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

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Abstract

Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo. In this placebo-controlled, double-blind, randomized trial (conducted 2005-2007), 65 intermediate risk patients (age 60+/-9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 microg), folic acid (300 microg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CAC>15% per year and an increase in TR above baseline was considered a favorable response. At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo. AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

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... These are plant-and animal-derived substances used in various skincare products. Alpha-hydroxy acids (AHAs) such as citric acid (CA), glycolic acid (GA), lactic acid (LA), malic acid (MA), and tartaric acid (TA), are the naturally-occurring organic acids found in many fruits, berries, and herbs [146][147][148][149]. They are mostly used to reduce the impact of acne and enhance dry and aging skin. ...
... Out of all of the AHAs available, glycolic and lactic acids have the most trusted sources and which have been most studied. However, both glycolic and lactic acids can irritate [146]. ...
... AHAs are first and foremost used to exfoliate. AHAs have important implications for lightening the complexion, correcting discoloration from scars and age spots, improving the appearance of surface lines and wrinkles, increasing product absorption, preventing acne breakouts and promoting collagen and blood flow [146]. Another acid particularly used in the skincare market is beta-hydroxy acid (BHA). ...
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Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro-and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants' fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water.
... Aged garlic extract (AGE) with the active ingredient S-allylcysteine (SAC) has been shown to have a positive effect on atherosclerosis, blood pressure, perfusion, blood lipids, and inflammation in cohorts with intermediate risk for CVD [6][7][8][9][10][11][12][13][14][15][16][17]. None of these studies have been carried out in a female cohort with a low risk of cardiovascular disease. ...
... (1) History of myocardial infarction, (2) symptoms of ischemic heart disease, (3) hypersensitivity to AGE therapy, (4) any unstable medical disorder, (5) bleeding disorder, (6) prior life-threatening arrhythmia, (7) resting hypotension (systolic <90 mmHg) or hypertension (resting blood pressure >170/110 mmHg), (8) heart failure, (9) history of malignancy within the last 5 years or evidence of active cancer, (10) serum creatinine >140 µmol/L, (11) stroke, (12) triglycerides >4.0 mmol/L baseline visit, (13) diabetic subjects with HbA1c >8.0, and (14) drug abuse. ...
... A power calculation was made prior to the start of the study to calculate the adequate cohort size based on the research questions. e power calculation was based on prior studies evaluating the effect of garlic and supplements on blood pressure, cholesterol, and inflammatory biomarkers [11,12,21]. All continuous data are presented as a mean value ± SD or ± SEM, and all categorical data are reported as percentages or absolute numbers. ...
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Background: Chronic inflammation is a risk factor for cardiovascular disease. The aim of the study was to evaluate whether a daily supplementation of aged garlic extract (AGE) could reduce inflammation in females with low risk for cardiovascular disease. The study was conducted at a single center, as a parallel randomized placebo-controlled trial. Method: 63 females with a Framingham risk score over 10 underwent cardiac computed tomography (CT) scan. Of those, patients with a coronary artery calcium (CAC) scores less than 5 (n = 31) met the inclusion criteria and were randomized, in a double-blind manner to an intake of placebo or AGE (2400 mg daily) for 1 year. Results: Main outcome measure was changes in inflammatory biomarkers, blood pressure, fastening blood glucose, and blood lipids. A total of 29 patients (14 in the AGE group and 15 in the placebo group) completed the study and were analyzed. Females treated with AGE showed lower levels of inflammatory marker IL-6 after 12 months of treatment compared to females receiving placebo (p < 0.05). The blood lipids had a trend towards a lowering effect in females treated with AGE; however, this trend was not significant. Conclusion: The present study concludes that AGE lowers IL-6 in females with a risk profile of cardiovascular disease. We could also conclude that risk prediction with cardiac CT scan turned out to be superior in estimating the risk of cardiac disease compared to Framingham risk score. This trial is registered with NCT03860350.
... Studies have evaluated the effect of AGE on coronary arteriosclerosis and biomarkers of inflammation in cohorts with low-to-intermediate risk for cardiovascular diseases calculated using the Framingham risk score in non-European cohorts [14,16,19,20]. None of these studies has been conducted on a European cohort with an intermediate-to-high risk of cardiovascular events. ...
... Study investigators, i.e. those assessing outcomes and patients, were blinded to treatment allocation. The dose and duration of AGE was determined based on prior publications [16,19,20]. ...
... A power analysis was based on previously published studies evaluating the effect of garlic and supplements on coronary atherosclerosis, blood pressure, cholesterol and inflammatory biomarkers [19,20]. All continuous data were presented as a mean value ± SD, and all categorical data were reported as percentages or absolute numbers. ...
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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 < 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 (AGE) has been shown to have a positive effect on endothelial function and atherosclerosis, [11][12][13][14][15][16][17][18][19][20][21][22][23] and exerts its effects, through NO dependent pathways. 17,[24][25][26][27] AGE has therefore been suggested to have a positive effect on vascular elasticity and endothelial function. ...
... A power analysis was based on previously published studies evaluating the effect of garlic and supplements on coronary atherosclerosis, blood pressure, cholesterol, and inflammatory biomarkers. 18,39 All continuous data are presented as a mean value ± SEM or mean value with 95% confidence interval. A repeated measures mixed-effect model ANOVA with a Greenhouse-Geisser correction was performed to test for differences between groups between time points 0-and 12 months. ...
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Patients with arteriolosclerosis have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract has shown to have a positive impact on vascular elasticity. The present study aimed to assess the effect of long-term treatment with AGE on peripheral tissue perfusion in patients with confirmed atherosclerosis. Ninety three patients with a CT-scan confirmed coronary artery arteriolosclerosis were randomised in a double-blind manner to placebo or 2400 mg AGE daily for 1 year. Peripheral tissue perfusion was evaluated at 0- and 12-months using Laser Speckle Contrast Imaging. Measurement of post occlusive reactive hyperemia (PORH) and cutaneous vascular conductance (CVC) using acetylcholine iontophoresis (Ach) was conducted. After 12 months a significant increase of 21.6% (95% CI 3.2%-40.0%, P < .05) was seen in the relative change of PORH in the AGE compared with the placebo group. The same response was seen for CVC and Ach with an increase of 21.4% (95% CI 3.4%-39.4%, P < .05) in the AGE group compared with the placebo group. Aged garlic extract regenerated peripheral tissue perfusion and increase microcirculation in patients with arteriolosclerosis. Adequate peripheral tissue perfusion and tissue oxygen tension are important prerequisites for successful tissue repair. Restored microcirculation in patients could hypothetically facilitate wound healing.
... Previous experiments performed in our laboratory have shown that the use of aged garlic extract (AGE) is associated with a significant reduction in low attenuation plaque (LAP) progression as compared to the placebo using CCTA in patients with metabolic syndrome (10). Furthermore, AGE has been shown to exert positive effects on several cardiovascular disease risk factors, including endothelial dysfunction, cholesterol and blood pressure (11)(12)(13)(14). The aim of the present study was to evaluate the effects of AGE over a period of 1 year on coronary atherosclerotic plaque in individuals with T2DM utilizing CCTA. ...
... AGE. AGE (Kyolic) is formulated by soaking sliced raw garlic in aqueous ethanol solution at room temperature for up to 20 months as previously described (11,12). The 2,400 mg of AGE capsules were provided by Wakunaga of America Co., Ltd. with a matched placebo pill. ...
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Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.
... A significant but relatively petty difference was found for garlic consumption (17.5% vs. 15.0% often consumed garlic; 35.3% vs. 35.1% occasionally consumed garlic; 47.1% vs. 49.9% rarely consumed garlic; p < 0.001), age (94.1 vs. 92.7 years; p < 0.001), hypertension (54.8% vs. 52.9%; ...
... Accordingly, evidence from a few interventional studies in humans has documented the antioxidant properties of garlic. Plasma oxidized low-density lipoprotein (OxLDL) levels were found to fall sharply in subjects who received garlic supplementation compared with controls [35]. Altogether, garlic and its OSCs have the potential to delay the onset and development of aging through suppressing the expression of NF-κB and lowering ROS concentration [36]. ...
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In vitro and in vivo experimental studies have shown garlic has protective effects on the aging process; however, there is no evidence that garlic consumption is associated with all-cause mortality among oldest-old individuals (≥80 years). From 1998 to 2011, 27,437 oldest-old participants (mean age: 92.9 years) were recruited from 23 provinces in China. The frequencies of garlic consumption at baseline and at age 60 were collected. Cox proportional hazards models adjusted for potential covariates were constructed to estimate hazard ratios (HRs) relating garlic consumption to all-cause mortality. Among 92,505 person-years of follow-up from baseline to September 1, 2014, 22,321 participants died. Participants who often (≥5 times/week) or occasionally (1–4 times/week) consumed garlic survived longer than those who rarely (less than once/week) consumed it (p < 0.001). Participants who consumed garlic occasionally or often had a lower risk for mortality than those who rarely consumed garlic at baseline; the adjusted HRs for mortality were 0.92(0.89–0.94) and 0.89(0.85–0.92), respectively. The inverse associations between garlic consumption and all-cause mortality were robust in sensitivity analyses and subgroup analyses. In this study, habitual consumption of garlic was associated with a lower all-cause mortality risk; this advocates further investigation into garlic consumption for promoting longevity.
... Atherosclerosis is recognized as a complex disease characterized by an excessive inflammatory, fibrofatty, and proliferative response to damage in the vascular endothelium and involving several cell types, particularly smooth muscle cells, monocyte-derived macrophages, T-lymphocytes, and platelets [101,102]. Clinical reports have revealed the potential benefits of garlic as a modulator of multiple cardiovascular features through lowering low-density lipoproteins (LDL) and blood pressure [103][104][105][106], reducing platelet aggregation and adhesion, preventing LDL oxidation, and reducing the progression of atherosclerosis [100,[107][108][109]. However, it is known that some garlic compounds, such as DADS and allyl mercaptan, did not inhibit the transcriptional activity of factor NF-B employing human umbilical endothelial cells, suggesting that they play a pivotal role in atherogenesis by regulating the expression of proinflammatory genes and of NF-B-regulated genes, suggesting that NF-B is not the major target of DADS and allyl mercaptan. ...
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The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.
... inhibiting oxidation of LDL cholesterol, suppressing inflammatory cell adhesion to endothelial cells, improving impaired endothelial function and promote cardiovascular health. Supplementation with garlic extract favorably modifies endothelial biomarkers (e.g., CRP, and PAI-I, and LDL cholesterol) could prevent carotid intimamedia thickness progression in patients with coronary artery Effendy et al., 1997;Koscielny et al. 1999;Durak et al., 2002;Ferri et al., 2003;Gonen et al., 2005;Williams et al., 2005;Lau, 2006;Gardner et al., 2007;Gorinstein et al., 2007;Lei et al., 2008;Butt et al., 2009;Galeone et al., 2009a;Galeone et al., 2009b;Budoff et al., 2009;Simons et al., 2009;Mahdavi-Roshan et al., 2013;Kwak et al., 2014;Durak et al., 2016;Szulinska et al., 2018 Blood pressure-lowering effects-garlic has anti-hypertensive effects, stimulates the synthesis of nitric oxide (NO) and inhibits angiotensionconverting enzyme. Garlic-derived organic polysulfides are converted by red blood cells into hydrogen sulfide gas (H 2 S) leading to vasorelaxation via vascular smooth muscle cell signaling pathway. ...
... inhibiting oxidation of LDL cholesterol, suppressing inflammatory cell adhesion to endothelial cells, improving impaired endothelial function and promote cardiovascular health. Supplementation with garlic extract favorably modifies endothelial biomarkers (e.g., CRP, and PAI-I, and LDL cholesterol) could prevent carotid intimamedia thickness progression in patients with coronary artery Effendy et al., 1997;Koscielny et al. 1999;Durak et al., 2002;Ferri et al., 2003;Gonen et al., 2005;Williams et al., 2005;Lau, 2006;Gardner et al., 2007;Gorinstein et al., 2007;Lei et al., 2008;Butt et al., 2009;Galeone et al., 2009a;Galeone et al., 2009b;Budoff et al., 2009;Simons et al., 2009;Mahdavi-Roshan et al., 2013;Kwak et al., 2014;Durak et al., 2016;Szulinska et al., 2018 Blood pressure-lowering effects-garlic has anti-hypertensive effects, stimulates the synthesis of nitric oxide (NO) and inhibits angiotensionconverting enzyme. Garlic-derived organic polysulfides are converted by red blood cells into hydrogen sulfide gas (H 2 S) leading to vasorelaxation via vascular smooth muscle cell signaling pathway. ...
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Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification , their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Another tried to investigate how specific dietary supplementation could impact fat levels, including those of EAT. Based on proven evidence that garlic is able to give potential cardiovascular benefits by retarding the progression of coronary atherosclerosis, lowering cholesterol levels and blood pressure, reducing platelet aggregation and adhesion, preventing low-density lipoprotein oxidation and suppressing atherosclerosis [102][103][104][105], authors studied the effect of aged garlic extract with B-vitamins, folic acid, and L-arginine on change in intrathoracic and subcutaneous adipose tissue depots over a -1year period, measured with CAC scans. A beneficial effect of this supplementation on fat volumes emerged and remained significant even after adjusting for cardiovascular risk factors, statin therapy and BMI [58]. ...
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The observation of correlations between obesity and chronic metabolic and cardiovascular diseases has led to the emergence of strong interests in “adipocyte biology”, in particular in relation to a specific visceral adipose tissue that is the epicardial adipose tissue (EAT) and its pro-inflammatory role. In recent years, different imaging techniques frequently used in daily clinical practice have tried to obtain an EAT quantification. We provide a useful update on comorbidities related to chronic inflammation typical of cardiac adiposity, analyzing how the EAT assessment could impact and provide data on the patient prognosis. We assessed for eligibility 50 papers, with a total of 10,458 patients focusing the review on the evaluation of EAT in two main contexts: cardiovascular and metabolic diseases. Given its peculiar properties and rapid responsiveness, EAT could act as a marker to investigate the basal risk factor and follow-up conditions. In the future, EAT could represent a therapeutic target for new medications. The assessment of EAT should become part of clinical practice to help clinicians to identify patients at greater risk of developing cardiovascular and/or metabolic diseases and to provide information on their clinical and therapeutic outcomes.
... In 2009, a placebo-controlled, double-blind, randomized study involved 65 intermediate-risk patients and supplied them a capsule containing aged garlic extract with vitamin B6, vitamin B12, folic acid, and L-arginine for 12 months. At the end of the clinical trial, the data suggested that aged garlic extract with supplements decreased TGs, LDL-C, homocysteine, immunoglobulin G, immunoglobulin M autoantibodies to malondialdehyde-low density lipoprotein and apolipoprotein B-immune complexes while high-density lipoprotein, oxidized phospholipids/apolipoprotein B and lipoprotein were significantly increased [153]. Furthermore, a study of 60 asymptomatic patients showed that aged garlic extract with supplements decreased the levels of epicardial adipose tissue, pericardial adipose tissue, periaortic adipose tissue, and subcutaneous adipose tissue after 12 months of treatment. ...
... In 2009, a placebo-controlled, double-blind, randomized study involved 65 intermediate-risk patients and supplied them a capsule containing aged garlic extract with vitamin B6, vitamin B12, folic acid, and L-arginine for 12 months. At the end of the clinical trial, the data suggested that aged garlic extract with supplements decreased TGs, LDL-C, homocysteine, immunoglobulin G, immunoglobulin M autoantibodies to malondialdehyde-low density lipoprotein and apolipoprotein B-immune complexes while high-density lipoprotein, oxidized phospholipids/apolipoprotein B and lipoprotein were significantly increased [153]. Furthermore, a study of 60 asymptomatic patients showed that aged garlic extract with supplements decreased the levels of epicardial adipose tissue, pericardial adipose tissue, periaortic adipose tissue, and subcutaneous adipose tissue after 12 months of treatment. ...
... Therefore, the healthy benefits of garlic may be associated with H 2 S production (Rose et al., 2018;Rodrigues and Percival, 2019). Actually, garlic extracts are effectively slowing the development and progression of atherosclerosis through the generation of H 2 S from S-allylcysteine and S-allylmercaptocysteine (Benavides et al., 2007;Budoff et al., 2009). ...
Article
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Cardiovascular diseases are the most common complications of diabetes, and diabetic cardiomyopathy is a major cause of people death in diabetes. Molecular, transcriptional, animal, and clinical studies have discovered numerous therapeutic targets or drugs for diabetic cardiomyopathy. Within this, hydrogen sulfide (H 2 S), an endogenous gasotransmitter alongside with nitric oxide (NO) and carbon monoxide (CO), is found to play a critical role in diabetic cardiomyopathy. Recently, the protective roles of H 2 S in diabetic cardiomyopathy have attracted enormous attention. In addition, H 2 S donors confer favorable effects in myocardial infarction, ischaemia-reperfusion injury, and heart failure under diabetic conditions. Further studies have disclosed that multiplex molecular mechanisms are responsible for the protective effects of H 2 S against diabetes-elicited cardiac injury, such as anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-necrotic properties. In this review, we will summarize the current findings on H 2 S biology and pharmacology, especially focusing on the novel mechanisms of H 2 S-based protection against diabetic cardiomyopathy. Also, the potential roles of H 2 S in diabetes-aggravated ischaemia-reperfusion injury are discussed.
... [64] The presence of different vitamins (B, folic acid) and antioxidant phytochemical slow down the progression of oxidative stress and atherosclerosis. [65] The major enzymes (catalase, glutathione peroxide superoxide dismutase) help in playing a key role against the oxygen reactive species and decreasing the total protein carbonyl content. [66,67] In the study, the antioxidant activity of raw and black garlic was compared along with the optimized aging for the production of black garlic. ...
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Functional foods play a key role in human health and disease. Garlic (Allium sativum) is an eminent plant and has been part of food since ancient times due to its high medicinal food value. The unpleasant taste and odor of raw garlic make consumers reluctant for its use. With consumer demand, the trend for black garlic is getting attention worldwide. Black garlic is obtained from fresh garlic after a controlled fermentation process at high humidity and temperature. The fermentation process causes implausible changes in its physicochemical properties. Several in vitro and in vivo studies have been conducted to elucidate the effect of this natural agent against different health disorders and it has been found that black garlic is an effective in decreasing diabetic, hypercholesterolemic atherosclerosis, hyperlipidemic hypertension, inflammation, oxidative stress, cancer, and different neuro risks. The market for black garlic is developing rapidly to its positive functionality for human health. In the present review article, we have recapitulated the nutritional, chemical, bioactivity, physiochemical modifications during processing, food, and medicinal use and current knowledge of the subject, as well as the sensory aspects, and proposed future prospects on their possible applications as a functional food product.
... In 2009, a placebo-controlled, double-blind, randomized study involved 65 intermediate-risk patients and supplied them a capsule containing aged garlic extract with vitamin B6, vitamin B12, folic acid, and L-arginine for 12 months. At the end of the clinical trial, the data suggested that aged garlic extract with supplements decreased TGs, LDL-C, homocysteine, immunoglobulin G, immunoglobulin M autoantibodies to malondialdehyde-low density lipoprotein and apolipoprotein B-immune complexes while high-density lipoprotein, oxidized phospholipids/apolipoprotein B and lipoprotein were significantly increased [153]. Furthermore, a study of 60 asymptomatic patients showed that aged garlic extract with supplements decreased the levels of epicardial adipose tissue, pericardial adipose tissue, periaortic adipose tissue, and subcutaneous adipose tissue after 12 months of treatment. ...
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Black garlic (BG) is a form of aged garlic obtained from raw garlic (Allium sativum) via Millard reaction under high temperature (60–90 �C) and humidity (70–90%) for a period of time. Several studies reported higher contents of water-soluble antioxidants compounds (S-allyl cysteine, S-allyl-mercapto cysteine), 5-hydroxymethylfurfural, organosulfur compounds, polyphenol, volatile compounds, and products of other Millard reactions compared to fresh garlic after the thermal processing. Recent studies have demonstrated that BG and its bioactive compounds possess a wide range of biological activities and pharmacological properties that preserve and show better efficacy in preventing different types of diseases. Most of these benefits can be attributed to its antioxidation, anti-inflammation, anti-obesity, hepatoprotection, hypolipidemia, anti-cancer, anti-allergy, immunomodulation, nephroprotection, cardiovascular protection, and neuroprotection. Substantial studies have been conducted on BG and its components against different common human diseases in the last few decades. Still, a lot of research is ongoing to find out the therapeutic effects of BG. Thus, in this review, we summarized the pre-clinical and clinical studies of BG and its bioactive compounds on human health along with diverse bioactivity, a related mode of action, and also future challenges.
... On clinical study also, Garlic were seen effective in the patients of-hypertension in which significant lowering of systolic and diasystolic blood pressure was recorded, Sobenin et al. [81], Ashraf et al., [82]; coronary artery disease, Bordia et al., [83], Williams et.al, [84]; peripheral arterial occlusive disease, Kiessewetter et al., [85]; atherosclerosis, Rapp et al., [86], Budoff et al., [87]; hyperlipedemia, Bordia et al., [88], Bhusan et/al., [89], Mahanta et al., [90], Vorberg & Schinder [91], Jung et al., [92]; type-2 diabetes, Soebinin et al., [93], Ashraf et al., [94], Kumar et al., [95]; systemic sclerosis, Rapp et al., [96]; Common cold, Josling [97]; cold and flu, Nantz et al., [98]; Rheumatoid arthritis, Denisov et al., [99]. ...
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Traditional Indian Medicine (TIM)- Ayurveda is a Sanskrit Language word, which signifies “true knowledge of life”. It is recognized as one of the oldest Traditional health care systems of the World by World Health Organization. In fact, it was a main stream health care system till the introduction of convention medicine in India. Plant, animal and mineral origin natural substances are used in Ayurveda for health and healing. Of them, Garlic is one of the plant origin substances. Garlic is known as Lasuna, which signifies, destroyer of diseases. The fresh plants of Garlic are used as edible food substance and also the dried cloves are on ripening to alleviate the disorders rationally in TIM. Garlic is recommended as physical strength promoting, intellect promoting and as aphrodisiac to maintain healthy state of life. Its properties like- unctuous, hot, pungent, heavy has been described to alleviates skin diseases, intra abdominal tumor, chronic rhinitis, hemicranias, epilepsy, fainting etc. Its continuous use causes internal hemorrhage. The medicated milk, medicated oil preparation are used orally as well topically. A number of pharmaceutical forms are seen in more than 3000 years old original scriptures of Ayurveda and also in later works as it was in use by successive generation in India. A comprehensive review on Garlic is highlighted here, including original references with scientific evidences.
... In a study conducted by Budoff et al., 65 patients with an intermediate risk for CVDs were randomly allocated to two groups: (I) the daily administration of a capsule containing AGE (250 mg) plus Vitamin B12 (100 µg), folic acid (300 µg), Vitamin B6 (12.5 mg), and L-arginine (100 mg) or (II) placebo. After one year of treatment, the homocysteine level was decreased in the AGE group [126]. In another experiment, 40 rats were employed to receive one of the following diets for six weeks (four groups of 10 each): (I) AIN-93G folic-acid sufficient (2 mg/kg of diet); (II) AIN-93G folic-acid deficient; (III) AIN-93G folic-acid sufficient that was supplemented with AGE (4% of diet, wt:wt); and, (IV) AIN-93G folic-acid deficient supplemented with AGE. ...
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Background: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. Results: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.
... AGE can promote vasodilatation by increasing vasodilatory prostaglandins or imitating the molecule [74]. AGE has been hence shown to improve vascular function (increase vasodilatation and decrease vasoconstriction) both in humans and rats [75][76][77]. Furthermore, in rats, giving 1.2-mL/kg AGE i.p. decreased the area of a cerebral arterial infarction that would have occurred at 2 h post-infarction induction [78,79]. ...
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Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.
... Fatty acid synthesis such as HDL and reduction in cholesterol absorption may be possible mechanisms of action. Previous studies have reported similar beneficial effect with the garlic supplementation in the lipid profile (Banerjee & Maulik, 2002;Budoff et al., 2009;Durak et al., 2004;Mohammadi & Oshaghi, 2014), with other studies obtaining controversial results in the lipid profile (Turner et al., 2004) and glucose reduction (Ali et al., 2000). Also, the lemon has been associated with hepatoprotective properties (Bhavsar et al., 2007;Minato et al., 2003). ...
... The impact of a series of other agents on coronary atheroma have been extensively analysed in a recent review. 19 In conclusion, the management of risk factors is currently operated by monitoring the risk factor itself: blood pressure, blood glucose or cholesterol, for instance. Recent studies, however, indicate that risk factors have a limited value for predicting the occurrence of serious adverse events, especially when compared with TOCAB, whose predictive value is higher than that of calcium score, or even the presence of a significant stenosis. ...
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The extent of coronary artery disease has been shown to be an important indicator of prognosis. Cardiac computed tomography (CT) has the ability to measure plaque, with both coronary artery calcium scanning and CT angiography (CTA), to give a measure of total atheroma burden. Beyond assessing stenosis and atherosclerosis, CTA can assess high-risk plaque. These plaques are thought to be consistent with plaques that are vulnerable and more likely to rupture and cause acute coronary syndromes. However, the high-risk plaque concept suffers from poor reproducibility and poor positive predictive power. Total coronary atheroma burden has been shown to be a better predictor of coronary events than high-risk plaques or stenosis. This paper reviews the literature in this regard and demonstrates total coronary atheroma burden to be the best predictor of future cardiovascular disease. We searched MEDLINE, EMBASE and the Cochrane library database for studies assessing plaque burden and outcomes by CT. We used text words and related Medical Subject Headings (MeSH) for cardiac, calcification, plaque burden, CT, prognosis, mortality, event, death, survival and myocardial infarction.
... As previously mentioned, antioxidants, including those found in garlic, have the capacity to protect against oxidative damage and prevent progression of cancer. Trials regarding oxidative/antioxidant markers and garlic are few in number and results vary by the type of garlic used in the intervention (Table 3) [153][154][155][156][157][158][159][160][161][162][163][164]. ...
Article
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Garlic, an Allium vegetable, contains rich flavonoids organosulfur compounds (OSCs) that have potent anticancer properties. The aim of the review is to provide an overview of the different types of garlic, their active compounds, and the potential anticancer benefits with a focus on antioxidant activity. Animal and cell line studies have provided convincing evidence that garlic and its organosulfur compounds inhibit carcinogenesis through a number of events including induction of apoptosis, inhibiting cellular proliferation, scavenging radical oxygen species (ROS), increasing the activities of enzymes such as glutathione S-transferase, and reducing tumor size. Epidemiological studies showed compelling evidence that garlic consumption is associated with decreased risk of colorectal cancer, but inconsistent evidence for stomach, breast, and prostate cancers. Studies also suggest that the presence and potency of garlic OSCs varies with respect to the preparation and form of garlic. Further epidemiological studies with information on garlic form consumed or preparation methods and molecular studies regarding its antioxidant mechanisms, such as increasing enzymatic and nonenzymatic antioxidants levels, are warranted.
... In this context, assessments of microvasculature function may be more indicative of CVD risk than FMD 3 with poor VRIs shown to be significantly associated with subclinical atherosclerosis and the presence and extent of CAD. 14 VRI assessments may also be used to assess the effectiveness of therapeutic interventions, shown to be responsive to a 1-year dietary intervention which improved coronary artery calcium and temperature rebound. 21 All of which suggest that DTM assessments provide a more feasible methodology for assessing vascular reactivity within the clinical setting. ...
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Digital thermal monitoring (DTM) is an alternative, noninvasive, methodology to evaluate endothelial function using temperature change on finger as a surrogate measure of the magnitude of vascular reactivity index (VRI). A most recent modification to the technique includes the application of occlusion cuff at the base of a finger. We evaluated the validity of DTM compared with the standard flow‐mediated dilation (FMD) protocol. Thirty‐eight (22 males; 38 ± 15 years) participants were studied. Occlusion cuff was placed over the right antecubital fossa or at the base of the right index finger. Temperature monitors were placed on bilateral index fingers to assess change in temperature throughout 5‐min occlusion and recovery phases. VRI values obtained with the finger occlusion (1.58 ± 0.29 AU) were not significantly different from VRI measured with the brachial artery occlusion (1.55 ± 0.26 AU; p = .47), and the agreement of VRI values was confirmed in the Bland‐Altman plot with a mean difference of −0.03 ± 0.34 (95% confidence interval: −0.15 to 0.09). Shear rateAUCI was significantly correlated with VRI obtained from brachial occlusion (r = .34) and finger occlusion VRI (r = .54; all p < .05). Moreover, brachial FMD was significantly correlated with brachial occlusion VRI (r = .69; p < .05) and finger occlusion VRI (r = .53; p < .05). Therefore, finger‐based VRI may be a valid and novel alternative measure of endothelial function that is more suitable than the standard FMD or hyperemic shear rate for the assessment of endothelial function in the routine clinical setting.
... Random, double blinded, placebo-controlled 50 90 days 3 g of raw garlic daily Garlic decreased hypercholesterolemia in significant number of cases, thus, reducing the atherosclerosis and cardiovascular events Lachhiramka and Patil, (2016) Random, double blinded, placebo-controlled 152 48 months Garlic powder (high dose) Plaque regression was the prominent effect which showed the curative role in atherosclerosis Koscielny et al. (1999) Random, double blinded 65 12 months Capsules of garlic (250 mg) Garlic was seen to improve oxidative stress, vascular functions, and reduced atherosclerosis progression Budoff et al. (2009) Random 65 ...
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Under physiological conditions, endothelial cells act as protective barrier which prevents direct contact of blood with circulating factors via production of tissue plasminogen activator. Risk factors of metabolic disorders are responsible to induce endothelial dysfunction and may consequently lead to prognosis of atherosclerosis. This article summarizes the process of atherosclerosis which involves number of sequences including formation and interaction of AGE‐RAGE, activation of polyol pathway, protein kinase C, and hexosamine‐mediated pathway. All these mechanisms can lead to the development of oxidative stress which may further aggravate condition. Different pharmacological interventions are being used to treat atherosclerosis, however, these might be associated with mild to severe side effects. Therefore, plant‐based bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are attaining recent focus. By understanding process of development and mechanisms involved in atherosclerotic plaque formation, these bioactive compounds can be better option for future therapeutic interventions for atherosclerosis treatment. Practical applications Atherosclerosis is one of major underlying disorders of cardiovascular diseases which occur through multiple mechanisms and is associated with metabolic disorders. Conventional therapeutic interventions are not only used to treat atherosclerosis, but are also commonly associated with mild to severe side effects. Therefore, nowadays, bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are preferred. By understanding mechanisms involved in atherosclerotic plaque formation, bioactive compounds can be better understood for treatment of atherosclerosis. In this manuscript, we have focused on treatment strategies of atherosclerosis using bioactive compounds notably alkaloids and flavonoids having diverse pharmacological and therapeutic potentials with special focus on the mechanism of action of these bioactive compounds suitable for treatment of atherosclerosis. This manuscript will provide the scientific insights of bioactive compounds to researchers who are working in the area of drug discovery and development to control pathogenesis and development of atherosclerosis and its associated cardiometabolic disorders.
... Previous studies have demonstrated the beneficial effect of AGE on hypertension (8)(9)(10)(11)(12), atherosclerosis (13)(14)(15), metabolic syndrome (16), and gingivitis (17). Furthermore, recent studies have revealed that AGE and its constituents, SAC and S1PC, exert such desirable effects as anti-hypertension (18)(19)(20)(21)(22), cardioprotection (23), antioxidation (24)(25)(26)(27), antiaging (27,28), i m munomodulation (29)(30)(31), a nti-fatig ue (32,33), anti-stress (34,35), anti-inflammation (36)(37)(38)(39), and liver protection (40). ...
Article
Aged garlic extract (AGE) has been shown to improve peripheral circulatory disturbances in both clinical trials and experimental animal models. To investigate the effect of S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, on cold-induced reduction in tail blood flow of rat, Wistar rats were individually placed in a restraint cage and given the treatment with cold water (15˚C) after the oral administration of AGE or its constituents S1PC, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC). After the cold-treatment the tail blood flow of rats was measured at the indicated times. The pretreatment with AGE (2 g/kg BW) and S1PC (6.5 mg/kg BW) significantly alleviated the reduction of rat tail blood flow induced by cold treatment. The effect of S1PC was dose-dependent and maximal at the dose of 6.5 mg/kg BW, whereas SAC and SAMC were ineffective. To gain insight into the mechanism of S1PC action, the concentration of nitrogen oxide metabolites (NOx) in the plasma and the levels of phosphorylated endothelial nitric oxide synthase (eNOS) and 5'-AMP-activated protein kinase (AMPK) in the aorta were measured. The pretreatment with S1PC significantly increased the plasma concentration of NOx as well as the level of phosphorylated form of AMPK and eNOS in the aorta after cold-treatment. The present findings suggest that S1PC is a major constituent responsible for the effect of AGE to alleviate the cold-induced reduction of peripheral blood flow in rat by acting on the AMPK/eNOS/NO pathway in the aorta.
... In an initial placebo controlled trial of participants with intermediate cardiac risk, a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 µg), folic acid (300 µg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a year was shown to significantly lower progression of coronary calcium/ subclinical atherosclerosis, compared to placebo (p < 0.05). This was accompanied with decrease in other risk markers such as total cholesterol, LDL cholesterol and homocysteine in treatment arm compared to placebo [51]. Matsumoto et al. further evaluated prospectively, the effect of 2400 mg AGE/day vs. placebo on different plaque compositions measured by CCTA in patients with metabolic syndrome (MetS) (Fig. 3). ...
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The purpose of this review is to highlight the utility of comprehensive plaque assessment by serial coronary computed tomography angiography (CCTA) to understand atherosclerosis and its effect on cardiovascular risk stratification and management. CCTA is a validated, noninvasive imaging modality for coronary atherosclerotic plaque characterization. Numerous clinical trials have used approach of serial CCTA to demonstrate the potential benefits of multiple treatment strategies to reduce coronary plaque progression and its translation to benefits with cardiovascular outcomes. Serial CCTA trials for cardiovascular therapies combined with clinical outcome studies are providing mechanistic correlations of coronary atherogenesis and cardiovascular risk reduction, thereby establishing a new standard of care in addressing cardiac disease. Advancements in CCTA imaging and plaque analysis continue to expand the potential for CCTA in the evaluation of cardiovascular risk and targeted treatment of CAD.
... Garlic has been used for medicinal purposes and as a traditional medicine not only in Asia but also in other countries for hundreds of years (Budoff et al., 2009;Colín-González et al., 2012;GÖKALP, 2018;Liang et al., 2015;Ried & Fakler, 2014;Toledano-Medina, Pérez-Aparicio, Moreno-Rojas, & Merinas-Amo, 2016). It has been reported as exerting many bioactivities such as antidiabetic activities, prevention of cardiovascular disease and antioxidant activities in vitro, in animal models and even in clinical trials (Ramirez, Locatelli, Torres-Palazzolo, Altamirano, & Camargo, 2017;Ried, Frank, & Stocks, 2013;Tsai et al., 2019;Zhai et al., 2018). ...
Article
This study investigated the effect of ultrasonic and freezing pretreatment on S-ally cysteine (SAC) content in garlic during heat-processing at 40 °C for 15 days and also compared the browning degree and cell structure of ultrasonic and freezing pretreatment in garlic. Processing different times at the same frequency showed that ultrasonic pretreatment at 28 kHz for 3 h (2.51 ± 0.22 mg/g dry weight) is significantly higher than that for 1 h (1.83 ± 0.29 mg/g) after being heated at 40 °C for 6 days. The results of ultrasonic pretreatment for processing different frequencies at the same time finds that a frequency of 28 kHz for 2 h (3.15 ± 0.19 mg/g dry weight) has a better effect at increasing the SAC content in garlic than does 56 kHz for 2 h (2.69 ± 0.22 mg/g dry weight) after being heated at 40 °C for 15 days. A comparison of both pretreatments shows that the SAC content in garlic undergoing freezing pretreatment is significantly higher than that for ultrasonic pretreatment. Hence, ultrasonic pretreatment has a shorter processing time but needs more applications in the food industry to enhance the SAC content in garlic; however, it also maintains garlic's whole appearance and original color.
... As regards cardiovascular health, garlic supplementation has been shown to lower total cholesterol levels (11), blood pressure (12) and to prevent oxidative DNA damage in essential hypertension (13). AGE has also been shown to attenuate the progression of coronary atherosclerosis, improve vascular function and exert favorable effects on oxidative biomarkers (14,15). However, to the best of our knowledge, no studies available to date have examined the effects of AGE on LVM. ...
Article
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Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.
... A power analysis was based on the previously published studies evaluating the effect of garlic and supplements on coronary atherosclerosis, blood pressure, cholesterol, and inflammatory biomarkers. 22,23 All continuous data are presented as a mean value ± SD. A repeated measures analysis of variance (ANOVA) with a Greenhouse-Geisser correction was performed to test for differences between groups between time points 0 and 12 months. ...
Article
Laser Doppler velocimetry estimates tissue perfusion providing a record of microvascular blood flow. Patients with heart disease or diabetes mellitus have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract (AGE) has a positive effect on vascular elasticity. This study aimed to assess the effect of long‐term treatment with AGE on cutaneous tissue perfusion. A total of 122 patients with Framingham Risk Score ≥ 10 were randomised in a double‐blinded manner to placebo or 2400 mg AGE daily for 1 year and monitored. Cutaneous microcirculation was measured at 0 and 12 months using laser Doppler velocimetry. A repeated measures analysis of variance (ANOVA) with a Greenhouse–Geisser correction determined that mean post‐occlusive reactive hyperaemia differed significantly between time points. The mean percent change between the two time points 0 and 12 months was 102, 64 (174, 15)% change for AGE and 78, 62 (107, 92)% change for the placebo group (F[1, 120] = 5. 95, P < 0.016), 12 months of AGE increases the microcirculation in patients with an increased risk for cardiovascular events estimated using the Framingham risk score. Increased microcirculation could hypothetically facilitate wound healing.
... inhibiting oxidation of LDL cholesterol, suppressing inflammatory cell adhesion to endothelial cells, improving impaired endothelial function and promote cardiovascular health. Supplementation with garlic extract favorably modifies endothelial biomarkers (e.g., CRP, and PAI-I, and LDL cholesterol) could prevent carotid intimamedia thickness progression in patients with coronary artery Effendy et al., 1997;Koscielny et al. 1999;Durak et al., 2002;Ferri et al., 2003;Gonen et al., 2005;Williams et al., 2005;Lau, 2006;Gardner et al., 2007;Gorinstein et al., 2007;Lei et al., 2008;Butt et al., 2009;Galeone et al., 2009a;Galeone et al., 2009b;Budoff et al., 2009;Simons et al., 2009;Mahdavi-Roshan et al., 2013;Kwak et al., 2014;Durak et al., 2016;Szulinska et al., 2018 Blood pressure-lowering effects-garlic has anti-hypertensive effects, stimulates the synthesis of nitric oxide (NO) and inhibits angiotensionconverting enzyme. Garlic-derived organic polysulfides are converted by red blood cells into hydrogen sulfide gas (H 2 S) leading to vasorelaxation via vascular smooth muscle cell signaling pathway. ...
Article
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Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification, their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Fresh garlic extracted over a prolonged period produces a less irritative and odorless aged garlic extract (AGE) [6], which contains stable and water-soluble sulfur-containing amino acids, such as S-allylcysteine (SAC) and S-1-propenylcysteine (S1PC) [10][11][12]. Clinical studies on human subjects have demonstrated favorable pharmacological effects of AGE in atherosclerosis [13,14], metabolic syndromes [15], and hypertension [16]. Numerous experimental studies have also revealed positive effects of AGE and its components, SAC and S1PC, in anti-oxidation [17], anti-aging [18,19], immunomodulation [20,21], anti-hypertensive [22,23], anti-fatigue [24,25], hepatoprotective [26], anti-inflammatory [27,28], and cardioprotective activities [29]. ...
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Background Plants of Allium spp., including garlic (A. sativum) and onions (A. cepa), are known to be oxidatively toxic to canine erythrocytes resulting in Heinz body hemolytic anemia in dogs. In humans, these plants have been used as medicinal agents for multiple diseases since ancient times. Especially, fresh garlic extracted over a prolonged period produces less irritative and odorless aged garlic extract (AGE), containing unique and beneficial organosulfur compounds that can help prevent many kinds of diseases. In this study, the safety and efficacy of long-term oral administration of AGE is evaluated in dogs. The objectives are to confirm the safe dosage for long-term use and beneficial functions of AGE for dogs and to plan and design a canine health supplement or a preventive agent for multiple diseases based on the data of this study. Results Beagles were orally administered AGE (45 or 90 mg/kg body weight once a day) or an equivalent amount of water as control for 12 weeks. In AGE-treated groups, at 12 weeks post-administration at a dose of 90 mg/kg, there were no observable changes in the clinical signs, complete blood count, and serum biochemical parameters. Heinz bodies and eccentrocytes, the markers of oxidative damage in erythrocytes, did not appear in blood smear examination. In order to further evaluate the beneficial effects of AGE on health of dogs, the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) gene (NFE2L2) and Nrf2-regulated phase II antioxidant enzyme genes (NQO1, GCLM, HMOX1, and SOD2) were determined in whole blood between pre- and post-AGE administration. The expression of NFE2L2 gene was significantly upregulated in the AGE-treated groups [45 (p < 0.05) and 90 mg/kg (p < 0.01), 8 weeks] as compared to in the control group. Among the Nrf2-regulated enzymes examined, the expressions of NQO1 [45 (p < 0.05) and 90 mg/kg (p < 0.01), 8 weeks] and GCLM [45 (p < 0.05) and 90 mg/kg (p < 0.01), 12 weeks] genes were significantly upregulated. Conclusion The long-term oral administration of AGE at a dose of 90 mg/kg/day for 12 weeks did not show any adverse effects in dogs. Furthermore, the administration of AGE upregulated the gene expressions of canine Nrf2 and Nrf2-regulated phase II antioxidant enzymes. These results suggest that AGE might safely contribute to the health of dogs provided that the appropriate dosage is used. Electronic supplementary material The online version of this article (10.1186/s12917-018-1699-2) contains supplementary material, which is available to authorized users.
... [34] Many studies have demonstrated that different extracts of garlic can alone lower the level of serum TC, LDL, and TG in humans and rodents. [35,36] Similarly, Maha et al [37] have revealed that the level of plasma TC and LDL-C can be decreased by adding 8% raw garlic into the diet of rats. In 1993, Warshafsky et al [38] have proved that intake of garlic can reduce the cholesterol level by about 10%. ...
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Background: This study aimed to understand the impact of garlic on improving blood lipids using a meta-analysis. Methods: A literature search of the PubMed, EMBASE, and Cochrane Library databases was performed using keywords such as "garlic" and "hypercholesterolemia," and the deadline "July 14 (th), 2017." After extracting relevant details, each selected literature was evaluated for quality according to the quality evaluation criteria of bias risk recommended by Cochrane Collaboration recommendations and heterogeneity tests were performed. Standardized mean difference (SMD) and 95% confidence interval (CI) were evaluated using R 3.12 software. The publication bias was assessed using Egger method. Results: A total of 14 eligible papers published from 1981 to 2016 were included. The quality of the literatures was of moderate to high qualities. The values of TC (SMD = -1.26, 95% CI, -1.86 to -0.66), low-density lipoprotein (LDL) (SMD = -1.07, 95% CI, -1.67 to -0.47), and high-density lipoprotein (HDL) (SMD = 0.50, 95% CI, 0.06-0.94) after taking garlic in the experimental group and the control group have statistical significance, while there was no significant difference of TG in the 2 groups (SMD = -0.16, 95% CI, -0.87-0.55). However, the result of HDL was reversed when removed some of the literatures. No significant publication bias among the eligible studies with values of TC (P = .0625), LDL (P = .0770), HDL (P = .2293), and TG (P = .3436). Conclusion: Garlic can reduce the level of TC and LDL instead of HDL and TG, indicating the ability of anti-hyperlipidemia.
Article
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.
Article
Previous clinical studies on the anti-inflammatory effects of folic acid (FA) in patients with metabolic syndrome (MetS) have shown controversial results. This study aimed to synthesize the evidence on the effect of FA on inflammatory marker levels in MetS patients. We screened PubMed, Embase, Medline, and the Cochrane Library (from inception to March 2022) to identify relevant randomized controlled trials (RCTs). DerSimonian and Laird random effects were used to estimate the pooled weighted mean difference (WMD) with 95% confidence interval (CI). Funnel plot, Egger’s test, and the Begg-Mazumdar correlation test was used to assess publication bias. Subgroup analysis, meta-regression and sensitivity analysis were performed to find out possible sources of between-study heterogeneity. Ten RCTs with a total of 511 participants were included. The analysis showed that FA reduced high sensitivity C-reactive protein (hs-CRP) (WMD, −0.94; 95% CI, −1.56 to −0.32; P = 0.00), interleukin-6 (IL-6) (WMD, −0.39; 95% CI, −0.51 to −0.28; P = 0.00), and tumor necrosis factor-alpha (TNF-α) (WMD, −1.28; 95% CI, −1.88 to −0.68; P = 0.00), but did not decrease the C-reactive protein (CRP) (WMD, 0.10; 95% CI, −0.13 to 0.33; P = 0.38). Sensitivity analysis, subgroup analysis, and meta-regression showed that the effect sizes remained stable. Our findings suggest that FA supplementation could reduce inflammatory markers, such as hs-CRP, IL-6, TNF-α in patients with MetS. This study is registered with PROSPERO (CRD42021223843).
Article
Garlic is a common cooking ingredient and used in traditional medicine in Asian countries. There is a growing attention on garlic due to its preventive characteristics in cardiovascular diseases (CVDs). Many studies have reviewed the association between garlic intake and CVDs; however, no consistent conclusions have been drawn. New clinical trials have also been conducted and could contribute to more solid statements. In order to systematically review the reliability of previous studies regarding the implication of garlic in the management of CVDs, we performed in-depth meta-analysis using the most up-to-date randomized clinical trials (RCTs) data with more systematic controls. According to the 22 studies included, the effects of garlic intake on lowering total cholesterol (TC) and low-density lipoprotein (LDL) are more noticeable with lower dosage and longer duration, especially in patients with CVDs. In addition, subgroup analysis indicated that appropriate diet intervention could be an important control factor that should be taken into consideration in any future study designs.
Article
Background Coronary artery disease (CAD) genomic risk scores (GRS), as FDR202, GRS46K, 1.7M, and MetaGRS, help in assessing cardiovascular related morbidity and mortality. Interventions to adhere to a healthy lifestyle as a means of prevention based on the GRS have a potential to greatly reduce incident CAD event rates. We performed a prospective observational study to see the relationship between GRS and coronary artery calcium (CAC) scoring in individuals who are at risk. Methods 104 subjects with mean age 55.1 ± 8.8 years were enrolled and consented and all the participants underwent CAC scoring. 55(53%) were male. CAC score was measured using the Agatston method. Spearman correlation analysis assessed relationships between GRS scores and CAC scores, in the entire sample and in subjects with CAC score greater than zero. Multivariable linear regression analyzed associations while adjusting potential confounding variables. Results Mean + SD CAC score of the study population was 49.0 ± 130. A significant negative correlation was noted between FDR202 Prevalence and total CAC Score in 39 subjects with CAC > 0, r=-0.35, p=0.02. Multivariable analysis shows a significant association between FDR202 prevalence and log adjusted CAC score in subjects with CAC >0 while adjusting age, gender, hypertension and hyperlipidemia (β= -0.2, SE=0.1, p=0.04). No significant correlations were found between GRS46K, 1.7M, and MetaGRS with CAC score. Conclusion Additional research is necessary in a larger population to evaluate the potential role of GRS for the detection of CAD. This allows the individuals to adopt a healthy lifestyle modification to minimize the cardiovascular risk and delays the onset of most diseases of old age to prolong the life.
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Because atherosclerotic cardiovascular disease is a leading cause of death worldwide, understanding inflammatory processes underpinning its pathology is critical. B cells have been implicated as a key immune cell type in regulating atherosclerosis. B-cell effects, mediated by antibodies and cytokines, are subset specific. In this review, we focus on elaborating mechanisms underlying subtype-specific roles of B cells in atherosclerosis and discuss available human data implicating B cells in atherosclerosis. We further discuss potential B cell-linked therapeutic approaches, including immunization and B cell-targeted biologics. Given recent evidence strongly supporting a role for B cells in human atherosclerosis and the expansion of immunomodulatory agents that affect B-cell biology in clinical use and clinical trials for other disorders, it is important that the cardiovascular field be cognizant of potential beneficial or untoward effects of modulating B-cell activity on atherosclerosis.
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Background Myocardial Infarction (MI), also known as heart attack, is one of the most common cardiovascular diseases. Although certain drugs or mechanical means are used, day by day natural products such as herbs and spices based MI treatment is getting much popularity over the drugs or mechanical means for their pharmacological effects and have low or no side effects. This study was designed to assess the cardio-protective effect of methanolic extract of Bangladeshi multi clove garlic ( Allium sativum ) cultivar, a highly believed spice having cardioprotective activity, against isoproterenol (ISO) induced MI through cardiac histopathology as well as cardiac apoptotic caspase-3 gene expression study in female Wistar albino rats. Four groups containing 35 rats treated with respective agents like distill water / garlic extract (200 mg/kg-body-weight/day) up to 28 days and normal saline / ISO (100 mg/kg-body-weight/day) on 29th and 30th day were sacrificed (two rats/group/sacrifice) on the day 31, 46 and 61 and collecting the heart, cardiac histology and gene expression analysis were performed. Results ISO induced MI rats pretreated with garlic extract revealed up regulated expression of the cardiac apoptotic caspase-3 gene at the initial stage but finally the expressions gradually getting down regulated along with gradual improving the cardiac damage caused by apoptosis. Furthermore, only garlic extract pretreated rats were found undamaged cardioarchitecture and normal expressions of this gene. Conclusions These findings suggested that garlic extract confers having significant cardioprotective effect and consuming this spice with regular diet may reduce the risk of MI.
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Cardiovascular disease (CVD) is the most important and the number one cause of mortality in both developing and industrialized nations. The co-morbidities associated with CVD are observed from infancy to old age. Apolipoprotein B100 (Apo B) is the primary apolipoprotein and structural protein of all major atherogenic particles derived from the liver including very-low-density lipoproteins (VLDL), intermediatedensity lipoprotein (IDL), and low-density lipoprotein (LDL) particles. It has been suggested that measurement of the Apo B concentration is a superior and more reliable index for the prediction of CVD risk than is the measurement of LDL-C. Nutraceuticals and medicinal plants have attracted significant attention as it pertains to the treatment of non-communicable diseases, particularly CVD, diabetes mellitus, hypertension, and nonalcoholic fatty liver disease (NAFLD). The effect of nutraceuticals and herbal products on CVD, as well as some of its risk factors such as dyslipidemia, have been investigated previously. However, to the best of our knowledge, the effect of these natural products, including herbal supplements and functional foods (e.g., fruits and vegetables as either dry materials, or their extracts) on Apo B has not yet been investigated. Therefore, the primary objective of this paper was to review the effect of bioactive natural compounds on plasma Apo B concentrations. It is concluded that, in general, medicinal plants and nutraceuticals can be used as complementary medicine to reduce plasma Apo B levels in a safe, accessible, and inexpensive manner in an attempt to prevent and treat CVD.
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This study attempts a systematic evaluation of the clinical evidence for the use of odourless garlic prepared by ageing or fermentation. By PubMed, CENTRAL, and handsearching, 59 clinical studies were identified for potential extraction, of which 24 fulfilled the inclusion criteria. The quality of the studies and evidence of effectiveness were assessed by an established set of conventional criteria. Even the 12 best clinical trials (50%) had fundamental flaws that prevented to grade them as confirmatory. On the basis of a subsample of 19 exploratory studies (79%), an impressive reduction of cardiovascular risk was found for odourless garlic (evidence of effectiveness, “moderate” and for other indications, “poor”). Evidence of effectiveness is further limited by the fact that most studies used aged garlic produced by one pharmaceutical company and that products differed in composition and dose of the marker substance S‐allyl‐cysteine. In case odourless garlic is potentially an effective remedy in particular for cardiovascular diseases, we discern an urgent need for long‐term confirmatory studies. The ultimate cardiovascular endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques or blood markers of cardiovascular risk would be useful surrogates. Sample sizes for various assumptions are provided.
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Spices and herbs have been in use for centuries both for culinary and medicinal purposes. Spices not only enhance the flavor, aroma, and color of food and beverages, but they can also protect from acute and chronic diseases. More Americans are considering the use of spices and herbs for medicinal and therapeutic/remedy use, especially for various chronic conditions. There is now ample evidence that spices and herbs possess antioxidant, anti-inflammatory, antitumorigenic, anticarcinogenic, and glucose- and cholesterol-lowering activities as well as properties that affect cognition and mood. Research over the past decade has reported on the diverse range of health properties that they possess via their bioactive constituents, including sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, especially flavonoids and polyphenols. Spices and herbs such as clove, rosemary, sage, oregano, and cinnamon are excellent sources of antioxidants with their high content of phenolic compounds. It is evident that frequent consumption of spicy foods was also linked to a lower risk of death from cancer and ischemic heart and respiratory system diseases. However, the actual role of spices and herbs in the maintenance of health, specifically with regards to protecting against the development of chronic, noncommunicable diseases, is currently unclear. This review highlights potential health benefits of commonly used spices and herbs such as chili pepper, cinnamon, ginger, black pepper, turmeric, fenugreek, rosemary, and garlic.
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Over the past decade, there has been intense investigation in trying to understand the pathological role that oxidized phospholipids play in cardiovascular disease. Phospholipids are targets for oxidation, particularly during conditions of excess free radical generation. Once oxidized, they acquire novel roles uncharacteristic of their precursors. Oxidized phosphatidylcholines have an important role in multiple physiological and pathophysiological conditions including atherosclerosis, neurodegenerative diseases, lung disease, inflammation, and chronic alcohol consumption. Circulating oxidized phosphatidylcholine may also serve as a clinical biomarker. The focus of this review, therefore, will be to summarize existing evidence that oxidized phosphatidylcholine molecules play an important role in cardiovascular pathology.
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The present study was designed to systematically review randomized controlled trials (RCTs) that report on the effects of garlic supplementation on serum C‐reactive protein (CRP) levels. We conducted a literature search of Scopus, PubMed, Cochrane Library, and Google Scholar up to January 2018. Weighted mean differences (WMD) were estimated for net change in serum CRP. Subgroup analyses were also performed by duration of study, dose of supplementation, baseline CRP level, and the quality of studies. From 438 articles found and screened in our initial search, nine RCTs with the sum of total sample size of 363 were included in the meta‐analysis. Compared with the controls, garlic intake significantly reduced the concentrations of serum CRP by 0.8 mg/L (95% CI [−1.5, −0.1], p = 0.02) with the evidence of heterogeneity among studies. Subgroup analyses showed that garlic significantly lowered CRP by 0.82 mg/L (95% CI [−1.02, −0.62], p < 0.001) among studies with a daily garlic dose ≥1,200 mg/day and by 2.44 mg/L (95% CI [−4.02, −0.87], p = 0.002) among studies with baseline CRP ≥2 mg/L. Current data confirmed that garlic supplementation would reduce serum CRP levels. However, the changes were related to the supplemental doses and baseline levels of serum CRP.
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Introduction: Coronary artery calcification(CAC) is reflective of atherosclerotic disease and incrementally predictive of future cardiovascular events, independent of traditional risk factors. Extra coronary calcium such as aortic valve calcification, which can be identified and quantified by Computed Tomography(CT) imaging, has shown to predict future cardiovascular events in both asymptomatic and symptomatic (ie - stable angina and acute coronary syndrome) settings. It has hence been a vital tool in studies involving new therapies for cardiovascular disease. Areas covered: In this review, promising therapies on the horizon are reviewed, and the role of cardiac CT and coronary calcification in these studies. A Medline search for peer-reviewed publications using keywords related to coronary calcium score, aortic valve calcium, and therapies targeting the same was carried out. Expert commentary: CT scanning provides a distinct means of detecting and quantifying coronary plaque as well as valvular calcification with excellent reproducibility. Based on voluminous data available, the absence of Coronary calcium serves as a factor to de-risk patients for cardiovascular risk stratification and management algorithms. Newer therapies have shown to lower progression of coronary calcification, hence being beneficial in slowing progression of atherosclerotic disease. As the British Epidemiologist Geoffrey Rose states, the best predictor of a life-threatening disease is the early manifestation of that disease. As CAC represents the early manifestation of atherosclerosis, it is the best-known stratifier of risk today, and its clinical use will continue to rise.
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Vascular diseases refer to medical conditions that narrow blood vessels. Narrowed cardiac or cerebral arteries can lead to myocardial infarction or ischemic stroke. Risk factors including atherosclerosis, hypertension, and diabetes may induce either cardiovascular or cerebral complications. Based on current research, garlic favorably affects atherosclerosis, hypertension and diabetes, and helps decrease the risk of myocardial infarction and ischemic stroke. Garlic has been utilized for hundreds of years as a natural health remedy. New research is emerging regarding its effectiveness in treating common diseases, including atherosclerosis, hypertension, and diabetes. The underlying mechanisms by which garlic, and its byproducts, can alter pathophysiology have begun to be elucidated by these studies. Garlic is a prominent topic for future research regarding its potential as an adjuvant to conventional pharmacotherapy for these common health conditions. In this mini-review, we discuss the current state of the literature regarding garlic and its effects in patients with vascular disease. Specifically, we decided to briefly discuss the key points regarding the mechanisms underlying garlic’s anti-hypertensive, anti-hyperlipidemic, and hypoglycemic effects. This allows the readers to understand each process while keeping the paper concise. These mechanisms can be further explored in the original articles, at the reader’s discretion.
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Aims: Increased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT. Methods: Sixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta. Results: At 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI. Conclusion: This study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.
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Previous studies have shown that vascular dysfunction measured by digital thermal monitoring (DTM) during an arm-cuff reactive hyperemia procedure correlates with the severity of coronary artery disease measured by coronary artery calcium in asymptomatic patients. Current study investigates the correlation between DTM and abnormal myocardial perfusion imaging (MPI). About 116 consecutive patients with chest discomfort, age 57 +/- 10 years, underwent MPI, DTM and Framingham Risk Score (FRS) assessment. Fingertip temperature rebound (TR), DTM index of vascular reactivity, was assessed after a 2-minute arm-cuff reactive hyperemia test. The extent of myocardial perfusion defect was measured by summed stress score (SSS). TR decreased from SSS < 4 (1.61 +/- 0.15) to 4 < or = SSS < or = 8 (0.5 +/- 0.22) to 9 < or = SSS < or = 13 (0.26 +/- 0.15) to SSS > 13 (-0.37 +/- 0.19) (P = .0001). After adjusting for cardiac risk factors, the odds ratio of the lowest versus two upper tertiles of TR was 3.93 for SSS > or = 4 and 9.65 for SSS > or = 8 compared to SSS < 4. TR correlated well with SSS (r = -0.88, P = .0001). Addition of TR to FRS increased the area under the ROC curve to predict abnormal MPI, SSS > or = 4, from 0.65 to 0.84 (P < .05). Vascular dysfunction measured by DTM is associated with the extent of myocardial perfusion defect independent of age, gender, and cardiac risk factors.
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To assess the size and consistency of garlic's effect on total serum cholesterol in persons with cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of the bibliographies of published studies and reviews. Trials were selected if they were randomized and placebo-controlled and if at least 75% of their patients had cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Studies were excluded if they did not provide enough data to compute effect size. Five of 28 studies were selected for review. Details of study design, patient characteristics, interventions, duration of therapy, and cholesterol measurements were extracted by one author and were verified by another. Study quality was evaluated by multiple reviewers using a closed-ended questionnaire. Patients treated with garlic consistently showed a greater decrease in total cholesterol levels compared with those receiving placebo. Meta-analysis of homogeneous trials estimated a net cholesterol decrease attributable to garlic of 0.59 mmol/L (95% CI, 0.44 to 0.74) (23 mg/dL [CI, 17 to 29]) (P < 0.001). Meta-analysis of the controlled trials of garlic to reduce hypercholesterolemia showed a significant reduction in total cholesterol levels. The best available evidence suggests that garlic, in an amount approximating one half to one clove per day, decreased total serum cholesterol levels by about 9% in the groups of patients studied.
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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.
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Various components of garlic and aged garlic extract, including allicin, S-allylcysteine (SAC) and volatile metabolites of allicin were determined in breath, plasma and simulated gastric fluids by HPLC, gas chromatography (GC) or HPLC- and GC-mass spectrometry (MS). Data indicate that allicin decomposes in stomach acid to release allyl sulfides, disulfides and other volatiles that are postulated to be metabolized by glutathione and/or S-adenosylmethionine to form allyl methyl sulfide. SAC can be absorbed by the body and can be determined in plasma by HPLC or HPLC-MS using atmospheric pressure chemical ionization (APCI)-MS.
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Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBxapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.
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Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We investigated whether levels of oxidized low-density lipoprotein (LDL) measured with use of monoclonal antibody E06 reflect the presence and extent of obstructive coronary artery disease, defined as a stenosis of more than 50 percent of the luminal diameter. Levels of oxidized LDL and Lp(a) lipoprotein were measured in a total of 504 patients immediately before coronary angiography. Levels of oxidized LDL are reported as the oxidized phospholipid content per particle of apolipoprotein B-100 (oxidized phospholipid:apo B-100 ratio). Measurements of the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels were skewed toward lower values, and the values for the oxidized phospholipid:apo B-100 ratio correlated strongly with those for Lp(a) lipoprotein (r=0.83, P<0.001). In the entire cohort, the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels showed a strong and graded association with the presence and extent of coronary artery disease (i.e., the number of vessels with a stenosis of more than 50 percent of the luminal diameter) (P<0.001). Among patients 60 years of age or younger, those in the highest quartiles for the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels had odds ratios for coronary artery disease of 3.12 (P<0.001) and 3.64 (P<0.001), respectively, as compared with patients in the lowest quartile. The combined effect of hypercholesterolemia and being in the highest quartiles of the oxidized phospholipid:apo B-100 ratio (odds ratio, 16.8; P<0.001) and Lp(a) lipoprotein levels (odds ratio, 14.2; P<0.001) significantly increased the probability of coronary artery disease among patients 60 years of age or younger. In the entire study group, the association of the oxidized phospholipid:apo B-100 ratio with obstructive coronary artery disease was independent of all clinical and lipid measures except one, Lp(a) lipoprotein. However, among patients 60 years of age or younger, the oxidized phospholipid:apo B-100 ratio remained an independent predictor of coronary artery disease. Circulating levels of oxidized LDL are strongly associated with angiographically documented coronary artery disease, particularly in patients 60 years of age or younger. These data suggest that the atherogenicity of Lp(a) lipoprotein may be mediated in part by associated proinflammatory oxidized phospholipids.
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Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO(4)-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages.
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The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), were measured in 504 patients undergoing clinically indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM apoB-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: MDA-LDL, 0.51 (0.32-0.82; P = 0.005); CuOxLDL, 0.63 (0.39-1.01; P = 0.05); OxCL, 0.63 (0.39-1.01; P = 0.05); and apoB-IC, 0.55 (0.34-0.88; P = 0.013). These relationships were accentuated in the setting of hypercholesterolemia, with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL autoantibodies nor apoB-ICs were independently associated with angiographically determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.
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Oxidized low-density lipoprotein (OxLDL) has been shown to exist in human circulating plasma. Several groups including ours have developed methods for immunologically measuring OxLDL, which have been applied to several clinical, both cross-sectional and prospective, studies. These data clearly show that OxLDL levels correlate well with the severity of cardiovascular diseases. In particular, recent observations suggest that plasma OxLDL levels could be a useful marker for predicting future cardiovascular events; however, substantial differences exist among the different methods of OxLDL measurement. To evaluate the clinical data on circulating OxLDL, a proper understanding of the similarity, differences, and limitation of the methods is needed. This paper summarizes the characteristics of the methods used and recent clinical findings.
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In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.
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Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.
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To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown. Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment. Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (-18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (-31.9% vs. -12.2%; p < 0.001), and total IgM apoB-IC (-25.5% vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044). Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.
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The aim of this study was to determine the relation between coronary artery calcification detected by ultrafast computed tomographic scanning and histopathologic coronary artery disease. Recent studies suggest that discrete coronary artery calcification as visualized by ultrafast computed tomographic scanning may facilitate the noninvasive detection or estimation, or both, of the in situ extent of coronary disease. Such quantitative relations have not been established. Thirteen consecutive perfusion-fixed autopsy hearts (from eight male and five female patients aged 17 to 83 years) were scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic sections. The major epicardial arteries were dissected free, positioned longitudinally and scanned again in cross section. Coronary artery calcification in a coronary segment was defined as the presence of one or more voxels with a computed tomographic density > 130 Hounsfield units. Each epicardial artery was sectioned longitudinally, stained and measured with a planimeter for quantification of cross-sectional and atherosclerotic plaque areas at 3-mm intervals, corresponding to the computed tomographic scans. A total of 522 paired coronary computed tomographic and histologic sections were studied. Direct relations were found between ultrafast computed tomographic scanning coronary artery calcium burden and atherosclerotic plaque area and percent lumen area stenosis. However, the range for plaque area or percent lumen stenosis, or both, associated with a given calcium burden was broad. Three hundred thirty-one coronary segments showed no calcification by computed tomography. Although atherosclerotic disease was found in several corresponding pathologic specimens, > 97% of these noncalcified segments were associated with nonobstructive disease (< 75% area stenosis); if no calcification was determined in an entire coronary vessel, all corresponding coronary disease was found to be nonobstructive. To determine the relation between arterial calcification and any atheromatous disease, computed tomographic calcium burden for each segment was paired with the histologic absence or presence of disease. Ultrafast computed tomographic scanning had a sensitivity and specificity of 59% and 90% and a negative and positive predictive value of 65% and 87%, respectively. A direct correlation was found (r = 0.99) between total calcium burden calculated from tomographic scans of the heart as a whole and scans of the arteries obtained in cross section. The detection of coronary calcification by ultrafast computed tomographic scanning is highly predictive of the presence of histopathologic coronary disease, but the use of this technique to define the extent of coronary disease may be limited. However, the absence of coronary calcification at any site is highly specific for the absence of obstructive disease.
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Ultrafast computed tomography was used to detect and quantify coronary artery calcium levels in 584 subjects (mean age 48 +/- 10 years) with (n = 109) and without (n = 475) clinical coronary artery disease. Fifty patients who underwent fluoroscopy and ultrafast computed tomography were also evaluated. Twenty contiguous 3 mm slices were obtained of the proximal coronary arteries. Total calcium scores were calculated based on the number, areas and peak Hounsfield computed tomographic numbers of the calcific lesions detected. In 88 subjects scored by two readers independently, interobserver agreement was excellent with identical total scores obtained in 70. Ultrafast computed tomography was more sensitive than fluoroscopy, detecting coronary calcium in 90% versus 52% of patients. There were significant differences (p less than 0.0001) in mean total calcium scores for those with versus those without clinical coronary artery disease by decade: 5 versus 132, age 30 to 39 years; 27 versus 291, age 40 to 49 years; 83 versus 462, age 50 to 59 years; and 187 versus 786, age 60 to 69 years. Sensitivity, specificity and predictive values for clinical coronary artery disease were calculated for several total calcium scores in each decade. For age groups 40 to 49 and 50 to 59 years, a total score of 50 resulted in a sensitivity of 71% and 74% and a specificity of 91% and 70%, respectively. For age group 60 to 69 years, a total score of 300 gave a sensitivity of 74% and a specificity of 81%. The negative predictive value of a 0 score was 98%, 94% and 100% for age groups 40 to 49, 50 to 59 and 60 to 69 years, respectively. Ultrafast computed tomography is an excellent tool for detecting and quantifying coronary artery calcium.
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A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
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To determine the effect of 900 mg/day of dried garlic powder (standardised to 1.3% allicin) in reducing total cholesterol. Double-blind, randomised six-month parallel trial. 115 individuals with a repeat total cholesterol concentration of 6.0-8.5 mmol/l and low-density lipoprotein (LDL) cholesterol of 3.5 mmol/l or above after six weeks of dietary advice. The active treatment group received dried garlic tablets (standardised to 1.3% allicin) at a dosage of 300 mg three times daily. The control group received a matching placebo. Primary end-point: total cholesterol concentration; secondary end-points: concentrations of LDL and high-density lipoprotein cholesterol, apolipoproteins (apo) A1 and B, and triglycerides. There were no significant differences between the groups receiving garlic and placebo in the mean concentrations of serum lipids, lipoproteins or apo A1 or B, by analysis either on intention-to-treat or treatment received. In a meta-analysis which included the results from this trial, garlic was associated with a mean reduction in total cholesterol of -0.65 mmol/l (95% confidence intervals: -0.53 to -0.76). In this trial, garlic was less effective in reducing total cholesterol than suggested by previous meta-analyses. Possible explanations are publication bias, overestimation of treatment effects in trials with inadequate concealment of treatment allocation, or a type 2 error. We conclude that meta-analyses should be interpreted critically and with particular caution if the constituent trials are small.
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A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [cholesterol concentrations 5.7-7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet, they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo, then switched to the other supplement for an additional 4 mo. Blood lipids, blood counts, thyroid and liver function measures, body weight, and blood pressure were followed over the entire study period. The major findings were a maximal reduction in total serum cholesterol of 6.1% or 7.0% in comparison with the average concentration during the placebo administration or baseline evaluation period, respectively. Low-density-lipoprotein cholesterol was also decreased by aged garlic extract, 4% when compared with average baseline values and 4.6% in comparison with placebo period concentrations. In addition, there was a 5.5% decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract. We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.
Article
The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P<.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, approximately 28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal (> or =130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27% in men and 34% in women. Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
Article
Garlic and some of its organosulfur components have been found to be potent inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in vivo, however, especially when administered over extended periods, is sparse. We recently performed a 10-month study comparing the effect of aged garlic extract (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men. In the course of the intervention trial, we examined platelet functions and susceptibility of lipoproteins to oxidation in a subgroup of this study population. Study subjects supplemented with 7.2 AGE per day showed a significant reduction of epinephrine- and, to a lesser degree, collagen-induced platelet aggregation but failed to demonstrate an inhibition of adenosine diphosphate (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar flow chamber at moderately high shear rate, was reduced by approximately 30% in subjects taking AGE compared with placebo supplement. A trend toward decreased susceptibility of lipoproteins to oxidation also was noted during AGE administration compared with the placebo period. We conclude that the beneficial effect of garlic preparations on lipids and blood pressure extends also to platelet function, thus providing a wider potential protection of the cardiovascular system.
Article
The present study examined the relation of plasma oxidized low-density lipoprotein (LDL) levels to plasma LDL cholesterol levels and the impairment of endothelium-dependent coronary vasorelaxation in patients with coronary artery disease (CAD). In the first study, the relationship between plasma levels of oxidized LDL and LDL cholesterol were investigated in 88 patients with CAD. In the second study, the changes in the diameter of the left anterior descending (LAD) and the left circumflex (LCX) coronary arteries were measured after intracoronary administration of acetylcholine (15 microg) and isosorbide dinitrate (2.5 mg) in 15 patients with CAD. Plasma oxidized LDL levels were determined with a sandwich enzyme-linked immunosorbent assay. Plasma oxidized LDL levels did not correlate with plasma LDL cholesterol levels (r=-0.03, p=NS). The % diameter changes (mean+/-SEM) in the LAD and LCX after intracoronary acetylcholine were -8.3+/-3.5% and -10+/-4.2%, respectively. The % diameter changes in the LAD and LCX after intracoronary isosorbide dinitrate were 23+/-4.8% and 23+/-5.1%, respectively. The % diameter changes in the LAD and LCX inversely correlated with plasma oxidized LDL levels after intracoronary acetylcholine (LAD: r=-0.55, p=0.03; LCX: r=-0.59, p=0.02), but were not after intracoronary isosorbide dinitrate. Plasma LDL cholesterol, triglyceride, and high-density lipoprotein cholesterol levels did not correlate with the coronary vasoreaction to acetylcholine. In conclusion, plasma oxidized LDL levels do not correlate with plasma LDL-cholesterol levels and are related to impairment of endothelium-dependent coronary vasodilation in patients with CAD.
Article
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.
Article
It has been known for several decades that hypercholesterolemia is a major risk factor for atherosclerosis and that lowering of cholesterol can significantly reduce risk for cardiovascular diseases. More recently, oxidation of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis. Oxidized LDL, but not native LDL, promotes vascular dysfunction by exerting direct cytotoxicity toward endothelial cells, by increasing chemotactic properties for monocytes, by transforming macrophages to foam cells via scavenger-receptors and by enhancing the proliferation of various cell types, e.g., endothelial cells, monocytes and smooth muscle cells; all of these events are recognized as contributing to atherogenesis. In this paper, experimental evidence is presented that shows that several garlic compounds can effectively suppress LDL oxidation in vitro. Short-term supplementation of garlic in human subjects has demonstrated an increased resistance of LDL to oxidation. These data suggest that suppressed LDL oxidation may be one of the powerful mechanisms accounting for the antiatherosclerotic properties of garlic.
Article
Oxidation of low-density lipoprotein (LDL) and activation of the pleiotropic transcription factor nuclear factor kappa B (NF-kappaB), are often the chemical and molecular alterations associated with the development of the atherosclerotic lesion. We have reported previously on the antioxidant properties of a garlic compound, S-allyl cysteine (SAC), and its ability to inhibit damage caused by oxidative stress in bovine endothelial cells. In this study, the antioxidant effects of SAC were further determined, using several in vitro assay systems. First, we determined the effect of SAC on Cu2+-induced oxidation of LDL. Varying concentrations of SAC were co-incubated with a standardized Cu2+/LDL solution, and LDL-oxidation was then ascertained by determining the formation of thiobarbituric acid reactive substances (TBARS). SAC inhibited LDL-oxidation at an optimum concentration of 1 mM. In another experiment, we determined the effects of SAC on oxidized-LDL (ox-LDL) activation of J774 murine macrophages and human umbilical vein endothelial cells (HUVEC). Cells were grown on 96-well plates, preincubated with SAC at 37 degrees C and 5% CO2 for 24 h, washed, and exposed to ox-LDL for 24 h. Levels of hydrogen peroxide (H2O2) were determined by a fluorometric assay. In both cell lines, SAC exhibited dose-dependent inhibition of H2O2 formation. We also studied the effects of SAC on NF-kappaB activation in HUVEC using tumor necrosis factor-a (TNF-alpha) or H2O2 as stimulators. Cells were grown in 75 cm2 flasks at 37 degrees C and 5% CO2 and were preincubated with SAC 24 h before stimulation with TNF-alpha or H2O2. Nuclear extracts were then prepared and NF-kappaB activation was determined using an electrophoretic mobility shift assay with a 32P-labeled probe. SAC exhibited dose-dependent inhibition of NF-kappaB activation. Our data suggest that SAC may act via antioxidant mechanisms to inhibit the atherogenic process.
Article
Our aim was to determine the usefulness of circulating oxidized low density lipoprotein (LDL) in the identification of patients with coronary artery disease (CAD). A total of 304 subjects were studied: 178 patients with angiographically proven CAD and 126 age-matched subjects without clinical evidence of cardiovascular disease. The Global Risk Assessment Score (GRAS) was calculated on the basis of age, total and high density lipoprotein cholesterol, blood pressure, diabetes mellitus, and smoking. Levels of circulating oxidized LDL were measured in a monoclonal antibody 4E6-based competition ELISA. Compared with control subjects, CAD patients had higher levels of circulating oxidized LDL (P<0.001) and a higher GRAS (P<0.001). The sensitivity for CAD was 76% for circulating oxidized LDL (55% for men and 81% for women) compared with 20% (24% for men and 12% for women) for GRAS, with a specificity of 90%. Logistic regression analysis revealed that the predictive value of oxidized LDL was additive to that of GRAS (P<0.001). Ninety-four percent of the subjects with high (exceeding the 90th percentile of distribution in control subjects) circulating oxidized LDL and high GRAS had CAD (94% of the men and 100% of the women). Thus, circulating oxidized LDL is a sensitive marker of CAD. Addition of oxidized LDL to the established risk factors may improve cardiovascular risk prediction.
Article
Nitric oxide (NO) controls several physiological functions of the cardiovascular system. Three kinds of NO synthases (NOSs), neuronal constitutive NOS (ncNOS), inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS), were responsible for NO biosynthesis. This study investigated the effect of aged garlic extract (AGE) on NO production by measuring the NO metabolites nitrite and nitrate in the plasma of mice. AGE (2.86 g/kg, p.o.) temporarily increased NO production by 30-40% from 15 to 60 min after administration. The time course of the fluctuation in NO levels in the AGE-treated group was clearly different to that in a group of mice treated with lipopolysaccharides, a typical iNOS inducer. Arginine (63 mg/kg, p.o.) at the equivalent dose of AGE did not increase NO production. However diphenyleneiodonium chloride (1 mg/kg, i.p.), a selective cNOS inhibitor, administered prior to AGE, overcame the effect of AGE. These results indicate that AGE increased NO production by activating cNOS, but not iNOS. The arginine contained in AGE was not responsible for the effect. AGE may be a useful tool for the prevention of cardiovascular disease.
Article
To assess the effects of dietary modifications on oxidized low-density lipoprotein (LDL). Thirty-seven healthy women were fed two diets. Both diets contained a reduced amount of total and saturated fat. In addition, one diet was low in vegetables and the other was high in vegetables, berries, and fruit. The dietary intake of total fat was 70 g per day at baseline and decreased to 56 g (low-fat, low-vegetable diet) and to 59 g (low-fat, high-vegetable diet). The saturated fat intake decreased from 28 g to 20 g and to 19 g, and the amount of polyunsaturated fat intake increased from 11 g to 13 g and to 19 g (baseline; low-fat, low-vegetable; low-fat, high-vegetable; respectively). The amount of oxidized LDL in plasma was determined as the content of oxidized phospholipid per ApoB-100 using a monoclonal antibody EO6 (OxLDL-EO6). The median plasma OxLDL-EO6 increased by 27% (P<0.01) in response to the low-fat, low-vegetable diet and 19% (P<0.01) in response to the low-fat, high-vegetable diet. Also, the Lp(a) concentration was increased by 7% (P<0.01) and 9% (P=0.01), respectively. Alterations in the dietary fat intake resulted in increased plasma concentrations of lipoprotein(a) and OxLDL-EO6.
Article
Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact. We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2+/-0.7 years. Mean LDL level did not differ between groups (118+/-25 mg/dL versus 122+/-30 mg/dL, MI versus no MI). On average, MI subjects demonstrated a CAC change of 42%+/-23% yearly; event-free subjects showed a 17%+/-25% yearly change (P=0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression (P<0.0001). In a Cox proportional hazard model, the follow-up score (P=0.034) as well as a score change >15% per year (P<0.001) were independent predictors of time to MI. Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.