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Black Garlic

 

Front Physiol. 2018; 9: 1435. 

Published online 2018 Nov 1. doi: 10.3389/fphys.2018.01435

PMCID: PMC6221913

PMID: 30443217

Black Garlic Improves Heart Function in Patients With Coronary Heart Disease by Improving Circulating Antioxidant Levels

Jingbo LiuGuangwei ZhangXiaoqiang Cong, and  Chengfei Wen*

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Abstract

Background: Black garlic (BG) has many health-promoting properties.

Objectives: We aimed to explore the clinical effects of BG on chronic heart failure (CHF) in patients with coronary heart disease (CHD).

Design: The main components of BG were measured by gas chromatography–mass spectrometry (GC–MS) and its antioxidant properties were determined by the clearance rate of free radicals. One hundred twenty CHF patients caused by CHD were randomly and evenly assigned into BG group and placebo group (CG). The duration of treatment was 6 months. Cardiac function was measured according to the New York Heart Association (NYHA) functional classification system. The following parameters were measured, including walking distance, BNP precursor N-terminal (Nt-proBNP), left-ventricular ejection fraction (LVEF) value, and the scores of quality of life (QOL). The circulating antioxidant levels were compared between two groups.

Results: There are 27 main compounds in BG with strong antioxidant properties. BG treatment improved cardiac function when compared with controls (P < 0.05). The QOL scores and LVEF values were higher in the BG group than in the CG group while the concentration of Nt-proBNP was lower in the BG group than in the CG group (P < 0.05). Circulating antioxidant levels were higher in the BG group than in the CG group. Antioxidant levels had positive relation with QOL and LVEF values, and negative relation with Nt-proBNP values.

Conclusion: BG improves the QOL, Nt-proBNP, and LVEF in CHF patient with CHD by increasing antioxidant levels.

Keywords: coronary heart disease, congestive heart failure, quality of life, left-ventricular ejection fraction, black garlic

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Introduction

Chronic heart failure (CHF) may be caused by myocardial abnormalities, which result in systolic and/or diastolic ventricular dysfunction, abnormalities of the valves, pericardium, endocardium, heart rhythm, a reduced cardiac output, or brain abnormalities (12). Vasomotor function cannot meet the needs of systemic metabolism, resulting in hemodynamic abnormalities and neurohormonal activation (Hammadah et al., 2017). There are 26 million CHF patients worldwide and the prevalence of CHF is still increasing with population aging (Schmid et al., 2017). CHF is a common cause of death in the elderly (Andres et al., 2018Clark, 2018). Five-year mortality rate of CHF is more than 20%, and seriously threatens human life (Nakajima et al., 2014). Considering its poor prognosis, it is critical to prevent the occurrence and development of CHF and to promote early rehabilitation of CHF patients.

Garlic is a kind of valuable atherosclerosis-preventing functional food (Alali et al., 2017). Many reports showed that garlic had lipid-lowering, plasma anticoagulant and antioxidant activities, and improves endothelial injuries (Gorinstein et al., 2007). The extract of garlic was effective to reduce blood pressure, arterial stiffness, inflammation, and other cardiovascular diseases (Ried et al., 2016). Garlic is a kind of feasible and promising functional food for individuals with cardiovascular disease (Aslani et al., 2016Siddiqui et al., 2017).

Black garlic (BG) is a kind of deep-processed food made of fresh garlic under high temperatures and humidity. It can improve immune activity with fewer side effects (Nakasone et al., 2016). BG has many health-promoting properties: BG prevented the growth and induced apoptosis of HT29 colon cancer cells via phosphatidylinositol 3-kinase (PI3K)/Akt pathway, suggesting that BG may be effective in the therapy of colon cancer (9); BG had potential beneficial effects in the treatment of diabetes by increasing in the numbers of monocytes and granulocytes, and decreasing lymphocyte proliferation (10); BG has anti-allergic actions and may be beneficial as functional food in the prevention of allergic disorders (11). BG has various biological functions, including antioxidant (Lu et al., 2017Sun and Wang, 2018), anti-inflammatory (Jeong et al., 2016), anticancer (Dong et al., 2014), antidiabetic (Abel-Salam, 2012), anti-allergic action (Yoo et al., 2014), and the improvement of lipid metabolism (Ha et al., 2015), cardiac (Czompa et al., 2018), and hepatic protection (Kim et al., 2011; Figure ​Figure1).1). However, the effects of BG on the CHF patients and the related molecular mechanisms remain unknown.

 

 

 

Integr Blood Press Control. 2016; 9: 9–21. 

Published online 2016 Jan 27. doi: 10.2147/IBPC.S93335

PMCID: PMC4734812

PMID: 26869811

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

Karin Ried,1,2,3 Nikolaj Travica,1 and  Avni Sali1

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Abstract

Background

Hypertension affects 30% of adults worldwide. Garlic supplements have shown promise in the treatment of uncontrolled hypertension, and the mechanism of action is biologically plausible. Our trial is the first to assess the effect of aged garlic extract on central blood pressure and arterial stiffness, regarded as important risk factors for cardiovascular morbidity.

Subjects and methods

A total of 88 general practice patients and community members with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12 weeks investigating the effect of daily intake of aged garlic extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, and secondary outcome measures of central-hemodynamics and other cardiovascular markers, including cholesterol, homocysteine, platelet function, and inflammatory markers.

Results

Mean blood pressure was significantly reduced by 5.0±2.1 mmHg (P=0.016) systolic, and in responders by 11.5±1.9 mmHg systolic and 6.3±1.1 mmHg diastolic compared to placebo (P<0.001). Central hemodynamic-measures tended to improve in the garlic group more than in the placebo group, including central blood pressure, central pulse pressure, mean arterial pressure, augmentation pressure, pulse-wave velocity, and arterial stiffness. While changes in other cardiovascular markers did not reach significance due to small numbers in subgroups with elevated levels, trends in beneficial effects of garlic on the inflammatory markers TNFα, total cholesterol, low-density lipid cholesterol, and apolipoproteins were observed. Aged garlic extract was highly tolerable and acceptable, and did not increase the risk of bleeding in patients on blood-thinning medication.

Conclusion

Our trial suggests that aged garlic extract is effective in reducing peripheral and central blood pressure in a large proportion of patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in patients with elevated levels. Aged garlic extract was highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment.

Keywords: hypertension, central blood pressure, arterial stiffness, cardiovascular risk factors, aged garlic extract

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Introduction

Hypertension affects 1 billion (one in four) adults worldwide, and attributes to about 40% of cardiovascular-related deaths.13 Standard antihypertensive medication is not always effective, leaving about 24% (3 million) of the adult population uncontrolled hypertensive.4 Garlic supplements have been associated with a blood pressure (BP)-lowering effect of clinical significance in hypertensive patients.58 The mechanism of action is biologically plausible, whereby garlic’s BP-lowering effect involves the hydrogen sulfide- and nitric oxide-signaling pathways.9 Garlic in the form of Kyolic aged garlic extract is particularly effective and tolerable with a high safety profile, and standardized by dosage of the active ingredient S-allylcysteine (SAC).6,10

While previous research has shown aged garlic extract to reduce peripheral BP,58 this study is the first to assess the effect of aged garlic extract on central hemodynamic measures, including central BP, central pulse pressure, pulse-wave velocity (PWV), and arterial stiffness.

Central hemodynamic measures and arterial stiffness are regarded as more important predictors or risk factors than peripheral BP for cardiovascular disease.11 Furthermore, arterial stiffness, an indicator of the loss of flexibility or hardening of the arteries, increases with age through loss of intact elastin and collagen fibers in the arterial wall, leading to atherosclerosis and contributing to increased BP.12 However, arterial stiffness is one of many other risk factors contributing to hypertension.

Here, we describe the effect and tolerability of aged garlic extract as an adjunct treatment on peripheral (office/clinical) BP, central hemodynamic measures, and cardiovascular markers in patients with uncontrolled hypertension.

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Subjects and methods

Trial design and methods

This study was approved by the Human Research Ethics Committee at National Institute of Integrative Medicine, and the trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12613000747729). Participants provided informed written consent.

Adults with uncontrolled hypertension (systolic BP [SBP] ≥140 mmHg and/or diastolic BP [DBP] ≥90 mmHg) were sought to participate in the double-blind randomized placebo-controlled parallel 12-week trial investigating the effect of aged garlic extract on BP and other cardiovascular markers/parameters. We recruited through seven general practices in metropolitan Melbourne, Australia, as well as by distribution locally of flyers, postcards, advertising in the local newspaper, our institute’s website, and social media. We included patients with a mean SBP ≥138 mmHg or mean DBP ≥85 mmHg under clinical trial conditions who had been either on an established plan of prescription antihypertensive medication for at least 2 months or did not take any BP medication and their doctor did not plan to change their BP-medication regime during the trial. We excluded patients with unstable or serious conditions, including dementia, terminal illness, secondary hypertension, or pregnancy. Patients were also excluded if they were not able to give informed consent or were taking daily supplements containing aged garlic extract.

Allocation and treatment

Consenting eligible patients were randomly allocated to the garlic or placebo group using a computer-generated permuted random-number table provided by an independent consulting statistician. Patients were assigned either two capsules daily of Kyolic aged garlic extract (Reserve formula; Wakunaga of America Co Ltd, Mission Viejo, CA, USA)13 containing 1.2 g of aged garlic extract powder and 1.2 mg SAC) or to two placebo capsules daily for 12 weeks.

Kyolic aged garlic extract powder is manufactured from organically grown garlic bulbs that have undergone a 20-month natural aging process at room temperature. During the aging process, volatile sulfur components found in raw garlic, such as allicin, are chemically converted into stable and standardizable components, including the main active component SAC.13,14

Placebo capsules were matched in appearance to the active capsules, and packaged in identical containers by independent staff not involved in the trial. Activated carbon sachets were added to each container to disguise any odor.

Patients, investigators, and research assistants were blinded to treatment allocation. Blinding success of patients was assessed at the end of the trial by questionnaire. Patients were instructed to take the trial capsules in the evening with food. Patients were reminded to take their usual prescription medication as instructed by their doctor. Compliance was assessed by daily entries in calendars provided. Baseline demographics, exercise, and stress levels were assessed at the first appointment by questionnaire.

Assessments

 

Blood pressure monitoring 

 

Clinical blood pressure 

Primary outcome measures were SBP and DBP at 4, 8, and 12 weeks compared with baseline. BP was measured by a trained research assistant using two independent devices: 1) a calibrated and validated digital sphygmomanometer (HEM-907; Omron Corporation, Kyoto, Japan), and 2) an oscillometric ambulatory BP monitor (Mobil-O-Graph; IEM GmbH, Stolberg, Germany), with appropriately sized brachial cuffs.

The displays of the BP monitors were positioned away from the patient to assure blinding to the BP readings. BP measurements were taken with the patient in a seated position with the arm supported at heart level, after 5 minutes’ rest, and after abstinence from food, caffeinated beverages, and smoking for a minimum of 2 hours prior to BP measurement at approximately the same time and day of the week. BP taken with the digital sphygmomanometer was recorded as three serial measurements at intervals of 30 seconds on both arms. Subsequently, BP was recorded with the Mobil-O-Graph device once on both arms, starting with the same arm as before. The mean of the BP measured with both devices on both arms was used in the analysis. If a BP reading deviated by more than 10 mmHg from the average reading, the BP reading on that arm was repeated.

 

Central blood pressure, arterial stiffness 

With the Mobil-O-Graph device, we also assessed central hemodynamic measures, including central BP, PWV, pulse pressure, and arterial stiffness at baseline and 4, 8, and 12 weeks. The Mobil-O-Graph uses brachial oscillometric BP waves for a noninvasive estimation of central BP, by taking a 10-second snapshot of the radial arterial pressure wave and calculating the ascending aortic pressure wave with the ARCSolver algorithm, which in turn provides central BP, aortic augmentation index, ejection duration, and subendocardial viability ratio.15 The Mobil-O-Graph has been validated for automated BP monitoring against invasive recordings using benchmark solid-state pressure sensor-tipped catheters (Millar Instruments, Houston, TX, USA) and against a validated US Food and Drug Administration-approved noninvasive system (SphygmoCor; AtCor Medical Inc., Sydney, Australia).16,17

Aortic PWV is considered the gold standard in the assessment of arterial stiffness,11 and can be measured non-invasively by brachial oscillometry or radial tonometry using the Mobil-O-Graph monitor.18 Measures of arterial stiffness, including augmentation pressure, augmentation index, and PWV, are strongly correlated with age and sex.19,20

 

Cardiovascular biomarkers 

Fasted blood samples were taken by a research nurse at baseline and at 12 weeks to assess cardiovascular biomarkers, including serum cholesterol and triglycerides, lipoproteins, homocysteine, platelet function, and the inflammatory markers of ultrasensitive CRP, TNFα, and IL-1β. Platelet function was measured by clotting time on epinephrine/collagen and adenosine diphosphate/collagen using the PFA-100 platelet-function analyzer (Siemens AG, Munich, Germany), indicating platelet adhesion, activation, and aggregation. Principally, results indicate the longer the closure time the thinner the blood, and the shorter the closure time the thicker or stickier the blood. Liver and kidney function and glucose levels were also assessed by standard pathology assays.

Tolerability and acceptability

The tolerability of trial supplements was monitored throughout the trial by questionnaire at the 4-weekly appointments, and long-term acceptability was assessed at 12 weeks using our previously developed questionnaire.5,6 Patients were followed up by phone to assess reasons for withdrawal.

Sample size

A sample size of 100 patients was calculated based on the following assumptions: 1) to detect a difference of 10 mmHg SBP (standard deviation 10) or 6.5 mmHg DBP (standard deviation 10) in BP change between the active treatment (n=50) and control groups (n=50) with a power of ≥80% and 95% confidence; and 2) to account for 20% dropout or nonattendance at all appointments. Based on the experience of our previous trials,5,6 assuming a response rate of 15% and 50% of patients meeting eligibility criteria under trial conditions, we aimed to invite 1,630 patients from seven general practices.

Statistical analysis

Analyses were performed using IBM SPSS version 22. Statistical significance was set at P<0.05. Descriptive analysis was carried out for baseline characteristics. Differences between the groups were assessed by χ2 test or Fisher’s exact test for binominal variables, Mann–Whitney U test for ordinal variables, and one-way analysis of variance with Bonferroni adjustment for continuous variables. Potential confounding variables were included in the analysis using analysis of covariance (ANCOVA), eg, age and sex relevant for some central hemodynamic measures, and any baseline variables significantly different between groups. Primary outcome measures were clinical and central BP, and secondary outcome measures were other hemodynamic measures and cardiovascular markers.

Repeated-measure ANCOVA was used to assess the mean differences between groups for variables with multiple time points at 4, 8, and 12 weeks compared to baseline, including SBP and DBP and other central hemodynamic measures. Primary analysis was conducted with all participants following the protocol, excluding data points owing to BP-medication change and participant noncompliance of less than 50%.

Exploratory subgroup analysis using ANCOVA adjusted for baseline differences was performed by response to treatment for the primary outcome measure – BP. We defined responders to garlic treatment as mean reduction by more than 3% in SBP (≥5 mmHg) or DBP (≥3 mmHg) over time compared to baseline, which is clinically and statistically meaningful and similar to definitions by others.21

Exploratory subgroup analysis of secondary outcome measures using ANCOVA adjusted for age and sex was done by baseline levels (elevated versus normal) of selected central hemodynamic measures (eg, PWV, augmentation pressure, and augmentation index), and selected cardiovascular blood markers (total cholesterol, low-density lipoprotein [LDL], apolipoprotein A/B (ApoA/B), homocysteine, and platelet-function markers).

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Results

Participants

The trial was conducted in Melbourne, Australia between September 2013 and August 2014. Two-thirds of the patients with uncontrolled hypertension on medical record were recruited from seven metropolitan general practices with the support of eleven doctors. A third of the patients were recruited by letterbox drop of flyers, postcard displays at local pharmacies, advertising in the local newspaper, and through our institute’s website and social media. Of the 1,170 invitations sent through general practices, 13% responded. A total of 185 patients were screened for eligibility, and 104 patients (56%) were enrolled in the trial and randomly allocated to the garlic or the placebo group. Nine patients withdrew after their baseline assessment, due to personal reasons unrelated to the trial (Figure 1). After assessment of brachial BP and central hemodynamic measures using the digital sphygmomanometer and the ambulatory BP monitor (Mobil-O-Graph), eligible enrolled patients were asked to return to the clinic within the next few days for a fasted blood sample. On the day of the baseline blood-sample test, patients were provided with a month’s supply of the trial medication and a calendar, until the next appointment in 4 weeks’ time.

 

 

 

 

J Nutr. 2016 Feb;146(2):389S-396S. doi: 10.3945/jn.114.202192. Epub 2016 Jan 13.

Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review.

Ried K1.

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Abstract

BACKGROUND: 

Garlic has been shown to have cardiovascular protective and immunomodulatory properties.

OBJECTIVES: 

We updated a previous meta-analysis on the effect of garlic on blood pressure and reviewed the effect of garlic on cholesterol and immunity.

METHODS: 

We searched the Medline database for randomized controlled trials (RCTs) published between 1955 and December 2013 on the effect of garlic preparations on blood pressure. In addition, we reviewed the effect of garlic on cholesterol and immunity.

RESULTS: 

Our updated meta-analysis on the effect of garlic on blood pressure, which included 20 trials with 970 participants, showed a mean ± SE decrease in systolic blood pressure (SBP) of 5.1 ± 2.2 mm Hg (P < 0.001) and a mean ± SE decrease in diastolic blood pressure (DBP) of 2.5 ± 1.6 mm Hg (P < 0.002) compared with placebo. Subgroup analysis of trials in hypertensive subjects (SBP/DBP ≥140/90 mm Hg) at baseline revealed a larger significant reduction in SBP of 8.7 ± 2.2 mm Hg (P < 0.001; n = 10) and in DBP of 6.1 ± 1.3 mm Hg (P < 0.001; n = 6). A previously published meta-analysis on the effect of garlic on blood lipids, which included 39 primary RCTs and 2300 adults treated for a minimum of 2 wk, suggested garlic to be effective in reducing total and LDL cholesterol by 10% if taken for >2 mo by individuals with slightly elevated concentrations [e.g., total cholesterol >200 mg/dL (>5.5 mmol/L)]. Garlic has immunomodulating effects by increasing macrophage activity, natural killer cells, and the production of T and B cells. Clinical trials have shown garlic to significantly reduce the number, duration, and severity of upper respiratory infections.

CONCLUSIONS: 

Our review suggests that garlic supplements have the potential to lower blood pressure in hypertensive individuals, to regulate slightly elevated cholesterol concentrations, and to stimulate the immune system. Garlic supplements are highly tolerated and may be considered as a complementary treatment option for hypertension, slightly elevated cholesterol, and stimulation of immunity. Future long-term trials are needed to elucidate the effect of garlic on cardiovascular morbidity and mortality.

© 2016 American Society for Nutrition.

KEYWORDS: 

cholesterol; garlic; hypertension; immunity; meta-analysis

PMID:

26764326

DOI:

10.3945/jn.114.202192

[Indexed for MEDLINE] 

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