Garlic

Garlic-Protection of the cardiovascular system

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Biological Activities–Protection of the cardiovascular system

Inhibition of cholesterol synthesis

Garlic and garlic-derived organosulfur compounds have been found to decrease the synthesis of cholesterol by hepatocytes. Several garlic-derived organosulfur compounds, including S-allylcysteine and ajoene, have been found to inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), a critical enzyme in the cholesterol biosynthesis pathway. Garlic-derived compounds may also inhibit other enzymes in this pathway, including sterol 4α-methyl oxidase.

Inhibition of platelet aggregation

An increase in the ability of platelets to aggregate has been linked to the narrowing of blood vessels and the occurrence of acute thrombotic events. A variety of garlic-derived organosulfur compounds have been found to inhibit platelet aggregation in the test tube. Aged garlic extract was found to inhibit chemically stimulated platelet aggregation by downregulating the fibrinogen binding activity of glycoprotein IIb/IIIa fibrinogen receptor found on platelets and/or by preventing intraplatelet calcium mobilization.

Inhibition of vascular smooth muscle cell (VSMC) proliferation

The proliferation and migration of normally quiescent VSMCs are central features of vascular diseases, including atherosclerosis and coronary restenosis (when treated arteries become blocked again). Although the significance of these findings for human cardiovascular disease is not yet clear, limited cell culture research suggested that organosulfur compounds from garlic could inhibit the proliferation and migration of VSMCs .

Inhibition of vascular cell adhesion molecules

An elevation of oxidized low-density lipoprotein (LDL) concentration in plasma has been involved in the pathogenesis of atherosclerosis. Oxidized LDL may stimulate the recruitment of inflammatory white blood cells from the blood to the arterial wall by inducing the expression of vascular cell adhesion molecules. DADS and DATS inhibited the expression of adhesion molecules, E-selectin and vascular cell adhesion molecule-1 (VCAM-1), on endothelial cell surface by reversing oxidized LDL-induced inhibition of PI3K/Akt and cAMP responsive element binding protein (CREB) signaling pathways.

Hydrogen sulfide-mediated vasodilatory activity

The preservation of normal arterial function plays an important role in cardiovascular disease prevention. Hydrogen sulfide (H2S), a gaseous signaling molecule produced by some cells within the body, acts as a vasodilator (relaxes blood vessels) and thus may have cardioprotective properties. H2S production may be involved in vascular smooth muscle cell relaxation through regulating the opening/closing of potassium channels and/or enhancing NO-dependent signaling pathway. A study found that garlic-derived compounds are converted to hydrogen sulfide by red blood cells in vitro. However, human consumption of a high dose of raw garlic does not increase breath hydrogen sulfide levels, suggesting that significant metabolism of garlic compounds to hydrogen sulfide does not occur in vivo.

Note that the potential benefits of garlic consumption/supplementation on cardiovascular health may also be attributed to antioxidant and anti-inflammatory activities described above.

Garlic-Anticancer activity

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Biological Activities- Anticancer activity

Effects on carcinogen metabolism

Inhibition of metabolic activation of carcinogens: Some chemical carcinogens do not become active carcinogens until they have been metabolized by Phase I biotransformation enzymes, such as those belonging to the cytochrome P450 (CYP) family. Inhibition of specific CYP enzymes involved in carcinogen activation inhibits the development of cancer in some animal models. In particular, DAS and its metabolites have been found to inhibit CYP2E1 activity in vitro. and when administered orally at high doses to animals. Oral administration of garlic oil and DAS to humans has also resulted in evidence of decreased CYP2E1 activity.

Induction of Phase II detoxifying enzymes: Reactions catalyzed by phase II detoxifying enzymes generally promote the elimination of drugs, toxins, and carcinogens from the body. Consequently, increasing the activity of phase II enzymes, such as glutathione S-transferases (GSTs) and NQO-1, may help prevent cancer by enhancing the elimination of potential carcinogens (see the Nrf2-dependent antioxidant pathway).In animal studies, oral administration of garlic preparations and organosulfur compounds was found to increase the expression and activity of phase II enzymes in a variety of tissues. For example, DADS protected rodent liver against carbon tetrachloride (CCl4; an environmental pollutant)-induced lipid peroxidation and cell necrosis by blocking CYP2E1-mediated CCL4 metabolic activation and by upregulating Nrf2 downstream genes for NQO-1, HO-1, GCL, GST, and superoxide dismutase (SOD1).

Induction of cell cycle arrest

In normal cells, the cell cycle is tightly regulated to ensure faithful DNA replication and chromosomal segregation prior to cell division. When defects occur during DNA replication or chromosomal segregation and in case of DNA damage, the cell cycle can be transiently arrested at check points to allow for repair. Apoptosis is triggered when repair fails. Defective check points and evasion of apoptosis allow the unregulated division of cancer cells. Organosulfur compounds, including allicin, DAS, DADS, DATS, ajoene, and SAMC, have been found to induce cell cycle arrest when added to cancer cells in cell culture experiments. DATS reduced the incidence of poorly differentiated prostate tumors and limited the number of metastatic lesions in the lungs of mice genetically modified to develop prostate adenocarcinomas. DATS was shown to inhibit cancer cell proliferation, as well as neuroendocrine differentiation — a hallmark of prostate cancer malignancy — but had no effect on apoptosis and markers of invasion.In a rat model of chemically induced colon cancer, inhibition of cell proliferation by aged garlic extract was associated with a reduction in the incidence of precancerous lesions and dysplastic adenomas, but not of adenocarcinomas.

Induction of apoptosis

Apoptosis is a physiological process of programmed death of cells that are genetically damaged or no longer necessary. Precancerous and cancerous cells are resistant to signals that induce apoptosis. Garlic-derived organosulfur compounds, including allicin, ajoene, DAS, DADS, DATS, and SAMC, have been found to induce apoptosis when added to various cancer cell lines grown in culture. Oral administration of aqueous garlic extract and S-allylcysteine has been reported to enhance apoptosis in an animal model of oral cancer. Garlic oil reduced the incidence of N-nitrosodiethylamine-induced liver nodules by preventing oxidative damage to lipids and DNA and by promoting apoptosis. Garlic oil upregulated the activity of various antioxidant enzymes and expression of pro-apoptotic effectors like Bax and Caspase-3 and downregulated the expression of the anti-apoptotic genes β-arrestin-2, Bcl-2, and Bcl-X.

Inhibition of angiogenesis

To fuel their rapid growth, invasive tumors must develop new blood vessels by a process known as angiogenesis. Anti-angiogenic properties of several organosulfur compounds, including alliin, DATS, and ajoene, have been observed in in vitro or ex vivo experiments. In human breast cancer cells, DADS inhibited TNF-α-induced release of MCP-1, a chemokine that promotes tissue remodeling, angiogenesis, and metastasis. Aged garlic extract was also found to suppress in vitro angiogenesis by inhibiting endothelial cell proliferation, loss of adhesion, motility, and tube formation.

Garlic-Antioxidant activity

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Biological Activities–Antioxidant activity

Glutathione

Low cellular concentrations of glutathione, a major intracellular antioxidant, and/or overproduction of reactive oxygen species (ROS) can lead to oxidative stress-induced damage to biological macromolecules and contribute to the development and progression of pathological conditions. In endothelial cells (that line the inner wall of blood vessels), garlic-derived allicin lowered ROS production and increased the concentration of glutathione. Oral administration of allicin to mice lowered ROS production and prevented ROS-induced cardiac hypertrophy by inhibiting pro-inflammatory pathways like mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) signaling pathways. It is thought that, upon crossing cell membranes, allicin interacts with glutathione and forms SAMG, which could prolong the antioxidant activity of allicin.

Nrf2-dependent antioxidant pathway

Allicin was also found to upregulate the expression of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis, and other Phase II detoxifying/antioxidant enzymes, likely via the activation of the nuclear factor E2-related factor 2 (Nrf2)-dependent pathway. Briefly, Nrf2 is a transcription factor that is bound to the protein Kelch-like ECH-associated protein 1 (Keap1) in the cytosol. Keap1 responds to oxidative stress signals by freeing Nrf2. Upon release, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE) located in the promoter of genes coding for antioxidant/detoxifying enzymes and scavengers. Nrf2/ARE-dependent genes code for numerous mediators of the antioxidant response, including GCL, glutathione S-transferases (GSTs), thioredoxin, NAD(P)H quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1). Like allicin, oil-soluble organosulfides, DADS and DATS, have been shown to stimulate Nrf2-dependent antioxidant pathway. For example, antioxidant and cytoprotective effects of DADS against acute ethanol-induced liver damage in mice were associated with the ability to trigger Nrf2-dependent HO-1 activation. DATS protected cardiac cells in vitro and in experimental diabetic rats from high glucose-induced oxidative stress and apoptosis by inducing PI3K/Akt-dependent Nrf2 antioxidant signaling .

Aged garlic extract have also been shown to increase expression of antioxidant enzymes via the Nrf2/ARE pathway. SAC, a major organosulfur compound in aged garlic extract, prevented renal damage caused by ROS in cisplatin-treated rats, by limiting cisplatin-induced reduction of glutathione level, Nrf2 expression, and activity of several antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase). SAC also protected neurons from oxidative damage and apoptosis in wild-type mice but not in mice without a functional Nrf2 signaling pathway.

Nitric oxide (NO) signaling cascade

The generation of nitric oxide (NO) catalyzed by endothelial nitric oxide synthase (eNOS) plays a critical role in protecting the vascular endothelium from oxidative and inflammatory insults. ROS-induced NO inactivation can impair vascular endothelial function, contributing to various pathologies like atherosclerosis, hypertension, cardiovascular disease, and central nervous system disorders. Interestingly, ingestion of 2 g of fresh garlic was found to increase NO plasma concentrations within two to four hours in healthy volunteers. DADS and DATS protected eNOS activity and NO bioavailability in cultured endothelial cells challenged with oxidized low-density lipoprotein (LDL). In a model of traumatic brain injury in rats, allicin attenuated brain edema, neurological deficits, and apoptotic neuronal death, and exhibited antioxidant and anti-inflammatory effects, partly by increasing Akt-mediated eNOS activation. Aged garlic extract and SAC were also found to stimulate NO production in different experimental settings . In a model of erectile dysfunction in diabetic rats, SAC restored electrically-induced penile erection by stimulating eNOS activity and inhibiting the expression of NADPH oxidase (Nox) responsible for ROS overproduction.

Garlic Against Viral

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Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide.

Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.

Additionally the composition of various commercial garlic products. Including garlic powder tablets and capsules, oil-macerated garlic. Steam-distilled garlic oils, garlic aged in anqueos alcohol. And fermented garlic oil was determined as well ass the virucidal activated of the products against herpes simplex virus type 1. and parainfluenza virus type 3. virucidal activities of commercial products were de-pendent upon their preparation process. Those products producing the highest level of allicin and other thiosulfinates has the best virucidal activities.

In Vitro Virucidal Effects of Allium Sativum (Garlic)

In Vitro Virucidal Effects of Allium Sativum (Garlic)-Allicin Pharm

Garlic Chemistry

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Organosulfur compounds from garlic

Two classes of organosulfur compounds are found in whole garlic cloves: L-cysteine sulfoxides and γ-glutamyl-L-cysteine peptides.

L-Cysteine sulfoxides

S-allyl-L-cysteine sulfoxide (alliin) accounts for approximately 80% of cysteine sulfoxides in garlic. When raw garlic cloves are crushed, chopped, or chewed, an enzyme known as alliinase is released. Alliinase catalyzes the formation of sulfenic acids from L-cysteine sulfoxides. Sulfenic acids spontaneously react with each other to form unstable compounds called thiosulfinates. In the case of alliin, the resulting sulfenic acids react with each other to form a thiosulfinate known as allicin (half-life in crushed garlic at 23°C is 2.5 days). The formation of thiosulfinates is very rapid and has been found to be complete within 10 to 60 seconds of crushing garlic. Allicin breaks down in vitro to form a variety of fat-soluble organosulfur compounds, including diallyl trisulfide (DATS), diallyl disulfide (DADS), and diallyl sulfide (DAS), or in the presence of oil or organic solvents, ajoene and vinyldithiins. In vivo, allicin can react with glutathione and L-cysteine to produce S-allylmercaptoglutathione (SAMG) and S-allylmercaptocysteine (SAMC), respectively.

γ-Glutamyl-L-cysteine peptides                                

Crushing garlic does not change its γ-glutamyl-L-cysteine peptide content. γ-Glutamyl-L-cysteine peptides include an array of water-soluble dipeptides, including γ-glutamyl-S-allyl-L-cysteine, γ-glutamylmethylcysteine, and γ-glutamylpropylcysteine. Water-soluble organosulfur compounds, such as S-allylcysteine and SAMC, are formed from γ-glutamyl-S-allyl-L-cysteine during long-term incubation of crushed garlic in aqueous solutions, as in the manufacture of aged garlic extracts.


Non-sulfur garlic phytochemicals

Although little is known about their bioavailability and biological activities, non-sulfur garlic phytochemicals, including flavonoids, steroid saponins, organoselenium compounds, and allixin, likely work in synergy with organosulfur compounds.

Garlic-Anti-inflammatory activity

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Biological Activities–Anti-inflammatory activity

Garlic-derived organosulfur compounds have been found to inhibit mediators of the inflammatory response, including cytokines, chemokines, adhesion molecules, and enzymes like cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). Nuclear factor-kappa B (NF-κB) is a transcription factor that binds DNA and induces the transcription of the COX-2 gene, other pro-inflammatory genes, as well as genes involved in cell proliferation, adhesion, survival, and differentiation. The anti-inflammatory effects of organosulfur compounds result from their ability to counteract the activation of pro-inflammatory pathways — like NF-κB-, MAPK-, and PI3K/Akt-dependent signaling pathways — by pro-inflammatory stimuli. DATS inhibited bacterial lipopolysaccharide (LPS)-induced macrophage activation by limiting LPS binding to toll-like receptor 4 (TLR4) and blocking the upregulation of TLR4 and TLR4-associated molecule MyoD88 expression. DATS also inhibited LPS-induced NF-κB-dependent expression of COX-2, iNOS, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). In a mouse model of inflammation, the decrease of LPS-induced paw edema by DATS was associated with reduced serum concentrations of the pro-inflammatory cytokines, TNF-α, IL-6, and monocyte chemotactic protein-1 (MCP-1).

Garlic-Cancer Prevention

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Disease Prevention- Cancer

Gastric cancer

A recent meta-analysis of 17 studies (mostly case-control studies) reported an inverse association between high versus low garlic consumption and the risk of gastric cancer. Nevertheless, this conclusion is hindered by a number of limitations, especially related to the retrospective design of most studies included in the analysis, as well as great variations in the amount and duration of garlic intakes. In a 2009 review of the literature, Kim et al. identified 20 human studies that examined garlic intake in relation to gastric cancer risk: three intervention studies, one case-cohort study, 13 case-control studies, and three cross-sectional/ecologic studies. Using the Food and Drug Administration (FDA)’s evidence-based criteria for the scientific evaluation of health claims, the authors excluded 16 studies for methodological flaws; only four studies (two case-control,one case-cohort,and one intervention ) received moderate-to-high quality ratings . Among these four studies, garlic intake during adolescence or 20 years prior to the interview was not found to be associated with the risk of gastric cancer in one of the case-control studies in Sweden (338 gastric cancer patients and 669 control subjects). Another case-control study in Korea failed to show an association between past garlic consumption and gastric cancer in 136 people diagnosed with gastric cancer and 136 cancer-free subjects . In addition, a prospective case-cohort study in the Netherlands found no association between the use of garlic supplements (unknown composition) and gastric cancer risk. Finally, a randomized, double-blind, placebo-controlled intervention study in 3,365 subjects from the Shandong province of China found that supplementation with aged garlic extract and steam-distilled garlic oil for 7.3 years did not reduce the prevalence of precancerous gastric lesions or the incidence of gastric cancer. An updated analysis of the data collected 7.3 years after garlic supplementation ended provided further confirmation for a lack of significant reduction in gastric cancer incidence or mortality with supplemental garlic.

Helicobacter pylori (H. pylori) infection and gastric cancer: Infection with some strains of H. pylori bacteriamarkedly increases the risk of gastric cancer. Although garlic preparations and organosulfur compounds could inhibit the growth of H. pylori in the laboratory, there is little evidence to suggest that high garlic intakes or garlic supplementation may help prevent or eradicate H. pylori infection in humans. Higher intakes of garlic were not associated with a significantly lower prevalence of H. pylori infection in China or Turkey.Moreover, clinical trials using garlic cloves, aged garlic extract, steam-distilled garlic oil, garlic oil macerate, or garlic powder have not found garlic supplementation to be effective in eradicating H. pyloriinfection in humans.

Colorectal cancer

A 2014 meta-analysis of prospective cohort studies in 335,923 subjects (including 4,610 colorectal cancer [CRC] cases) found no association of consuming raw or cooked garlic (three studies, four cohorts) or supplemental garlic (four studies, five cohorts) with CRC. Another recent systematic review and meta-analysis that combined data from seven cohort and seven case-control studies also failed to find a statistically significant reduction in CRC riskwith garlic intake. Yet, these results are in contrast with previous pooled analyses of data from case-control studies or from both case-control and prospective studies that reported an approximate 30% lower CRC risk in individuals with the highest garlic intakes compared to those with the lowest intakes. Inclusion of case-control studies, which are more susceptible to bias, may explain these discrepancies among meta-analyses . For information regarding different types of epidemiological studies, see the Spring/Summer 2016 LPI Research Newsletter.

A small preliminary intervention trial in 37 patients with colorectal adenomas examined whether supplementation with aged garlic extract for 12 months affected adenoma size and recurrence. Both the number and size of adenomas were significantly reduced in patients given a high dose of aged garlic extract compared to those given a much lower dose (0.16 mL/day) Larger randomized controlled trials are needed to determine whether garlic or garlic extracts can substantially reduce adenoma progression to advanced cancer and recurrence.

Other types of cancer

In a small, placebo-controlled intervention study in 50 patients with cancer (42 with liver cancer, seven with pancreatic cancer, and one with colon cancer), supplementation with 500 mg/day of aged garlic extract for six months failed to prevent quality of life deterioration caused by disease progression and chemotherapy-associated adverse effects. Yet, the active treatment limited the decline in natural killer cell count and activity that accompanies digestive cancer progression and reduces patient survival.

At present, evidence from trials is limited and results from observational studies do not suggest a role of high intakes of garlic in the prevention of cancer in humans.

Garlic-Cardiovascular disease Prevention

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Disease Prevention- Cardiovascular disease

Interest in garlic and its potential to prevent cardiovascular disease began with observations that people living near the Mediterranean basin had lower mortality from cardiovascular disease. Garlic is a common ingredient in Mediterranean cuisine, but a number of characteristics of the “Mediterranean diet” have been proposed to explain its cardioprotective effects. Although few observational studies have examined associations between garlic consumption and cardiovascular disease risk, numerous intervention trials have explored the effects of garlic supplementation on cardiovascular disease risk factors.

Platelet aggregation

Platelet aggregation is one of the first steps in the formation of blood clots that can occlude coronary or cerebral arteries, leading to myocardial infarction or ischemic stroke, respectively. Evidence that garlic inhibits platelet aggregation is based mainly on in vitro experiments and a small number of ex vivo assays. Of 10 randomized controlled trials that tested the antithrombotic effect of garlic preparation, four reported a modest but significant decrease in ex vivo platelet aggregation with garlic supplementation compared to placebo. Because garlic oil extract in particular may have antithrombotic activity, a small randomized controlled trial in 12 healthy adults was conducted to test the acute effect of one large dose of garlic oil (extracted from 9.9 g of fresh garlic) on ex vivo platelet aggregation. The garlic oil extract had a mild effect on adrenaline-induced platelet aggregation (12% reduction) but had no effect on adenosine diphosphate (ADP)- or collagen-induced aggregation measured four hours post-consumption. Another study in 14 healthy volunteers showed that aged garlic extract dose-dependently inhibited ADP-stimulated platelet aggregation by downregulating the fibrinogen binding activity of glycoprotein IIb/IIIa fibrinogen receptor found on platelets.

Serum lipid profiles

A recent systematic review of randomized controlled trials examining the effect of supplementation with various garlic preparations on serum lipid profiles in individuals with elevated and normal serum cholesterol levels reported mixed results. The most recent and comprehensive meta-analysis compared the results from 39 randomized controlled trials published between 1955 and 2011 that tested the effect of garlic preparations on serum lipid concentrations. These 39 trials studied 2,298 adult participants (mean age, 49.5 years), administered garlic-only preparations, used a true placebo, and lasted for at least two weeks. The majority of included trials recruited subjects with elevated total cholesterol at baseline (>200 mg/dL [>5.2 mmol/L], 29 trials) and lasted more than eight weeks (30 trials). The authors found that garlic preparations significantly lowered total cholesterol and low-density lipoprotein (LDL)-cholesterol compared to placebo. High-density lipoprotein (HDL)-cholesterol concentrations were mildly increased and triglyceride concentrations were not affected by garlic supplementation. All administered garlic preparations (garlic powder, aged garlic extract, garlic oil, and fresh garlic) were well tolerated and associated with only minor side effects (garlic odor and mild gastrointestinal discomfort).

Although garlic supplementation for a minimum of two months may lower total- and LDL-cholesterol concentrations in individuals with elevated total cholesterol, the benefits may not last beyond the short term . Whether garlic possesses long-lasting lipid-lowering effects remain questionable and future investigations may focus on ways to maximize potential benefits of garlic preparations on serum lipids.

Atherosclerosis

Very few studies have attempted to assess the effect of garlic supplementation on the progression of atherosclerosis in humans. One early study in Germany used ultrasound imaging to assess the effect of 900 mg/day of dehydrated garlic on the progression of atherosclerotic plaque in the carotid and femoral arteries. After four years, the increase in plaque volume was significantly greater in women taking the placebo (+53.1%) than in women taking the garlic supplement (-4.6%), while no significant difference in plaque volume was found between garlic (+1.1%) and placebo (+5.5%) in men. In a smaller pilot study, investigators measured coronary artery calcium using electron-beam computed tomography to assess the effect of supplementation with aged garlic extract on the progression of atherosclerosis in 19 adults already taking HMG-CoA reductase inhibitors (lipid-lowering drugs also known as statins).After one year, increases in coronary artery calcium score were significantly lower in those taking aged garlic extract than in those taking a placebo. Nevertheless, although coronary calcium scores may have a predictive value regarding future cardiac events in asymptomatic subjects, it may not be a reliable marker of plaque burden in symptomatic patients. In a recent double-blind, controlled study, the extent of coronary atherosclerosis was assessed with cardiac computed tomography angiography in 72 individuals (55 at study completion) at high risk of coronary heart disease randomized to receive either 2,400 mg of aged garlic extract or placebo for 52 weeks. The result suggested a significant decrease in the extent of coronary plaques with low-attenuation area (a type of vulnerable plaques prone to rupture).with aged garlic extract compared to placebo, but no differences in total plaque volume and proportions of non-calcified plaques and dense calcium were found between treatment and placebo groups.

Hypertension

Most systematic reviews and/or meta-analyses of randomized controlled trials to date have provided mixed results regarding the potential blood pressure-lowering effect of garlic, possibly because most of these trials enrolled both normotensive and hypertensive subjects.

A systematic review and meta-analysis by Xiong et al. included seven randomized, placebo-controlled trials that exclusively enrolled individuals with high blood pressure, i.e., with systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. Five out of seven trials identified in this systematic review reported statistically significant reductions in SBP and DBP with several garlic preparations (dried garlic homogenate, garlic powder, and aged garlic extract). Another recent meta-analysis included nine randomized controlled trials in 482 hypertensive individuals who were given garlic powder (six studies), garlic homogenate (one study), aged garlic extract (two studies), or placebo for 8 to 26 weeks. Garlic preparations were found to significantly reduce SBP by a mean of 9.1 mm Hg and DBP by a mean of 3.8 mm Hg compared to placebo. The most recent meta-analysis found that garlic preparations reduced SBP by a mean 8.7 mm Hg (10 trials, 440 subjects) and DBP by 6.1 mm Hg (8 trials, 257 subjects). Such reductions in blood pressure seem comparable to those reported with currently used classes of blood pressure-lowering medications (average reduction, -9.1 mm Hg for SBP and -5.5 mm Hg for DBP). The effect of blood pressure reduction from such medications at standard dose has been estimated to lower the risk of coronary heart disease events by about one-quarter and the risk of strokeby about one-third. Nonetheless, evidence showing that garlic supplements may reduce the risk of cardiovascular morbidity and mortality is still lacking.

In a recent 12-week, randomized, placebo-controlled trial in untreated hypertensive subjects, daily intake of aged garlic extract (1.2 g of which contained 1.2 mg of S-allyl-L-cysteine [SAC]) was shown to significantly lower SBP by 11 mm Hg and DBP by 6 mm Hg on average in 50%-60% of participants, but reductions in blood pressure were not reported in 40%-50% of participants compared to placebo. Whether interindividual differences in nutritional status and genetic polymorphisms can explain differences in blood pressure response to garlic treatment need to be explored in future studies.

Overall, short-term garlic supplementation appears to effectively reduce blood pressure with minimal side effects in hypertensive patients.

Summary

The results of randomized controlled trials have suggested that garlic supplementation modestly improves serumlipid profiles in individuals with elevated serum cholesterol and reduces blood pressure in hypertensive subjects. It is not yet clear whether garlic supplementation can reduce atherosclerosis or prevent cardiovascular events, such as myocardial infarction or stroke.