Aged garlic (kyolic)

Kyolic aged garlic extract improves aerobic fitness in middle‑aged recreational endurance athletes: A randomized double‑blind placebo‑controlled 3 month trial

Type of study: rct

Number of citations: 0

Year: 2025

Authors: K. Ried, Yeah Paye, David Beale, Avni Sali

Journal: Experimental and Therapeutic Medicine

Journal ranking: brak

Key takeaways: Kyolic aged garlic extract significantly improves aerobic fitness, lactate threshold, recovery, and cardiovascular biomarkers in middle-aged endurance athletes within 12 weeks.

Abstract: Arterial stiffness is a cardiovascular risk factor that increases with age. Kyolic aged garlic extract has been shown to reduce arterial stiffness, while normalizing blood pressure, cholesterol and blood thickness. The present study hypothesized that increased flexibility of arteries could lead to slower blood flow and increased oxygen uptake and overall aerobic fitness. The present 12 week trial aimed to assess the effect of Kyolic aged garlic extract (AGE) on arterial stiffness, aerobic fitness, lactate threshold, recovery from muscle soreness and cardiovascular proteomic biomarkers in middle-aged (40-65 years) endurance athletes with elevated arterial stiffness. A total of 75 middle-aged recreational endurance athletes completed the trial, after being randomly allocated for 12 weeks to either the placebo or Kyolic aged garlic extract groups: low-dose cohort 1 (n=37), 2 capsules/day containing 1.2 g AGE powder and 1.2 mg S-allylcysteine (SAC); and the high-dose cohort 2 (n=38), 4 capsules/day of 2.4 g AGE powder and 2.4 mg SAC. Arterial stiffness was assessed through pulse wave velocity measurements and aerobic fitness was measured by volume-maximal-oxygen-consumption (VO2max) and lactate thresholds during high-intensity exercise using a cycle-ergometer-test-station, as well as measuring the levels of muscle fatigue and recovery time at 12 weeks compared with the baseline results. Urinary proteomic analysis was performed in a subgroup of participants and measured the levels of certain relevant proteins used as biomarkers for risk of cardiovascular events, at 12 weeks compared with baseline results. The Kyolic aged garlic extract group significantly improved their aerobic fitness, as was evidenced by increased VO2max, increased aerobic power, higher lactate threshold-to-oxygen uptake, higher lactate threshold-to-power output and quicker recovery times compared with the placebo group. Pulse wave velocity, a measure for arterial flexibility, was improved in the Kyolic aged garlic extract group compared with the placebo. The proteomics analysis demonstrated that a subset of polypeptides associated with cardiovascular risk, such as heart attacks and stroke, decreased in the Kyolic aged garlic extract group at 12 weeks compared with the baseline, which was contrary to the effects observed in the placebo group. Therefore, the results of the present study suggested that Kyolic aged garlic extract significantly improved aerobic fitness, lactate threshold, recovery and cardiovascular proteomic biomarkers in middle-aged endurance athletes within 12 weeks. The present clinical trial was registered on 11/03/2020 at the Australian New Zealand Clinical Trial Registry (trial registration no. ACTRN12620000340932).

The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial

Type of study: rct

Number of citations: 75

Year: 2018

Authors: K. Ried, N. Travica, A. Sali

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: Kyolic-aged-garlic-extract effectively reduces blood pressure in hypertensive patients and may improve arterial stiffness, inflammation, and gut microbial profile, offering multiple cardiovascular health benefits.

Abstract: Background: Previous research suggests Kyolic-aged-garlic-extract to be effective in reducing blood pressure in a large proportion of hypertensive patients similar to first-line standard antihypertensive medication. High blood pressure has been linked to gut dysbiosis, with a significant decrease in microbial richness and diversity in hypertensives compared to normotensives. Furthermore, gut dysbiosis has been associated with increased inflammatory status and risk of cardiovascular events. Objective: To assess the effect of Kyolic aged GARlic extract on Gut microbiota, Inflammation, and Cardiovascular markers, including blood pressure, pulse wave velocity and arterial stiffness. Methods: A total of 49 participants with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12-weeks, investigating the effect of daily intake of aged-garlic-extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, pulse wave velocity and arterial stiffness, inflammatory markers, and gut microbiota. Results: Mean blood pressure was significantly reduced by 10 ± 3.6 mmHg systolic and 5.4 ± 2.3 mmHg diastolic compared to placebo. Vitamin B12 status played a role in responsiveness to garlic on blood pressure in 17% of patients. Garlic significantly lowered central blood pressure, pulse pressure and arterial stiffness (p < 0.05). Trends observed in inflammatory markers TNF-α and IL-6 need to be confirmed in larger trials. Furthermore, aged-garlic-extract improved gut microbiota, evident by higher microbial richness and diversity with a marked increase in Lactobacillus and Clostridia species after 3 months of supplementation. Conclusions: Kyolic-aged-garlic-extract is effective in reducing blood pressure in patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and gut microbial profile. Aged-garlic-extract is highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment, with multiple benefits for cardiovascular health. Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN12616000185460 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370096)

Anti-Inflammatory and Vasorelaxant Effects Induced by an Aqueous Aged Black Garlic Extract Supplemented with Vitamins D, C, and B12 on Cardiovascular System

Type of study: non-rct in vitro

Number of citations: 13

Year: 2023

Authors: L. Recinella, M. Libero, V. Citi, A. Chiavaroli, A. Martelli, Roberta Foligni, C. Mannozzi, Alessandra Acquaviva, S. D. Di Simone, V. Calderone, G. Orlando, C. Ferrante, S. Veschi, Anna Piro, L. Menghini, L. Brunetti, S. Leone

Journal: Foods

Journal ranking: Q1

Key takeaways: Aged black garlic extract, alone or combined with multivitamins, exhibits protective effects on mouse hearts and increases intracellular hydrogen sulfide formation, suggesting potential use in cardiovascular disease.

Abstract: Multiple studies demonstrated biological activities of aged black garlic, including anti-inflammatory, antioxidant, and cardioprotective effects. We aimed to investigate the protective effects of an aged black garlic water extract (ABGE) alone or in association with multivitamins consisting of combined Vitamins D, C, and B12, on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS). Moreover, we studied the hydrogen sulphide (H2S) releasing properties and the membrane hyperpolarization effect of the Formulation composed by ABGE and multivitamins, using Human Aortic Smooth Muscle Cells (HASMCs). ABGE, vitamins D and C, and the Formulation suppressed LPS-induced gene expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor-kB (NF-kB), and inducible nitric oxide synthase (iNOS) on mouse heart specimens. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin. The Formulation also increased fluorescence values compared to the vehicle, and it caused a significant membrane hyperpolarization of HASMCs compared to ABGE. To conclude, our present findings showed that ABGE, alone and in association with multivitamins, exhibited protective effects on mouse heart. Moreover, the Formulation increased intracellular H2S formation, further suggesting its potential use on cardiovascular disease.

The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial

Type of study: rct

Number of citations: 100

Year: 2016

Authors: K. Ried, N. Travica, A. Sali

Journal: Integrated Blood Pressure Control

Journal ranking: Q2

Key takeaways: Aged garlic extract effectively reduces blood pressure and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in uncontrolled hypertension patients.

Abstract: Background Hypertension affects 30% of adults worldwide. Garlic supplements have shown promise in the treatment of uncontrolled hypertension, and the mechanism of action is biologically plausible. Our trial is the first to assess the effect of aged garlic extract on central blood pressure and arterial stiffness, regarded as important risk factors for cardiovascular morbidity. Subjects and methods A total of 88 general practice patients and community members with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12 weeks investigating the effect of daily intake of aged garlic extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, and secondary outcome measures of central-hemodynamics and other cardiovascular markers, including cholesterol, homocysteine, platelet function, and inflammatory markers. Results Mean blood pressure was significantly reduced by 5.0±2.1 mmHg (P=0.016) systolic, and in responders by 11.5±1.9 mmHg systolic and 6.3±1.1 mmHg diastolic compared to placebo (P<0.001). Central hemodynamic-measures tended to improve in the garlic group more than in the placebo group, including central blood pressure, central pulse pressure, mean arterial pressure, augmentation pressure, pulse-wave velocity, and arterial stiffness. While changes in other cardiovascular markers did not reach significance due to small numbers in subgroups with elevated levels, trends in beneficial effects of garlic on the inflammatory markers TNFα, total cholesterol, low-density lipid cholesterol, and apolipoproteins were observed. Aged garlic extract was highly tolerable and acceptable, and did not increase the risk of bleeding in patients on blood-thinning medication. Conclusion Our trial suggests that aged garlic extract is effective in reducing peripheral and central blood pressure in a large proportion of patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in patients with elevated levels. Aged garlic extract was highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment.

Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies.

Type of study: rct

Number of citations: 433

Year: 2001

Authors: Y. Yeh, Lijuan Liu

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Garlic extracts and organosulfur compounds effectively lower cholesterol levels in humans and animals, with multiple compounds playing a role in this effect.

Abstract: The medicinal use of garlic dates back thousands of years, but there was little scientific support of its therapeutic and pharmacologic properties until recently. In the past decade, the cancer-protective effects of garlic have been well established by epidemiologic studies and animal experiments. However, the cardiovascular-protective properties of garlic are less well understood. In particular, despite the reported hypocholesterolemic effect of garlic, the mechanism of the effect is unclear. In a recent randomized, double-blind, placebo-controlled intervention study, we showed that aged garlic extract (AGE) supplementation was effective in lowering plasma concentration of total cholesterol by 7% and LDL cholesterol by 10% in hypercholesterolemic men compared with subjects consuming a placebo. Supplementation of AGE in animal diets similarly reduced plasma concentrations of total cholesterol and triacylglycerol by 15 and 30%, respectively. In subsequent experiments using cultured rat hepatocytes, we found 44--87% inhibition of cholesterol synthesis by the water-extractable fraction (WEF), methanol-extractable fraction (MEF) and petroleum ether-extractable fraction (PEF) of fresh garlic, and Kyolic (liquid form of AGE). These observations suggested that hydrophilic and hydrophobic compounds of garlic are inhibitory to cholesterol synthesis. Because S-allylcysteine (SAC) alone was less potent than Kyolic, which contains SAC and other sulfur compounds, a maximal inhibition appears to require a concerted action of multiple compounds of garlic. In a series of experiments, we further characterized the inhibitory potency of individual water-soluble and lipid-soluble compounds of garlic. Among water-soluble compounds, SAC, S-ethylcysteine (SEC), and S-propylcysteine (SPC) inhibited cholesterol synthesis by 40--60% compared with 20--35% by gamma-glutamyl-S-allylcysteine (GSAC), gamma-glutamyl-S-methylcysteine (GSMC) and gamma-glutamyl-S-propylcysteine (GSPC). Lipid-soluble sulfur compounds (i.e., diallyl sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl trisulfide) at low concentrations (0.05--0.5 mol/L) slightly (10--15%) inhibited cholesterol synthesis but became highly cytotoxic at high concentrations (1.0--4.0 mol/L). All water-soluble compounds, except S-allylmercaptocysteine, were not cytotoxic, judging from the release of cellular lactate dehydrogenase into the culture medium. Taken together, the results of our studies indicate that the cholesterol-lowering effects of garlic extract, such as AGE, stem in part from inhibition of hepatic cholesterol synthesis by water-soluble sulfur compounds, especially SAC.

Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study

Type of study: rct

Number of citations: 19

Year: 2022

Authors: R. Valls, J. Companys, L. Calderón-Pérez, P. Salamanca, L. Pla-Pagà, B. Sandoval-Ramírez, A. Bueno, J. Puzo, A. Crescenti, J. M. D. Bas, A. Caimari, Aurora Salamanca, Alberto E. Espinel, A. Pedret, L. Arola, R. Solà

Journal: Nutrients

Journal ranking: Q1

Key takeaways: An optimized aged black garlic extract with 1.25 mg of S-allyl-L-cysteine can reduce diastolic blood pressure in men with moderate hypercholesterolemia, potentially contributing to optimal blood pressure.

Abstract: The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP.

Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis

Type of study: meta-analysis

Number of citations: 61

Year: 2019

Authors: K. Ried

Journal: Experimental and Therapeutic Medicine

Journal ranking: brak

Key takeaways: Garlic supplements effectively lower blood pressure in hypertensive patients, improve arterial stiffness, and enhance gut microbiota, offering multiple cardiovascular health benefits.

Abstract: Garlic supplements have shown effectiveness in reducing blood pressure in hypertensive patients, similarly to first-line standard anti-hypertensive medications. Kyolic garlic has also shown promise in improving cardiovascular health by reducing arterial stiffness, elevated cholesterol levels and blood ‘stickiness’. In addition, the prebiotic properties in garlic increase gut microbial richness and diversity. This article systematically reviews previously published trials investigating the effects of garlic on blood pressure, and provides an updated meta-analysis of hypertensive participants. In addition, we summarise the findings of recent clinical trials investigating the effects of Kyolic aged garlic extract on arterial stiffness, and gut microbiota in hypertensive subjects. We searched online electronic databases, including PubMed and Google Scholar for randomised controlled trials (RCTs) published between 1955 and December, 2018 examining the effects of garlic on high blood pressure. The meta-analysis of 12 trials and 553 hypertensive participants confirmed that garlic supplements lower systolic blood pressure (SBP) by an average of 8.3±1.9 mmHg and diastolic blood pressure (DBP, n=8 trials, n=374 subjects) by 5.5±1.9 mmHg, similarly to standard anti-hypertensive medications. This reduction in blood pressure was associated with a 16–40% reduction in the risk of suffering from cardiovascular events. Additionally, this review summarises new evidence for the vitamin B12 status playing an important role in the responsiveness of blood pressure to garlic. Furthermore, Kyolic aged garlic extract significantly lowered central blood pressure, pulse pressure, pulse wave velocity and arterial stiffness, and improved the gut microbiota, evidenced by higher microbial richness and diversity, with a marked increase in the numbers of Lactobacillus and Clostridia species found following 3 months of supplementation. Thus, Kyolic aged garlic extract is considered to be highly tolerable with a high safety profile either as a stand-alone or adjunctive anti-hypertensive treatment, with multiple benefits for cardiovascular health.

Molecular basis by which garlic suppresses atherosclerosis.

Type of study: non-rct experimental

Number of citations: 112

Year: 2001

Authors: Julie H. Campbell, J. Efendy, Nicole J. Smith, Gordon R. Campbell

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Kyolic, an aged garlic extract, protects against atherosclerosis by inhibiting smooth muscle phenotypic change and proliferation, and possibly by reducing lipid accumulation in the artery wall.

Abstract: The aim of this study was to determine the mechanism by which the aged garlic extract "Kyolic" has a protective effect against atherosclerosis. Plasma cholesterol of rabbits fed a 1% cholesterol-enriched diet for 6 wk was not reduced by supplementation with 800 microL Kyolic/(kg body. d). In spite of this, Kyolic reduced by 64% (P < 0.05) the surface area of the thoracic aorta covered by fatty streaks and significantly reduced aortic arch cholesterol. Kyolic also significantly inhibited by approximately 50% the development of thickened, lipid-filled lesions in preformed neointimas produced by Fogarty 2F balloon catheter injury of the right carotid artery in cholesterol-fed rabbits. In vitro studies found that Kyolic completely prevented vascular smooth muscle phenotypic change from the contractile, high volume fraction of filament (V(v)myo) state, and inhibited proliferation of smooth muscle cells in the synthetic state with a 50% effective dose (ED(50)) of 0.2%. Kyolic also slightly inhibited the accumulation of lipid in cultured macrophages but not smooth muscle, and had no effect on the expression of adhesion molecules on the surface of the endothelium or the adherence of leukocytes. It is concluded that Kyolic exerts antiatherogenic effects through inhibition of smooth muscle phenotypic change and proliferation, and by another (unclarified) effect on lipid accumulation in the artery wall.

Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans.

Type of study: non-rct experimental

Number of citations: 199

Year: 2000

Authors: K. Rahman, D. Billington

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) may protect against cardiovascular disease by inhibiting platelet aggregation in normolipidemic subjects without affecting lipid profiles or thromboxane B(2) concentrations.

Abstract: Garlic has been widely reported to protect against cardiovascular disease by reducing serum cholesterol concentrations and blood pressure and by inhibiting platelet aggregation. However, most of these studies have been performed in hypercholesterolemic subjects or in animal models. We performed a 13-wk study in normolipidemic subjects who ingested 5 mL of aged garlic extract (AGE, Kyolic) per day. Blood was drawn from these subjects at the beginning and end of the study. Aggregation of platelet-rich plasma was induced by ADP; full lipid profiles and liver function tests were determined on serum, and plasma concentrations of eicosanoids were also measured. Dietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 micromol/L. The K:(M) for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected. No significant changes in plasma thromboxane B(2) and 6-ketoprostaglandin F(1alpha) concentrations or serum lipid profiles were observed. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation.

Antioxidant health effects of aged garlic extract.

Type of study:

Number of citations: 696

Year: 2001

Authors: Carmia Borek

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) has antioxidant properties, reducing the risk of cardiovascular disease, stroke, cancer, and aging, and may have antiaging effects.

Abstract: Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease.

The effect of aged garlic extract on the atherosclerotic process – a randomized double-blind placebo-controlled trial

Type of study: rct

Number of citations: 31

Year: 2020

Authors: Martiné Wlosinska, A. Nilsson, J. Hlebowicz, A. Hauggaard, Maria Kjellin, M. Fakhro, S. Lindstedt

Journal: BMC Complementary Medicine and Therapies

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) inhibits coronary atherosclerosis progression, lowers IL-6, glucose levels, and blood pressure in patients at increased risk of cardiovascular events, with an algorithm accurately predicting reduced CAC progression with 80% precision.

Abstract: Abstract Background One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP–DM). Method This was a single-center parallel randomized controlled study in a university hospital in Europe. Patients were randomized, in a double-blind manner, through a computer-generated randomization chart. Patients with a Framingham risk score ≥ 10 after CT scan ( n = 104) were randomized to an intake of placebo or AGE (2400 mg daily) for 1 year. Main outcome measures were changes in CAC score and secondary outcome measures changes in blood pressure, fasting blood glucose, blood lipids and inflammatory biomarkers. Result 104 patients were randomized and 46 in the active group and 47 in the placebo group were analyzed. There was a significant ( p &lt; 0.05) change in CAC progression (OR: 2.95 [1.05–8.27]), blood glucose (OR: 3.1 [1.09–8.85]) and IL-6 (OR 2.56 [1.00–6.53]) in favor of the active group. There was also a significant ( p = 0.027) decrease in systolic blood pressure in the AGE group, from a mean of 148 (SD: 19) mmHg at 0 months, to 140 (SD: 15) mmHg after 12 months. The AGE Algorithm, at a selected probability cut-off value of 0.5, the accuracy score for CAC progression was 80%, precision score of 79% and recall score 83%. The score for blood pressure was 74% (accuracy, precision and recall). There were no side-effects in either group. Conclusions AGE inhibits CAC progression, lowers IL–6, glucose levels and blood pressure in patients at increased risk of cardiovascular events in a European cohort. An algorithm was made and was used to predict with 80% precision which patient will have a significantly reduced CAC progression using AGE. The algorithm could also predict with a 74% precision which patient will have a significant blood pressure lowering effect pressure using AGE. Trial registration Clinical trials NCT03860350 , retrospectively registered (1/32019).

Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial.

Type of study: rct

Number of citations: 145

Year: 2009

Authors: M. Budoff, N. Ahmadi, K. Gul, Sandy Liu, F. Flores, J. Tiano, J. Takasu, E. Miller, S. Tsimikas

Journal: Preventive medicine

Journal ranking: Q1

Key takeaways: Aged garlic extract with B vitamins, folic acid, and L-arginine improves oxidative biomarkers, vascular function, and reduces atherosclerosis progression compared to placebo.

The effect of the aged garlic extract, 'Kyolic', on the development of experimental atherosclerosis.

Type of study: rct

Number of citations: 111

Year: 1997

Authors: J. Efendy, Danielle L. Simmons, G. Campbell, Julie H. Campbell

Journal: Atherosclerosis

Journal ranking: Q1

Key takeaways: Kyolic treatment reduces fatty streak development, vessel wall cholesterol accumulation, and the development of fibro fatty plaques in cholesterol-fed rabbits, providing protection against atherosclerosis onset.

Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta‐analysis

Type of study: meta-analysis

Number of citations: 14

Year: 2023

Authors: Sai Kumar Gadidala, Ebin Johny, Christy Thomas, Mounika Nadella, K. Undela, Ramu Adela

Journal: Phytotherapy Research

Journal ranking: Q1

Key takeaways: Garlic intake significantly reduces cardiovascular disease risk factors and may be a safe natural medicine to reduce inflammation in coronary artery disease patients.

Abstract: Several preclinical studies have focused on the beneficial effects of garlic on cardiovascular diseases, but the results were inconsistent. We performed a systematic review and meta‐analysis on the effect of garlic powder tablets and aged garlic extract (AGE) in CAD patients, mainly focusing on blood pressure, coronary artery calcification, lipid profile, and inflammatory markers. We searched PubMed, Cochrane CENTRAL, and Google Scholar to identify randomized controlled trials which examined garlic's effect on CAD patients. The standardized mean difference with 95% CI was calculated using fixed‐effect or random‐effect models. Garlic has shown statistically significant changes of HDL (SMD = 0.18; 95% CI = −0.00 to 0.37; p = .05); LDL (SMD = −0.27; 95% CI = −0.46 to −0.08; p = .004), apolipoprotein‐A (SMD = 0.68; 95% CI = 0.24 1.13; p = .002), C‐RP (SMD = −0.59; 95% CI = −0.92 to −0.25; p = .0007), IL‐6 (SMD = −1.08; 95% CI = −2.17 to 0.01; p = .05), homocysteine (SMD = −0.66; 95% CI = −1.04 to −0.28; p = .0007) and CAC score (SMD = −1.61; 95% CI = −2.66 to −0.57; p = .003). In the case of subgroup analysis, the overall effect was significantly effective in reducing TC, LDL levels and improving HDL levels in CV risk patients. Our study findings provide consistent evidence that intake of garlic reduces CVD risk factors. However, garlic could be considered a safe natural medicine to debilitate inflammation in CAD patients.

Garlic reduces dementia and heart-disease risk.

Type of study:

Number of citations: 173

Year: 2006

Authors: C. Borek

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Garlic, especially aged garlic extract, may help reduce the risk of dementia and heart disease by reducing oxidative damage, reducing cholesterol synthesis, and improving cognitive decline.

Abstract: Risk factors for cardiovascular disease, including high cholesterol, high homocysteine, hypertension and inflammation, increase the risk of dementia, including its most common form, Alzheimer's disease (AD). High cholesterol is also associated with elevated beta-amyloid (Abeta), the hallmark of AD. Oxidative damage is a major factor in cardiovascular disease and dementia, diseases whose risk increases with age. Garlic, extracted and aged to form antioxidant-rich aged garlic extract (AGE or Kyolic), may help reduce the risk of these diseases. AGE scavenges oxidants, increases superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibits lipid peroxidation and inflammatory prostaglandins. AGE reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase and is additive with statins in its action. Inhibition of cholesterol, LDL oxidation, and platelet aggregation by AGE, inhibits arterial plaque formation; AGE decreases homocysteine, lowers blood pressure, and increases microcirculation, which is important in diabetes, where microvascular changes increase heart disease and dementia risks. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemia- or reperfusion-related neuronal death and improving learning and memory retention. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE in helping prevent cardiovascular and cerebrovascular diseases and lowering the risk of dementia and AD.

Effect of aged garlic extract on blood pressure and other cardiovascular markers in hypertensive patients and its relationship with dietary intake

Type of study: rct

Number of citations: 5

Year: 2024

Authors: Tiago Marcel Santos Vila-Nova, Kiriaque B. F. Barbosa, Analícia R. S. Freire, Dennys E. C. Cintra, Danielle G. Silva, Tânia M. de Andrade Rodrigues, Brenda M. Costa, Laryssa. G. S. Aragão

Journal: Journal of Functional Foods

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) significantly reduces systolic blood pressure and improves stool consistency, glycemic parameters, and low-density lipoprotein in hypertensive patients, with a correlation to vitamin B9 and B12 intake.

Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions.

Type of study: rct

Number of citations: 195

Year: 2001

Authors: M. Steiner, W. Li

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract selectively inhibits platelet aggregation and adhesion, potentially reducing cardiovascular risk factors like myocardial infarction and ischemic stroke.

Abstract: Aged garlic extract (AGE) has been shown previously to have moderate cholesterol-lowering and blood pressure-reducing effects. We have now investigated whether platelet function, a potential risk factor for cardiovascular disease, can be inhibited by AGE administration. In a randomized, double-blind study of normal healthy individuals (n = 34), both men and women, the effect of AGE was evaluated in doses between 2.4 and 7.2 g/d vs. equal amounts of placebo. Platelet aggregation and adhesion were measured at 2-wk intervals throughout the study. Threshold concentrations for epinephrine and collagen increased moderately during AGE administration compared with the placebo and baseline periods. Only at the highest supplementation level did AGE show a slight increase in the threshold level of ADP-induced aggregation. Platelet adhesion to collagen, fibrinogen and von Willebrand factor was investigated by perfusing whole blood through a laminar flow chamber under controlled flow conditions. Adherence of platelets was inhibited by AGE in a dose-dependent manner when collagen was the adhesive surface perfused at low shear rates ( approximately 30 s(-1)). At high shear rates (1200 s(-1)), AGE also inhibited platelet adhesion to collagen but only at higher intake levels. Adhesion to von Willebrand factor was reduced only at 7.2 g/d AGE, but adherence to fibrinogen was potently inhibited at all levels of supplementation. Thus, AGE exerts selective inhibition on platelet aggregation and adhesion, platelet functions that may be important for the development of cardiovascular events such as myocardial infarction and ischemic stroke. We briefly review the effect of garlic preparations in general on cardiovascular risk factors and point out differences between AGE and other garlic preparations that we feel are important to explain the efficacy of AGE.

Garlic: A systematic review of the effects on cardiovascular diseases

Type of study: systematic review

Number of citations: 34

Year: 2022

Authors: Vitor Massami Imaizumi, LUCAS FORNARI LAURINDO, Barbara Manzan, É. Guiguer, M. Oshiiwa, A. M. Otoboni, A. Araújo, R. J. Tofano, S. Barbalho

Journal: Critical Reviews in Food Science and Nutrition

Journal ranking: Q1

Key takeaways: Garlic can reduce blood pressure, waist circumference, and inflammatory markers, while increasing HDL-c levels and improving cardiovascular parameters, making it a potential preventive and treatment option for cardiovascular diseases.

Abstract: Abstract Allium sativum (garlic) certainly is one of the oldest horticultural crops in the world and presents bioactive compounds that are related to the garlic’s effects on human health. Several authors have shown beneficial effects on diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases (CVD), which are among the most relevant causes of mortality in the world. The aim of this systematic review was to evaluate the effects of garlic in the risk factors of CVD and evaluate its economic importance. MEDLINE–PubMed, COCHRANE, EMBASE, and Google Scholar databases were searched. The included studies showed that the use of garlic can reduce blood pressure, waist circumference, body mass index, LDL-c, non-HDL-c, total cholesterol, triglycerides, and inflammatory markers. It also can increase the levels of HDL-c and can improve cardiovascular parameters such as coronary artery calcium, microcirculation, epicardial and periaortic adipose tissue, post occlusive reactive hyperemia, low attenuation plaque, carotid intima-media thickness; and carotid intima-media thickness. Due to these reasons, garlic can be considered in the prevention and treatment of CVD risk factors.

Effect of garlic on cardiovascular disorders: a review

Type of study: literature review

Number of citations: 691

Year: 2002

Authors: S. Banerjee, S. Maulik

Journal: Nutrition Journal

Journal ranking: Q1

Key takeaways: Garlic has shown positive effects on various cardiovascular conditions, but more recent studies have cast doubt on its cholesterol-lowering effect.

Abstract: Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic.

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

Type of study: rct

Number of citations: 63

Year: 2013

Authors: D. Gómez-Arbeláez, V. Lahera, P. Oubiña, M. Valero-Muñoz, N. de Las Heras, Yudy Rodríguez, R. García, P. Camacho, P. López-Jaramillo

Journal: Mediators of Inflammation

Journal ranking: Q2

Key takeaways: Aged garlic extract (AGE) for 12 weeks increased adiponectin levels in patients with metabolic syndrome, suggesting it could be a useful nonpharmacological therapeutic intervention to prevent cardiovascular complications.

Abstract: Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS.

Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

Type of study:

Number of citations: 34

Year: 2016

Authors: I. Pérez-Torres, J. C. Torres-Narváez, J. Pedraza-Chaverri, M. Rubio-Ruíz, E. Díaz-Diaz, L. Del Valle-Mondragón, R. Martínez-Memije, Elvira Varela López, V. Guarner-Lans

Journal: Molecules

Journal ranking: Q1

Key takeaways: Aged garlic extract reduces metabolic syndrome-induced cardiovascular risk through its anti-oxidant properties.

Abstract: The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats (30% sucrose in drinking water from weaning) plus saline solution (MS + SS), control rats receiving AGE (C + AGE 125 mg/Kg/12 h) and MS rats with AGE (MS + AGE) were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01). Cholesterol was decreased by AGE (p = 0.05). Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05). Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001). Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation) and AGE improved it (p = 0.001). Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001). Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01). In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.

An umbrella review of garlic intake and risk of cardiovascular disease.

Type of study: meta-analysis

Number of citations: 55

Year: 2016

Authors: L. Schwingshackl, B. Missbach, G. Hoffmann

Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology

Journal ranking: Q1

Key takeaways: Garlic preparations and garlic intake may have positive effects on cardiovascular disease indicators and biomarkers without causing serious side effects.

Effects of aged garlic extract on arterial elasticity in a placebo-controlled clinical trial using EndoPAT™ technology

Type of study: rct

Number of citations: 6

Year: 2019

Authors: J. Gruenwald, U. Bongartz, G. Bothe, R. Uebelhack

Journal: Experimental and Therapeutic Medicine

Journal ranking: brak

Key takeaways: Aged garlic extract (AGE) has a positive effect on blood pressure and arterial elasticity, potentially reducing cardiovascular disease risk factors and improving arterial elasticity.

Abstract: Cardiovascular diseases are the main cause of death in the industrialized world, with the main risk factors being elevated blood pressure and blood lipid levels, leading to arterial stiffness and arteriosclerosis. In this study, we examined the effect of aged garlic extract (AGE) on arterial elasticity, using the EndoPAT™ technology in subjects with slightly elevated blood pressure. This randomized double-blind, placebo-controlled clinical trial examined 57 subjects over a period of 12 weeks, with EndoPAT™ measurements taken at 0 and 12 weeks; in addition, changes in blood pressure were analyzed. The positive effect of AGE on blood pressure values previously reported was confirmed. The results revealed a significant decrease in blood pressure in the AGE group, and in particular diastolic blood pressure. Using the EndoPAT™ technology, the augmentation index (AI) was analyzed, which measures arterial stiffness calculated via pulse waveform analysis of the PAT signal; lower AI values reflect better arterial elasticity. The AGE group exhibited a significant improvement in arterial elasticity, measured as AI75, by 21.6%. The result of this well-controlled clinical trial confirmed the positive effect of AGE on blood pressure. To the best of our knowledge, for the first time, the effect of AGE on arterial elasticity could be proven using the EndoPAT™ methodology. These results not only demonstrate the positive effects of AGE on the relevant risk factors of cardiovascular diseases, but also the direct effect on arterial elasticity. These data clearly indicate that AGE may exert several positive direct effects on the development and progression of cardiovascular diseases.

Homocysteine-lowering action is another potential cardiovascular protective factor of aged garlic extract.

Type of study: non-rct experimental

Number of citations: 43

Year: 2006

Authors: Y. Yeh, S. Yeh

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract has a hypohomocysteinemic action, potentially offering another cardiovascular protective factor in addition to its cholesterol-lowering, blood pressure-lowering, and antioxidant properties.

Abstract: We investigated hypohomocysteinemic action as a cardiovascular protective property of aged garlic extract (AGE). Hyperhomocysteinemia was induced in rats by feeding folate-depleted diets. Plasma folate concentrations of 5, 24, and 202 nmol/L were detected in rats fed a folate-deficient L-amino acid diet containing succinyl sulfathiazole, an AIN-93G folate-deficient diet, and an AIN-93G folate-sufficient diet, respectively. Plasma concentrations of total homocysteine were elevated to the highest level (32 micromol/L) by severe folate deficiency and to a moderate level (9 micromol/L) by mild folate deficiency, compared with the lowest level of (5 micromol/L), noted for the folate-sufficient group. The addition of AGE to the severely folate-deficient diet decreased plasma total homocysteine concentration by 30%. Hyperhomocysteinemia caused by mild folate deficiency remained unaltered by AGE supplementation. The reduction in total homocysteine of the severely folate-deficient rats was accompanied by a proportional decrease in protein-bound and free homocysteine, resulting in an unchanged protein-bound:free homocysteine ratio. AGE added to the diet did not alter plasma concentrations of other aminothiol compounds: cysteine, glutathione, and cysteinylglycine. These data, together with increased S-adenosylmethionine and decreased S-adenosylhomocysteine concentrations in the liver, suggest that the hypohomocysteinemic effect of AGE most likely stems from impaired remethylation of homocysteine to methionine and enhanced transsulfuration of homocysteine to cystathionine. More importantly, in addition to its cholesterol-lowering potential, blood pressure-lowering effect, and antioxidant property, a hypohomocysteinemic action may be another important cardiovascular protective factor of AGE.

Garlic and Heart Disease.

Type of study: systematic review

Number of citations: 91

Year: 2016

Authors: R. Varshney, M. Budoff

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Garlic supplementation has the potential for cardiovascular protection by reducing risk factors like hypertension and total cholesterol, and improving atherosclerosis surrogate markers.

Abstract: BACKGROUND Thousands of studies have been published based on animal and human studies evaluating garlic's effects and safety. OBJECTIVE We reviewed the available literature investigating the effects of garlic supplements on hypertension, hypercholesterolemia, C-reactive protein (CRP), pulse wave velocity (PWV), and coronary artery calcium (CAC), as well as available data on side effects. METHODS We searched PubMed for all human studies using medical subject heading words through 30 May 2013 and assessed relevant review articles and original studies. Only double-blind, randomized, controlled trials and meta-analyses of double-blind, randomized, controlled trials were included. The review of articles and data extraction were performed by 2 independent authors, with any disagreements resolved by consensus. RESULTS Garlic supplementation reduced blood pressure by 7-16 mm Hg (systolic) and 5-9 mm Hg (diastolic) (4 meta-analyses and 2 original studies). It reduced total cholesterol by 7.4-29.8 mg/dL (8 meta-analyses). The most consistent benefits were shown in studies that used aged garlic extract (AGE). A few small studies that used AGE also showed favorable effects on CAC, CRP, and PWV. Although garlic is generally safe, rare adverse reactions have been documented with limited causality established. CONCLUSION We conclude that garlic supplementation has the potential for cardiovascular protection based on risk factor reduction (hypertension and total cholesterol) and surrogate markers (CRP, PWV, and CAC) of atherosclerosis. Larger studies are warranted to evaluate these effects further.

Benefits of aged garlic extract in modulating toxicity biomarkers against p-dimethylaminoazobenzene and phenobarbital induced liver damage in Rattus norvegicus

Type of study: non-rct experimental

Number of citations: 14

Year: 2018

Authors: S. Pathak, R. Catanzaro, Dharani Vasan, F. Marotta, Y. Chabria, Ganesan Jothimani, R. Verma, R. Murugesan, A. Khuda-Bukhsh, A. Banerjee

Journal: Drug and Chemical Toxicology

Journal ranking: Q2

Key takeaways: Aged garlic extract-Kyolic effectively protects against liver damage and oxidative stress in rats, indicating its potential use in treating liver diseases like hepatocarcinoma.

Abstract: Abstract Garlic (Allium sativum L.), a popular spice, has been used for decades in treating several medical conditions. Although Allicin, an active ingredient of garlic has been extensively studied on carcinogen-induced hepatotoxicity and oxidative stress in rats (Rattus norvegicus), no systematic study on the beneficial effects of generic aged garlic and specific aged garlic extract-Kyolic has been done. The present study involves rats fed chronically with two liver carcinogens, p-dimethylaminoazobenzene and phenobarbital, to produce hepatotoxicity. The aged garlic extract was characterized by UV-spectra, FTIR, HPLC and GC-MS. Biochemical and pathophysiological tests were performed by keeping suitable controls at four fixation intervals, namely, 30, 60, 90, and 120 days, utilizing several widely accepted toxicity biomarkers. Compared to the controls, remarkable elevation in the activities of lactate dehydrogenase, gamma glutamyl transferase and decline in catalase and glucose-6-phosphate dehydrogenase were observed in the carcinogen fed rats. Daily administration of aged garlic extract, could favorably modulate the elevated levels of various toxicity biomarkers including serum triglyceride, creatinine, urea, bilirubin, blood urea nitrogen except total cholesterol. It also altered the levels of blood glucose, HDL-cholesterol, albumin, AST, ALT, and hemoglobin contents in carcinogen intoxicated rats, indicating its protective potential against hepatotoxicity and oxidative stress in the experimental rats. Down-regulation of Bcl-2 and p53 proteins caused cell cycle arrest and apoptosis in garlic fed group. Kyolic exhibited additional benefits by arresting cell viability of cancer cells. This study would thus validate the use of aged garlic extract in the treatment of diseases causing liver toxicity including hepatocarcinoma.

Aged garlic extract maintains cardiovascular homeostasis in mice and rats.

Type of study: non-rct experimental

Number of citations: 37

Year: 2006

Authors: N. Morihara, I. Sumioka, N. Ide, T. Moriguchi, N. Uda, E. Kyo

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract increases nitric oxide production and protects against peroxynitrite-induced membrane damage, potentially aiding in preventing cardiovascular diseases linked to oxidative stress or nitric oxide dysfunction.

Abstract: Nitric oxide (NO) plays an important role in controlling the physiological functions of the cardiovascular system. However, toxic peroxynitrite is produced by the reaction of NO with superoxide. We investigated the effect of aged garlic extract (AGE) on NO production, and on oxidative stress induced by peroxynitrite. A single dose of AGE temporarily increased NO production by 30-40% between 15 and 60 min after administration to mice. The time course of the fluctuation in NO levels in the AGE-treated group clearly differed from that in a group treated with an inducible NO synthase (iNOS) inducer. A selective constitutive NOS (cNOS) inhibitor overcame the effect of AGE. These results indicate that AGE increases NO production by activating cNOS, but not iNOS. In another experiment, the addition of AGE to a rat erythrocyte suspension reduced the rate of peroxynitrite-induced hemolysis in a concentration-dependent manner, suggesting that AGE protects erythrocytes from membrane damage induced by peroxinitrite. Because an increase in NO derived from cNOS and protection against peroxynitrite are important factors in the prevention of cardiovascular disease, our data strongly suggest that AGE could be useful in preventing cardiovascular diseases associated with oxidative stress or dysfunctions of NO production.

Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease Garlic Reduces Dementia and Heart-Disease Risk 1 , 2

Type of study:

Number of citations: 2

Year: 2006

Authors: C. Borek

Journal:

Journal ranking: brak

Key takeaways: Garlic, especially aged garlic extract (AGE), may help reduce the risk of cardiovascular diseases and dementia by reducing oxidative damage, promoting cognitive decline, and improving learning and memory retention.

Abstract: Risk factors for cardiovascular disease, including high cholesterol, high homocysteine, hypertension and inflammation, increase the risk of dementia, including its most common form, Alzheimer’s disease (AD). High cholesterol is also associated with elevated b-amyloid (Abeta), the hallmark of AD. Oxidative damage is a major factor in cardiovascular disease and dementia, diseases whose risk increases with age. Garlic, extracted and aged to form antioxidant-rich aged garlic extract (AGE or Kyolic), may help reduce the risk of these diseases. AGE scavenges oxidants, increases superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibits lipid peroxidation and inflammatory prostaglandins. AGE reduces cholesterol synthesis by inhibiting 3-hydroxy-3methylglutaryl-CoA reductase and is additive with statins in its action. Inhibition of cholesterol, LDL oxidation, and platelet aggregation by AGE, inhibits arterial plaque formation; AGE decreases homocysteine, lowers blood pressure, and increases microcirculation, which is important in diabetes, where microvascular changes increase heart disease and dementia risks. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemiaor reperfusion-related neuronal death and improving learning and memory retention. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE in helping prevent cardiovascular and cerebrovascular diseases and lowering the risk of dementia and AD. J. Nutr. 136: 810S–812S, 2006.

Aged (Black) versus Raw Garlic against Ischemia/Reperfusion-Induced Cardiac Complications

Type of study: rct

Number of citations: 29

Year: 2018

Authors: Attila Czompa, Kitti Szőke, J. Prokisch, Alexandra Gyongyosi, I. Bak, G. Balla, Á. Tósaki, István Lekli

Journal: International Journal of Molecular Sciences

Journal ranking: Q1

Key takeaways: Both raw and aged black garlic possess cardioprotective effects, with raw garlic showing greater benefits in postischemic cardiac recovery and reduced infarct size.

Abstract: Recent evidence from studies suggests that aged black garlic also has an effect on health. The major aim of the present study is to compare the effect of raw and aged black garlic on postischemic cardiac recovery. Male Sprague Dawley rats were randomly divided into three groups. Animals of the first group were fed with raw garlic, animals of the second group received aged black garlic, while the third group served as vehicle-treated controls. Upon conclusion of the treatment, isolated hearts were undertaken to ischemia/reperfusion. Heart function and infarct size were measured and the level of HO-1 and iNOS were studied. Superior postischemic cardiac function and reduced infarct size in both garlic treated groups compared to the drug-free control group, indicated cardioprotective effects. However, no significant differences between the garlic treated groups were observed. Western blot analysis revealed that raw garlic enhanced the level of HO-1 before ischemia, while in ischemic samples, we found elevated HO-1 expression in both garlic treated groups. The level of iNOS was the same before ischemia in all groups, however, a markedly reduced iNOS level in ischemic/reperfused hearts originating from control and raw garlic treated animals was observed. Samples from aged black garlic treated animals demonstrated that the level of iNOS was not significantly reduced after ischemia/reperfusion. Taken together these results indicate that not only raw but also aged black garlic possess a cardioprotective effect.

Garlic and cardiovascular disease: a critical review.

Type of study: literature review

Number of citations: 424

Year: 2006

Authors: K. Rahman, G. Lowe

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Garlic shows promise in reducing cardiovascular disease-related parameters, but more in-depth and appropriate studies are needed to confirm these findings.

Abstract: Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. Cardiovascular disease is associated with multiple factors such as raised serum total cholesterol, raised LDL and an increase in LDL oxidation, increased platelet aggregation, hypertension, and smoking. Numerous in vitro studies have confirmed the ability of garlic to reduce these parameters. Thus, garlic has been shown to inhibit enzymes involved in lipid synthesis, decrease platelet aggregation, prevent lipid peroxidation of oxidized erythrocytes and LDL, increase antioxidant status, and inhibit angiotension-converting enzyme. These findings have also been addressed in clinical trials. The studies point to the fact that garlic reduces cholesterol, inhibits platelet aggregation, reduces blood pressure, and increases antioxidant status. Since 1993, 44% of clinical trials have indicated a reduction in total cholesterol, and the most profound effect has been observed in garlic's ability to reduce the ability of platelets to aggregate. Mixed results have been obtained in the area of blood pressure and oxidative-stress reduction. The findings are limited because very few trials have addressed these issues. The negative results obtained in some clinical trials may also have resulted from usage of different garlic preparations, unknown active constituents and their bioavalability, inadequate randomization, selection of inappropriate subjects, and short duration of trials. This review analyzes in vitro and in vivo studies published since 1993 and concludes that although garlic appears to hold promise in reducing parameters associated with cardiovascular disease, more in-depth and appropriate studies are required.

Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials

Type of study: systematic review

Number of citations: 4

Year: 2023

Authors: Shashank Murali, Edward R Smith, M. Tiong, Sven-Jean Tan, Nigel D Toussaint

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Journal ranking: Q1

Key takeaways: Aged garlic extract shows promise in attenuating cardiovascular calcification, but other interventions show mixed results or insufficient data.

Abstract: Background Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and mortality and is commonly seen in aging, diabetes, and chronic kidney disease. Whether evidence‐based interventions could significantly attenuate cardiovascular calcification progression remains uncertain. Methods and Results We conducted a systematic review of randomized controlled trials involving interventions, compared with placebo, another comparator, or standard of care, to attenuate cardiovascular calcification. Included clinical trials involved participants without chronic kidney disease, and the outcome was cardiovascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations assessment. Forty‐nine randomized controlled trials involving 9901 participants (median participants 104, median duration 12 months) were eligible for inclusion. Trials involving aged garlic extract (n=6 studies) consistently showed attenuation of cardiovascular calcification. Trials involving 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (n=14), other lipid‐lowering agents (n=2), hormone replacement therapies (n=3), vitamin K (n=5), lifestyle measures (n=4), and omega‐3 fatty acids (n=2) consistently showed no attenuation of cardiovascular calcification with these therapies. Trials involving antiresorptive (n=2), antihypertensive (n=2), antithrombotic (n=4), and hypoglycemic agents (n=3) showed mixed results. Singleton studies involving salsalate, folate with vitamin B6 and 12, and dalcetrapib showed no attenuation of cardiovascular calcification. Overall, Cochrane risk of bias was moderate, and the Grading of Recommendations, Assessment, Development, and Evaluations assessment for a majority of analyses was moderate certainty of evidence. Conclusions Currently, there are insufficient or conflicting data for interventions evaluated in clinical trials for mitigation of cardiovascular calcification. Therapy involving aged garlic extract appears most promising, but evaluable studies were small and of short duration.

Aged garlic extract enhances production of nitric oxide.

Type of study: non-rct experimental

Number of citations: 113

Year: 2002

Authors: N. Morihara, I. Sumioka, T. Moriguchi, N. Uda, E. Kyo

Journal: Life sciences

Journal ranking: Q1

Key takeaways: Aged garlic extract increases nitric oxide production by activating cNOS, but not iNOS, potentially aiding in the prevention of cardiovascular disease.

Potential Health Benefit of Garlic Based on Human Intervention Studies: A Brief Overview

Type of study: literature review

Number of citations: 147

Year: 2020

Authors: Johura Ansary, T. Forbes-Hernández, E. Gil, Danila Cianciosi, Jiaojiao Zhang, María Elexpuru-Zabaleta, J. Simal-Gándara, F. Giampieri, M. Battino

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: Garlic consumption has shown health-promoting effects on various common diseases, such as cancer, cardiovascular and metabolic disorders, blood pressure, and diabetes, due to its antioxidant, anti-inflammatory, and lipid-lowering properties.

Abstract: Garlic is a polyphenolic and organosulfur enriched nutraceutical spice consumed since ancient times. Garlic and its secondary metabolites have shown excellent health-promoting and disease-preventing effects on many human common diseases, such as cancer, cardiovascular and metabolic disorders, blood pressure, and diabetes, through its antioxidant, anti-inflammatory, and lipid-lowering properties, as demonstrated in several in vitro, in vivo, and clinical studies. The present review aims to provide a comprehensive overview on the consumption of garlic, garlic preparation, garlic extract, and garlic extract-derived bioactive constituents on oxidative stress, inflammation, cancer, cardiovascular and metabolic disorders, skin, bone, and other common diseases. Among the 83 human interventional trials considered, the consumption of garlic has been reported to modulate multiple biomarkers of different diseases; in addition, its combination with drugs or other food matrices has been shown to be safe and to prolong their therapeutic effects. The rapid metabolism and poor bioavailability that have limited the therapeutic use of garlic in the last years are also discussed.

Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis.

Type of study: rct

Number of citations: 49

Year: 2013

Authors: N. Ahmadi, Vahid Nabavi, Fereshteh Hajsadeghi, I. Zeb, F. Flores, R. Ebrahimi, M. Budoff

Journal: International journal of cardiology

Journal ranking: Q1

Key takeaways: Aged garlic extract with supplement (AGE-S) increases brown adipose tissue, reduces homocysteine, and predicts a lack of coronary atherosclerosis progression and plaque stabilization.

Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation.

Type of study: rct

Number of citations: 61

Year: 2006

Authors: N. Weiss, N. Ide, T. Abahji, Lars Nill, C. Keller, U. Hoffmann

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) effectively reduces endothelial dysfunction caused by acute hyperhomocysteinemia in both macro- and microcirculation, potentially improving cardiovascular health.

Abstract: Endothelial dysfunction caused by increases in vascular oxidant stress that decrease bioavailable nitric oxide (NO) plays a critical role in the vascular pathobiology of hyperhomocysteinemia. Boosting cellular glutathione levels or increasing the activity of cellular glutathione peroxidase can compensate for homocysteine's effects on endothelial function. Aged garlic extract (AGE) contains water- and oil-soluble sulfur compounds that modify the intracellular thiol and redox state, minimize intracellular oxidant stress, and stimulate NO generation in endothelial cells and animals. We performed a placebo-controlled, blinded, crossover trial to examine whether AGE reduces macro- and microvascular endothelial dysfunction during acute hyperhomocysteinemia induced by an oral methionine challenge in healthy subjects. Acute hyperhomocysteinemia leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular endothelial dysfunction. In addition, acute hyperhomocysteinemia leads to a decrease in acetylcholine-stimulated skin perfusion as measured by laser-Doppler flowmetry. This indicates microvascular endothelial dysfunction, which is presumably a result of impairment of the endothelium-derived hyperpolarizing factor pathway. Pretreatment with AGE for 6 wk significantly diminished the adverse effects of acute hyperhomocysteinemia in both vascular territories. We conclude that AGE may at least partly prevent a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor during acute hyperhomocysteinemia. This pilot study warrants further investigations on the effects of AGE on endothelial dysfunction in patients with other cardiovascular risk factors or established vascular disease and on the clinical outcome of patients with cardiovascular disease.

Aged garlic extract suppresses platelet aggregation by changing the functional property of platelets

Type of study: non-rct experimental

Number of citations: 25

Year: 2016

Authors: N. Morihara, Atsuko Hino

Journal: Journal of Natural Medicines

Journal ranking: Q1

Key takeaways: Aged garlic extract suppresses platelet aggregation by changing platelets' functional properties to respond to collagen, but does not affect bleeding time.

Abstract: Aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, has been reported to have multiple beneficial effects on cardiovascular disease including inhibition of platelet aggregation. However, the mode of AGE action on platelets has not been clear. In this study, we examined the effect of AGE on the functional property of platelet by administering AGE to rats and evaluating the platelet aggregation in response to collagen in vitro. We found that AGE treatment significantly reduced the ability of platelet to aggregate and this effect of AGE was manifested on the 14 day, but not 7 day of treatment. In addition, AGE treatment produced platelets that responded to collagen by significantly increasing the amount of both the extracellular ATP and the extra- and intracellular TXB_2. AGE treatment also dose-dependently suppressed the phosphorylation of collagen-induced ERK, p38 and JNK. However, AGE administration did not affect the bleeding time. These findings suggest that AGE treatment results in suppression of platelet aggregation by changing the functional property of platelets to respond to collagen.

The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial.

Type of study: rct

Number of citations: 95

Year: 2016

Authors: M. Atkin, D. Laight, M. Cummings

Journal: Journal of diabetes and its complications

Journal ranking: Q1

Key takeaways: Aged Garlic Extract (AGE) did not significantly improve endothelial function, vascular inflammation, oxidative stress, or insulin resistance in high-risk type 2 diabetic patients.

Effects of Aged Garlic Extract on blood pressure in hypertensive patients: A systematic review and meta-analysis of randomized controlled trials.

Type of study: meta-analysis

Number of citations: 1

Year: 2024

Authors: M. Saadh, Muthena Kariem, Madhu Shukla, S. Ballal, Abhishek Kumar, Mamata Chahar, Suman Saini, Ish Kapila, Shirn Hasaanzadeh

Journal: Prostaglandins & other lipid mediators

Journal ranking: Q2

Key takeaways: Aged garlic extract supplements may improve blood pressure in hypertensive patients, but significant effects are observed only at doses over 1200 mg/day.

THE EFFECTS OF AGED GARLIC EXTRACT ON CORONARY ARTERY CALCIFICATION PROGRESSION AND BLOOD PRESSURE

Type of study: rct

Number of citations: 4

Year: 2015

Authors: Christopher Hom, M. Budoff, Yanting Luo

Journal: Journal of the American College of Cardiology

Journal ranking: Q1

Key takeaways: Aged Garlic Extract (AGE) can significantly inhibit coronary artery calcium progression over 1 year, regardless of statin therapy or gender, without significant differences in serum cholesterol or C-reactive protein levels.

Aged Garlic Extract Attenuates CaCl2‐Induced Abdominal Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase 9 Expression in Macrophages

Type of study: non-rct experimental

Number of citations: 0

Year: 2025

Authors: Kohei Karasaki, M. Ishida, Hiroki Kokubo, C. Sakai, Yusuke Kobayashi, Masao Yoshizumi

Journal: Molecular Nutrition & Food Research

Journal ranking: Q1

Key takeaways: Aged garlic extract reduces abdominal aortic aneurysm formation by mitigating tissue destruction, offering potential cardiovascular benefits.

Abstract: Abdominal aortic aneurysm (AAA) is a local enlargement of the abdominal aorta with the risk of its fatal rupture. With lack of established medical treatments reducing the AAA growth, the development of treatment strategies for AAA is warranted. In this study, we examined whether aged garlic extract (AGE), which reportedly has vasoprotective effects, attenuates AAA formation in an animal model. AAAs were induced via CaCl2 application to the abdominal aortas of C57BL/6J mice. The intake of an AGE-containing diet attenuated the aortic dilatation after AAA induction. Histological analysis showed that the degradation of elastic fibers in AAAs was mild in mice fed AGE compared to that in control mice. In addition, the expression of matrix metalloproteinase 9 (MMP9), a proteolytic enzyme degrading aortic tissue, was decreased in AAAs from mice fed with AGE. In cultured macrophages, AGE significantly inhibited tumor necrosis factor (TNF)-α-induced Mmp9 mRNA expression. Furthermore, AGE attenuated TNF-α-induced extracellular signal-regulated kinase (ERK) phosphorylation and c-fos mRNA expression, suggesting the suppressive effect of AGE on ERK-c-Fos-MMP9 axis induced by TNF-α. The present findings indicate that AGE diminishes AAA formation by mitigating tissue destruction, highlighting the potential cardiovascular benefits of AGE intake.

Effects of aged garlic extract on aging?related changes in gastrointestinal function and enteric nervous system cells

Type of study: non-rct experimental

Number of citations: 0

Year: 2025

Authors: Kensuke Ohishi, Ahmed A Rahman, Takahiro Ohkura, Alan J. Burns, Allan M Goldstein, Ryo Hotta

Journal: Experimental and Therapeutic Medicine

Journal ranking: brak

Key takeaways: Aged garlic extract (AGE) can improve gastrointestinal motility in older mice by enhancing enteric nervous system cell viability and reducing oxidative stress.

Abstract: Dysmotility of the gastrointestinal (GI) tract is commonly seen in elderly individuals, where it causes significant morbidity and can lead to more severe conditions, including sarcopenia and frailty. Although the precise mechanisms underlying aging-related GI dysmotility are not fully understood, neuronal loss or degeneration in the enteric nervous system (ENS) may be involved. Aged garlic extract (AGE) has been shown to have several beneficial effects in the GI tract; however, it is not known whether AGE can improve GI motility in older animals. The aim of the present study was to examine the effects of AGE on the ENS and gut motility in older mice and elucidate potential mechanisms of action. An AGE-formulated diet was given to 18-month-old female mice for 2 weeks. Organ bath studies and cell culture demonstrated that AGE: i) Altered gut contractile activity; ii) enhanced viability of ENS cells; and iii) exhibited neuroprotective effects on the ENS via reduction in oxidative stress. These findings suggest that AGE could be used to develop novel dietary therapeutics for aging-related GI dysmotility by targeting the associated loss and damage of the ENS.

Aged garlic therapeutic intervention targeting inflammatory pathways in pathogenesis of bowel disorders

Type of study:

Number of citations: 3

Year: 2024

Authors: Juan Liu

Journal: Heliyon

Journal ranking: Q1

Key takeaways: Aged Garlic Extract (AGE) shows potential as an alternative therapeutic regimen for inflammatory bowel diseases (IBD), with its absence of allicin and structural alterations highlighting its unique properties.

Oral aged garlic (Allium sativum) alleviates ulcerative colitis in mice by improving gut homeostasis.

Type of study: non-rct experimental

Number of citations: 2

Year: 2024

Authors: Deping Han, Xuke Guan, Fengxia Zhu, Qing Yang, Dingding Su

Journal: Food & function

Journal ranking: Q1

Key takeaways: Oral aged garlic alleviates ulcerative colitis in mice by improving gut homeostasis and promoting gut microbiota balance, making it a potential functional food for treating and preventing colitis.

Abstract: Aged garlic, obtained by heating raw garlic (Allium sativum) under high temperature and controlled humidity for a period, possesses a wide range of bioactivities, but its role in ulcerative colitis and its mechanism are not fully elucidated. We investigated the bioactive constituents in aged garlic (AG) and explored the effect of oral AG delivery on DSS-induced murine colitis. The results revealed that the aging process up-regulated anti-oxidative, anti-inflammatory and anti-microbial compounds such as dihydrocaffeic acid, 5-acetylsalicylic acid, verticine, S-allyl-L-cysteine and D-fucose. Oral AG obviously alleviated colitis, reducing colon damage and enhancing anti-oxidative and anti-inflammatory effects. Escherichia coli and Streptococcus equinus dramatically were enriched in the colon of mice with colitis that were strongly associated with Parkinson's disease, bacterial invasion of epithelial cells, aerobactin biosynthesis, and heme biosynthesis, but a distinct AG-mediated alteration in the colon due to increasing abundance of Akkermansia muciniphila, Lactobacillus sp. L-YJ, Bifidobacterium breve, Blautia wexlerae, Desulfomicrobium sp. P100A, and Lentilactobacillus hilgardii was observed. Next, we demonstrated that colonic microbiome reconstruction by oral AG significantly increased the production of short-chain fatty acids such as acetic acid, propionic acid, isobutyric acid, and isovaleric acid. This study provides the first data indicating that oral AG ameliorates colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into the AG-mediated remission of colitis and AG as a functional food for modulating the gut microbiota to prevent and treat colitis.

Effect of aged garlic extract against methotrexate‐induced damage to the small intestine in rats

Type of study: rct

Number of citations: 28

Year: 2006

Authors: M. Yüncü, A. Eralp, Ahmet Celõk

Journal: Phytotherapy Research

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) may protect the small intestine of rats from methotrexate-induced damage, with its protective effect derived from its interaction with crypt cells.

Abstract: Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX‐induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX‐induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells. Copyright © 2006 John Wiley & Sons, Ltd.

Alleviation by garlic of antitumor drug-induced damage to the intestine.

Type of study: non-rct experimental

Number of citations: 31

Year: 2001

Authors: Toshiharu Horie, Shoji Awazu, Shoji Awazu, Yoichi Itakura, Tohru Fuwa

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) may protect the small intestine of rats from antitumor drug-induced damage.

Abstract: Antitumour drugs such as methotrexate (MTX) and 5-fluorouracil (5-FU) induce intestinal damage. This is a serious side effect of cancer chemotherapy. The present studies examined whether or not aged garlic extract (AGE) protects against damage from these antitumor drugs. Both drugs were administered orally for 4 or 5 d to rats fed a standard laboratory diet with and without 2% AGE. The small intestinal absorption of the poorly absorbable compound, fluorescein isothiocyanate--labeled dextran (FD-4; average molecular weight, 4400) was used to evaluate the damage to the intestine using the in vitro everted intestine technique and the in situ intestinal loop technique. FD-4 absorption increased in the antitumour drug-treated rats fed the diet without garlic. Interestingly, FD-4 absorption was depressed in rats fed the diet containing AGE. These results suggest that AGE may protect the small intestine of rats from antitumour drug-induced damage.

Aged garlic extract stimulates p-glycoprotein and multidrug resistance associated protein 2 mediated effluxes.

Type of study: non-rct in vitro

Number of citations: 19

Year: 2009

Authors: K. Berginc, S. Žakelj, D. Ursic, A. Kristl

Journal: Biological & pharmaceutical bulletin

Journal ranking: Q2

Key takeaways: Aged garlic extract increases P-glycoprotein and multidrug resistance associated protein 2 mediated effluxes in the small intestinal, potentially altering the pharmacokinetic properties of conventional medicines when taken together.

Abstract: The growing concomitant consumption of drugs and herbal preparations such as garlic, and the numerous reports about the influence of herbal preparations on intestinal transport, led us to evaluate the influence of aged garlic extract on the transport function and electrophysiological parameters of the small intestinal mucosa. Aged garlic extract induced increase of the absolute value of the transepithelial potential difference and of the short-circuit current in both permeability models tested (rat jejunum, Caco-2 cell monolayers) without affecting transepithelial electrical resistance. It also caused a significant increase of the P-glycoprotein and multidrug resistance associated protein 2 mediated effluxes through rat jejunum of marker substrates Rhodamine 123 and 2,4-dinitrophenyl-S-glutathione, respectively. Rhodamine 123 efflux through the Caco-2 cell monolayers was not altered by aged garlic extract, whereas the efflux of 2,4-dinitrophenyl-S-glutathione increased significantly. So altered activity of the important transport proteins could significantly change the pharmacokinetic properties of conventional medicines taken concomitantly with aged garlic extract.

Aged garlic extract ameliorates fatty liver and insulin resistance and improves the gut microbiota profile in a mouse model of insulin resistance.

Type of study: non-rct experimental

Number of citations: 30

Year: 2019

Authors: Toshio Maeda, Satomi Miki, N. Morihara, Y. Kagawa

Journal: Experimental and therapeutic medicine

Journal ranking: brak

Key takeaways: Aged garlic extract improves fatty liver and insulin resistance, and alters intestinal flora in a mouse model of insulin resistance, suggesting potential related effects.

Abstract: Aged garlic extract (AGE) produced by the aging process has various beneficial pharmacological effects. In this study, the effects of AGE on fatty liver, insulin resistance and intestinal microbiota were compared between ddY-H mice, an insulin resistance mouse, and ddY-L mice, normal mice. Mice were fed an AGE-supplemented diet (4% w/w) for 7 weeks. The administration of AGE had no effect on the body weight and dietary intake of both types of mice. In the ddY-H mice, the serum levels of glucose and insulin were increased and glucose tolerance was impaired; however, the administration of AGE ameliorated these abnormal conditions. AGE did not have these effects in ddY-L mice. Triglyceride (TG) accumulation in the liver and fat absorption from the digestive tract were increased in the ddY-H mice; however, the administration of AGE reduced this increase. On the other hand, AGE exerted no such effects in the ddY-L mice. In addition, the gut microbiota has been shown to be closely associated with obesity, diabetes, dyslipidemia and non-alcoholic fatty liver disease in human and animal models. The bacterial composition of the gut microbiota in the feces of the ddY-H mice did not differ from that of the ddY-L mice at 5 weeks of age; however, it was altered in the mice at 9 and 12 weeks of age even when the mice were fed a standard diet. In the ddY-H mice, the relative presence of Lactobacillales was increased, while that of Bifidobacterium, Clostridium cluster XVIII and Prevotella was decreased. The alteration of the bacterial composition in the ddY-H mice was reversed by the administration of AGE; however, this effect of AGE was not observed in the ddY-L mice. On the whole, the findings of this study indicate that AGE improves abnormal fat accumulation and insulin resistance, and also alters the intestinal flora in ddY-H mice, suggesting the possibility that these effects of AGE may be related.

Aged garlic extract has chemopreventative effects on 1,2-dimethylhydrazine-induced colon tumors in rats.

Type of study: non-rct experimental

Number of citations: 49

Year: 2006

Authors: Takefumi Katsuki, K. Hirata, H. Ishikawa, N. Matsuura, S. Sumi, H. Itoh

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract has a chemopreventive effect on colon carcinogenesis by suppressing cell proliferation in rats.

Abstract: Garlic has been reported to have chemopreventive effects against a variety of cancers. However, different garlic preparations contain different constituents. We investigated the chemopreventive effect of aged garlic extract (AGE), an odorless product from prolonged extraction of fresh garlic, on colon carcinogenesis and cell proliferation in 1,2-dimethylhydrazine (DMH)-induced colon neoplastic rats. Rats were given weekly subcutaneous injections of DMH (20 mg/kg) for 20 wk, and fed either a basal diet or one containing 4% AGE. Serum from AGE-treated rats contained detectable S-allylcysteine. The AGE diet significantly reduced the number of colon tumors and aberrant crypt foci compared to the basal diet. Cell proliferation of normal-appearing colonic mucosa was assessed by MIB-5 immunohistochemistry. AGE treatment significantly decreased the mean MIB-5-labeling index. These findings suggest AGE has a chemopreventive effect on colon carcinogenesis through suppression of cell proliferation.

Garlic (Allium sativum L.) as an Ally in the Treatment of Inflammatory Bowel Diseases

Type of study:

Number of citations: 19

Year: 2023

Authors: Silvana Zugaro, E. Benedetti, Giulia Caioni

Journal: Current Issues in Molecular Biology

Journal ranking: Q2

Key takeaways: Aged Garlic Extract (AGE) shows potential in maintaining immune system homeostasis, potentially contributing to the treatment and prevention of chronic inflammatory bowel diseases.

Abstract: For centuries, garlic (Allium sativum) has been used both as a traditional remedy for most health-related ailments and for culinary purposes. Current preclinical investigations have suggested that dietary garlic intake has beneficial health effects, such as antioxidant, anti-inflammatory, antitumor, antiobesity, antidiabetic, antiallergic, cardioprotective, and hepatoprotective effects. Its therapeutic potential is influenced by the methods of use, preparation, and extraction. Of particular importance is the Aged Garlic Extract (AGE). During the aging process, the odorous, sour, and irritating compounds in fresh raw garlic, such as allicin, are naturally converted into stable and safe compounds that have significantly greater therapeutic effects than fresh garlic. In AGE, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) are the major water-soluble organosulfurized compounds (OSCs). SAC has been extensively studied, demonstrating remarkable antioxidant, anti-inflammatory, and immunomodulatory capacities. Recently, AGE has been suggested as a promising candidate for the maintenance of immune system homeostasis through modulation of cytokine secretion, promotion of phagocytosis, and activation of macrophages. Since immune dysfunction plays an important role in the development and progress of various diseases, given the therapeutic effects of AGE, it can be thought of exploiting its immunoregulatory capacity to contribute to the treatment and prevention of chronic inflammatory bowel diseases (IBD).

Garlic oil improves small intestinal motility in experimentally induced type II diabetes mellitus in female Wistar rats

Type of study: rct

Number of citations: 2

Year: 2024

Authors: N. Saleh, Abd El-Hamid A Mohamed, Manal H Moussa, Yasmin Assal, Noha N Lasheen

Journal: PLOS ONE

Journal ranking: Q1

Key takeaways: Garlic oil treatment improves small intestinal motility and reduces oxidative stress in diabetic rats, potentially due to its antioxidant properties.

Abstract: Diabetes mellitus adversely affects the contractile ability of the small intestine. However, there is a paucity of studies investigating the impact of garlic oil on small intestinal motility. This study aimed to evaluate the potential beneficial effects of garlic oil on type 2 diabetes mellitus in rats. Thirty-six adult female Wistar rats (n = 36) were divided into four groups: control, non-diabetic rats supplemented with garlic oil, diabetic rats, and diabetic rats treated with garlic oil. The rats were anesthetized using pentobarbitone (40 mg/kg BW); various motility parameters and oxidative markers were determined in small intestinal segments. Measurements were taken for naso-anal length, waist circumference, fasting blood glucose level (FBG), and plasma insulin level. Compared to the control group, the diabetic rats exhibited a reduction in the average force of contraction and motility index in all small intestinal segments. Furthermore, the rats exhibited a reduction in the average duration of muscle contraction only in the jejunum. The rats also exhibited hyperglycemia, insulin resistance, significant oxidative stress, and obesity. This was proven by changes in motility parameters, fasting blood glucose levels, HOMA-IR values, intestinal MDA levels, and waist circumference. The non-diabetic rats supplemented with garlic oil also exhibited a decrease in the average force of contraction and motility index in all small intestinal segments, despite having consistently higher Lee index and waist circumference values. However, the diabetic rats treated with garlic oil demonstrated improved small intestinal motility in nearly all small intestinal segments and a reduction in oxidative stress. In conclusion, rats with diabetes mellitus experienced a decrease in small intestinal motility, which is primarily driven by oxidative stress. Normal rats administered with garlic oil supplements exhibited similar effects. In contrast, garlic oil treatment in diabetic rats led to enhanced small intestinal motility and a notable anti-hyperglycemic effect, which can be attributed to the potent antioxidant properties of garlic oil.

Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation.

Type of study: rct

Number of citations: 45

Year: 2015

Authors: Hiroshi Jikihara, Guangying Qi, Koichi Nozoe, M. Hirokawa, Hiromi Sato, Y. Sugihara, F. Shimamoto

Journal: Oncology reports

Journal ranking: Q2

Key takeaways: Aged garlic extract inhibits colon tumor development by suppressing cell proliferation, suggesting potential antitumor effects through this mechanism.

Abstract: Garlic and its constituents are reported to have a preventive effect against colorectal cancer in animal models. Aged garlic extract (AGE), which is produced by natural extraction from fresh garlic for more than 10 months in aqueous ethanol, also has reputed chemopreventive effects on colon carcinogenesis, but has never been studied for its effects on colon cancer development. We investigated the antitumor effects of AGE in rats with 1,2-dimethylhydrazine (DMH)-induced carcinogenesis, and the mechanism of AGE in human colon cancer cell proliferation. F344 rats randomly divided into three groups were administered DMH (20 mg/kg weight) subcutaneously once a week for 8 weeks in a basal diet. After the last injection, one group of rats was then moved onto a basal diet containing 3% wt/wt AGE, and rats were sacrificed at 8 or 31 weeks. The number of aberrant crypt foci (ACF), histological type of tumor and proliferative activity of the tumor lesions were analyzed by macroscopic, pathological and immunohistochemical methods. DLD-1 human colon cancer cells were utilized to investigate the effect of AGE on anti-cell proliferation. AGE decreased the number of ACF but had no effect on gross tumor pathology. AGE showed a lower number of adenoma and adenocarcinoma lesions by histological analysis. Immunohistochemical staining indicated that AGE suppressed the proliferative activity in adenoma and adenocarcinoma lesions, but showed no effect on normal colon mucosa. Moreover, we demonstrated that AGE delayed cell cycle progression by downregulating cyclin B1 and cdk1 expression via inactivation of NF-κB in the human colorectal cancer cells but did not induce apoptosis. These findings suggest that AGE has an antitumor effect through suppression of cell proliferation.

The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats

Type of study: rct

Number of citations: 44

Year: 2014

Authors: G. Badr, Jawaher Abdulaziz AL-Mulhim

Journal: Evidence-based Complementary and Alternative Medicine : eCAM

Journal ranking: Q2

Key takeaways: Aged garlic extract (AGE) has a more potent gastroprotective effect than 100 mg/kg dose, promoting gastric mucosal healing and reducing microbial damage caused by indomethacin in male rats.

Abstract: Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.

Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells.

Type of study: non-rct in vitro

Number of citations: 99

Year: 2006

Authors: N. Matsuura, Yumiko Miyamae, K. Yamane, Y. Nagao, Y. Hamada, N. Kawaguchi, Takefumi Katsuki, K. Hirata, S. Sumi, H. Ishikawa

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract inhibits colorectal cancer cell growth and angiogenesis, making it a potential chemopreventive agent.

Abstract: Because colorectal cancer is likely to develop in many people at some point during their lives, prevention has become a high priority. Diet and nutrition play an important role during the multistep colon carcinogenic process. Garlic has been traditionally used as a spice and is well known for its medicinal properties; several studies have indicated its pharmacologic functions, including its anticarcinogenic properties. However, the mechanisms by which garlic can prevent colorectal cancer remain to be elucidated. This study investigated the effect of aged garlic extract (AGE) on the growth of colorectal cancer cells and their angiogenesis, which are important microenvironmental factors in carcinogenesis. AGE suppressed the proliferation of 3 different colorectal cancer cell lines-HT29, SW480, and SW620-in the same way, but its effects on the invasive activities of these 3 cell lines were different. the invasive activities of SW480 and SW620 cells were inhibited by AGE, whereas AGE had no effect on the invasive activity of Ht29 cells. The action of AGE appears to be dependent on the type of cancer cell. On the other hand, AGE enhanced the adhesion of endothelial cells to collagen and fibronectin and suppressed cell motility and invasion. AGE also inhibited the proliferation and tube formation of endothelial cells potently. These results suggest that AGE could prevent tumor formation by inhibiting angiogenesis through the suppression of endothelial cell motility, proliferation, and tube formation. AGE would be a good chemopreventive agent for colorectal cancer because of its antiproliferative action on colorectal carcinoma cells and inhibitory activity on angiogenesis.

Aged Garlic Extract Prevents Alcohol-Induced Cytotoxicity through Induction of Aldehyde Dehydrogenase 2 in the Liver of Mice.

Type of study: non-rct experimental

Number of citations: 3

Year: 2023

Authors: T. Kitakaze, M. Inoue, H. Ashida

Journal: Molecular nutrition & food research

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) prevents alcohol-induced liver damage by enhancing acetaldehyde detoxification through the Nrf2-dependent induction of mitochondrial ALDH2.

Abstract: SCOPE Acetaldehyde is a highly toxic primary metabolite of ethanol, and converted to non-toxic acetic acid by aldehyde dehydrogenase (ALDH). Accumulation of acetaldehyde causes significant damage to our body. Aged garlic extract (AGE) is a functional food material and possesses various health beneficial effects. In this study, we investigated whether AGE contributes to acetaldehyde detoxification through ALDH induction and its underlying mechanism. METHODS AND RESULTS C57BL/6J mice were orally administrated 10 - 1000 mg/kg BW of AGE for 1week before ethanol administration. AGE suppressed ethanol-caused accumulation of acetaldehyde level in the plasma through inducing mitochondrial ALDH2 but not cytosolic ALDH1A1. AGE also induced antioxidant enzymes, heme oxigenase-1 and NAD(P)H:quinone oxidoreductase 1, resulting in prevention of lipid peroxidation in the liver. In HepG2 cells, AGE prevented ethanol- and acetaldehyde-caused cytotoxicity. AGE induced mitochondrial ALDH2 through activating nuclear factor-erythroid 2-related factor 2 (Nrf2). AGE inhibited protein degradation of Nrf2 and enhanced protein degradation of kelch-like ECH-associated protein 1. Furthermore, S-allyl cysteine and S-allyl mercaptocysteine as the bioactive compounds in AGE also induce ALDH2 and Nrf2. CONCLUSION AGE prevented acetaldehyde-induced hepatotoxicity through enhancing acetaldehyde detoxification through Nrf2-dependent induction of mitochondrial ALDH2. This article is protected by copyright. All rights reserved.

Treatment with aged garlic extract protects against bromobenzene toxicity to precision cut rat liver slices.

Type of study: non-rct experimental

Number of citations: 44

Year: 1999

Authors: Bo Han Wang, K. Zuzel, Khalid Rahman, D. Billington

Journal: Toxicology

Journal ranking: Q1

Key takeaways: Pretreatment with aged garlic extract significantly reduces bromobenzene toxicity in rat liver slices, involving both increased GSH content and a GSH sparing effect.

Protective effect of aged garlic extract against the oxidative stress induced by cisplatin on blood cells parameters and hepatic antioxidant enzymes in rats

Type of study: rct

Number of citations: 80

Year: 2014

Authors: A. Nasr

Journal: Toxicology Reports

Journal ranking: Q2

Key takeaways: Aged garlic extract (AGE) has antioxidant and protective effects against cisplatin-induced oxidative stress and changes in blood cell parameters and liver structure in rats, suggesting it could be used as a dietary supplement to reduce toxic side effects of anticancer drugs.

Protective effect of aged garlic extracts against hepatotoxicity induced by ethephon in Wistar albino rat

Type of study: rct

Number of citations: 10

Year: 2019

Authors: Ashraf Al-Brakati

Journal: Environmental Science and Pollution Research

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) can protect against ethephon-induced liver toxicity in rats by restoring antioxidant balance and reducing hepatic injury.

Abstract: The current study was designed to demonstrate the hepatoprotective effect of aged garlic extract (AGE) against ethephon-induced liver toxicity in rats. Sixty male Wistar albino rats were divided into four groups as follows: the control group; AGE group was administered with 250 mg/kg; the ethephon group was orally given 200 mg/kg; and AGE + ethephon group was treated with ethephon for 4 weeks and then given AGE for another 4 weeks using the same dosage. The ethephon administration impaired the balance between oxidants and antioxidants as evidenced by the increased level of malondialdehyde (MDA) and the decreased concentration of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Biochemical findings showed a significant decrease in the red blood corpuscles (RBCs) count, hemoglobin (Hb) content, and hematocrit (HCT) level, with a significant increase in the white blood cells count. In addition, ethephon produced a significant decrease in levels of aspartate transaminase (AST) and alanine transaminase (ALT) with a decrease in albumin level. Furthermore, histological investigation showed dilation of the hepatic central vein and dilation of blood sinusoids which were congested with inflammatory cellular infiltrate. Moreover, examination of the liver using transmission electron microscopy showed a disturbance in the nuclear membranes and degenerating mitochondria with a rise in the cytoplasmic vacuoles by cellular edema. Interestingly, AGE administration was found to attenuate the histological deformations and biochemical alteration produced by ethephon. These findings suggest that AGE supplementation could be used to reverse the hepatic injury following ethephon exposure through its antioxidant capacity.

Oral Intake of Aged Garlic Extract (AGE) Ameliorates Oxidative Stress and Other Streptozotocin-induced Diabetic Complications in Rats

Type of study:

Number of citations: 5

Year: 2017

Authors: M. Thomson, K. Al-Qattan, D. Jayasree, Muslim Ali

Journal: International Journal of Pharmacology

Journal ranking: brak

Key takeaways: Oral intake of Aged Garlic Extract (AGE) improves oxidative stress and other diabetic complications in streptozotocin-induced diabetic rats.

Abstract: Background and Objective: Aged Garlic Extract (AGE), an aqueous extract of ethanol-soaked macerated garlic, contains many of raw garlicʼs bioactive components; however, causes considerably fewer physically and socially unpleasant side effects.This study aimed to investigate the antidiabetic and antioxidant potentials of oral intake of AGE (Kyolic, Wakunaga-USA) in streptozotocin (STZ, 60 mg kgG 1 ) induced diabetic rats.Methodology: Diabetic rats (blood sugar >20 mM) were divided into 2 groups and daily given a single oral dose of either normal saline (0.5 mL, control diabetic: C-D) or AGE (600 mg kgG 1 , AGE-diabetic: AGE-D).Normal rats given normal saline (0.5 mL, C-N) were included for comparison and all treatments were carried out for a period of 8 weeks.Body weight, blood glucose and 24 h food and water intake were measured weekly.Serum, liver and kidney total antioxidants were determined as trolox equivalent antioxidant capacity.Serum insulin, total cholesterol and triglycerides were determined using commercial kits.Catalase was assessed using H 2 O 2 as substrate.Lipid peroxidation was determined by reaction of malondialdenyde (MDA) with thiobarbituric acid.Serum fructosamine and liver protein oxidation were assessed colorimetically.A p<0.05 was considered significant using ANOVA and independent sample t-test.Results: Compared to C-N, the C-D rats showed significant weight loss and decrease in serum insulin and serum, kidney and liver total antioxidants levels and catalase activity (p< 0.05).Concurrently, the C-D rats had elevated food and water intake and urine output, blood glucose, serum cholesterol, triglycerides, fructosamine, MDA levels in kidney and liver and liver protein oxidation.Compared to C-D rats, the orally treated AGE-D rats demonstrated significantly increased body weight and serum insulin (p<0.05) as well as significantly decreased food and water intake, urine output, blood glucose and serum cholesterol, triglycerides and fructosamine (p<0.05).Indicators of oxidative stress were significantly ameliorated in serum, liver and kidneys of AGE-D rats (p<0.05).Conclusion: The data of this study suggested that oral intake of AGE ameliorates oxidative stress and other complications of diabetes in STZ-induced diabetic rats.

Aged garlic extract inhibits development of putative preneoplastic lesions in rat hepatocarcinogenesis.

Type of study: non-rct experimental

Number of citations: 30

Year: 2006

Authors: N. Uda, N. Kashimoto, I. Sumioka, E. Kyo, S. Sumi, S. Fukushima

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract (AGE) inhibits the development of preneoplastic lesions in rat hepatocarcinogenesis by slowing liver cell proliferation after partial hepatectomy.

Abstract: A unique garlic preparation, aged garlic extract (AGE), was examined for its modifying effect on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats, using the medium-term bioassay system based on the 2-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular foci. GST-P-positive foci were significantly decreased in rats treated with AGE at doses of 2, 5, and 10 mL/kg, i.g., 5 times per week during the promotion phase. In addition, to clarify the mechanism underlying the inhibitory effect of AGE, the effect of AGE on hepatocellular proliferation was evaluated using partially hepatectomized rats as a liver-regeneration model. The bromodeoxyuridine-labeling indices in the livers of the AGE group were significantly lower than those in the control group at 24 h, the maximum proliferation period after partial hepatectomy. These findings indicate that AGE inhibited the development of putative preneoplastic lesions in rat hepatocarcinogenesis, involving a slowing in the proliferation rate of liver cells after partial hepatectomy.

Immunomodulatory effects of aged garlic extract.

Type of study: non-rct experimental

Number of citations: 243

Year: 2001

Authors: E. Kyo, N. Uda, S. Kasuga, Y. Itakura

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Aged garlic extract shows potential as an immune modifier, maintaining homeostasis and reducing allergic reactions, tumor growth, and psychological stress-induced spleen weight loss.

Abstract: Using various kinds of models, we examined the effects of aged garlic extract (AGE) on immune functions. In the immunoglobulin (Ig)E-mediated allergic mouse model, AGE significantly decreased the antigen-specific ear swelling induced by picryl chloride ointment to the ear and intravenous administration of antitrinitrophenyl antibody. In the transplanted carcinoma cell model, AGE significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in natural killer (NK) and killer activities of spleen cells were observed in Sarcoma-180--bearing mice administered AGE. In the psychological stress model, AGE significantly prevented the decrease in spleen weight and restored the reduction of anti-SRBC hemolytic plaque-forming cells caused by the electrical stress. These studies strongly suggest that AGE could be a promising candidate as an immune modifier, which maintains the homeostasis of immune functions; further studies are warranted to determine when it is most beneficial.

In vitro, in vivo, and in silico analysis of synbiotics as preventive interventions for lipid metabolism in ethanol-induced adipose tissue injury

Type of study:

Number of citations: 7

Year: 2023

Authors: Dhara Patel, P. Rathaur, K. Parwani, Farhin Patel, Dixa Sharma, Kaid Johar, P. Mandal

Journal: Lipids in Health and Disease

Journal ranking: Q1

Key takeaways: Synbiotics improve adipose tissue metabolism and prevent alcoholic liver disease by reducing oxidative stress and promoting adiponectin overexpression.

Abstract: Abstract The risk of alcoholic liver disease (ALD) is increased by excessive ethanol drinking. For the prevention of ALD, the effects of ethanol on the liver, adipose tissue, and gut are crucial. Interestingly, garlic and a few probiotic strains can protect against ethanol-induced hepatotoxicity. However, the relationship between adipose tissue inflammation, Kyolic aged garlic extract (AGE), and Lactobacillus rhamnosus MTCC1423 in developing ALD is unknown. Therefore, the present study explored the effect of synbiotics (a combination of prebiotics and probiotics) on adipose tissue to prevent ALD. To investigate the efficacy of synbiotics administration on adipose tissue in preventing ALD, in vitro (3T3-L1 cells, N = 3) groups: control, control + LPS (lipopolysaccharide), ethanol, ethanol + LPS, ethanol + synbiotics, ethanol + synbiotics + LPS; in vivo (Wistar male rats, N = 6) groups: control, ethanol, pairfed, ethanol + synbiotics and in silico experiments were conducted. Lactobacillus multiplies in accordance with the growth curve when exposed to AGE. Additionally, Oil red O staining and scanning electron microscopy (SEM) demonstrated that synbiotics therapy maintained the morphology of adipocytes in the alcoholic model. In support of the morphological changes, quantitative real-time PCR demonstrated overexpression of adiponectin and downregulation of leptin, resistin, PPARγ, CYP2E1, iNOS, IL-6, and TNF-α after administration of synbiotics compared to the ethanol group. In addition, MDA estimation by high-performance liquid chromatography (HPLC) indicated that the synbiotics treatment reduced oxidative stress in rat adipose tissue. Consequently, the in-silico analysis revealed that AGE inhibited the C-D-T networks as PPARγ acting as the main target protein. The current study demonstrates that using synbiotics improves adipose tissue metabolism in ALD. Graphical Abstract