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The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation.
Rahman, MM, Islam, F, -Or-Rashid, MH, Mamun, AA, Rahaman, MS, Islam, MM, Meem, AFK, Sutradhar, PR, Mitra, S, Mimi, AA, et al
Frontiers in cellular and infection microbiology. 2022;12:903570
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Cardiovascular disease (CVD) accounts for 31% of all-cause mortality worldwide. Irregularities in the composition of intestinal microbial composition, genetic factors, nutrition, metabolic irregularities, and smoking are among the potential causes of CVD. Intestinal permeability and translocation of endotoxins and bacterial metabolites to systemic circulation may trigger an immune response and inflammation, which may increase the risk of CVD. Synthesis of bacterial metabolites such as trimethylamine N-oxide (TMAO) by choline-inducing gut bacteria and reduced consumption of dietary TMAO precursors may elevate the CVD risk. This review explores the latest research on the role of gut microbiota in the development of atherosclerosis and CVD, as well as potential strategies to prevent CVD by targeting TMAO-producing gut bacteria. Elevated levels of TMAO in the bloodstream can lead to the buildup of cholesterol and ultimately result in atherosclerosis. However, consuming probiotics and fibre-rich foods can help regulate gut bacteria, reduce inflammation, and improve lipid profiles, all of which contribute to better cardiovascular health. More future robust studies are required to examine the mechanistic insights and confirm whether TMAO can serve as a biomarker for preventing CVD through the therapeutic modulation of intestinal bacteria.
Abstract
In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.
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Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials.
Bernasconi, AA, Wiest, MM, Lavie, CJ, Milani, RV, Laukkanen, JA
Mayo Clinic proceedings. 2021;96(2):304-313
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There is mixed evidence to support the use of omega-3 fatty acids for the prevention and treatment of cardiovascular disease. Animal studies have shown promising results, but randomised control trials are inconsistent, possibly due to differing doses used, or differences in the subject’s omega-3 levels at the start of the trial. This meta-analysis of 40 studies with over 135,000 subjects aimed to determine whether omega-3 supplementation reduces heart disease risk and whether dosage has a role. The results showed that omega-3 supplementation reduced the risk of heart attacks, death from heart attacks and deaths due to heart disease, and the higher the dose, the greater the protection. The majority of studies were on individuals who had already had a heart attack or who had suffered from a related condition. It was concluded that supplementation with omega-3 is effective in preventing heart disease and heart attacks and the protective effect increases with dosage. This study could be used by healthcare professionals to prevent further heart disease and heart attacks in individuals who have already suffered from one of these conditions.
Abstract
OBJECTIVES To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage. METHODS This study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS A total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI. CONCLUSION Cardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.
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Coenzyme Q10 for heart failure.
Al Saadi, T, Assaf, Y, Farwati, M, Turkmani, K, Al-Mouakeh, A, Shebli, B, Khoja, M, Essali, A, Madmani, ME
The Cochrane database of systematic reviews. 2021;(2):CD008684
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As per the definition given by the NHS, heart failure happens when the heart fails to pump blood around the body due to stiffness or weakness of the heart muscle. Coenzyme Q10 reduces oxidative stress and toxic effects in the body by acting as a fat-soluble antioxidant nutrient. Due to these beneficial effects, CoQ10 may effectively reduce damage to cardiac cells and disruption to cellular signalling. CoQ10 is also a cell membrane stabiliser, and previous studies have shown a correlation between the severity of heart failure and CoQ10 deficiency. In addition, dietary absorption of CoQ10 is relatively slow and ineffective; therefore, supplementation is effective and safe with no side effects. This review included eleven randomised controlled studies to compare the beneficial effects of Coenzyme Q10 for the treatment of people with heart disease. This review showed that Coenzyme Q10 might reduce all-cause mortality and hospitalisation due to heart failure. In addition, CoQ10 may stabilise myocardial calcium‐dependent ion channels and encourage adenosine‐5'‐triphosphate (ATP) synthesis. However, the effectiveness of CoQ10 in lowering the risk of myocardial infarction or stroke, left ventricular ejection fraction and exercise capacity is inconclusive. Healthcare professionals can use this study's results to understand the potential beneficial effects of CoQ10 supplementation on maintaining heart health. However, due to the high heterogeneity in the current research, further robust long-term studies are required to evaluate the therapeutic value of Coenzyme Q10 in managing heart disease.
Abstract
BACKGROUND Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014. OBJECTIVES To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions. SELECTION CRITERIA We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection. MAIN RESULTS We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision. AUTHORS' CONCLUSIONS The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.
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The effects of coenzyme Q10 supplementation on biomarkers of inflammation and oxidative stress in among coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.
Jorat, MV, Tabrizi, R, Kolahdooz, F, Akbari, M, Salami, M, Heydari, ST, Asemi, Z
Inflammopharmacology. 2019;27(2):233-248
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Cardiovascular disease is the leading cause of death worldwide. Systemic inflammation and oxidative stress significantly contribute to the narrowing of the blood supply to the heart leading to coronary artery disease (CAD). Increased levels of several markers of inflammation, such as C-reactive protein (CRP), tumour necrosis factor-α (TNF- α), and interleukin-6 (IL-6), appear to be indicative of heart attack risk. Coenzyme Q10 (CoQ10) is a naturally occurring nutrient made in the body but can also be found in some foods or taken via supplements. It is an antioxidant that protects cell membranes and mitochondria against oxidative damage and also does so in the heart by preventing endothelial damage and the associated narrowing of blood vessels. Several trials investigated the effects of CoQ10 on inflammation and oxidative stress, with some noteworthy results and yet also some conflicting evidence. Hence this systematic review and meta-analysis aimed to shed some light on the controversial findings regarding coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress amongst patients with CAD. The authors included 13 clinical randomised controlled trials, amounting to 364 cardiac patients in the intervention groups. The treatment duration ranged from 4 to 48 weeks, and the dosage of CoQ10 varied between 60 to 300 mg/day. In conclusion, the meta-analysis showed that CoQ10 supplementation increased antioxidant markers of superoxide dismutase (SOD) and catalase (CAT), and decreased the oxidative stress marker malondialdehyde (MDA) and its derivative forms. There was no consistent effect on inflammatory markers of CRP, TNF-α, IL-6 or the levels of the antioxidant glutathione peroxidase. The discrepancies amongst the different studies may be a result of the divergent study designs, different population characteristics, the dosage of CoQ10 used and the duration of intervention.
Abstract
OBJECTIVE Systemic inflammation and oxidative stress significantly contribute in developing coronary artery disease (CAD). This systematic review and meta-analysis was aimed to determine the effects of coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress among patients with CAD. METHODS The electronic databases including MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library databases were systematically searched until Oct 2018. The quality assessment and heterogeneity of the selected randomized clinical Trials (RCTs) were examined using the Cochrane Collaboration risk of bias tool, and Q and I2 tests, respectively. Given the presence of heterogeneity, random-effects model or fixed-effect model were used to pool standardized mean differences (SMDs) as summary effect sizes. RESULTS A total of 13 clinical RCTs of 912 potential citations were found to be eligible for the current meta-analysis. The pooled findings for biomarkers of inflammation and oxidative stress demonstrated that CoQ10 supplementation significantly increased superoxide dismutase (SOD) (SMD 2.63; 95% CI, 1.17, 4.09, P < 0.001; I2 = 94.5%) and catalase (CAT) levels (SMD 1.00; 95% CI, 0.57, 1.43, P < 0.001; I2 = 24.5%), and significantly reduced malondialdehyde (MDA) (SMD - 4.29; 95% CI - 6.72, - 1.86, P = 0.001; I2 = 97.6%) and diene levels (SMD - 2.40; 95% CI - 3.11, - 1.68, P < 0.001; I2 = 72.6%). We did not observe any significant effect of CoQ10 supplementation on C-reactive protein (CRP) (SMD - 0.62; 95% CI - 1.31, 0.08, P = 0.08; I2 = 87.9%), tumor necrosis factor alpha (TNF-α) (SMD 0.22; 95% CI - 1.07, 1.51, P = 0.73; I2 = 89.7%), interleukin-6 (IL-6) (SMD - 1.63; 95% CI - 3.43, 0.17, P = 0.07; I2 = 95.2%), and glutathione peroxidase (GPx) levels (SMD 0.14; 95% CI - 0.77, 1.04, P = 0.76; I2 = 78.7%). CONCLUSIONS Overall, this meta-analysis demonstrated CoQ10 supplementation increased SOD and CAT, and decreased MDA and diene levels, but did not affect CRP, TNF-α, IL-6, and GPx levels among patients with CAD.