Garlic (Blood Pressure)

Numerous clinical trials have examined the effects of aged garlic (AG) on metabolic factors, yielding inconsistent results. This systematic review and meta-analysis aimed to evaluate the impact of aged garlic on blood pressure (BP) and lipid profiles (LP). A comprehensive search was conducted across Scopus, PubMed, Medline via Ovid, ISI Web of Science, and Google Scholar until May 2024. We included clinical trials that assessed various forms of aged garlic as an intervention on systolic and diastolic blood pressure (SBP and DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Nineteen trials were included in this analysis. AG consumption significantly reduced SBP (WMD: -2.49 mmHg; 95% CI: -4.02 to -0.95; I2 = 29.76%) and LDL (WMD: -4.41 mg/dL; 95% CI: -8.28 to -0.54; I2 = 55.78%). However, it did not significantly affect DBP and HDL, although the effect on TC approached significance (WMD: -4.74 mg/dL; 95% CI: -9.49 to 0.01; I2 = 74.84%). Subgroup analyses indicated that AG significantly affected SBP and TG in participants with cardiovascular diseases (CVDs), while it also considerably impacted DBP in patients with hypercholesterolemia. Aged garlic may be a beneficial complementary approach for reducing BP and lipid levels in specific populations. Further high-quality trials are needed to confirm these findings. © 2025 John Wiley & Sons Ltd.

BACKGROUND: There is no consensus based on the existing literature regarding the effect of aged garlic extract (AGE) on blood pressure. The present systematic review and meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of AGE supplementation on blood pressure in hypertensive patients. METHODS: We searched English web databases including, PubMed, Scopus, Embase, Web of Science until August 2024. Random-effects meta-analysis was used to pool weighted mean differences (WMD) and 95 % CI for the outcomes. RESULTS: Overall, nine RCTs with584 participants met inclusion criteria. AGE tea supplementation reduces systolic blood pressure (SBP) (WMD: -4.03; %95CI: -6.87, -1.20; I2: 57.1 %) and diastolic blood pressure (DBP) (WMD: -1.44; 95 % CI= -2.87, -0.02; P = 0.052; I2: 36.8 %; P: 0.105). Moreover, subgroup analysis indicated that higher doses of AGE supplementation in hypertensive patients significantly decreased DBP, and SBP. CONCLUSION: The results of this study suggest that AGE supplements may be beneficial for improving blood pressure in hypertensive patients, but significant effects are observed only at doses over 1200 mg/day. To confirm these results, well-designed future trials will be needed.

3. Prostaglandins Other Lipid Mediat. 2024 Dec;175:106914. doi: 10.1016/j.prostaglandins.2024.106914. Epub 2024 Oct 20. Effects of aged garlic extract on blood pressure in hypertensive patients: A systematic review and meta-analysis of randomized controlled trials. Saadh MJ(1), Kariem M(2), Shuk

BACKGROUND: Garlic (Allium sativum), the underground bulb of the Allium genus, has been consumed on Earth for thousands of years. Many clinical trials of garlic supplementation on components of metabolic syndrome (MetS) have emerged in recent years, but there is no consensus on the effect. This meta-analysis aimed at systematically evaluating the effect of garlic supplementation on components of MetS. METHODS: In this meta-analysis, we searched Pubmed, Embase, Cochrane, Medline, Web of Science databases, and clinical trials online sites from inception to November 1, 2022, with language restrictions to English. We engaged participants > 18 years and eligible for the clinical diagnosis of MetS or those with metabolic disorders and garlic was the only intervention. Outcomes included waist circumference, and body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure, and fasting blood glucose. Meta-regression and subgroup analyses were conducted based on six covariates (total sample size, the mean age, the mean dose, the duration of intervention, the oral form of garlic, and the dietary intervention). RESULTS: Results from 19 RCTs were included engaging 999 participants. Compared to placebo, garlic significantly reduced TG [SMD (95%CI) = -0.66 (-1.23, -0.09)], TC [SMD (95%CI) = -0.43 (-0.86, -0.01)], LDL [SMD (95%CI) = -0.44(-0.88, -0.01)], DBP [SMD (95%CI) = -1.33 (-2.14, -0.53)], BMI [SMD (95%CI) = -1.10(-1.90, -0.20)], and WC [SMD (95%CI) = -0.78(-1.09, -0.47)]. Meta-regression showed age and sample size are potential effect modifiers. CONCLUSION: According to the results of meta-analysis, the modulatory effect of garlic on some MetS components is evident. More high-quality, large-scale RCTs are needed to confirm iat based on the high heterogeneity and potential publication bias of the current data. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=373228 , ID: CRD42022373228. © 2023. The Author(s).

AIMS: The aim of the present study was to review and comment on the available evidence on nutraceuticals with a clinically demonstrable blood pressure (BP)-lowering effect. METHODS: We reviewed studies published in the English language from 1990 to 2015 on dietary supplements or nutraceuticals claiming to show an effect on human BP. An initial list of possibly effective agents and studies was obtained from the online reference, the Natural Medicine Comprehensive Database. Using PubMed, we searched agents identified from this list using the MeSH terms 'hypertension', 'blood pressure', 'dietary supplement' and 'nutraceuticals', alone and in combination. We then focused our attention on meta-analyses and randomized clinical trials. RESULTS: Beyond the well-known effects on BP of the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, a large number of studies have investigated the possible BP-lowering effect of different dietary supplements and nutraceuticals, most of which are antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence supports the use of potassium, magnesium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin and aged garlic extract. The antihypertensive effect of all these nutraceuticals seems to be dose related and the overall tolerability is good. CONCLUSION: Some nutraceuticals might have a positive impact on BP in humans. Further clinical research is needed, to identify from the available active nutraceuticals those with the best cost-effectiveness and risk-benefit ratio for widespread and long-term use in the general population with a low-added cardiovascular risk related to uncomplicated hypertension. © 2016 The British Pharmacological Society.

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 Ame

Garlic supplements are thought to reduce blood pressure (BP). The authors performed a meta-analysis to investigate garlic's effect on BP. Ovid Medline, Cochrane Library, and PubMed (1946 to November 2013) were used to search for randomized controlled trials. Seventeen trials were included. Pooled analysis showed that garlic intake caused a 3.75-mm Hg reduction (95% confidence interval [CI], -5.04 to -2.45, I(2) =30.7%; P<.001) in systolic BP and a 3.39-mm Hg reduction (95% CI, -4.14 to -2.65, I(2) =67%; P<.001) in diastolic BP compared with controls. Meta-analysis of subgroups showed a significant reduction in systolic BP in hypertensive (-4.4 mm Hg; 95% CI, -7.37 to -1.42, I(2) =0.0%; P=.004) but not normotensive patients. No significant reduction in diastolic BP was seen. After sensitivity analysis, heterogeneity disappeared and significant diastolic BP reduction (-2.68 mm Hg, 95% CI, -4.93 to -0.42, I(2) =0.0%; P=.020) was shown in hypertensive patients. This meta-analysis suggests that garlic supplements are superior to controls (placebo in most trails) in reducing BP, especially in hypertensive patients. ©2015 Wiley Periodicals, Inc.

BACKGROUND: This study aimed to illustrate the effect of garlic supplementation on metabolic syndrome (MetS) components in women with polycystic ovary syndrome (PCOS). METHODS: From 2020 to 2021, a randomized controlled clinical trial was conducted on 97 women with PCOS and MetS. Participants were randomly assigned to receive either garlic tablets (500 mg containing 2-3 mg allicin; n = 49) or placebo tablets (n = 48) twice daily for 8 weeks. The study assessed changes in MetS indices, quality of life (QoL), and sexual function before and after the intervention. RESULTS: After 8 weeks, the garlic group showed significant reductions in fasting blood sugar (FBS) by 10.5% (from 107.2 to 95.9 mg/dL; P < 0.001), triglycerides (TG) by 17.8% (P = 0.002), low-density lipoprotein cholesterol (LDL-C) by 14.2% (P < 0.001), total cholesterol (TC) by 12.6% (P < 0.001), and C-reactive protein (CRP) by 24.7% (P < 0.001), compared to the placebo group. A significant increase in sex hormone-binding globulin (SHBG) levels was also observed (18.3%; P = 0.005). Systolic and diastolic blood pressure decreased significantly by 5.2% and 6.1%, respectively (P < 0.001 and P = 0.001), and both weight and body mass index (BMI) were significantly reduced (P < 0.01). However, the waist-to-hip ratio (WHR) did not change significantly (P = 0.86). Notable improvements were also observed in all six domains of the Female Sexual Function Index (FSFI)- desire, arousal, lubrication, orgasm, satisfaction, and pain (P < 0.05 for all). Moreover, significant enhancements were recorded in all domains of the Modified Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (MPCOSQ), including hirsutism, acne, weight, infertility, menstrual, and emotional disturbances (P < 0.001 for all). The study's limitations include a relatively short follow-up period, lack of strict dietary control, and the omission of some relevant hormonal assays (e.g., androstenedione, DHEA, and DHEAS) due to budgetary constraints. CONCLUSIONS: The results suggest that garlic supplementation may be an effective strategy for managing MetS markers in women with PCOS. TRIAL REGISTRATION: IRCT20150905023897N4, Registratio

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.

OBJECTIVES: Hypertension, substantially heightens the risk of cardiovascular disease. This study aims to evaluate the effectiveness of freeze-dried garlic extract in blood pressure and lipid profiles in prehypertensive individuals. METHODS: Participants (age of 30-70 years) were allocated to intervention (n=47) or control (n=49) groups. The intervention group received two capsules of freeze-dried garlic extract daily for eight weeks, while the control group received identical placebo capsules. Primary outcomes, SBP, DBP, PP, MAP, TC, TG, LDL and HDL levels, serum NO levels, were assessed at baseline, four weeks, and eight weeks. RESULTS: At the end of study, results showed significant changes in the values of SBP, DBP, and MAP except for PP. In comparison to those who received the placebo, a significant drop in SBP, DBP (p<0.001), and MAP (p<0.001) was observed in the intervention group. Also, there were significant changes in TG, LDL, TC, and HDL levels in the interventional group. A noticeable decline was reported in TG (p<0.001), LDL (p<0.001), and TC (p<0.001), while HDL levels increased (p<0.001) in the intervention group compared to those receiving the placebo. Following garlic supplementation, a significant increase in blood NO levels was reported in the intervention group (p<0.001). CONCLUSIONS: The study showed that garlic supplementation was effective in lowering blood pressure, improving lipid profile, and increasing nitric oxide levels in prehypertensive participants. These results indicate that garlic could be a valuable complementary therapy for managing prehypertension. © 2024 Walter de Gruyter GmbH, Berlin/Boston.

The use of garlic (Allium sativum) for treating arterial hypertension has been recognized as effective for several decades. However, tolerance to treatment is low, and several technological modifications have been developed to improve its tolerability, such as the aging process at controlled temperature and humidity. This study aims to validate the antihypertensive effects of an optimized extract of aged black garlic with low doses of s-allyl-cysteine (SAC) in a Grade I hypertensive population with drug treatment. A randomized, triple-blind, placebo-controlled parallel trial was developed, where a daily supplementation with 0.25 mg/day of SAC for 12 weeks was performed. A reduction in systolic and diastolic blood pressure of 1.8 mmHg (0.7 to 4.1 95% CI) and 1.5 mmHg (0.3 to 3.0 95% CI), respectively, was observed. Similarly, an increase in blood nitric oxide (10.3 µM, 1.1 to 19.5 95% CI) and antioxidant capacity (7 × 10-3 µM TE/min, (1.2 to 13 × 10-3 95% CI) and a reduction in uric acid levels (-0.3 mg/dL, -0.5 to -0.001 95% CI) and ACE activity (-9.3 U/L; -18.4 to -0.4 95% CI) were observed. No changes in endothelial function and inflammatory cytokines were observed. It was concluded that low-dose SAC supplementation in an optimized black-garlic extract allows for an extra-significant reduction in blood pressure in a Grade I hypertensive population receiving drug treatment.

Aged or fermented garlic extract (FGE) is a natural remedy that improves vascular function through increasing vascular nitric oxide (NO) bioavailability. This is because nitrite (NO2-), a NO metabolite, can be produced through bioconversion with macrobacteria during the fermentation of foods like garlic. We aimed to evaluate the effects of NO2- in FGE on blood flow (BF), blood pressure (BP), velocity of the common carotid artery (CCA) and internal carotid artery (ICA), regional cerebral BF (rCBF), and peripheral BF (PBF). The study was divided into two parts: (1) Thirty healthy adults were divided into FGE and placebo groups to compare BP and velocity of the CCA and ICA; and (2) Twenty-eight healthy adults were divided into FGE and placebo groups to compare rCBF and PBF and determine changes before/after ingestion. Significant changes were noted in BP and the velocity of both CCA 30-60 min after FGE ingestion. FGE ingestion resulted in significant increases in rCBF and increases in body surface temperature through alterations in PBF. No detectable clinical side effects were noted. Overall, oral administration of NO2- containing FGE demonstrated acute positive effects in upregulating BF, including the CCA, BP, rCBF, and PBF. Follow-up studies with larger sample sizes and long-term ingestion may be needed.

PURPOSE: This study aimed to investigate the effects of AGE on microvascular reactivity, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in older individuals at high risk for cardiovascular disease (CVD). Urinary thiosulfate was also investigated as an indirect marker of endogenous hydrogen sulfide (H2S) synthesis. The study was conducted in a randomized, double-blind, crossover, and placebo-controlled way. METHODS: Twenty-eight participants (14 male), 67 ± 6 years old with CVD risk factors, ingested 2.4 g of AGE or placebo (PLA). Near-infrared spectroscopy evaluated tissue oxygen saturation (StO2) during a vascular occlusion test (30 s baseline, 5 min occlusion, and 2 min reperfusion). The upslope of StO2 signal after cuff release was calculated to measure microvascular reactivity. Urinary thiosulfate levels were measured using a high-performance liquid chromatography system. RESULTS: The upslope of StO2 was significantly faster after AGE (1.01 ± 0.37% s-1) intake compared to PLA (0.83 ± 0.35% s-1; P < 0.001; d = 0.50). Relative changes in Δ% SBP from pre- to post-AGE intake (- 5.17 ± 5.77%) was significantly different compared to Δ% PLA (0.32 ± 5.99%; P = 0.001; d = 0.93). No significant changes in urinary thiosulfate concentrations were observed between interventions. Moreover, no significant gender effect in any parameter assessed was found. CONCLUSION: This study demonstrated that a single dose of AGE improved microvascular reactivity in older adults at risk of CVD despite such an effect was not linked with urinary thiosulfate levels. This trial was registered at clinicaltrials.gov as NCT04008693 (May 19, 2020). © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

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

This study aimed to investigate the health-related effects of microencapsulated fermented garlic extract (FGE) containing dark chocolate in hypertensive adults. For this purpose, 36 hypertensive adults (15 males vs. 21 females) were randomized to receive the FGE (5 g/day) dark chocolate containing 650 mg of FGE powder or the placebo. Intervention periods lasted for 6 weeks and were separated by a 3-week wash-out period. The response variables included blood pressure, anthropometric indices, lipid profile, and inflammatory and oxidative stress indices. Statistical analyses were performed using the Pkcross procedure, and Cohen's d was estimated for all response variables. There was no significant inter-period difference between the mean changes of body weight, waist circumference, and body mass index (BMI). Furthermore, no significant change was confirmed in participants' blood pressure, triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), serum homocysteine, high-sensitive c-reactive protein (hs-CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC). It seems that the dose of FGE used in this study was not sufficient to cause any significant changes in the outcomes. Therefore, further studies with dose-response designs and longer durations are recommended. © 2022 John Wiley & Sons Ltd.

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrine-related disorder in reproductive ages. The aim of the study was to investigate the effect of garlic on the lipid parameters and blood pressure levels in women with PCOS. The present study was a randomized, double-blinded control trial, conducted on 80 PCOS patients. Participants were taught to intake either a total 800 mg/day garlic supplement or an identical placebo (starch) after lunch for 8 weeks. Physical activity, diet intake, anthropometric measures, and blood pressure were evaluated at baseline and end of the study. The blood sample was also taken to assess the change in outcomes of interest at the pre- and post-intervention. Garlic supplementation significantly reduced serum total cholesterol (change mean difference: -8.05, 95% CI: -15.47, -0.62) and LDL-C (change mean difference: -7.67, 95%CI: -14.64, -0.70) levels in comparison to the control group. In addition, a trend to a significant decrease was found in serum triglyceride levels and Systolic blood pressure; however, no significant difference was observed between two groups in HDL-C and diastolic blood pressure levels. The present study suggested that garlic supplementation might be effective on lipid markers improvement. Further studies are needed to confirm our findings. © 2021 John Wiley & Sons Ltd.

The prevalence of metabolic syndrome (MetS) is increasing. It is closely linked to nonalcoholic fatty liver disease. Garlic consumption as a strategy for the management of MetS has been suggested. We investigated the effect of garlic supplementation on MetS components, insulin resistance, fatty liver index (FLI), and appetite in subjects with MetS. Ninety subjects were assigned to receive 1,600 mg/d garlic powder or placebo for 3 months. The primary outcomes included MetS components. The secondary outcomes included insulin resistance, FLI, and appetite. Garlic supplementation compared with the placebo led to a significant increase in high density lipoprotein-cholesterol (4.5 vs. -1.8, p < .001) and a significant reduction in waist circumference (-1.3 vs. 0.0, p = .001), diastolic blood pressure (-6.7 vs. 0.0, p < .001), systolic blood pressure (-7.7 vs. 0.5, p < .001), triglyceride (-40.0 vs. 0.1, p < .001), γ-glutamyl transferase (-3.2 vs. 0.6, p = .01), FLI (-5.5 vs. 0.1, p < .001), insulin (-2.9 vs. -1.1, p < .001), homeostatic model of assessment for insulin resistance (-0.5 vs. -0.3, p < .001) and appetite (hunger: -11.7 vs. 1.7, p < .001; fullness: 10.0 vs. 0.3, p = .001; desire to eat: -6.7 vs. 2.1, p < .001; and ability to eat: -11.5 vs. -1.0, p < .001). Garlic improves MetS components, insulin resistance, FLI, and appetite. © 2021 John Wiley & Sons Ltd.

Clinical studies and case reports have identified a number of herb-drug interactions potentiated by the concurrent use of herbal medicines with prescription drugs. The purpose of this paper is to discuss the mechanisms and clinical implications of such herb-drug interactions by reviewing published human studies. Both pharmacokinetic and pharmacodynamic components may be involved in herbdrug interactions, although metabolic induction or inhibition is a common underlying mechanism for many herb-drug interactions. Drugs that have a high potential to interact with herbal medicines usually have a narrow therapeutic index, including warfarin, digoxin, cyclosporine, tacrolimus, amitriptyline, midazolam, indinavir, and irinotecan. Many of them are substrates of cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). Herbal medicines that are reported to interact with drugs include garlic (Allium sativum), ginger (Zingiber officinale), ginkgo (Ginkgo biloba), ginseng (Panax ginseng), and St. John's wort (Hypericum perforatum). For example, garlic has been shown to increase the clotting time and international normalized ratio (INR) of warfarin, cause hypoglycaemia when taken with chlorpropamide, and reduce the area under the plasma concentration-time curve (AUC) and maximum concentration of saquinavir in humans. Similarly, case reports have demonstrated that ginkgo may potentiate bleeding when combined with warfarin or aspirin, increases blood pressure when combined with thiazide diuretics, and has even led to a coma when combined with trazodone, a serotonin antagonist and reuptake inhibitor used to treat depression. Furthermore, ginseng reduced the blood levels of warfarin and alcohol as well as induced mania if taken concomitantly with phenelzine, a non-selective and irreversible monoamine oxidase inhibitor used as an antidepressant and anxiolytic agent. Lastly, multiple herb-drug interactions have been identified with St. John's wort that involve significantly reduced AUC and blood concentrations of warfarin, digoxin, indinavir, theophylline, cyclosporine, tacrolimus, amitriptyline, midazolam, and phenprocoumon. The clinical consequence of herb-drug interactions varies,

The purpose of the present study was to investigate the role of fresh garlic homogenate (FGH) and its bioactive sulphur compound S-allyl cysteine sulphoxide (SACS) in potentiating antihypertensive and cardioprotective activities of captopril in rats. SACS was extracted from the fresh garlic using ion exchange resins with yield of 890 mg/kg garlic. The dose of SACS was calculated based on the amount of SACS extracted from 125 to 250 mg of FGH. Albino rats weighing 150-200 g were fed with 10% fructose in fluid for 3 weeks for induction of hypertension and subsequently administered FGH (125 and 250 mg/kg, p.o.) or SACS (0.111 and 0.222 mg/kg/day, p.o.) for the next 3 weeks in their respective groups. In CAP alone and interactive groups (GH+CAP; SACS+CAP), captopril 30 mg/kg was given during sixth week of 10% fructose in fluid. At the end of drug treatment, animals were given isoproterenol 175 mg/kg subcutaneously for two consecutive days. Additionally, varying concentrations of SACS (4, 8, 16, 32 and 64 ng), CAP (1, 2, 4, 8 and 16 ng) and their combination (4:1) were checked for fall in blood pressure in hypertensive rats (10% fructose in fluid without pretreatment) as well as angiotensin-converting enzyme (ACE) inhibiting activity using guinea pig ileum. An isobolographic analysis was used to characterise the interaction between SACS and CAP for fall in blood pressure and ACE inhibiting evaluations. Administration of captopril, low and high doses of FGH (125, 250 mg/kg), either alone or together showed fall in fluid intake and body weight. The combined therapy of FGH 250 mg/kg and CAP was more effective in reducing systolic blood pressure, cholesterol, triglycerides and glucose. The SOD and catalase activities in heart tissue were significantly elevated in groups treated with FGH, SACS, CAP, FGH+CAP and SACS+CAP. Further, combined therapy of FGH 250 mg/kg and CAP caused significant fall in LDH and CK-MB activities in serum and elevation in heart tissue homogenate. SACS in low dose was less effective than low dose of FGH; similarly, high dose of FGH was more efficacious than high dose of SACS. Corroborating with this, combined therapy of garlic (250 mg/kg) with CAP

The present study was undertaken to determine the pharmacokinetic and pharmacodynamic interaction of hydrochlorothiazide (HCTZ) with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of HCTZ was studied by HPLC method, while pharmacodynamic interaction was studied using diuretic activity, ECG and BP changes and isoproterenol (ISO) induced myocardial injury. HCTZ was given orally at 10mg/kg and GH was administered at three different doses of 125, 250 and 500 mg/kg, p.o. The CK-MB, LDH, SOD, catalase and histopathological studies were carried out. The administration of HCTZ in GH pretreated rats found to decrease the QRS duration, RR interval, QT segment, systolic blood pressure, heart rate, serum potassium level, serum LDH and serum CK-MB activities significantly. The diuretic effect of HCTZ was significantly increased in presence of GH; however, kaliuresis was significantly reduced in presence of GH 250 mg/kg. Histopathological studies of heart tissue reveal the protective effect of GH 250 mg/kg in presence or absence of HCTZ during ISO stress to myocardium. The pharmacokinetic studies show that GH increases the bioavailability and half-life, along with decrease in clearance and elimination rate of HCTZ when administered orally. It was concluded that careful addition of garlic in moderate doses might result in beneficial effect during treatment of hypertension in patients with myocardial stress as garlic causes substantial fall in excretion of potassium when compared to HCTZ alone treatment in rats. This could be important in reducing the dose of HCTZ to achieve enhanced therapeutic effect with minimal adverse effect.

Garlic has been known to have antiplatelet properties. Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy. During this project we tested aged garlic extract (AGE), a commercial garlic preparation, with warfarin (Coumadin). Sixty-six (66) patients were screened for a double-blind, randomized, placebo-controlled pilot study. Fifty-two (52) patients were randomized for the project. Forty-eight patients (30 men and 18 women, with a mean age of 56+/-10 years) completed the study. Eighteen patients (14 before randomization, 4 after randomization) were dropped from the study. The study medication (AGE or placebo) was administered at a dose of 5 mL twice a day for 12 wk. Potential bleeding and thromboembolic episodes were monitored. There was no evidence of increased hemorrhage in either the placebo or the AGE group. Adverse events included headache, fatigue, colds, and dizziness. However, no significant difference was found in the incidence of these minor adverse events between the groups. Thus, the adverse events are unlikely to be attributable to AGE. The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy. Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary, its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications.

PURPOSE: To define complementary and alternative medicine (CAM); describe one type of CAM, garlic (Allium sativum L); and discuss its effects on blood pressure as a treatment for hypertension. DATA SOURCES: Literature review from professional journals, abstracts, natural therapy books, and the World Wide Web (Internet). Information from the following professional organizations and agencies: The World Health Organization, Agency of Healthcare Research and Quality, National Cancer Institute, National Center for Complementary and Alternative Medicine, American Botanical Council, and Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. CONCLUSION: Garlic is widely used throughout the world as a CAM. It is one of the most popular herbal products sold in the United States. However, while some studies have shown small positive effects in reducing blood pressure, there are insufficient scientific data to draw conclusions regarding its efficacy on clinical blood pressure outcomes. Thus, healthcare providers should be cautious in recommending this herbal product as an antihypertensive CAM. IMPLICATIONS FOR PRACTICE: CAMs may be used by clients for a variety of conditions including hypertension. Healthcare providers must be cognizant of the use, efficacy, adverse affects, and scientific evidence concerning CAM in order to provide safe and effective practice as well as appropriate and accurate information to their clients.

Garlic has long been used medicinally, most recently for its cardiovascular, antineoplastic, and antimicrobial properties. Sulfur compounds, including allicin, appear to be the active components in the root bulb of the garlic plant. Studies show significant but modest lipid-lowering effects and antiplatelet activity. Significant blood pressure reduction is not consistently noted. There is some evidence for antineoplastic activity and insufficient evidence for clinical antimicrobial activity. Side effects generally are mild and uncommon. Garlic appears to have no effect on drug metabolism, but patients taking anticoagulants should be cautious. It seems prudent to stop taking high dosages of garlic seven to 10 days before surgery because garlic can prolong bleeding time.

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations. Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the bl

BACKGROUND: Use of herbs and nutritional supplements (known as naturoceuticals) is increasing in the USA, with about 50% of Americans taking naturoceuticals and spending over 10 billion dollars per year for them. This raises concerns regarding their use instead of proven therapies, their side effects, and drug interaction potential. HYPOTHESIS: The study sought to characterize cardiology patients who used supplements and to examine whether their use was diagnosis or doctor dependent, whether it affected patients' compliance, and what supplements were used. METHODS: In all, 187 patients attending our cardiology clinic were interviewed, examined, and followed for up to 1 year. The users and nonusers of naturoceuticals were compared. RESULTS: Supplements were used in 106 patients (an average of 3.1 naturoceutical per patient). There were no significant differences in their use by gender, age, primary care doctor specialty, or cardiovascular medications prescribed (except for statins). Patients with a history of myocardial infarction, coronary revascularization, hyperlipidemia, and a family history of coronary artery disease were more likely to use the supplements. Average low-density lipoprotein (106 vs. 108 mg/dl), average blood pressure (132/77 vs. 138/78 mmHg), and average hemoglobin (Hb)A1c (8.7 vs. 7.7%) showed no statistically significant differences between users and nonusers. Patients most commonly took multivitamins, vitamin E, vitamin C, vitamin B, folate, garlic, calcium, coenzyme Q10, and gingko. CONCLUSION: This study indicates that naturoceutical use is widespread among cardiovascular patients and it is difficult to predict clinically who the users are. Fortunately, according to our limited compliance measures, it appears that the naturoceutical use has not affected patients' compliance with traditional medications. Also, possibly a detrimental interaction potential between traditional medications and naturoceuticals has been demonstrated.

OBJECTIVES: To review use of alternative pharmacotherapy (AP) in patients with cardiovascular disease (CVD) and significant drug interactions between AP and traditional CVD medications. STUDY DESIGN: A literature search of MEDLINE and the National Complementary and Alternative Medicine database was done using these search terms: supplements, vitamins, garlic, fish oil, L-arginine, soy, coenzyme Q10, herbs, phytosterols, chelation therapy, alternative medicine, and CVD. PATIENTS AND METHODS: English human clinical trials measuring surrogate and clinical end points. RESULTS: Antioxidants have not been consistently proven beneficial in reducing cardiovascular mortality. Fish oils may be beneficial in patients with hypertension and hypercholesterolemia, but therapeutic doses need to be defined. Use of coenzyme Q10 in patients with heart failure has not demonstrated consistent benefits. Garlic may lower blood pressure and cholesterol levels, but also may increase bleeding, so its use in CVD patients should be monitored. Clinical studies with small sample sizes have demonstrated that L-arginine may be useful to prevent and treat CVD. The Food and Drug Administration recommends 25 g/day of soy protein as part of a diet low in saturated fats for cholesterol reduction. Plant sterols are recommended by the American Heart Association and the National Cholesterol Education Program Expert Panel as adjunct therapy to reduce low-density lipoprotein. No data support use of chelation therapy. Some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). CONCLUSIONS: The benefits of APs as part of the treatment for CVD are controversial. Routine use is not recommended.

Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical conseque