Effect of cocoa on blood pressure.

BACKGROUND: High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. OBJECTIVES: To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. SEARCH METHODS: This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. MAIN RESULTS: Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review.Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants.Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I2 = 60%), requiring further research to confirm the findings.Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference.Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated.Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias.Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate.Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons.Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). AUTHORS' CONCLUSIONS: This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance.Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Effect of cocoa on blood pressure.

BACKGROUND: High blood pressure is an important risk factor for cardiovascular disease attributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular related deaths in Western populations. Epidemiological studies suggest that cocoa rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Recently additional trials had conflicting results. OBJECTIVES: To determine the effect of flavanol-rich chocolate or cocoa products on blood pressure in people with or without hypertension. SEARCH METHODS: We searched the following electronic databases from inception to November 2011: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and EMBASE. In addition we searched international trial registries, and the reference lists of review articles and included trials. SELECTION CRITERIA: Randomised controlled trials (RCT) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in each trial in consultation with a third author. Random effects meta-analyses on all studies fitting the inclusion criteria were conducted using Review Manager version 5.1 and Stata version 12. Heterogeneity was explored by subgroup analyses and univariate meta-regression analysis of several variables including dosage of flavanol content (total or monomers) in chocolate or cocoa products, blinding, baseline blood pressure, theobromine content, sugar content, body-mass-index (BMI), duration and age. MAIN RESULTS: Twenty studies met the inclusion criteria. Meta-analyses of the 20 studies involving 856 mainly healthy participants revealed a statistically significant blood pressure reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2-18 weeks duration: Mean difference SBP (95%CI): -2.77 (-4.72, -0.82) mm Hg, p=0.005, n=20; mean difference DBP (95%CI): - 2.20 (-3.46, -0.93) mm Hg, p=0.006, n=19 available for DBP.Trials provided participants with 30-1080 mg of flavanols (mean=545.5 mg) in 3.6-105 g of cocoa products per day in the active intervention group. In half of the trials (n=10) the active group consumed 500-750 mg of flavanols per day. The control group received either a flavanol-free product (n=12) or a low-flavanol containing cocoa powder (6.4 and 41 mg flavanols, n=8). Subgroup meta-analysis of trials with a flavanol-free control group revealed a significant blood pressure reducing effect, in contrast to trials using a low-flavanol product in the control group. This analysis may have been confounded by trial duration and the level of blinding of participants.Trial duration was short (mean 4.4 weeks, range 2-8 weeks, n=19, and one trial of 18 weeks). A significant blood pressure reducing effect was evident in trials of 2 weeks duration (n=9), but not in trials of >2 weeks duration (n=11). It is important to note that seven out of the nine trials (78%) of 2 weeks duration also had a flavanol-free control group. Therefore, subgroup analysis by duration might be confounded by flavanol dosage used in the control groups, and the level of blinding of participants.Adverse effects including gastrointestinal complaints and distaste of the trial product were reported by 5% of patients in the active cocoa intervention group and 1% of patients in the control groups. AUTHORS' CONCLUSIONS: Flavanol-rich chocolate and cocoa products may have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term.Our findings are limited by the heterogeneity between trials, which was explored by univariate meta-regression and subgroup analyses. Subgroup meta-analysis of trials using a flavanol-free control group revealed a significant blood pressure reducing effect of cocoa, whereas analysis of trials using a low-flavanol control product did not. While it appears that shorter trials of 2 weeks duration were more effective, analysis may be confounded by type of control and unblinding of participants, as the majority of 2-week trials also used a flavanol-free control and unblinding of participants. Results of these and other subgroup analyses based on, for example, age of participants, should be interpreted with caution and need to be confirmed or refuted in trials using direct randomized comparison.Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Does chocolate reduce blood pressure? A meta-analysis.

BACKGROUND: Dark chocolate and flavanol-rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Previous meta-analyses concluded that cocoa-rich foods may reduce blood pressure. Recently, several additional trials have been conducted with conflicting results. Our study summarises current evidence on the effect of flavanol-rich cocoa products on blood pressure in hypertensive and normotensive individuals. METHODS: We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP) for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive). Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P < 0.05. RESULTS: Fifteen trial arms of 13 assessed studies met the inclusion criteria. Pooled meta-analysis of all trials revealed a significant blood pressure-reducing effect of cocoa-chocolate compared with control (mean BP change +/- SE: SBP: -3.2 +/- 1.9 mmHg, P = 0.001; DBP: -2.0 +/- 1.3 mmHg, P = 0.003). However, subgroup meta-analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 +/- 3.0 mmHg; P = 0.0009; DBP: -2.7 +/- 2.2 mm Hg, P = 0.01), while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 +/- 2.3 mmHg, P = 0.17; DBP: -1.3 +/- 1.6 mmHg, P = 0.12). Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30 mg to 1000 mg in the active treatment groups, and interventions ran for 2 to 18 weeks. Meta-regression analysis found study design and type of control to be borderline significant but possibly indirect predictors for blood pressure outcome. CONCLUSION: Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension. Flavanol-rich chocolate did not significantly reduce mean blood pressure below 140 mmHg systolic or 80 mmHg diastolic.

Effect of garlic on blood pressure: a systematic review and meta-analysis.

BACKGROUND: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. METHODS: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. RESULTS: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 +/- 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 +/- 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 +/- 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). CONCLUSION: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.

Rare Fungal Infection Linked to a Case of Juvenile Arthritis.

Juvenile arthritis with unknown disease etiology is also known as juvenile idiopathic arthritis. Symptoms include joint pain, swelling, and stiffness, and standard treatment involves immunosuppressant medication. Here we present a case of juvenile idiopathic arthritis with severe malnutrition and worsening of symptoms, which restrained a nine-year-old girl to a wheelchair with minimal movement capacity and low energy during standard immunosuppressant therapies over the course of three years. Our innovative Pathogen Blood Test combining cytology-based microscopy and genetic analysis using a pan-fungal primer assay and sequencing identified a systemic fungal infection with Sagenomella species, closely related to Aspergillus, and a soil-dwelling highly pathogenic fungus, which had previously been linked to a fatal veterinary case of arthritis and malnutrition. Our test results encouraged a radical change of the patient's treatment plan, including cessation of the regular immunosuppressants, including steroids, over six months. The patient made a progressive recovery, including complete reversion of the previously swollen and painful joints, development of a good appetite, and return to liveliness. Within the year of change from immunosuppressants to immune-supportive integrative nutritional therapies, including regular intravenous vitamin C, and oral vitamin D, as well as gentle aqua- and physiotherapy, the patient started to gain weight including muscle mass and regained strength and movement in the hands, arms, and legs. She was able to walk again within 18 months. Her mood and energy levels continued to improve and she was able to return to school full-time.

Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance.

Garlic supplements have shown promise in the treatment of uncontrolled hypertension, lowering blood pressure (BP) by about 10 mmHg systolic and 8 mmHg diastolic, similar to standard BP medication. Aged garlic extract, which contains S-allylcysteine as the bioactive sulfur compound, in particular is standardizable and highly tolerable, with little or no known harmful interaction when taken with other BP-reducing or blood-thinning medication. Here we describe biologically plausible mechanisms of garlic's BP-lowering effect. Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S) and enhance the regulation of endothelial nitric oxide (NO), which induce smooth muscle cell relaxation, vasodilation, and BP reduction. Several dietary and genetic factors influence the efficiency of the H2S and NO signaling pathways and may contribute to the development of hypertension. Sulfur deficiency might play a part in the etiology of hypertension, and could be alleviated with supplementation of organosulfur compounds derived from garlic.

Effect of garlic on serum lipids: an updated meta-analysis.

Hypercholesterolemia is associated with an increased risk of heart disease. The effect of garlic on blood lipids has been studied in numerous trials and summarized in meta-analyses, with conflicting results. This meta-analysis, the most comprehensive to date, includes 39 primary trials of the effect of garlic preparations on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. The findings suggest garlic to be effective in reducing total serum cholesterol by 17 ± 6 mg/dL and low-density lipoprotein cholesterol by 9 ± 6 mg/dL in individuals with elevated total cholesterol levels (>200 mg/dL), provided garlic is used for longer than 2 months. An 8% reduction in total serum cholesterol is of clinical relevance and is associated with a 38% reduction in risk of coronary events at 50 years of age. High-density lipoprotein cholesterol levels improved only slightly, and triglycerides were not influenced significantly. Garlic preparations were highly tolerable in all trials and were associated with minimal side effects. They might be considered as an alternative option with a higher safety profile than conventional cholesterol-lowering medications in patients with slightly elevated cholesterol.

Protective effect of lycopene on serum cholesterol and blood pressure: Meta-analyses of intervention trials.

BACKGROUND: Cardiovascular disease is associated with oxidative stress, inflammatory processes, and vascular dysfunction. Lycopene, a carotenoid found in tomatoes, is an antioxidant with a protective effect on lipid peroxidation and anti-atherosclerotic capacity. This review summarises current evidence on the effect of lycopene on serum lipid concentrations and blood pressure. METHODS: We searched the PubMed and Cochrane databases for intervention studies between 1955 and September 2010 investigating the effect of lycopene on blood lipids or blood pressure for a minimum duration of 2 weeks. We conducted meta-analyses using a random effect model of all studies fitting the inclusion criteria. Additionally, we conducted subgroup meta-analysis of serum lipid concentrations by lycopene dosage and subgroup meta-analysis by baseline blood pressure. RESULTS: Twelve studies (13 trial arms) meeting the inclusion criteria investigated the effect of lycopene on serum lipids, and four studies examined its effect on blood pressure. Meta-analysis on serum lipids revealed a significant cholesterol-lowering effect of lycopene for total serum cholesterol (mean change±SE: -7.55±6.15mg/dl; p=0.02) and low-density-lipoprotein (LDL) cholesterol (mean change±SE: -10.35±5.64mg/dl, p=0.0003) in the subgroup of trials using lycopene dosages of ≥25mg daily, whereas subgroup meta-analysis of trials using lower lycopene dosages was not significant. Meta-analysis of the effect of lycopene on systolic blood pressure of all trials suggested a significant blood pressure reducing effect (mean systolic blood pressure change±SE: -5.60±5.26mm Hg, p=0.04). CONCLUSIONS: Our meta-analysis suggests that lycopene taken in doses ≥25mg daily is effective in reducing LDL cholesterol by about 10% which is comparable to the effect of low doses of statins in patient with slightly elevated cholesterol levels. More research is needed to confirm suggested beneficial effects on total serum cholesterol and systolic blood pressure.