Cardio Health Research

[BACKGROUND] Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified. [OBJECTIVES] The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes. [METHODS] This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events. [RESULTS] A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. β-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17). [CONCLUSIONS] Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).

Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges'

[AIM] This systematic review and meta-analysis aimed to evaluate the effects of Nigella sativa (N. sativa) supplementation on metabolic and cardiovascular health outcomes. [METHODS] A comprehensive search of EMBASE, Scopus, PubMed, CENTRAL, and Web of Science databases was conducted up to August 2024. Study quality and certainty of evidence were assessed using the Cochrane Risk of Bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tools, respectively. [RESULTS] Eighty-two studies, including 79 quantitative and 3 qualitative studies published between 2008 and 2024, involving 5026 participants with interventions ranging from 1 to 48 weeks and doses varying from 200 to 4600 mg/day, were included. N. sativa supplementation significantly improved body fat percentage (BF%), body mass index (BMI), skeletal muscle mass (SMM), waist circumference (WC), weight, waist-to-hip ratio (WHR), diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), postprandial blood glucose (PPBG), quick insulin sensitivity check index (QUICKI), C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), atherogenic index (AI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) to HDL-C ratio, TC, triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, catalase (CAT), malondialdehyde (MDA), superoxide dismutase activity (SOD) activity, and total antioxidant capacity (TAC). [CONCLUSIONS] Our findings suggest that N. sativa could be a promising adjunct therapy for improving cardiovascular disease (CVD) risk factors.

[BACKGROUND] Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. [OBJECTIVES] To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids. [SEARCH METHODS] We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors. [SELECTION CRITERIA] We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake. [DATA COLLECTION AND ANALYSIS] Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. [MAIN RESULTS] We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence). [AUTHORS' CONCLUSIONS] This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.

[PURPOSE] L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of l-carnitine supplementation on cardiometabolic risk factors in patients with type 2 diabetes. [METHODS] PubMed/Medline, Scopus, and Web of Science were searched until May 2022 for randomized controlled trials that examined the impact of l-carnitine supplementation on cardiometabolic risk factors in adults with type 2 diabetes. The mean difference (MD) and its 95% confidence interval (CI) were estimated utilizing a random-effects model. Nonlinear dose-response associations were modeled with restricted cubic splines. The certainty of evidence was rated using the GRADE approach. [FINDINGS] Twenty-one randomized trials with 2041 patients with type 2 diabetes were included. We found that every 1 g/d supplementation with l-carnitine significantly reduced body mass index (MD: -0.37 kg/m [IMPLICATIONS] L-carnitine supplementation resulted in a small reduction in serum lipids and plasma glucose in patients with type 2 diabetes. However, due to high statistical heterogeneity, the results should be interpreted very cautiously.

[BACKGROUND] Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related. [METHODS] The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model. [RESULTS] Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; [CONCLUSIONS] In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.

[BACKGROUND] It is widely accepted that omega-3 fatty acids are beneficial in the prevention of cardiovascular disease, but many large randomized controlled trial studies and meta-analyses have come to different conclusions. The evidence for omega-3 fatty acids supplementation to prevent cardiovascular disease remains insufficient. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of several types of omega-3 fatty acids supplements. [METHODS] We comprehensively searched the online database and found 15 RCTs. The primary efficacy outcomes included major cardiovascular events, myocardial infarction, heart failure, atrial fibrillation, stroke, cardiovascular death, and all-cause death. The safety endpoints included gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis was conducted according to the main characteristics of the population, and the dose-response relationship of omega-3 fatty acids was evaluated by meta-regression. All results were calculated by the random effect model. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics. [RESULTS] The incidence of major cardiovascular events (RR 0.95, 95%CI 0.91 to 0.99, P = 0.026), myocardial infarction (RR 0.90, 95%CI 0.83 to 0.98; P = 0.021), and cardiovascular death (RR 0.94, 95%CI 0.88 to 0.99; P = 0.028) was reduced in the omega-3 fatty acid group compared with the control group. An increased risk of atrial fibrillation (RR 1.25, 95%CI 1.10 to 1.41; P = 0.000) was observed in patients in the omega-3 fatty acid group. No statistical differences were observed between the two groups in heart failure, stroke, and all-cause death. For safety endpoints, there were no statistically significant differences between the two groups in gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis showed that the cardiovascular benefit of omega-3 fatty acids was primarily attributable to the prescription of EPA ethyl ester. Omega-3 fatty acids may reduce the risk of major cardiovascular events in patients with cardiovascular disease or risk factors, and reduce the risk of myocardial infarction in patients without cardiovascular disease; however, they may increase the risk of stroke in patients with myocardial infarction. In addition, prescription omega-3 acid ethyl ester has a good safety profile, and prescription EPA ethyl ester has a high risk of bleeding. [CONCLUSION] Moderate evidence showed that the use of omega-3 fatty acids may reduce the risk of major cardiovascular events, myocardial infarction, and cardiovascular death. Compared to other types of omega-3 fatty acids supplements, we support the use of prescription EPA ethyl ester formulations for the prevention of cardiovascular disease, but the potential risk of atrial fibrillation and bleeding cannot be ignored. It is important to note that omega-3 fatty acids should be applied with caution in patients with previous myocardial infarction, which may increase the risk of stroke. Finally, omega-3 fatty acids are relatively safe and in general do not increase gastrointestinal problems, bleeding-related disorders, or cancer, but attention needs to be paid to the risk of bleeding with prescription EPA ethyl ester formulations.

[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.