Review Article Role of Garlic Usage in Cardiovascular...

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Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 125649, 9 pages http://dx.doi.org/10.1155/2013/125649 Review Article Role of Garlic Usage in Cardiovascular Disease Prevention: An Evidence-Based Approach Waris Qidwai and Tabinda Ashfaq Department of Family Medicine, Aga Khan University Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan Correspondence should be addressed to Tabinda Ashfaq; [email protected] Received 20 February 2013; Accepted 23 March 2013 Academic Editor: Kashmira Nanji Copyright © 2013 W. Qidwai and T. Ashfaq. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. is study was done to find out the role of garlic usage in cardiovascular disease prevention. Methodology. Major databases including Google, PubMed, MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing role of garlic usage in cardiovascular disease prevention and the possible mechanisms responsible for such therapeutic actions were assessed. Results. Various clinical trials and meta-analyses conducted have shown positive impact of garlic in cardiovascular-disease prevention especially its effects on lipid levels; however, some contradictory results are also reported. Similarly, its effects on hypertension control, and platelet are also mild with limited data availability. e possible reason for these inconsistent results is the difference in preparations with diverse composition, variations in sulphur content present in different garlic preparations used, and methodological variations in subject recruitment, duration of study, dietary control and so forth. Conclusion. Garlic can be used as an adjuvant with lipid-lowering drugs for control of lipids, however, its role as a main therapeutic agent cannot be recommended and it is suggested that more meta- analyses using standardized preparations with a close watch on methodological shortfalls should be conducted to prove its role. 1. Introduction e epidemic of cardiovascular disease is growing at an alarming pace throughout the world [1]. It is recognized as one of the leading causes of mortality worldwide caus- ing more than 80% of deaths in low- and middle-income countries [2]. Cardiovascular disease refers to spectrum of illnesses that includes heart disease, vascular diseases of the brain, kidney, and peripheral arterial disease [3]. According to an estimate by World Health Organization, approximately 17.3 million people died from CVDs in 2008, representing 30% of all global deaths. Out of these deaths, 7.3 million occurred secondary to coronary heart disease and 6.2 million as a consequence of stroke [2]. It is anticipated that by 2020 cardiovascular diseases are predicted to be the major cause of morbidity and mortality in most developing nations around the globe [4]. Atherosclerosis and hypertension are measured as the major risk factor along with smoking, obesity, and sed- entary life styles leading to increasing trend of this major threat [5]. Today, in this era of rapid advancement in medical tech- nology, herbal or botanical preparations, commonly referred to as complementary and alternate medicine (CAM), approaches have gained lots of popularity in terms of health care maintenance, and a large number of population in the developing as well as developed world prefer to use (CAM) as a source of curative and preventive remedy for various ill- nesses [6, 7]. CAM is defined as a group of diverse medical and health systems practices and products that are not generally considered as part of conventional medicine [8]. According to 2007 National Health Interview Survey (NHIS) report, approximately 38% of US adults and 12% of child- ren are using CAM in the past 12 months; lifetime prevalence of CAM use in the United States and worldwide has

Transcript of Review Article Role of Garlic Usage in Cardiovascular...

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 125649 9 pageshttpdxdoiorg1011552013125649

Review ArticleRole of Garlic Usage in Cardiovascular Disease PreventionAn Evidence-Based Approach

Waris Qidwai and Tabinda Ashfaq

Department of Family Medicine Aga Khan University Stadium Road PO Box 3500 Karachi 74800 Pakistan

Correspondence should be addressed to Tabinda Ashfaq tabindaashfaqakuedu

Received 20 February 2013 Accepted 23 March 2013

Academic Editor Kashmira Nanji

Copyright copy 2013 W Qidwai and T Ashfaq This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Introduction Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developingworld warranting urgent need of intervention Complementary and alternative medicines are gaining popularity among generalpopulation because of their safety profile and easy administration Garlic in particular is considered to be one of the bestdisease-preventive foods because of its potent and widespread effects This study was done to find out the role of garlic usagein cardiovascular disease preventionMethodology Major databases including Google PubMed MEDLINE and Cochrane libraryview were used for the literature search Clinical trials conducted on humans assessing role of garlic usage in cardiovascular diseaseprevention and the possible mechanisms responsible for such therapeutic actions were assessed Results Various clinical trials andmeta-analyses conducted have shown positive impact of garlic in cardiovascular-disease prevention especially its effects on lipidlevels however some contradictory results are also reported Similarly its effects on hypertension control and platelet are alsomild with limited data availability The possible reason for these inconsistent results is the difference in preparations with diversecomposition variations in sulphur content present in different garlic preparations used and methodological variations in subjectrecruitment duration of study dietary control and so forthConclusion Garlic can be used as an adjuvant with lipid-lowering drugsfor control of lipids however its role as a main therapeutic agent cannot be recommended and it is suggested that more meta-analyses using standardized preparations with a close watch on methodological shortfalls should be conducted to prove its role

1 Introduction

The epidemic of cardiovascular disease is growing at analarming pace throughout the world [1] It is recognizedas one of the leading causes of mortality worldwide caus-ing more than 80 of deaths in low- and middle-incomecountries [2] Cardiovascular disease refers to spectrum ofillnesses that includes heart disease vascular diseases of thebrain kidney and peripheral arterial disease [3] Accordingto an estimate by World Health Organization approximately173 million people died from CVDs in 2008 representing30 of all global deaths Out of these deaths 73 millionoccurred secondary to coronary heart disease and 62 millionas a consequence of stroke [2] It is anticipated that by 2020cardiovascular diseases are predicted to be the major cause ofmorbidity and mortality in most developing nations aroundthe globe [4] Atherosclerosis and hypertension aremeasured

as the major risk factor along with smoking obesity and sed-entary life styles leading to increasing trend of this majorthreat [5]

Today in this era of rapid advancement in medical tech-nology herbal or botanical preparations commonly referredto as complementary and alternate medicine (CAM)approaches have gained lots of popularity in terms of healthcare maintenance and a large number of population in thedeveloping as well as developed world prefer to use (CAM)as a source of curative and preventive remedy for various ill-nesses [6 7] CAM is defined as a group of diverse medicaland health systems practices and products that are notgenerally considered as part of conventional medicine [8]According to 2007 National Health Interview Survey (NHIS)report approximately 38 of US adults and 12 of child-ren are using CAM in the past 12 months lifetime prevalenceof CAM use in the United States and worldwide has

2 Evidence-Based Complementary and Alternative Medicine

increased steadily since 1950 (910) Most common typesof CAM therapies used were natural products such as fishoilomega 3 glucosamine Echinacea and flaxseed (177)deep breathing (127) meditation (94) chiropractic andosteopathic (86) and massage (83) followed by yogadiet-based therapies progressive relaxation guided imageryand homeopathic treatment [9]

Among all these remedies plants-based functional foodshave gained lots of recognition throughout the world and itis believed that these natural substances have the potential toreduce the detrimental effect of a number of cardiovasculardiseases and associated risk factors [10] The probable reasonfor this rising trend is skeptic approach of general publictowards conventional medicine due to fear of more sideeffects and increasing costThis fact was further driven by thebelief of increased safety profile and easy availability of plant-based natural products in comparison to orthodox medicineGarlic has been used as a therapeutic agent for many illnessesover centuries as evident from various studies however itsrole in cardiovascular disease prevention is still questionableThis review was done to find out the efficacy of garlic incardiovascular disease prevention through evidence-basedapproach by analyzing clinical trials and systematic review inthe above mentioned area

2 Garlic as a Potential Herb

Garlic (Allium sativum) has played an important dietary aswell as medicinal role in human history The role of garlic(Allium sativum) as a potential herb has been acknowledgedfor over 5000 years Garlic and its various preparations arebeing readily consumed as a food and spice by various cul-tures for centuries [11] It was also documented as a choice ofmedical therapy to combat many diseases among Egyptians[12] Similarly it is also considered as an imperative partof Indian traditional medicine that is Ayurveda Tibbi andUnani and so forth In addition it is also claimed to pos-sess beneficial effects for the prevention of various aspectsof cardiovascular disease including hypertension and dyslipi-demia [13]

3 Garlic Composition

Garlic is available in many forms among these raw garlic andaqueous extract preparation is used more frequently Allicinis the principal bioactive compound present in garlic andprimarily contains sulphur as a main constituent which onbreak down gives garlic its characteristic odor It is producedas a result of activation of alliinase enzyme after crushing orchopping of raw garlicThe enzyme Allinase is inactivated byheat leaving behind alliin as the main constituent present inthe water extract of heat-treated garlic The composition ofgarlic powderwhich is produced after dehydration and crush-ing is the same as raw garlic and alliinase activity is preservedhowever caution needs to be taken regarding temperatureregulation as Allinase is inactivated if temperature exceedsbeyond 60∘C Apart from Alliin other important sulfur-containing compounds present in garlic homogenate includeallyl methyl thiosulfonate 1-propenyl allyl thiosulfonate and

120574-L-glutamyl-S-alkyl-L-cysteine On an average a garlic bulbcontains up to 09 g-glutamylcysteines and up to 18 alliin[14]

4 AGE Preparation

Another important and extensively studied garlic preparationis aged garlic extract (AGE)This form is produced by storageof sliced rawgarlic in 15ndash20ethanol for 20monthsThis pro-cess of storage leads to alteration in composition of the garlicextract the odorous harsh and irritating compounds ingarlic are converted naturally into stable and safe sulfur com-pounds with substantial loss of allicin activity and increasedactivity of new compounds like S-allylcysteine (SAC) S-allylmercaptocysteine and allixin [15] SAC can be used forstandardization because of its bioavailability property

5 Garlic Oil

Garlic oil another important preparation is produced as aresult of distillation process of raw garlic Garlic essential oilis obtained by steam distillation of garlic The essential oilcontent of garlic cloves is 02ndash05 and consists of a varietyof sulfides such as diallyl disulphide (DADS) and diallyltrisulfide (DATS) [16 17] All the water soluble contentsincluding allicin are completely eliminated from the oil Oilmacerates were originally developed for use as condimentsOil macerate products are made of encapsulated mixtures ofwhole garlic cloves ground into vegetable oilThis preparationcontains allicin-decomposed compounds such as dithiinsajoene and sulfides residual amounts of alliin and otherconstituents in garlic [16]

6 Garlic Powder

Garlic powder is primarily used as a flavoring agent for con-diments and processed foods Garlic cloves are sliced orcrushed dried and ground into powder The composition ofgarlic powder is the same as that of raw garlic however theproportions and amounts of various constituents differ sig-nificantly that is average content of alliin present in garlic is08 however raw garlic contains around 37mggm of alliin[18]

7 Garlic and CardiovascularDisease Prevention

Cardiovascular disease is one of the leading cause of morbid-ity and mortality worldwide Role of garlic in cardiovasculardisease prevention has been a topic of concerns for manyyears Various observational and experimental studies doneon animals showed encouraging results However theseclaimed benefits were not supported by evidence-based clin-ical studies This fact prompted many researchers to conductclinical trials in order to explore and address the efficacy andassociation of garlic with various aspects of cardiovasculardisease

In recent years garlic has been a focus of attentionbecause of its potential role in the prevention of various

Evidence-Based Complementary and Alternative Medicine 3

aspects of cardiovascular disease [19 20] Evidence fromnumerous studies suggests that garlic works through variousmechanisms to achieve this favorable effect including reduc-tion of serum lipids and blood pressure levels inhibition ofplatelet aggregation and increasing fibrinolytic antioxidantactivity Majority of the studies reported have shown positiveimpact however few numbers of contradictory studies have[21 22] made the role of garlic questionable especially withregards to its effects on lipid levels and hypertension Thisreview will critically examine the current scientific literatureconcerning claims of cardiovascular benefits from regularconsumption of garlic or its preparations and the possiblemechanisms responsible for such therapeutic actions

8 Methodology

This paper is based on a literature search of clinical trialsand systematic reviews published from 1990ndash2012 to see theeffect of Garlic on cardiovascular disease prevention Forthis purpose multiple search engines including MEDLINEPubMed Google and Cochrane library were used Searchwas validated by other author

9 Inclusion Criteria

All human studies (clinical trials) in English assessing theeffect of garlic on cardiovascular disease prevention amongpatients with dyslipidemia hypertension or cardiovasculardisease were included

10 Exclusion Criteria

Studies conducted among animalswere excludedTheses dis-sertations unpublished data and letter to editor were also ex-cluded

A number of keywords were used for data searchingincluding garlic and cardiovascular disease clinical trialgarlic hypertension and dyslipidemia platelet aggregationand clinical trial

11 Garlic Role in Dyslipidemia

Dyslipidemia is documented as a major risk factor respon-sible for the development of atherosclerosis and cardiovas-cular disease [23] Lipid abnormalities include high LDL-C (low-density lipoprotein cholesterol) high triglyceridesand low HDL-C (high-density lipoproteins cholesterol) lev-els Cholesterol present in 120573-lipoprotein (LDL) and pre-B-lipoprotein gets deposited into the blood vessels while 120572-lipoprotein (HDL) helps to reduce serum cholesterol [24]Impact of garlic on elevated lipid level is themost widely stud-ied outcome of interest as evident from Table 1 Considerableevidence from the literature supports the invaluable role ofgarlic in the treatment of hypercholesterolemia through inhi-bition of cholestrol biosynthesis in the liver and also by inhi-bition of oxidation of low-density lipoproteins [25] Dietaryapproach is the initial step in the management of dyslipi-demia andmany people with dyslipidemia are using garlic asan alternative medicine to normalize their raised lipid levels

A number of randomized controlled trials were carriedout to see the effect of different preparation of garlic on lipidlevels In the early 1980s a trial done [19] on human sub-ject after ingestion of 40 gm garlic demonstrated significantreduction in total cholestrol and triglyceride levels Similarlyone study conducted by Mader [20] in 1990 among patientssuffering from dyslipidemia over a period of 16 weeks using800mg of garlic (standardized to 13 of Alliin) showed12 reduction in serum cholestrol levels and 17 reductionin triglyceride levels in comparison to placebo however itwas also noticed that the greatest cholesterol-lowering effectswere seen in patients with initial total cholesterol valuesbetween 250 and 300mgdL The results of this trial weresomewhat contradicted by findings of a trial by Saradeth etal [26] where 600mg of dried garlic powder (Kwai Lichwerstandardized to 13 alliin) was given to healthy patients withnormal lipid levels over a period of 10 weeks There wasa significant reduction in total cholestrol and triglycerideslevels confirming the fact that it can induce changes inblood lipids even if these variables had been normal tostart with Similarly another trial by Gadkari and Joshi onhealthy medical students after consumption of 10 gm rawgarlic showed significant reduction in serum cholesterol andincrease in clotting time and fibrinolytic activity [27]

Clinical trials using different types of garlic preparationsin hypercholesterolemia patients have demonstrated debat-able results and it was assumed that these discrepancies mayhave resulted due to the differences of the composition ofgarlic preparations and the response they may induce Thisfact was well proven by a study done by Sobenin et al [28]in which patients with mildly raised lipid levels were givengarlic powder tablets (allicor) containing 600mg of garliccontent A moderate decrease in lipid levels was seen (76decrease in cholesterol 117 decrease in LDL levels) in addi-tion a substantial rise in HDL level 115 was also noticed Itwas assumed that this hypocholesterolemic action of garlicpreparations may be due to the use of a time-released formof garlic powder tablets Similarly a commonly used prepa-ration of garlic in the form of AGE extract of 72 gm daily for6 months also showed beneficial effects on the lipid profileof moderately hypercholesterolemia subjects There was anoverall 61 decrease in cholestrol levels and 4 decrease inLDL levels noticed thus confirming its efficacy [29]

Another randomized placebo control trial using 5 gm ofraw garlic on patients with mildly raised lipids was used for42 days and demonstrated significant reduction in cholestroland triglyceride levels with a rise in HDL levels howeverthese effects were not sustainable and returned to baselinelevels as soon as the garlic use was withdrawnThis suggestedthat garlic consumption alone can decrease serum lipids inpatients with mildly raised lipid levels however it cannot beused as the main therapeutic agent for hyperlipidemia [30]

Dyslipidemia refers to increase in cholestrol triglyc-erides and LDL levels with a decrease in HDL level (below40mg) It was expected that apart from decreasing cholestrolLDL and triglycerides levels garlic also has an impact onlow HDL which was further established by a trial conductedon healthy individuals with a decreased HDL levels below10mg at baseline They were given high-fat diet followed

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Effects of garlic on lipid levels

Study Type Target Durationof Rx Dose Casecontrol Outcome

Mader (1990) [20]Randomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 800mg garlicpowder 130131 Dec in T chol levelmdash12

TG levelmdash17

Gadkari and Joshi(1991) [27]

Randomizedcontrol trial Normal individuals 2 months 10 gm of raw

garlic 2525Dec T chol increaseclotting time andfibrinolytic activity

Rotzsch et al(1992) [31]

Randomizedplacebo-controlleddouble-blind trial

Healthyindividuals with

low HDL6 weeks 900mg garlic

powder 1212 Dec TG levels and increaseHDL levels

Saradeth et al(1994) [26]

Randomizeddouble-blind studyplacebo-controlledtrial

Healthyindividuals withnormal lipid levels

15 weeks 600mg driedgarlic powder 3434

T chol dec from 223 to214mgdLTG dec from 124 to118mgdL

Steiner et al(1996) [29]

Double-blindcrossover trial Hyperlipidemic 11 months 72 g aged garlic 2021

Dec T chol 61 dec LDL4 systolic BP 55 decand modest dec in diastolicBp noticed

Isaacsohn et al(1998) [38]

Randomizeddouble-blindplacebo-controltrial

Hyperlipidemic 12 weeks 900mg garlicpowder (Kwai) 2822 No change in lipid levels

noticed

Berthold et al(1998) [39]

Double-blindrandomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 10mg garlic oil 1213 No change in lipids orlipoproteins levels noticed

Satitvipawee et al(2003) [37]

Randomizeddouble-blindplacebo-controlledtrial

Hyperlipidemic 4 weeks12weeks Garlic extract 7076 No dec in T chol DL TG

and HDL levels noticed

Mahmoodi et al(2006) [30] Clinical trial Hyperlipidemic 42 days Raw garlic 5 gm

twice daily 30Dec T chol dec LDL decTG increase HDL levelReversed after stopping ofgarlic

Sobenin et al(2008) [28]

Double blindedplacebo controlled Hyperlipidemic 12 weeks Allicor

(600mg daily) 2121 T chol 76 dec LDL 118and HDL inc 115

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein and VLDL very low-density lipoprotein

by garlic powder preparation (Sapec Kwai) of 900mg dailyfor 6 weeks A significant decrease in triglyceride levels wasobserved in the treatment group in comparison to placebogroup with a significant rise in HDL levels above baseline[31] Similarly another study reported that 3 g of fresh garlic(1 clove) daily for 16 weeks had a 21 decrease in cholesterollevels [32]

Despite the existence of various clinical trials the role ofgarlic in treating dyslipidemia is still debatable In order toaddress this query a various meta-analyses were also con-ducted A meta-analyses done by Silagy and Neil studied 16trials among 952 patients using garlic both in powder andnonpowder form There was an overall reduction in cho-lestrol level seen that is 8 with powdered form while15 with nonpowder preparations Significant lowering ofserum triglyceride was also noticed while HDL level remainsunchanged [33]

Similarly another meta-analyses by Warshafsky et alamong patients with cholestrol levels greater than 200mgshowed significant reduction in total cholesterol levels It wassuggested that garlic in an amount approximately one half toone clove per day is effective in reducing cholesterol levels byabout 9 [34]

A recent meta-analyses conducted by Zeng et al in 2012clearly illustrated that garlic therapy is more effective if usedfor a long term with higher baseline total cholestrol levelsthey also concluded that garlic powder and aged garlic extractwere more effective in reducing serum TC levels while garlicoil was more effective in lowering serum TG levels [35] Atrial comparing garlic with a commercial lipid-lowering drug(bezafibrate) found them to be equally effective in decreasinglipids to a statistically significant extent [36]

There were few clinical trials which did not show anyeffects on lipid levels A trial done by Satitvipawee et al for

Evidence-Based Complementary and Alternative Medicine 5

Table 2 Effect of garlic on blood pressure levels

Study Type Target Duration of Rx Dose Casecontrol OutcomeZhang et al(2001) [48]

Parallel-controlledtrial Hypertensives 16 weeks Distilled garlic oil

123mgd 1413 Garlic oil lowers SBP and DBP

Dhawan and Jain(2004) [49]

Not placebocontrolled Hypertensives 2 months Garlic pearls

250mg 2020 Dec Bp dec ox-LDL and8-iso-PGF2alpha levels

Capraz et al(2007) [55]

Randomizedplacebo controltrial

Hypertensives 70 minutes Rw garlic Garlictablets 252525 No effects on BP levels

Duda et al(2008) [51]

Prospective anduncontrolledclinical study

Hypertensives 30 daysAntihypertensivedrug + Garlic

capsules3832 Dec total lipids and lipid

peroxidation noticed

Ried et al(2010) [50]

Randomizedplacebo controltrial

Hypertensives 12 weeks 960mg AGE 2525 SBPmdash102 plusmn 43mmHg dec

Ried et al(2013) [53]

Double-blindrandomizedplacebo-controlleddose-response trial

Hypertensives 12 weeks Aged garlic240480960mg 262627

SBPmdash118 plusmn 54mmHg (2capsule) 74 plusmn 41mmHg (4capsule)

T chol total cholesterol HDL high density lipoprotein TG triglyceride LDL low-density lipoprotein VLDL very low-density lipoprotein 8-OHdG (8-Hydroxy-21015840-deoxyguanosine) and 8-iso-PGF2alpha (8-iso-Prostaglandin F2alpha)

a period of 12 weeks using 56 mgtablet garlic tablets showedno significant improvement in lipids levels [37]

An RCT in which 900mg garlic in the form of tablets(Kwai) was given daily to patients with hypercholesterolemiashowed no significant change in lipid levels in comparisonto placebo group [38] Similarly in other trial steams distilledgarlic oil in a quantity of 5mg twice daily for 12 weeks showedno influence on lipid levels [39] A trial with garlic usage inthe form of dried form in a dose of 600mg to 1500mg didnot show any effects suggesting that dried preparation in thedosage studied were ineffective in reducing lipid levels [40]Similarly a meta-analyses by Khoo and Aziz also showedinsignificant outcomes [41]

One trial of garlic extract treatment in children withhypercholesterolemia found no adverse effects and no signif-icant beneficial effect on lipid levels [42]

Clinical investigations exploring the effects of garlicand its various preparations in hypercholesterolemia havedemonstrated somewhat contradictory results The diversecomposition and amount of active sulfur compounds ofdifferent garlic preparations used in various trials might beresponsible for the above mentioned inconsistent findingsOther factors like subject recruitment duration of studydietary control lifestyle and methods of lipid analyses mayalso have an influenceThese findings emphasize the need forstandardization of garlic preparations in order to reach to avalid conclusion

12 Effects of Garlic on Hypertension

Hypertension is an important risk factor for leading tocardiovascular disease Currently it affects 1 billion peopleworldwide and this number is expected to rise to 16 billionby 2025 [43 44] Garlic regular consumption has shownsome association with blood pressure control Blood pressurereducing properties of garlic are related with the hydrogen

sulphide production [45] and allicin content liberated fromalliin and the enzyme alliinase [46] which is assumed to pos-sess angiotensin II inhibiting and vasodilating effects Garlicis used as a treatment remedy by many people worldwideto control blood pressure According to one survey approxi-mately 29 of people are using garlic for their blood pressurecontrol [47]

The antihypertensive effects of garlic have been studiedbut the remaining controversial various studies done showedcontroversial results as evident from Table 2 Clinical trialdone by Zhang et al consuming garlic oil in hypertensivepatients over the 16-week period showed significant results[48] A trial using garlic pearls containing 250mg of garlicamong hypertensive patients for 2 months demonstrateddecrease in blood pressure level and also showed decrease inbiomarkers responsible for oxidative stress in blood (plasma-oxidized LDL plasma and urinary concentration of 8-iso-Prostaglandin F2alpha) ultimately decreasing the risk ofcardiovascular disease [49]

Majority of patients used garlic as a remedy for preventionfrom dyslipidemia and hypertension various illnesses AnRCT conducted by Ried et al on patients with uncontrolledblood pressure used AGE preparation of 900mg garlic con-taining (24mg salicystine) for 12 weeks and concluded thatsignificant reduction in blood pressure level was noted onlyamong patients who had blood pressure values of more than140mmHg at baseline [50] suggesting that its role in primaryprevention is questionable

Another trial by Duda et al assessed the role of garlic onblood pressure and lipids levels and concluded that garlic canbe used as a tentative treatment along with antihypertensivedrug because of its positive effect on lipid levels and antioxi-dant properties [51]

Few meta-analyses were also done to see the efficacyIn 1994 a meta-analyses assessed the effect of garlic onhypertension among which three trials showed significant

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

2 Evidence-Based Complementary and Alternative Medicine

increased steadily since 1950 (910) Most common typesof CAM therapies used were natural products such as fishoilomega 3 glucosamine Echinacea and flaxseed (177)deep breathing (127) meditation (94) chiropractic andosteopathic (86) and massage (83) followed by yogadiet-based therapies progressive relaxation guided imageryand homeopathic treatment [9]

Among all these remedies plants-based functional foodshave gained lots of recognition throughout the world and itis believed that these natural substances have the potential toreduce the detrimental effect of a number of cardiovasculardiseases and associated risk factors [10] The probable reasonfor this rising trend is skeptic approach of general publictowards conventional medicine due to fear of more sideeffects and increasing costThis fact was further driven by thebelief of increased safety profile and easy availability of plant-based natural products in comparison to orthodox medicineGarlic has been used as a therapeutic agent for many illnessesover centuries as evident from various studies however itsrole in cardiovascular disease prevention is still questionableThis review was done to find out the efficacy of garlic incardiovascular disease prevention through evidence-basedapproach by analyzing clinical trials and systematic review inthe above mentioned area

2 Garlic as a Potential Herb

Garlic (Allium sativum) has played an important dietary aswell as medicinal role in human history The role of garlic(Allium sativum) as a potential herb has been acknowledgedfor over 5000 years Garlic and its various preparations arebeing readily consumed as a food and spice by various cul-tures for centuries [11] It was also documented as a choice ofmedical therapy to combat many diseases among Egyptians[12] Similarly it is also considered as an imperative partof Indian traditional medicine that is Ayurveda Tibbi andUnani and so forth In addition it is also claimed to pos-sess beneficial effects for the prevention of various aspectsof cardiovascular disease including hypertension and dyslipi-demia [13]

3 Garlic Composition

Garlic is available in many forms among these raw garlic andaqueous extract preparation is used more frequently Allicinis the principal bioactive compound present in garlic andprimarily contains sulphur as a main constituent which onbreak down gives garlic its characteristic odor It is producedas a result of activation of alliinase enzyme after crushing orchopping of raw garlicThe enzyme Allinase is inactivated byheat leaving behind alliin as the main constituent present inthe water extract of heat-treated garlic The composition ofgarlic powderwhich is produced after dehydration and crush-ing is the same as raw garlic and alliinase activity is preservedhowever caution needs to be taken regarding temperatureregulation as Allinase is inactivated if temperature exceedsbeyond 60∘C Apart from Alliin other important sulfur-containing compounds present in garlic homogenate includeallyl methyl thiosulfonate 1-propenyl allyl thiosulfonate and

120574-L-glutamyl-S-alkyl-L-cysteine On an average a garlic bulbcontains up to 09 g-glutamylcysteines and up to 18 alliin[14]

4 AGE Preparation

Another important and extensively studied garlic preparationis aged garlic extract (AGE)This form is produced by storageof sliced rawgarlic in 15ndash20ethanol for 20monthsThis pro-cess of storage leads to alteration in composition of the garlicextract the odorous harsh and irritating compounds ingarlic are converted naturally into stable and safe sulfur com-pounds with substantial loss of allicin activity and increasedactivity of new compounds like S-allylcysteine (SAC) S-allylmercaptocysteine and allixin [15] SAC can be used forstandardization because of its bioavailability property

5 Garlic Oil

Garlic oil another important preparation is produced as aresult of distillation process of raw garlic Garlic essential oilis obtained by steam distillation of garlic The essential oilcontent of garlic cloves is 02ndash05 and consists of a varietyof sulfides such as diallyl disulphide (DADS) and diallyltrisulfide (DATS) [16 17] All the water soluble contentsincluding allicin are completely eliminated from the oil Oilmacerates were originally developed for use as condimentsOil macerate products are made of encapsulated mixtures ofwhole garlic cloves ground into vegetable oilThis preparationcontains allicin-decomposed compounds such as dithiinsajoene and sulfides residual amounts of alliin and otherconstituents in garlic [16]

6 Garlic Powder

Garlic powder is primarily used as a flavoring agent for con-diments and processed foods Garlic cloves are sliced orcrushed dried and ground into powder The composition ofgarlic powder is the same as that of raw garlic however theproportions and amounts of various constituents differ sig-nificantly that is average content of alliin present in garlic is08 however raw garlic contains around 37mggm of alliin[18]

7 Garlic and CardiovascularDisease Prevention

Cardiovascular disease is one of the leading cause of morbid-ity and mortality worldwide Role of garlic in cardiovasculardisease prevention has been a topic of concerns for manyyears Various observational and experimental studies doneon animals showed encouraging results However theseclaimed benefits were not supported by evidence-based clin-ical studies This fact prompted many researchers to conductclinical trials in order to explore and address the efficacy andassociation of garlic with various aspects of cardiovasculardisease

In recent years garlic has been a focus of attentionbecause of its potential role in the prevention of various

Evidence-Based Complementary and Alternative Medicine 3

aspects of cardiovascular disease [19 20] Evidence fromnumerous studies suggests that garlic works through variousmechanisms to achieve this favorable effect including reduc-tion of serum lipids and blood pressure levels inhibition ofplatelet aggregation and increasing fibrinolytic antioxidantactivity Majority of the studies reported have shown positiveimpact however few numbers of contradictory studies have[21 22] made the role of garlic questionable especially withregards to its effects on lipid levels and hypertension Thisreview will critically examine the current scientific literatureconcerning claims of cardiovascular benefits from regularconsumption of garlic or its preparations and the possiblemechanisms responsible for such therapeutic actions

8 Methodology

This paper is based on a literature search of clinical trialsand systematic reviews published from 1990ndash2012 to see theeffect of Garlic on cardiovascular disease prevention Forthis purpose multiple search engines including MEDLINEPubMed Google and Cochrane library were used Searchwas validated by other author

9 Inclusion Criteria

All human studies (clinical trials) in English assessing theeffect of garlic on cardiovascular disease prevention amongpatients with dyslipidemia hypertension or cardiovasculardisease were included

10 Exclusion Criteria

Studies conducted among animalswere excludedTheses dis-sertations unpublished data and letter to editor were also ex-cluded

A number of keywords were used for data searchingincluding garlic and cardiovascular disease clinical trialgarlic hypertension and dyslipidemia platelet aggregationand clinical trial

11 Garlic Role in Dyslipidemia

Dyslipidemia is documented as a major risk factor respon-sible for the development of atherosclerosis and cardiovas-cular disease [23] Lipid abnormalities include high LDL-C (low-density lipoprotein cholesterol) high triglyceridesand low HDL-C (high-density lipoproteins cholesterol) lev-els Cholesterol present in 120573-lipoprotein (LDL) and pre-B-lipoprotein gets deposited into the blood vessels while 120572-lipoprotein (HDL) helps to reduce serum cholesterol [24]Impact of garlic on elevated lipid level is themost widely stud-ied outcome of interest as evident from Table 1 Considerableevidence from the literature supports the invaluable role ofgarlic in the treatment of hypercholesterolemia through inhi-bition of cholestrol biosynthesis in the liver and also by inhi-bition of oxidation of low-density lipoproteins [25] Dietaryapproach is the initial step in the management of dyslipi-demia andmany people with dyslipidemia are using garlic asan alternative medicine to normalize their raised lipid levels

A number of randomized controlled trials were carriedout to see the effect of different preparation of garlic on lipidlevels In the early 1980s a trial done [19] on human sub-ject after ingestion of 40 gm garlic demonstrated significantreduction in total cholestrol and triglyceride levels Similarlyone study conducted by Mader [20] in 1990 among patientssuffering from dyslipidemia over a period of 16 weeks using800mg of garlic (standardized to 13 of Alliin) showed12 reduction in serum cholestrol levels and 17 reductionin triglyceride levels in comparison to placebo however itwas also noticed that the greatest cholesterol-lowering effectswere seen in patients with initial total cholesterol valuesbetween 250 and 300mgdL The results of this trial weresomewhat contradicted by findings of a trial by Saradeth etal [26] where 600mg of dried garlic powder (Kwai Lichwerstandardized to 13 alliin) was given to healthy patients withnormal lipid levels over a period of 10 weeks There wasa significant reduction in total cholestrol and triglycerideslevels confirming the fact that it can induce changes inblood lipids even if these variables had been normal tostart with Similarly another trial by Gadkari and Joshi onhealthy medical students after consumption of 10 gm rawgarlic showed significant reduction in serum cholesterol andincrease in clotting time and fibrinolytic activity [27]

Clinical trials using different types of garlic preparationsin hypercholesterolemia patients have demonstrated debat-able results and it was assumed that these discrepancies mayhave resulted due to the differences of the composition ofgarlic preparations and the response they may induce Thisfact was well proven by a study done by Sobenin et al [28]in which patients with mildly raised lipid levels were givengarlic powder tablets (allicor) containing 600mg of garliccontent A moderate decrease in lipid levels was seen (76decrease in cholesterol 117 decrease in LDL levels) in addi-tion a substantial rise in HDL level 115 was also noticed Itwas assumed that this hypocholesterolemic action of garlicpreparations may be due to the use of a time-released formof garlic powder tablets Similarly a commonly used prepa-ration of garlic in the form of AGE extract of 72 gm daily for6 months also showed beneficial effects on the lipid profileof moderately hypercholesterolemia subjects There was anoverall 61 decrease in cholestrol levels and 4 decrease inLDL levels noticed thus confirming its efficacy [29]

Another randomized placebo control trial using 5 gm ofraw garlic on patients with mildly raised lipids was used for42 days and demonstrated significant reduction in cholestroland triglyceride levels with a rise in HDL levels howeverthese effects were not sustainable and returned to baselinelevels as soon as the garlic use was withdrawnThis suggestedthat garlic consumption alone can decrease serum lipids inpatients with mildly raised lipid levels however it cannot beused as the main therapeutic agent for hyperlipidemia [30]

Dyslipidemia refers to increase in cholestrol triglyc-erides and LDL levels with a decrease in HDL level (below40mg) It was expected that apart from decreasing cholestrolLDL and triglycerides levels garlic also has an impact onlow HDL which was further established by a trial conductedon healthy individuals with a decreased HDL levels below10mg at baseline They were given high-fat diet followed

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Effects of garlic on lipid levels

Study Type Target Durationof Rx Dose Casecontrol Outcome

Mader (1990) [20]Randomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 800mg garlicpowder 130131 Dec in T chol levelmdash12

TG levelmdash17

Gadkari and Joshi(1991) [27]

Randomizedcontrol trial Normal individuals 2 months 10 gm of raw

garlic 2525Dec T chol increaseclotting time andfibrinolytic activity

Rotzsch et al(1992) [31]

Randomizedplacebo-controlleddouble-blind trial

Healthyindividuals with

low HDL6 weeks 900mg garlic

powder 1212 Dec TG levels and increaseHDL levels

Saradeth et al(1994) [26]

Randomizeddouble-blind studyplacebo-controlledtrial

Healthyindividuals withnormal lipid levels

15 weeks 600mg driedgarlic powder 3434

T chol dec from 223 to214mgdLTG dec from 124 to118mgdL

Steiner et al(1996) [29]

Double-blindcrossover trial Hyperlipidemic 11 months 72 g aged garlic 2021

Dec T chol 61 dec LDL4 systolic BP 55 decand modest dec in diastolicBp noticed

Isaacsohn et al(1998) [38]

Randomizeddouble-blindplacebo-controltrial

Hyperlipidemic 12 weeks 900mg garlicpowder (Kwai) 2822 No change in lipid levels

noticed

Berthold et al(1998) [39]

Double-blindrandomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 10mg garlic oil 1213 No change in lipids orlipoproteins levels noticed

Satitvipawee et al(2003) [37]

Randomizeddouble-blindplacebo-controlledtrial

Hyperlipidemic 4 weeks12weeks Garlic extract 7076 No dec in T chol DL TG

and HDL levels noticed

Mahmoodi et al(2006) [30] Clinical trial Hyperlipidemic 42 days Raw garlic 5 gm

twice daily 30Dec T chol dec LDL decTG increase HDL levelReversed after stopping ofgarlic

Sobenin et al(2008) [28]

Double blindedplacebo controlled Hyperlipidemic 12 weeks Allicor

(600mg daily) 2121 T chol 76 dec LDL 118and HDL inc 115

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein and VLDL very low-density lipoprotein

by garlic powder preparation (Sapec Kwai) of 900mg dailyfor 6 weeks A significant decrease in triglyceride levels wasobserved in the treatment group in comparison to placebogroup with a significant rise in HDL levels above baseline[31] Similarly another study reported that 3 g of fresh garlic(1 clove) daily for 16 weeks had a 21 decrease in cholesterollevels [32]

Despite the existence of various clinical trials the role ofgarlic in treating dyslipidemia is still debatable In order toaddress this query a various meta-analyses were also con-ducted A meta-analyses done by Silagy and Neil studied 16trials among 952 patients using garlic both in powder andnonpowder form There was an overall reduction in cho-lestrol level seen that is 8 with powdered form while15 with nonpowder preparations Significant lowering ofserum triglyceride was also noticed while HDL level remainsunchanged [33]

Similarly another meta-analyses by Warshafsky et alamong patients with cholestrol levels greater than 200mgshowed significant reduction in total cholesterol levels It wassuggested that garlic in an amount approximately one half toone clove per day is effective in reducing cholesterol levels byabout 9 [34]

A recent meta-analyses conducted by Zeng et al in 2012clearly illustrated that garlic therapy is more effective if usedfor a long term with higher baseline total cholestrol levelsthey also concluded that garlic powder and aged garlic extractwere more effective in reducing serum TC levels while garlicoil was more effective in lowering serum TG levels [35] Atrial comparing garlic with a commercial lipid-lowering drug(bezafibrate) found them to be equally effective in decreasinglipids to a statistically significant extent [36]

There were few clinical trials which did not show anyeffects on lipid levels A trial done by Satitvipawee et al for

Evidence-Based Complementary and Alternative Medicine 5

Table 2 Effect of garlic on blood pressure levels

Study Type Target Duration of Rx Dose Casecontrol OutcomeZhang et al(2001) [48]

Parallel-controlledtrial Hypertensives 16 weeks Distilled garlic oil

123mgd 1413 Garlic oil lowers SBP and DBP

Dhawan and Jain(2004) [49]

Not placebocontrolled Hypertensives 2 months Garlic pearls

250mg 2020 Dec Bp dec ox-LDL and8-iso-PGF2alpha levels

Capraz et al(2007) [55]

Randomizedplacebo controltrial

Hypertensives 70 minutes Rw garlic Garlictablets 252525 No effects on BP levels

Duda et al(2008) [51]

Prospective anduncontrolledclinical study

Hypertensives 30 daysAntihypertensivedrug + Garlic

capsules3832 Dec total lipids and lipid

peroxidation noticed

Ried et al(2010) [50]

Randomizedplacebo controltrial

Hypertensives 12 weeks 960mg AGE 2525 SBPmdash102 plusmn 43mmHg dec

Ried et al(2013) [53]

Double-blindrandomizedplacebo-controlleddose-response trial

Hypertensives 12 weeks Aged garlic240480960mg 262627

SBPmdash118 plusmn 54mmHg (2capsule) 74 plusmn 41mmHg (4capsule)

T chol total cholesterol HDL high density lipoprotein TG triglyceride LDL low-density lipoprotein VLDL very low-density lipoprotein 8-OHdG (8-Hydroxy-21015840-deoxyguanosine) and 8-iso-PGF2alpha (8-iso-Prostaglandin F2alpha)

a period of 12 weeks using 56 mgtablet garlic tablets showedno significant improvement in lipids levels [37]

An RCT in which 900mg garlic in the form of tablets(Kwai) was given daily to patients with hypercholesterolemiashowed no significant change in lipid levels in comparisonto placebo group [38] Similarly in other trial steams distilledgarlic oil in a quantity of 5mg twice daily for 12 weeks showedno influence on lipid levels [39] A trial with garlic usage inthe form of dried form in a dose of 600mg to 1500mg didnot show any effects suggesting that dried preparation in thedosage studied were ineffective in reducing lipid levels [40]Similarly a meta-analyses by Khoo and Aziz also showedinsignificant outcomes [41]

One trial of garlic extract treatment in children withhypercholesterolemia found no adverse effects and no signif-icant beneficial effect on lipid levels [42]

Clinical investigations exploring the effects of garlicand its various preparations in hypercholesterolemia havedemonstrated somewhat contradictory results The diversecomposition and amount of active sulfur compounds ofdifferent garlic preparations used in various trials might beresponsible for the above mentioned inconsistent findingsOther factors like subject recruitment duration of studydietary control lifestyle and methods of lipid analyses mayalso have an influenceThese findings emphasize the need forstandardization of garlic preparations in order to reach to avalid conclusion

12 Effects of Garlic on Hypertension

Hypertension is an important risk factor for leading tocardiovascular disease Currently it affects 1 billion peopleworldwide and this number is expected to rise to 16 billionby 2025 [43 44] Garlic regular consumption has shownsome association with blood pressure control Blood pressurereducing properties of garlic are related with the hydrogen

sulphide production [45] and allicin content liberated fromalliin and the enzyme alliinase [46] which is assumed to pos-sess angiotensin II inhibiting and vasodilating effects Garlicis used as a treatment remedy by many people worldwideto control blood pressure According to one survey approxi-mately 29 of people are using garlic for their blood pressurecontrol [47]

The antihypertensive effects of garlic have been studiedbut the remaining controversial various studies done showedcontroversial results as evident from Table 2 Clinical trialdone by Zhang et al consuming garlic oil in hypertensivepatients over the 16-week period showed significant results[48] A trial using garlic pearls containing 250mg of garlicamong hypertensive patients for 2 months demonstrateddecrease in blood pressure level and also showed decrease inbiomarkers responsible for oxidative stress in blood (plasma-oxidized LDL plasma and urinary concentration of 8-iso-Prostaglandin F2alpha) ultimately decreasing the risk ofcardiovascular disease [49]

Majority of patients used garlic as a remedy for preventionfrom dyslipidemia and hypertension various illnesses AnRCT conducted by Ried et al on patients with uncontrolledblood pressure used AGE preparation of 900mg garlic con-taining (24mg salicystine) for 12 weeks and concluded thatsignificant reduction in blood pressure level was noted onlyamong patients who had blood pressure values of more than140mmHg at baseline [50] suggesting that its role in primaryprevention is questionable

Another trial by Duda et al assessed the role of garlic onblood pressure and lipids levels and concluded that garlic canbe used as a tentative treatment along with antihypertensivedrug because of its positive effect on lipid levels and antioxi-dant properties [51]

Few meta-analyses were also done to see the efficacyIn 1994 a meta-analyses assessed the effect of garlic onhypertension among which three trials showed significant

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

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Disease Markers

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OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 3

aspects of cardiovascular disease [19 20] Evidence fromnumerous studies suggests that garlic works through variousmechanisms to achieve this favorable effect including reduc-tion of serum lipids and blood pressure levels inhibition ofplatelet aggregation and increasing fibrinolytic antioxidantactivity Majority of the studies reported have shown positiveimpact however few numbers of contradictory studies have[21 22] made the role of garlic questionable especially withregards to its effects on lipid levels and hypertension Thisreview will critically examine the current scientific literatureconcerning claims of cardiovascular benefits from regularconsumption of garlic or its preparations and the possiblemechanisms responsible for such therapeutic actions

8 Methodology

This paper is based on a literature search of clinical trialsand systematic reviews published from 1990ndash2012 to see theeffect of Garlic on cardiovascular disease prevention Forthis purpose multiple search engines including MEDLINEPubMed Google and Cochrane library were used Searchwas validated by other author

9 Inclusion Criteria

All human studies (clinical trials) in English assessing theeffect of garlic on cardiovascular disease prevention amongpatients with dyslipidemia hypertension or cardiovasculardisease were included

10 Exclusion Criteria

Studies conducted among animalswere excludedTheses dis-sertations unpublished data and letter to editor were also ex-cluded

A number of keywords were used for data searchingincluding garlic and cardiovascular disease clinical trialgarlic hypertension and dyslipidemia platelet aggregationand clinical trial

11 Garlic Role in Dyslipidemia

Dyslipidemia is documented as a major risk factor respon-sible for the development of atherosclerosis and cardiovas-cular disease [23] Lipid abnormalities include high LDL-C (low-density lipoprotein cholesterol) high triglyceridesand low HDL-C (high-density lipoproteins cholesterol) lev-els Cholesterol present in 120573-lipoprotein (LDL) and pre-B-lipoprotein gets deposited into the blood vessels while 120572-lipoprotein (HDL) helps to reduce serum cholesterol [24]Impact of garlic on elevated lipid level is themost widely stud-ied outcome of interest as evident from Table 1 Considerableevidence from the literature supports the invaluable role ofgarlic in the treatment of hypercholesterolemia through inhi-bition of cholestrol biosynthesis in the liver and also by inhi-bition of oxidation of low-density lipoproteins [25] Dietaryapproach is the initial step in the management of dyslipi-demia andmany people with dyslipidemia are using garlic asan alternative medicine to normalize their raised lipid levels

A number of randomized controlled trials were carriedout to see the effect of different preparation of garlic on lipidlevels In the early 1980s a trial done [19] on human sub-ject after ingestion of 40 gm garlic demonstrated significantreduction in total cholestrol and triglyceride levels Similarlyone study conducted by Mader [20] in 1990 among patientssuffering from dyslipidemia over a period of 16 weeks using800mg of garlic (standardized to 13 of Alliin) showed12 reduction in serum cholestrol levels and 17 reductionin triglyceride levels in comparison to placebo however itwas also noticed that the greatest cholesterol-lowering effectswere seen in patients with initial total cholesterol valuesbetween 250 and 300mgdL The results of this trial weresomewhat contradicted by findings of a trial by Saradeth etal [26] where 600mg of dried garlic powder (Kwai Lichwerstandardized to 13 alliin) was given to healthy patients withnormal lipid levels over a period of 10 weeks There wasa significant reduction in total cholestrol and triglycerideslevels confirming the fact that it can induce changes inblood lipids even if these variables had been normal tostart with Similarly another trial by Gadkari and Joshi onhealthy medical students after consumption of 10 gm rawgarlic showed significant reduction in serum cholesterol andincrease in clotting time and fibrinolytic activity [27]

Clinical trials using different types of garlic preparationsin hypercholesterolemia patients have demonstrated debat-able results and it was assumed that these discrepancies mayhave resulted due to the differences of the composition ofgarlic preparations and the response they may induce Thisfact was well proven by a study done by Sobenin et al [28]in which patients with mildly raised lipid levels were givengarlic powder tablets (allicor) containing 600mg of garliccontent A moderate decrease in lipid levels was seen (76decrease in cholesterol 117 decrease in LDL levels) in addi-tion a substantial rise in HDL level 115 was also noticed Itwas assumed that this hypocholesterolemic action of garlicpreparations may be due to the use of a time-released formof garlic powder tablets Similarly a commonly used prepa-ration of garlic in the form of AGE extract of 72 gm daily for6 months also showed beneficial effects on the lipid profileof moderately hypercholesterolemia subjects There was anoverall 61 decrease in cholestrol levels and 4 decrease inLDL levels noticed thus confirming its efficacy [29]

Another randomized placebo control trial using 5 gm ofraw garlic on patients with mildly raised lipids was used for42 days and demonstrated significant reduction in cholestroland triglyceride levels with a rise in HDL levels howeverthese effects were not sustainable and returned to baselinelevels as soon as the garlic use was withdrawnThis suggestedthat garlic consumption alone can decrease serum lipids inpatients with mildly raised lipid levels however it cannot beused as the main therapeutic agent for hyperlipidemia [30]

Dyslipidemia refers to increase in cholestrol triglyc-erides and LDL levels with a decrease in HDL level (below40mg) It was expected that apart from decreasing cholestrolLDL and triglycerides levels garlic also has an impact onlow HDL which was further established by a trial conductedon healthy individuals with a decreased HDL levels below10mg at baseline They were given high-fat diet followed

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Effects of garlic on lipid levels

Study Type Target Durationof Rx Dose Casecontrol Outcome

Mader (1990) [20]Randomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 800mg garlicpowder 130131 Dec in T chol levelmdash12

TG levelmdash17

Gadkari and Joshi(1991) [27]

Randomizedcontrol trial Normal individuals 2 months 10 gm of raw

garlic 2525Dec T chol increaseclotting time andfibrinolytic activity

Rotzsch et al(1992) [31]

Randomizedplacebo-controlleddouble-blind trial

Healthyindividuals with

low HDL6 weeks 900mg garlic

powder 1212 Dec TG levels and increaseHDL levels

Saradeth et al(1994) [26]

Randomizeddouble-blind studyplacebo-controlledtrial

Healthyindividuals withnormal lipid levels

15 weeks 600mg driedgarlic powder 3434

T chol dec from 223 to214mgdLTG dec from 124 to118mgdL

Steiner et al(1996) [29]

Double-blindcrossover trial Hyperlipidemic 11 months 72 g aged garlic 2021

Dec T chol 61 dec LDL4 systolic BP 55 decand modest dec in diastolicBp noticed

Isaacsohn et al(1998) [38]

Randomizeddouble-blindplacebo-controltrial

Hyperlipidemic 12 weeks 900mg garlicpowder (Kwai) 2822 No change in lipid levels

noticed

Berthold et al(1998) [39]

Double-blindrandomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 10mg garlic oil 1213 No change in lipids orlipoproteins levels noticed

Satitvipawee et al(2003) [37]

Randomizeddouble-blindplacebo-controlledtrial

Hyperlipidemic 4 weeks12weeks Garlic extract 7076 No dec in T chol DL TG

and HDL levels noticed

Mahmoodi et al(2006) [30] Clinical trial Hyperlipidemic 42 days Raw garlic 5 gm

twice daily 30Dec T chol dec LDL decTG increase HDL levelReversed after stopping ofgarlic

Sobenin et al(2008) [28]

Double blindedplacebo controlled Hyperlipidemic 12 weeks Allicor

(600mg daily) 2121 T chol 76 dec LDL 118and HDL inc 115

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein and VLDL very low-density lipoprotein

by garlic powder preparation (Sapec Kwai) of 900mg dailyfor 6 weeks A significant decrease in triglyceride levels wasobserved in the treatment group in comparison to placebogroup with a significant rise in HDL levels above baseline[31] Similarly another study reported that 3 g of fresh garlic(1 clove) daily for 16 weeks had a 21 decrease in cholesterollevels [32]

Despite the existence of various clinical trials the role ofgarlic in treating dyslipidemia is still debatable In order toaddress this query a various meta-analyses were also con-ducted A meta-analyses done by Silagy and Neil studied 16trials among 952 patients using garlic both in powder andnonpowder form There was an overall reduction in cho-lestrol level seen that is 8 with powdered form while15 with nonpowder preparations Significant lowering ofserum triglyceride was also noticed while HDL level remainsunchanged [33]

Similarly another meta-analyses by Warshafsky et alamong patients with cholestrol levels greater than 200mgshowed significant reduction in total cholesterol levels It wassuggested that garlic in an amount approximately one half toone clove per day is effective in reducing cholesterol levels byabout 9 [34]

A recent meta-analyses conducted by Zeng et al in 2012clearly illustrated that garlic therapy is more effective if usedfor a long term with higher baseline total cholestrol levelsthey also concluded that garlic powder and aged garlic extractwere more effective in reducing serum TC levels while garlicoil was more effective in lowering serum TG levels [35] Atrial comparing garlic with a commercial lipid-lowering drug(bezafibrate) found them to be equally effective in decreasinglipids to a statistically significant extent [36]

There were few clinical trials which did not show anyeffects on lipid levels A trial done by Satitvipawee et al for

Evidence-Based Complementary and Alternative Medicine 5

Table 2 Effect of garlic on blood pressure levels

Study Type Target Duration of Rx Dose Casecontrol OutcomeZhang et al(2001) [48]

Parallel-controlledtrial Hypertensives 16 weeks Distilled garlic oil

123mgd 1413 Garlic oil lowers SBP and DBP

Dhawan and Jain(2004) [49]

Not placebocontrolled Hypertensives 2 months Garlic pearls

250mg 2020 Dec Bp dec ox-LDL and8-iso-PGF2alpha levels

Capraz et al(2007) [55]

Randomizedplacebo controltrial

Hypertensives 70 minutes Rw garlic Garlictablets 252525 No effects on BP levels

Duda et al(2008) [51]

Prospective anduncontrolledclinical study

Hypertensives 30 daysAntihypertensivedrug + Garlic

capsules3832 Dec total lipids and lipid

peroxidation noticed

Ried et al(2010) [50]

Randomizedplacebo controltrial

Hypertensives 12 weeks 960mg AGE 2525 SBPmdash102 plusmn 43mmHg dec

Ried et al(2013) [53]

Double-blindrandomizedplacebo-controlleddose-response trial

Hypertensives 12 weeks Aged garlic240480960mg 262627

SBPmdash118 plusmn 54mmHg (2capsule) 74 plusmn 41mmHg (4capsule)

T chol total cholesterol HDL high density lipoprotein TG triglyceride LDL low-density lipoprotein VLDL very low-density lipoprotein 8-OHdG (8-Hydroxy-21015840-deoxyguanosine) and 8-iso-PGF2alpha (8-iso-Prostaglandin F2alpha)

a period of 12 weeks using 56 mgtablet garlic tablets showedno significant improvement in lipids levels [37]

An RCT in which 900mg garlic in the form of tablets(Kwai) was given daily to patients with hypercholesterolemiashowed no significant change in lipid levels in comparisonto placebo group [38] Similarly in other trial steams distilledgarlic oil in a quantity of 5mg twice daily for 12 weeks showedno influence on lipid levels [39] A trial with garlic usage inthe form of dried form in a dose of 600mg to 1500mg didnot show any effects suggesting that dried preparation in thedosage studied were ineffective in reducing lipid levels [40]Similarly a meta-analyses by Khoo and Aziz also showedinsignificant outcomes [41]

One trial of garlic extract treatment in children withhypercholesterolemia found no adverse effects and no signif-icant beneficial effect on lipid levels [42]

Clinical investigations exploring the effects of garlicand its various preparations in hypercholesterolemia havedemonstrated somewhat contradictory results The diversecomposition and amount of active sulfur compounds ofdifferent garlic preparations used in various trials might beresponsible for the above mentioned inconsistent findingsOther factors like subject recruitment duration of studydietary control lifestyle and methods of lipid analyses mayalso have an influenceThese findings emphasize the need forstandardization of garlic preparations in order to reach to avalid conclusion

12 Effects of Garlic on Hypertension

Hypertension is an important risk factor for leading tocardiovascular disease Currently it affects 1 billion peopleworldwide and this number is expected to rise to 16 billionby 2025 [43 44] Garlic regular consumption has shownsome association with blood pressure control Blood pressurereducing properties of garlic are related with the hydrogen

sulphide production [45] and allicin content liberated fromalliin and the enzyme alliinase [46] which is assumed to pos-sess angiotensin II inhibiting and vasodilating effects Garlicis used as a treatment remedy by many people worldwideto control blood pressure According to one survey approxi-mately 29 of people are using garlic for their blood pressurecontrol [47]

The antihypertensive effects of garlic have been studiedbut the remaining controversial various studies done showedcontroversial results as evident from Table 2 Clinical trialdone by Zhang et al consuming garlic oil in hypertensivepatients over the 16-week period showed significant results[48] A trial using garlic pearls containing 250mg of garlicamong hypertensive patients for 2 months demonstrateddecrease in blood pressure level and also showed decrease inbiomarkers responsible for oxidative stress in blood (plasma-oxidized LDL plasma and urinary concentration of 8-iso-Prostaglandin F2alpha) ultimately decreasing the risk ofcardiovascular disease [49]

Majority of patients used garlic as a remedy for preventionfrom dyslipidemia and hypertension various illnesses AnRCT conducted by Ried et al on patients with uncontrolledblood pressure used AGE preparation of 900mg garlic con-taining (24mg salicystine) for 12 weeks and concluded thatsignificant reduction in blood pressure level was noted onlyamong patients who had blood pressure values of more than140mmHg at baseline [50] suggesting that its role in primaryprevention is questionable

Another trial by Duda et al assessed the role of garlic onblood pressure and lipids levels and concluded that garlic canbe used as a tentative treatment along with antihypertensivedrug because of its positive effect on lipid levels and antioxi-dant properties [51]

Few meta-analyses were also done to see the efficacyIn 1994 a meta-analyses assessed the effect of garlic onhypertension among which three trials showed significant

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Effects of garlic on lipid levels

Study Type Target Durationof Rx Dose Casecontrol Outcome

Mader (1990) [20]Randomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 800mg garlicpowder 130131 Dec in T chol levelmdash12

TG levelmdash17

Gadkari and Joshi(1991) [27]

Randomizedcontrol trial Normal individuals 2 months 10 gm of raw

garlic 2525Dec T chol increaseclotting time andfibrinolytic activity

Rotzsch et al(1992) [31]

Randomizedplacebo-controlleddouble-blind trial

Healthyindividuals with

low HDL6 weeks 900mg garlic

powder 1212 Dec TG levels and increaseHDL levels

Saradeth et al(1994) [26]

Randomizeddouble-blind studyplacebo-controlledtrial

Healthyindividuals withnormal lipid levels

15 weeks 600mg driedgarlic powder 3434

T chol dec from 223 to214mgdLTG dec from 124 to118mgdL

Steiner et al(1996) [29]

Double-blindcrossover trial Hyperlipidemic 11 months 72 g aged garlic 2021

Dec T chol 61 dec LDL4 systolic BP 55 decand modest dec in diastolicBp noticed

Isaacsohn et al(1998) [38]

Randomizeddouble-blindplacebo-controltrial

Hyperlipidemic 12 weeks 900mg garlicpowder (Kwai) 2822 No change in lipid levels

noticed

Berthold et al(1998) [39]

Double-blindrandomizedplacebo-controlledtrial

Hyperlipidemic 12 weeks 10mg garlic oil 1213 No change in lipids orlipoproteins levels noticed

Satitvipawee et al(2003) [37]

Randomizeddouble-blindplacebo-controlledtrial

Hyperlipidemic 4 weeks12weeks Garlic extract 7076 No dec in T chol DL TG

and HDL levels noticed

Mahmoodi et al(2006) [30] Clinical trial Hyperlipidemic 42 days Raw garlic 5 gm

twice daily 30Dec T chol dec LDL decTG increase HDL levelReversed after stopping ofgarlic

Sobenin et al(2008) [28]

Double blindedplacebo controlled Hyperlipidemic 12 weeks Allicor

(600mg daily) 2121 T chol 76 dec LDL 118and HDL inc 115

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein and VLDL very low-density lipoprotein

by garlic powder preparation (Sapec Kwai) of 900mg dailyfor 6 weeks A significant decrease in triglyceride levels wasobserved in the treatment group in comparison to placebogroup with a significant rise in HDL levels above baseline[31] Similarly another study reported that 3 g of fresh garlic(1 clove) daily for 16 weeks had a 21 decrease in cholesterollevels [32]

Despite the existence of various clinical trials the role ofgarlic in treating dyslipidemia is still debatable In order toaddress this query a various meta-analyses were also con-ducted A meta-analyses done by Silagy and Neil studied 16trials among 952 patients using garlic both in powder andnonpowder form There was an overall reduction in cho-lestrol level seen that is 8 with powdered form while15 with nonpowder preparations Significant lowering ofserum triglyceride was also noticed while HDL level remainsunchanged [33]

Similarly another meta-analyses by Warshafsky et alamong patients with cholestrol levels greater than 200mgshowed significant reduction in total cholesterol levels It wassuggested that garlic in an amount approximately one half toone clove per day is effective in reducing cholesterol levels byabout 9 [34]

A recent meta-analyses conducted by Zeng et al in 2012clearly illustrated that garlic therapy is more effective if usedfor a long term with higher baseline total cholestrol levelsthey also concluded that garlic powder and aged garlic extractwere more effective in reducing serum TC levels while garlicoil was more effective in lowering serum TG levels [35] Atrial comparing garlic with a commercial lipid-lowering drug(bezafibrate) found them to be equally effective in decreasinglipids to a statistically significant extent [36]

There were few clinical trials which did not show anyeffects on lipid levels A trial done by Satitvipawee et al for

Evidence-Based Complementary and Alternative Medicine 5

Table 2 Effect of garlic on blood pressure levels

Study Type Target Duration of Rx Dose Casecontrol OutcomeZhang et al(2001) [48]

Parallel-controlledtrial Hypertensives 16 weeks Distilled garlic oil

123mgd 1413 Garlic oil lowers SBP and DBP

Dhawan and Jain(2004) [49]

Not placebocontrolled Hypertensives 2 months Garlic pearls

250mg 2020 Dec Bp dec ox-LDL and8-iso-PGF2alpha levels

Capraz et al(2007) [55]

Randomizedplacebo controltrial

Hypertensives 70 minutes Rw garlic Garlictablets 252525 No effects on BP levels

Duda et al(2008) [51]

Prospective anduncontrolledclinical study

Hypertensives 30 daysAntihypertensivedrug + Garlic

capsules3832 Dec total lipids and lipid

peroxidation noticed

Ried et al(2010) [50]

Randomizedplacebo controltrial

Hypertensives 12 weeks 960mg AGE 2525 SBPmdash102 plusmn 43mmHg dec

Ried et al(2013) [53]

Double-blindrandomizedplacebo-controlleddose-response trial

Hypertensives 12 weeks Aged garlic240480960mg 262627

SBPmdash118 plusmn 54mmHg (2capsule) 74 plusmn 41mmHg (4capsule)

T chol total cholesterol HDL high density lipoprotein TG triglyceride LDL low-density lipoprotein VLDL very low-density lipoprotein 8-OHdG (8-Hydroxy-21015840-deoxyguanosine) and 8-iso-PGF2alpha (8-iso-Prostaglandin F2alpha)

a period of 12 weeks using 56 mgtablet garlic tablets showedno significant improvement in lipids levels [37]

An RCT in which 900mg garlic in the form of tablets(Kwai) was given daily to patients with hypercholesterolemiashowed no significant change in lipid levels in comparisonto placebo group [38] Similarly in other trial steams distilledgarlic oil in a quantity of 5mg twice daily for 12 weeks showedno influence on lipid levels [39] A trial with garlic usage inthe form of dried form in a dose of 600mg to 1500mg didnot show any effects suggesting that dried preparation in thedosage studied were ineffective in reducing lipid levels [40]Similarly a meta-analyses by Khoo and Aziz also showedinsignificant outcomes [41]

One trial of garlic extract treatment in children withhypercholesterolemia found no adverse effects and no signif-icant beneficial effect on lipid levels [42]

Clinical investigations exploring the effects of garlicand its various preparations in hypercholesterolemia havedemonstrated somewhat contradictory results The diversecomposition and amount of active sulfur compounds ofdifferent garlic preparations used in various trials might beresponsible for the above mentioned inconsistent findingsOther factors like subject recruitment duration of studydietary control lifestyle and methods of lipid analyses mayalso have an influenceThese findings emphasize the need forstandardization of garlic preparations in order to reach to avalid conclusion

12 Effects of Garlic on Hypertension

Hypertension is an important risk factor for leading tocardiovascular disease Currently it affects 1 billion peopleworldwide and this number is expected to rise to 16 billionby 2025 [43 44] Garlic regular consumption has shownsome association with blood pressure control Blood pressurereducing properties of garlic are related with the hydrogen

sulphide production [45] and allicin content liberated fromalliin and the enzyme alliinase [46] which is assumed to pos-sess angiotensin II inhibiting and vasodilating effects Garlicis used as a treatment remedy by many people worldwideto control blood pressure According to one survey approxi-mately 29 of people are using garlic for their blood pressurecontrol [47]

The antihypertensive effects of garlic have been studiedbut the remaining controversial various studies done showedcontroversial results as evident from Table 2 Clinical trialdone by Zhang et al consuming garlic oil in hypertensivepatients over the 16-week period showed significant results[48] A trial using garlic pearls containing 250mg of garlicamong hypertensive patients for 2 months demonstrateddecrease in blood pressure level and also showed decrease inbiomarkers responsible for oxidative stress in blood (plasma-oxidized LDL plasma and urinary concentration of 8-iso-Prostaglandin F2alpha) ultimately decreasing the risk ofcardiovascular disease [49]

Majority of patients used garlic as a remedy for preventionfrom dyslipidemia and hypertension various illnesses AnRCT conducted by Ried et al on patients with uncontrolledblood pressure used AGE preparation of 900mg garlic con-taining (24mg salicystine) for 12 weeks and concluded thatsignificant reduction in blood pressure level was noted onlyamong patients who had blood pressure values of more than140mmHg at baseline [50] suggesting that its role in primaryprevention is questionable

Another trial by Duda et al assessed the role of garlic onblood pressure and lipids levels and concluded that garlic canbe used as a tentative treatment along with antihypertensivedrug because of its positive effect on lipid levels and antioxi-dant properties [51]

Few meta-analyses were also done to see the efficacyIn 1994 a meta-analyses assessed the effect of garlic onhypertension among which three trials showed significant

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

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Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 5

Table 2 Effect of garlic on blood pressure levels

Study Type Target Duration of Rx Dose Casecontrol OutcomeZhang et al(2001) [48]

Parallel-controlledtrial Hypertensives 16 weeks Distilled garlic oil

123mgd 1413 Garlic oil lowers SBP and DBP

Dhawan and Jain(2004) [49]

Not placebocontrolled Hypertensives 2 months Garlic pearls

250mg 2020 Dec Bp dec ox-LDL and8-iso-PGF2alpha levels

Capraz et al(2007) [55]

Randomizedplacebo controltrial

Hypertensives 70 minutes Rw garlic Garlictablets 252525 No effects on BP levels

Duda et al(2008) [51]

Prospective anduncontrolledclinical study

Hypertensives 30 daysAntihypertensivedrug + Garlic

capsules3832 Dec total lipids and lipid

peroxidation noticed

Ried et al(2010) [50]

Randomizedplacebo controltrial

Hypertensives 12 weeks 960mg AGE 2525 SBPmdash102 plusmn 43mmHg dec

Ried et al(2013) [53]

Double-blindrandomizedplacebo-controlleddose-response trial

Hypertensives 12 weeks Aged garlic240480960mg 262627

SBPmdash118 plusmn 54mmHg (2capsule) 74 plusmn 41mmHg (4capsule)

T chol total cholesterol HDL high density lipoprotein TG triglyceride LDL low-density lipoprotein VLDL very low-density lipoprotein 8-OHdG (8-Hydroxy-21015840-deoxyguanosine) and 8-iso-PGF2alpha (8-iso-Prostaglandin F2alpha)

a period of 12 weeks using 56 mgtablet garlic tablets showedno significant improvement in lipids levels [37]

An RCT in which 900mg garlic in the form of tablets(Kwai) was given daily to patients with hypercholesterolemiashowed no significant change in lipid levels in comparisonto placebo group [38] Similarly in other trial steams distilledgarlic oil in a quantity of 5mg twice daily for 12 weeks showedno influence on lipid levels [39] A trial with garlic usage inthe form of dried form in a dose of 600mg to 1500mg didnot show any effects suggesting that dried preparation in thedosage studied were ineffective in reducing lipid levels [40]Similarly a meta-analyses by Khoo and Aziz also showedinsignificant outcomes [41]

One trial of garlic extract treatment in children withhypercholesterolemia found no adverse effects and no signif-icant beneficial effect on lipid levels [42]

Clinical investigations exploring the effects of garlicand its various preparations in hypercholesterolemia havedemonstrated somewhat contradictory results The diversecomposition and amount of active sulfur compounds ofdifferent garlic preparations used in various trials might beresponsible for the above mentioned inconsistent findingsOther factors like subject recruitment duration of studydietary control lifestyle and methods of lipid analyses mayalso have an influenceThese findings emphasize the need forstandardization of garlic preparations in order to reach to avalid conclusion

12 Effects of Garlic on Hypertension

Hypertension is an important risk factor for leading tocardiovascular disease Currently it affects 1 billion peopleworldwide and this number is expected to rise to 16 billionby 2025 [43 44] Garlic regular consumption has shownsome association with blood pressure control Blood pressurereducing properties of garlic are related with the hydrogen

sulphide production [45] and allicin content liberated fromalliin and the enzyme alliinase [46] which is assumed to pos-sess angiotensin II inhibiting and vasodilating effects Garlicis used as a treatment remedy by many people worldwideto control blood pressure According to one survey approxi-mately 29 of people are using garlic for their blood pressurecontrol [47]

The antihypertensive effects of garlic have been studiedbut the remaining controversial various studies done showedcontroversial results as evident from Table 2 Clinical trialdone by Zhang et al consuming garlic oil in hypertensivepatients over the 16-week period showed significant results[48] A trial using garlic pearls containing 250mg of garlicamong hypertensive patients for 2 months demonstrateddecrease in blood pressure level and also showed decrease inbiomarkers responsible for oxidative stress in blood (plasma-oxidized LDL plasma and urinary concentration of 8-iso-Prostaglandin F2alpha) ultimately decreasing the risk ofcardiovascular disease [49]

Majority of patients used garlic as a remedy for preventionfrom dyslipidemia and hypertension various illnesses AnRCT conducted by Ried et al on patients with uncontrolledblood pressure used AGE preparation of 900mg garlic con-taining (24mg salicystine) for 12 weeks and concluded thatsignificant reduction in blood pressure level was noted onlyamong patients who had blood pressure values of more than140mmHg at baseline [50] suggesting that its role in primaryprevention is questionable

Another trial by Duda et al assessed the role of garlic onblood pressure and lipids levels and concluded that garlic canbe used as a tentative treatment along with antihypertensivedrug because of its positive effect on lipid levels and antioxi-dant properties [51]

Few meta-analyses were also done to see the efficacyIn 1994 a meta-analyses assessed the effect of garlic onhypertension among which three trials showed significant

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

6 Evidence-Based Complementary and Alternative Medicine

Table 3 Effect of garlic on cardiovascular disease

Study Type Target Duration oftreatment Dose Route Casecontrol Outcome

Bordia et al(1998) [63]

Placebo controltrial

Coronary arterydisease patients 3 months 1 gm garlic

(capsules) Oral 3030Dec T chol and TGincrease HDL level andno effect on fibrinogenand glucose level

Sobenin et al(2010) [71]

Randomizedcontrol trial

Coronary arterydisease patients 1 year Time-released

garlic powder Oral 2625Dec LDLmdash329mgdLin males 273mgdL infemales

T chol total cholesterol HDL high-density lipoprotein TG triglyceride LDL low-density lipoprotein

reductions in systolic blood pressure (77mmHg greaterreduction) and four trials showed reductions in diastolicblood pressure (5mmHg greater reduction) in comparisonto placebo [52]

A meta-analyses conducted by Ried et al showed signifi-cant results with decrease in systolic blood pressure of about163mmHg and diastolic blood pressure of about 93mmHgin comparison to placebo group however these effects wereonly observed in patient having systolic blood pressure valuesmore than 140mmHg [53]

Another meta-analyses done concluded that garlicreduces mean supine systolic and diastolic blood pressure byapproximately 10ndash12mmHg and 6ndash9mmHg respectivelyover and above the effect of placebo but the confidence inter-vals for these effect estimates are not clear cut and this differ-ence in blood pressure reduction may be due to subjectivevariation in blood pressure measurements suggesting moreclinical trials [54]

Few trials done by Capraz et al and Pittler and Ernstshowed insignificant results [55 56] Similarly a meta-ana-lyses done by Simons et al also showed insignificant resultswith no effects on blood pressure levels and concluded thatthe effect of garlic on blood pressure cannot be established[57]

To ascertain the effectiveness of garlic in blood pressurereduction very few studies are available which have shownsmall positive effects insufficient to draw any conclusionsInformation gathered from the previousmeta-analyses is alsoinconclusive due tomethodological shortcomingsThereforein our view use of garlic cannot be recommended as antihy-pertensive advice for hypertensive patients in daily practiceFurther meta-analyses are required to prove its efficacy

13 Effects on Platelets andFibrinolytic Activity

Garlic has a beneficial effect on platelet adhesion or aggre-gation a potential risk factor for cardiovascular disease Theself-condensation products of allicin and ajeones are said tohave antithrombotic action in addition to its potential effectin the inhibition of platelet aggregation [58] 23 Dissolutionof clots and thrombi through fibrinolysis is also improved bygarlic

A number of trials have been conducted to find out theusefulness of garlic or its preparation against platelets Atrial by Rahman and Billington reported that garlic causes

inhibition of platelet aggregation by various mechanismsincluding inhibition of cyclooxygenase activity leading tothromboxane A2 formation by suppressing mobilizationof calcium into the platelets and by increasing levels ofmessengers (cAMP and cGMP) with in the platelets It alsoexhibits strong antioxidant property by increasing produc-tion of platelet-derived NO Simultaneously it also reducesthe ability of platelets to bind to fibrinogen thus overallresulting in inhibition of platelet aggregations and enhancefibrinolytic activity [59]

This fact was further confirmed by a trial by Allison et alwhich showed that AGE extract modified raw preparation ofgarlic-inhibited platelet aggregation by suppressing the influxof calcium ions through their chelationwithin platelet cytosolor by altering other intracellular second messengers withinthe platelets [60]

A trial using AGE preparation of garlic recommendeddose-dependent inhibition of platelet aggregation that isAGE inhibited platelet aggregation at dose of 72 gm howeverfibrinolytic activity was inhibited at all doses among hyperc-holesterolemia patients [61] A trial on ischemic heart diseasepatients after using rawfried garlic significantly increasedfibrinolytic activity [62]

A study using garlic oil as an ingredient reported twoimportant paraffinic polysulphides diallyl disulphide (DADS)and diallyl trisulphide (DATS)mainly responsible for causingantiplatelet inhibition Action of DATS was found morepotent as compared to DADS however it was seen thatinhibition of platelet by DATS was reversible The results ofthis trial conclude that garlic oil should not be used in patientswith comorbid demanding necessary inhibition of plateletsactivity [63]

When discussing its efficacy in comparison to statins itsaction was found comparable to compar to clopidogrel [64]Similarly it was also suggested that AGE preparation if takenas a dietary supplement by healthy individuals may be bene-ficial in protection against cardiovascular disease throughinhibition of platelet aggregation [65]

All of the above results showed some beneficial effectshowever two studies done by [66] Legnani et al and [67]Scharbert et al on healthy individuals showed no effect onfibrinolysis and platelet activity

It is concluded that garlic inhibits platelet aggregationby multiple mechanisms and may have a role in preventingcardiovascular disease However data is scarce and furtherstudies are required to prove this fact

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 7

14 Garlic Role on Endothelium andVascular Dilatation

Though garlic mainly protect against cardiovascular diseasethrough reduction of lipid levels however few studies sug-gest that it has some effects on endothelium and vasculardilatation through inhibition of oxidation process Garliccontains allicin as themain active ingredient with prospect toprovide beneficial effects on cardiovascular system A studyby Chan et al [68] showed that allicin caused enhancementof antioxidant state by lowering of reactive oxygen speciesand increasing the production of glutathione Similarly garlicprevents from cardiovascular disease through inhibition ofLDL oxidation thus inhibiting atherosclerosis of vesselsimportant risk factors for cardiovascular disease [69] Budoffin 2006 conducted a pilot study in which patients who werealready on statin therapywere givenAGE extract of garlic andplacebo and their degree of coronary artery calcification wasassessedwhich slowed down in patient whowere givenGarlictherapy plus statin as compared to the other group [70]

Garlic role in primary and secondary prevention of car-diac disease was also questionable as few trials done showedpositive results as demonstrated by Table 3 This fact wastested among patients with cardiovascular disease by givinggarlic powder tablets allicor and their 10-year prognosticrisk of acute myocardial infarction and sudden death wereassessed It was seen that after 12-month treatment withallicor there was significant decrease of cardiovascular riskthat is 15 fold in men and 13 fold in womenThemain influ-ence that played a role in cardiovascular risk reduction wasthe decrease in LDL cholesterol by 329mgdL in men and by273mgdL in women thus proving the fact that it has effec-tive role in secondary cardiovascular disease prevention [71]

15 Side Effects of Garlic

A couple of case reports have published the adverse effectsof garlic ingestion where one claimed allergic dermatitisobserved in a patient taking raw garlic [72] Another statedthat the antithrombotic activity of garlic might interact withoral anticoagulants therefore caution must be taken whenusing in concordance with oral anticoagulants [73]

16 Conclusion

We conclude that the beneficial effect of garlic preparationson lipids and blood pressure extends also to platelet functionthus providing a wider potential protection of the cardiovas-cular system through itsmajor effects on cholestrol reductionHowever its efficacy in blood pressure reduction is mildwith some beneficial effects on platelet aggregation Thiswarrants the need formoremeta-analyses using standardizedpreparations with a close watch onmethodological shortfalls

Disclosure

The authors have no relationships with pharmaceutical com-panies or products to disclose and they do not discuss off-label or investigative products in this paper

References

[1] B J Gersh K Sliwa B M Mayosi and S Yusuf ldquoNoveltherapeutic concepts the epidemic of cardiovascular diseasein the developing world global implicationsrdquo European HeartJournal vol 31 no 6 pp 642ndash648 2010

[2] Cardiovascular diseases (CVDs) key facts 2013 httpwwwwhointcardiovascular diseasesen

[3] World Health Organization ldquoCardiovascular diseasesrdquo 2013httpwwweurowhointenwhat-we-dohealth-topicsnon-communicable-diseasescardiovascular-diseasesdefinition

[4] D S Celermajer C K Chow E Marijon N M Anstey andK S Woo ldquoCardiovascular disease in the developing worldprevalencersquos patterns and the potential of early disease detec-tionrdquo Journal of the American College of Cardiology vol 60 no14 pp 1207ndash1216 2012

[5] World Health Organization ldquoCardiovascular diseases factsheetrdquo 2012 httpwwwwhointmediacentrefactsheetsfs317enindexhtml

[6] W Qidwai S R Alim R H Dhanani S Jehangir A Nasrullahand A Raza ldquoUse of folk remedies among patients in KarachiPakistanrdquo Journal of Ayub Medical College Abbottabad vol 15no 2 pp 31ndash33 2003

[7] M Frass R P Strassl H Friehs M Mullner M Kundi and AD Kaye ldquoUse and acceptance of complementary and alternativemedicine among the general population andmedical personnela systematic reviewrdquoThe Ochsner Journal vol 12 no 1 pp 45ndash56 2012

[8] E Ernst ldquoComplementary medicine common misconcep-tionsrdquo Journal of the Royal Society of Medicine vol 88 no 5pp 244ndash247 1995

[9] P M Barnes B Bloom and R L Nahin ldquoComplementary andalternative medicine use among adults and children UnitedStates 2007rdquo National Health Statistics Reports no 12 pp 1ndash232009

[10] A F Omeish W Abbadi I M Ghanma et al ldquoHospital-basedstudy on the use of herbal medicine in patients with coro-nary artery disease in Jordanrdquo Journal of the Pakistan MedicalAssociation vol 61 no 7 pp 683ndash687 2011

[11] R Rivlin ldquoHistorical perspective on the use of garlicrdquo Journal ofNutrition vol 131 no 3 pp 951Sndash954S 2001

[12] H P Koch andLD LawsonGarlicThe Science andTherapeuticApplication of Allium Sativum L and Related Species WilliamsampWilkins Baltimore Md USA 2nd edition 1996

[13] M Steiner and W Li ldquoAged garlic extract a modulator ofcardiovascular risk factors a dose-finding study on the effectsof AGE on platelet functionsrdquo Journal of Nutrition vol 131 no3 pp 980Sndash984S 2001

[14] L D Lawson ldquoGarlic a review of its medicinal effects andindicated active compoundsrdquo in Phytomedicines of EuropeChemistry and Biological Activity L D Lawson and R BauerEds vol 691 of ACS Symposium Series pp 176ndash209 AmericanChemical Society Washington DC USA 1998

[15] C Borek ldquoAntioxidant health effects of aged garlic extractrdquoJournal of Nutrition vol 131 no 3 pp 1010Sndash1015S 2001

[16] E Block ldquoThe chemistry of garlic and onionsrdquo Scientific Ameri-can vol 252 no 3 pp 114ndash119 1985

[17] X Yan ZWang and P Barlow ldquoQuantitative estimation of gar-lic oil content in garlic oil based health productsrdquo Food Chem-istry vol 45 no 2 pp 135ndash139 1992

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

8 Evidence-Based Complementary and Alternative Medicine

[18] B Iberl G Winkler B Muller and K Knobloch ldquoQuantitativedetermination of allicin and alliin from garlic by HPLCrdquo PlantaMedica vol 56 no 3 pp 320ndash326 1990

[19] R Bakhsh and M I Chughtai ldquoInfluence of garlic on serumcholesterol serum triglycerides serum total lipids and serumglucose in human subjectsrdquoDie Nahrung vol 28 no 2 pp 159ndash163 1984

[20] F HMader ldquoTreatment of hyperlipidaemia with garlic-powdertablets Evidence from the German association of general prac-titionersrsquo multicentric placebo-controlled double-blind studyrdquoArzneimittel-Forschung vol 40 no 10 pp 1111ndash1116 1990

[21] R C Arora S Arora and R K Gupta ldquoThe long-term use ofgarlic in ischemic heart disease An appraisalrdquo Atherosclerosisvol 40 no 2 pp 175ndash179 1981

[22] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[23] P S Yusuf S Hawken S Ounpuu et al ldquoEffect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study) case-control studyrdquoThe Lancet vol 364 no 9438 pp 937ndash952 2004

[24] V K Singh and D K Singh ldquoPharmacological effects of garlic(Allium sativum L)rdquo Annual Review of Biomedical Sciences vol10 pp 6ndash26 2008

[25] H Sumiyoshi ldquoNew pharmacological activities of garlic and itsconstituentsrdquo Folia Pharmacologica Japonica vol 110 supple-ment 1 pp 93Pndash97P 1997

[26] T Saradeth S Seidl K L Resch and E Ernst ldquoDoes garlic alterthe lipid pattern in normal volunteersrdquo Phytomedicine vol 1no 3 pp 183ndash185 1994

[27] J V Gadkari and V D Joshi ldquoEffect of ingestion of raw garlic onserum cholesterol level clotting time and fibrinolytic activity innormal subjectsrdquo Journal of Postgraduate Medicine vol 37 no3 pp 128ndash131 1991

[28] I A Sobenin I V Andrianova O N Demidova T V Gor-chakova and A N Orekhov ldquoLipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-con-trolled randomized studyrdquo Journal of Atherosclerosis andThrom-bosis vol 15 no 6 pp 334ndash338 2008

[29] M Steiner A H Khan D Holbert and R I S Lin ldquoA double-blind crossover study in moderately hypercholesterolemic menthat compared the effect of aged garlic extract and placeboadministration on blood lipidsrdquoThe American Journal of Clini-cal Nutrition vol 64 no 6 pp 866ndash870 1996

[30] M Mahmoodi M R Islami G R A Karam et al ldquoStudy ofthe effects of raw garlic consumption on the level of lipids andother blood biochemical factors in hyperlipidemic individualsrdquoPakistan Journal of Pharmaceutical Sciences vol 19 no 4 pp295ndash298 2006

[31] W Rotzsch V Richter F Rassoul and A Walper ldquoPostpran-dial lipaemia under treatment with Allium sativumcontrolleddouble-blind study in healthy volunteers with reduced HDL2-cholesterol levelsrdquo Arzneimittel-Forschung vol 42 no 10 pp1223ndash1227 1992

[32] M Ali and M Thomson ldquoConsumption of a garlic clove a daycould be beneficial in preventing thrombosisrdquo ProstaglandinsLeukotrienes and Essential Fatty Acids vol 53 no 3 pp 211ndash2121995

[33] C Silagy and A Neil ldquoGarlic as a lipid lowering agentmdashameta-analysisrdquo Journal of the Royal College of Physicians of Londonvol 28 no 1 pp 39ndash45 1994

[34] S Warshafsky R S Kamer and S L Sivak ldquoEffect of garlicon total serum cholesterol a meta-analysisrdquo Annals of InternalMedicine vol 119 no 7 pp 599ndash605 1993

[35] T Zeng F F Guo C L Zhang F Y Song X L Zhao and KQ Xie ldquoAmeta-analysis of randomized double-blind placebo-controlled trials for the effects of garlic on serum lipid profilesrdquoJournal of the Science of Food and Agriculture vol 92 no 9 pp1892ndash1902 2012

[36] H Holzgartner U Schmidt and U Kuhn ldquoComparison of theefficacy and tolerance of a garlic preparation versus bezafibraterdquoArzneimittel-Forschung vol 42 no 12 pp 1473ndash1477 1992

[37] P Satitvipawee P Rawdaree S Indrabhakti T Ratanasuwan PGetn-gern and C Viwatwongkasem ldquoNo effect of garlic extractsupplement on serum lipid levels in hypercholesterolemicsubjectsrdquo Journal of Medical Association vol 86 no 8 pp 750ndash757 2003

[38] J L Isaacsohn M Moser E A Stein et al ldquoGarlic powderand plasma lipids and lipoproteins a multicenter randomizedplacebo-controlled trialrdquo Archives of Internal Medicine vol 158no 11 pp 1189ndash1194 1998

[39] H K Berthold T Sudhop and K von Bergmann ldquoEffect ofa garlic oil preparation on serum lipoproteins and cholesterolmetabolism a randomized controlled trialrdquo The Journal of theAmerican Medical Association vol 279 no 23 pp 1900ndash19021998

[40] C Luley W Lehmann-Leo and B Moller ldquoLack of efficacyof dried garlic in patients with hyperlipoproteinemiardquo Arznei-mittel-Forschung vol 36 no 4 pp 766ndash768 1986

[41] Y S K Khoo and Z Aziz ldquoGarlic supplementation and serumcholesterol a meta-analysisrdquo Journal of Clinical Pharmacy andTherapeutics vol 34 no 2 pp 133ndash145 2009

[42] B W McCrindle E Helden and W T Conner ldquoGarlic extracttherapy in children with hypercholesterolemiardquo Archives ofPediatrics and Adolescent Medicine vol 152 no 11 pp 1089ndash1094 1998

[43] The Seventh Report of the Joint National Committee on Preven-tion Detection Evaluation and Treatment of High Blood Pres-sure NIH publication 03-5233 National Institutes of HealthNational Heart Lung and Blood Institute National High BloodPressure Education Program Bethesda Md USA 2003

[44] P M Kearney M Whelton K Reynolds P Muntner P KWhelton and J He ldquoGlobal burden of hypertension analysisof worldwide datardquo The Lancet vol 365 no 9455 pp 217ndash2232005

[45] G A Benavides G L Squadrito R W Mills et al ldquoHydrogensulfide mediates the vasoactivity of garlicrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 104 no 46 pp 17977ndash17982 2007

[46] S K Banerjee P K Mukherjee and S K Maulik ldquoGarlic as anantioxidant the good the bad and the uglyrdquo Phytotherapy Re-search vol 17 no 2 pp 97ndash106 2003

[47] P E Osamor and B E Owumi ldquoComplementary and alterna-tive medicine in the management of hypertension in an urbanNigerian communityrdquo BMC Complementary and AlternativeMedicine vol 10 article 36 2010

[48] X H Zhang D Lowe P Giles et al ldquoA randomized trial of theeffects of garlic oil upon coronary heart disease risk factors intrained male runnersrdquo Blood Coagulation and Fibrinolysis vol12 no 1 pp 67ndash74 2001

[49] V Dhawan and S Jain ldquoEffect of garlic supplementation onoxidized low density lipoproteins and lipid peroxidation in

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 9

patients of essential hypertensionrdquoMolecular and Cellular Bio-chemistry vol 266 no 1-2 pp 109ndash115 2004

[50] K Ried O R Frank and N P Stocks ldquoAged garlic extractlowers blood pressure in patients with treated but uncontrolledhypertension a randomised controlled trialrdquoMaturitas vol 67no 2 pp 144ndash150 2010

[51] G Duda J Suliburska and D Pupek-Musialik ldquoEffects ofshort-term garlic supplementation on lipid metabolism andantioxidant status in hypertensive adultsrdquo PharmacologicalReports vol 60 no 2 pp 163ndash170 2008

[52] C A Silagy and H A W Neil ldquoA meta-analysis of the effect ofgarlic on blood pressurerdquo Journal of Hypertension vol 12 no 4pp 463ndash468 1994

[53] K Ried O R Frank and N P Stocks ldquoAged garlic extractreduces blood pressure in hypertensives a dose-response trialrdquoEuropean Journal of Clinical Nutrition vol 67 no 1 pp 64ndash702013

[54] S N Stabler A M Tejani F Huynh and C Fowkes ldquoGarlicfor the prevention of cardiovascular morbidity and mortalityin hypertensive patientsrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007653 2009

[55] M Capraz M Dilek and T Akpolat ldquoGarlic hypertension andpatient educationrdquo International Journal of Cardiology vol 121no 1 pp 130ndash131 2007

[56] M H Pittler and E Ernst ldquoClinical effectiveness of garlic(Allium sativum)rdquo Molecular Nutrition and Food Research vol51 no 11 pp 1382ndash1385 2007

[57] S Simons H Wollersheim and T Thien ldquoA systematic reviewon the influence of trial quality on the effect of garlic on bloodpressurerdquoNetherlands Journal ofMedicine vol 67 no 6 pp 212ndash219 2009

[58] K Teranishi R Apitz-Castro S C Robson E Romano and DK C Cooper ldquoInhibition of baboon platelet aggregation in vitroand in vivo by the garlic derivative ajoenerdquo Xenotransplanta-tion vol 10 no 4 pp 374ndash379 2003

[59] K Rahman and D Billington ldquoDietary supplementation withaged garlic extract inhibits ADP-induced platelet aggregation inhumansrdquo Journal of Nutrition vol 130 no 11 pp 2662ndash26652000

[60] G L Allison G M Lowe and K Rahman ldquoAged garlic extractmay inhibit aggregation in human platelets by suppressingcalcium mobilizationrdquo Journal of Nutrition vol 136 no 3 pp789Sndash792S 2006

[61] M Steiner andW Li ldquoAged garlic extract a modulator of card-iovascular risk factors a dose-finding study on the effects ofAGE on platelet functionsrdquo Journal of Nutrition vol 131 no 3pp 980Sndash984S 2001

[62] S KChutani andA Bordia ldquoThe effect of fried versus raw garlicon fibrinolytic activity in manrdquo Atherosclerosis vol 38 no 3-4pp 417ndash421 1981

[63] A Bordia S K Verma and K C Srivastava ldquoEffect of garlic(Allium sativum) on blood lipids blood sugar fibrinogen andfibrinolytic activity in patients with coronary artery diseaserdquoProstaglandins Leukotrienes and Essential Fatty Acids vol 58no 4 pp 257ndash263 1998

[64] B Hiyasat D Sabha K Grotzinger et al ldquoAntiplatelet activityof Allium ursinum and Allium sativumrdquo Pharmacology vol 83no 4 pp 197ndash204 2009

[65] K Rahman ldquoEffects of garlic on platelet biochemistry and phy-siologyrdquo Molecular Nutrition and Food Research vol 51 no 11pp 1335ndash1344 2007

[66] C Legnani M Frascaro G Guazzaloca S Ludovici GCesarano and S Coccheri ldquoEffects of a dried garlic preparationon fibrinolysis and platelet aggregation in healthy subjectsrdquoArz-neimittel-Forschung vol 43 no 2 pp 119ndash122 1993

[67] G Scharbert M L Kalb M Duris C Marschalek and S AKozek-Langenecker ldquoGarlic at dietary doses does not impairplatelet functionrdquo Anesthesia and Analgesia vol 105 no 5 pp1214ndash1218 2007

[68] J Y Chan A C Yuen R Y Chan and S W Chan ldquoA reviewof the cardiovascular benefits and antioxidant properties of alli-cinrdquo Phytotherapy Research 2012

[69] B H S Lau ldquoSuppression of LDL oxidation by garlicrdquo Journalof Nutrition vol 131 no 3 pp 985Sndash988S 2001

[70] M Budoff ldquoAged garlic extract retards progression of coronaryartery calcificationrdquo Journal of Nutrition vol 136 no 3 supple-ment pp 741Sndash744S 2006

[71] I A Sobenin V V Pryanishnikov L M Kunnova Y A Rabi-novich D M Martirosyan and A N Orekhov ldquoThe effects oftime-released garlic powder tablets on multifunctional cardio-vascular risk in patients with coronary artery diseaserdquo Lipids inHealth and Disease vol 9 article 119 2010

[72] S Ma and J Yin ldquoAnaphylaxis induced by ingestion of rawgarlicrdquo Foodborne Pathogens and Disease vol 9 no 8 pp 773ndash775 2012

[73] K D Rose P D Croissant C F Parliament and M B LevinldquoSpontaneous spinal epidural hematoma with associated plate-let dysfunction from excessive garlic ingestion a case reportrdquoNeurosurgery vol 26 no 5 pp 880ndash882 1990

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom