfide bonds from forming. This disrupts the structure and function of the GpIIb/IIIa receptor leading to a significant decrease in its activity and thus significantly inhibiting plateletplatelet aggregation. Allisona et al (2012) also found supporting evidence that AGE can work in a disaggregatory mechanism. Endogenously, prostaglandin reverses platelet aggregation by having a large stimulatory effect on cAMP causing significant inhabitation of human platelet aggregation stimulated with ADP. Allisona et al found AGE can disaggregate ADP stimulated human platelets. Addition of AGE produced a significant increase in the intracellular levels of cAMP in basal and ADP stimulated platelets. Allisona et al proposed that AGE disaggregates platelets by sustaining high levels of platelet cAMP through cAMP phosphodiesterase which directly decreases intracellular calcium and DAG levels preventing the conformational change

for GpIIb/IIIa to bind fibrinogen and thus significantly decreases aggregatory activity and thrombus formation. A rabbit study proposed that garlics antiaggregatory effect is due to AGEs ability to maintain the expression of the contractile phenotype of smooth muscle cells under conditions of vascular injury (Campbell JH, 2001). Contractile is the phenotype for noninjured, mature smooth muscles in blood vessels. In this phenotype, cells do not migrate, synthesize appreciable matrixes, respond to mutogens present in serum, or accumulate lipids. Campbell et al (2001) found a significant cellular effect on AGEs ability to inhibit phenotypic change to a state in which these functions can occur, and thus maintain healthy blood vessel functioning in the contractile phenotype even when eating a poor diet. This study is limited by the fact that it is an animal study. Yet Lei et al (2008) propose garlics antithrombotic mechanism is a combination of the two proceeding- inhibiting intermediates in the active metabolic transduction pathway of platelet aggregation along with the suppression of key genes that would lead to physiological promoting activities of atherosclerosis. A dosage finding study found that AGE is selective for platelet adhesion receptors and is not strictly dose dependent. The lowest dose of AGE (2.4g AGE/ day) was as effective as the highest dose used in the study (7.2g AGE/day) for inhibiting platelet aggregation with epinephrine and ADP as stimulants. When collagen was the stimulant, there was an increase in antiaggregatory effects from a dose of 2.4 to 4.8g AGE/day, but no difference between 4.8g and the highest dose of 7.2g/day. The study observed a two week washout period to eliminate the antiaggregatory activity. This study is the only dose finding study on platelet aggregation and has limitations in being ex vivo. (Steiner & Li, 2001) Since 1993, seven clinical trials have been performed, and all show that garlic inhibits platelet aggregation. Four of these studies were on healthy patients while the other three had subjects with coronary artery disease or mild hypercholesterolemia (Rahman & Lowe, 2008). Various primary studies using AGE supplementation have found a significant antiaggregatory effect and increased fibrolytic activity over placebo. Yet, many of these are small scale in vitro studies. There have been a few ex vivo or in vivo experiments showing varying results (Steiner & Li, 2001).

The efficacy of garlic as a dietary supplement for cardioprotective purposes has been widely studied. The magnitude of the change observed in small-scale studies using different preparations makes it difficult to ascertain the health benefits of the preparations when evaluated individually. The situation with this dietary supplement is similar to that of other dietary manipulations that have been studied. It is important to give definite conclusions about effectiveness only after pooling large numbers of studies. This will achieve the statistical power required to define significance. While there are significant findings within many individual studies, the results cannot be applied to the interpolated. Reviews and meta-analyses also encounter difficulty ascertaining an unequivocal conclusion for various reasons that contribute to large heterogeneity among individual studies. The biggest contributor to the large heterogeneity is the varying use of different garlic preparations and dosages used in studies. The largest obstacle in analyzing the data collected from garlic research is that there has yet to be a consensus on the mechanism or metabolism of garlic (Steiner & Li, 2001). This is largely due to the complexity and array of biomolecules within garlic. Garlic is composed of high concentrations of organosulfur compounds. It is ambiguous which of these compounds or metabolites actually reach target tissues. Various types of garlic preparations are available commercially, each providing a different profile of organosulfur compounds. Not all garlic preparations are standardized, and even standardized brands may vary with respect to the amount and the bioavailability of the organosulfur compounds they provide (Linus Pauling Institute, 2005- 2013).While no definitive mechanism has been established, it is understood that a sulfhydryl groupmediated effect may be responsible from the observed chemistry (Steiner & Li, 2001). There is corroboration of this amongst primary research. Since it has been continually shown that garlic has an effect on prevention and treatment of cardiovascular diseases, much of the research is now turning to defining the mechanism which will lead to insight on dosage, usage, and significance as a nutraceutical.
Effects of Preparation and Cooking

The organosulfur compounds responsible for anti-platelet aggregation are formed when fresh garlic cloves are chopped and cytoplasmic precursors, collectively called S-alk(en)yl-Lcysteine sulfoxides (ACSOs), are cleaved by the endogenous enzyme, alliinase (EC

4.4.1.4). Alliinase converts ACSOs to the respective sulfenic acids, pyruvate, and ammonia. Sulfenic acids, such as allicin, are highly unstable and condense, in pairs, to form thiosulfinates. The antiplatelet properties of Allium species are attributed to these sulfur compounds formed after alliinase-mediated cleavage of the ACSOs and subsequent reactions. Thus, when consuming garlic, it should always first be chopped or crushed. (Cavagnaro PF and others , 2007; Linus Pauling Institute, 2005- 2013) Raw garlic preparations or oils extracted from raw garlic are the most commonly used in research. These preparations have clearly demonstrated an anti-aggregatory efficacy. However, worldwide garlic is cooked before consumption due to its disagreeable, pungent flavor in raw form. Cavagnaro et al (2007) tested different cooking preparations, heat and time on garlics invitro anti-aggregatory activity (IVAA). The studied resulted in the following findings: 1. Oven-heating at 200 degrees C (392 degrees F) or immersing in boiling water for 3 min or less did not affect the ability of garlic to inhibit platelet aggregation in comparison to raw garlic 2. Oven-heating at 200 degrees C (392 degrees F) or immersing in boiling water for 6 min completely suppressed IVAA in uncrushed garlic, but did not affect the ability of previously crushed garlic to inhibit platelet aggregation. 3. Cooking garlic at the above temperatures for longer than ten minutes completely destroyed IVAA. 4. The partial loss of antithrombotic effect in crushed-cooked garlic may be compensated by increasing the amount consumed. The major conclusions of this study suggest that crushing garlic and letting it stand for ten to fifteen minutes before applying moderate heat for six minutes or less will keep garlicinduced IVAA intact in comparison to raw garlic. Thus, cooking garlic in this manner can allow for cooked garlic consumption to be just as therapeutic as raw forms. To aid in optimal flavor with less coking time, garlic can be cut extremely thin using a crusher or a food processor and applied to heat in the last six minutes of cooking time.
Safety and Side Effects The most commonly reported side effects of dietary supplementation are adverse breath and body odor. Also, gastrointestinal distress has been reported such as heart burn, abdominal pain, and diarrhea.

10

The most serious effect has been seen in a few cases of serious postoperative or spontaneous bleeding associated with the consumption of garlic supplementation. Furthermore, garlic has been found to inhibit platelet aggregation and there could be an additive effect when taken with other medications, such as warfarin (Coumadin), that inhibit platelet aggregation or possibly even other supplements such as high dose fish oil or vitamin E. More research is needed to determine the association, risk, and severity of the hemorrhagic risk for people on anticoagulatory therapy. Furthermore, there are inconsistent results in garlic supplementation significantly reducing the bioavailability of HIV protease inhibitor drugs in healthy subjects. Thus, it is not advised for clients on HIV protease inhibitors to supplement with garlic until further research has been conducted. There have been no reports of adverse side effects in the

outcome of pregnancy and lactation while the mother is supplementing with garlic. (Linus Pauling Institute, 2005- 2013)A

Conclusion
Professional Position for Practice Garlic has a long extended use in the human diet. Furthermore, it is virtually very safe for the majority of the general public with little to no side effects and no reported toxicity. Thus, it is of the professional opinion that it is a safe supplement. Corresponding with the Academy of Nutrition and Dietetics, supplements should as often as possible be consumed as a functional food in its whole product form included in a varied diet; it is advised that garlic be consumed as part of the diet instead of in supplement form ( American Dietetic Association, 2009). It is easy to incorporate in any meal, and if tolerated should be consumed raw. If the raw form is not tolerated, cooking and preparation should follow the instructions presented in this paper to keep bioactive molecules intact. Garlic should be advised to clients who are at risk or have a family history of CVD due to its preventative efficacy. Patients with hyper-cholesterol, hyperlipidemia, hypertension, and patients with other cardiovascular disease states/symptoms should consult with their physician before using garlic as a supplement or in high doses within their diet. It should not be taken by clients taking anticoagulant medication, on a high dose of fish oils, on a high dose of Vitamin E, taking HIV protease medication, and/ or have irritable bowel syndrome. In Summary Allium sativum is a rich source of organosulfur compounds that have a vast variety of purported health benefits, which are under investigation. Most importantly under research are its effects on CVD. Epidemiological studies show an inverse correlation between garlic and CVD. Extensive in vitro, preclinical trials have proved the efficacy of garlic on cardio-protective measures by cholesterol and lipid lowering effects, antithrombotic and antiplatelet aggregratory effects, increased fibrolysis, induction of

11

vasorelaxation, increased endogenous antioxidant defenses, prevention of cardiac hypertrophy, prevention of angiogenesis, and prevention of hyperglycemia. There have been a select few in vivo studies on subjects with CVD, but these show varying results and have statistical and experimental limitations. Meta analyses have difficulty making definitive conclusions on garlics actions because of the large degree of heterogeneity among primary research due mostly to lack of standardization among the wide variety of garlic supplements. Future research should strive to standardize preparations used in clinical trials. Research should focus on establishing the constituents of supplements, their bioavailability, and absorption. This information will aid in a conclusive mechanism and a stronger clinical trial. Clinical trials should also conduct well-designed, double blind randomized trials that are of sufficient duration to measure morbidity and mortality, as well as lipid and thrombotic profiles. Furthermore, clinical trials need to investigate garlics use as a dietary preventive measure in a healthy population. Future studies should incorporate new findings on CVD biomarkers and use these to measure outcomes and analyze the mechanism of action. CVD is a complex disease and it is important to ask the right, specific questions when formulating a study design.

12

REFERENCES
Lei, Y.-P., Chen, H.-W., & Sheen, L.-Y. (2008). Diallyl Disulfide and Diallyl Trisulfide Suppress Oxidized LDLInduced Vascular Cell Adhesion Molecule and E-Selectin Expression through Protein Kinase A and BDependent Signaling Pathways. Journal of Nutrition. Linus Pauling Institute. (2005- 2013). Retrieved from Micronutrient Information Center: Garlic: http://lpi.oregonstate.edu/infocenter/phytochemicals/garlic/ Wikipedia. (2013, April 21). Retrieved from Garlic: http://en.wikipedia.org/wiki/Garlic#Origin_and_major_types Allisona, G. L., Loweb, G. M., & Rahma, K. (2012). Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sciences, 1275- 1280. Association, A. D. (2009). Position of the American Dietetic Association: Functional Foods. Journal of the American Dietetic Association, 736-746. Campbell JH, E. J. (2001). Molecular basis by which garlic suppresses atherosclerosis. Journal of Nutrition, 131, 10065-10095. Cavagnaro PF, P., Camargo A, A., Galmarini CR, C., & Simon , P. (2007, Feb). Effect of cooking on garlic (Allium sativum L.) antiplatelet activity and thiosulfinates content. Journal of Agricultural and Food Chemistry, 55, 1280-1288. Chan, J. Y.-Y., Yuen, A. C.-Y., Chan, R. Y.-K., & Chan, S.-W. (2012). A Review of the Cardiovascular Benefits and Antioxidant Pproperties of Allicin. Phytotherapy research. Rahman , K., & Lowe, G. M. (2008). Garlic and Cardiovascular Disease: A Critical Review. American Society for Nutrition, 136, 7365- 7405. Rivlin, R. S. (2001). Historical Perspective on the Use of Garlic. Journal of Nutrition, 131, 9515-9545. Sobenin, I., Andrianova, I., Ionova, V., Karagodin, V., & Orekhov, A. (2012). Anti-aggregatory and fibrinolytic effects of time-released garlic powder tablets. Applied Technologies and Innovations, 40-45. Steiner, & Li. (2001). Aged Garlic Extract, a Modulator of Cardiovascular Risk Factors: A Dose-Finding Study on the Effects of AGE on Platelet Functions. Journal of Nutrition. WHO. (2011). The top 10 causes of death. Retrieved from World Health Organization: http://who.int/mediacentre/factsheets/fs310/en/ Zeng T, G. F. (2012). A meta-analysis of randomized, double-blind, placebo-controlled trials for the effects of garlic on serum lipid profiles. Journal of the Science of Food and Agriculture, July.

13

APPENDIX
FIGURE 1abc:

14

TABLE 1: Beliefs of ancients cultures regarding garlic

Ancient Egypt Ancient Greece Part of daily diet, found in the tomb of Tutankhamen Taken by athletes and soldiers, used against skin poisoning medical text Charaka Samhita prescribed for treating heart disease and arthritis Used as a food preservative, part of daily diet and for treating digestion and respiration Taken by troops and sailors for strength, prescribed for convulsions and arthritis Used for treating lung diseases, flu-like symptoms, and as a diuretic

Ancient Indian
Ancient China and Japan Ancient Rome Early America

(Rivlin, 2001)

Table 2: Purported Benefits of Garlic

Antibiotic (anti-bacterial) Anti-viral Fungicide Preventative of Cardiovascular Disease and promotes Cardiovascular health Cancer preventative- stomach and colon cancers. Due to large antioxidant quantities In countries with high garlic consumption, there is a lower prevalence of cancer Reduces platelet aggregation Gastric stimulant. Helps with digestion Testosterone- Garlic may boost testosterone in humans Stimulates the kidneys and is diuretic in nature. Tonic for strength & vitality. Symbiotic. Garlic seems to increase the potency of whatever other remedies you combine it with.

15

TABLE 3:
Principal Organosulfur Compounds in Commercial Garlic Preparations

Product

Principal Organosulfur Compounds

Delivers allicin-derived compounds?

Fresh garlic cloves

Cysteine sulfoxides (Alliin) Gamma-glutamylcysteines

Yes, when chopped, crushed, or chewed raw. Minimal, when garlic cloves are cooked before crushing or chopping.

Powdered garlic (tablets)

Cysteine sulfoxides (Alliin) Gamma-glutamylcysteines

Varies greatly among commercial products. Enteric-coated tablets that pass the USP allicin release test are likely to provide the most.

Steam distilled

Diallyl disulfide

Yes

garlic oil (capsules) Diallyl trisulfide Allyl methyl trisulfide Garlic oil macerate (capsules) Vinyldithiins Ajoene Diallyl trisulfide Aged garlic extract S-Allylcysteine S-Allylmercaptocysteine Minimal Yes

(tablets or capsules) S-1-Propenylcysteine (Linus Pauling Institute, 2005- 2013)

16