Comparative effectiveness of dietary supplements in dilated cardiomyopathy: a systematic review and network meta-analysis

Abstract

Abstract Background Dilated cardiomyopathy (DCM) is a major cause of heart failure and cardiovascular mortality, partly due to impaired myocardial energy metabolism. Dietary supplements may offer benefits through improved mitochondrial function and antioxidant effects, and randomized controlled trials (RCTs) suggest they can enhance cardiac function in DCM. However, direct comparisons among supplements are lacking, and the optimal strategy and dose–response relationship remain undetermined. Methods Eight databases were searched for RCTs evaluating dietary supplements in DCM. Continuous outcomes were analysed by frequentist random-effects network meta-analysis (NMA; Stata/MP 18.0); N-terminal pro-B-type natriuretic peptide (NT-proBNP) and New York Heart Association (NYHA) class were synthesised by pairwise meta-analysis. Risk of bias was assessed with the Cochrane Risk-of-Bias 2 (RoB 2) tool and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Fourteen RCTs (1,259 participants) were included. For left ventricular ejection fraction (LVEF), coenzyme Q 10 (CoQ 10 ) 150 mg/d produced the largest improvement versus conventional treatment (CT) (mean difference [MD] = 11.26, 95% confidence interval [CI] 8.55 ~ 13.98; surface under the cumulative ranking curve [SUCRA] 93.4%), followed by taurine and CoQ 10 90 mg/d. CoQ 10 150 mg/d also ranked first for reducing left ventricular end-diastolic diameter (LVEDD; −5.40, − 8.14 ~ − 2.66) and end-systolic diameter (LVESD; −6.31, − 8.60 ~ − 4.01). For heart rate, n-3 polyunsaturated fatty acids (n-3 PUFAs) gave the most robust reduction (− 3.94 bpm, − 5.11 ~ − 2.77). In pairwise meta-analysis, CoQ 10 lowered NT-proBNP and improved NYHA status (risk ratio [RR] for ≥ 1-class improvement 1.23, 1.10 ~ 1.38). Network inconsistency was significant for LVESD ( P = 0.008). Certainty of evidence (GRADE) was low to very low, and moderate only for n-3 PUFAs; all supplements were well tolerated. Conclusions In this network, higher-dose CoQ 10 (150 mg/d) showed the most favourable overall profile for systolic function and ventricular dimensions, while n-3 PUFAs offered the most reliable benefit for heart rate. Given small samples, predominantly Chinese open-label trials, a heterogeneous and time-varying CT comparator, local inconsistency, and poor safety reporting, these findings should be regarded as hypothesis-generating and require confirmation in larger, well-designed international RCTs with longer follow-up.