Ubiquinol supplementation in cardiovascular diseases: A systematic review of clinical efficacy and therapeutic potential

Cardiovascular diseases (CVDs) are a leading global cause of morbidity and mortality, with oxidative stress and mitochondrial dysfunction playing key roles in their progression. Though conventional therapies exist, interest in adjunct treatments such as ubiquinol—a bioactive form of coenzyme Q10 with superior bioavailability—has grown due to its potential to improve cardiac function and reduce oxidative damage. This systematic review aimed to evaluate the efficacy of ubiquinol in managing CVDs, with a focus on its comparative benefits over ubiquinone. The review followed the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines, analysing randomized controlled trials (RCTs) from various databases. Databases including Cochrane (1,441 records), PubMed (1,178), Web of Science (252), and Scopus (1,514) were searched, identifying 4,385 records. After removing duplicates and the studies not meeting inclusion criteria, eight studies were included in the systematic review, encompassing a total of 393 patients. Interventions used a dosage range of 200 to 600 mg/day. Outcomes assessed included ejection fraction (EF), the New York Heart Association (NYHA) functional classification, B-type natriuretic peptide (BNP) levels, mortality, hospitalization rates, and quality of life (QoL). Evidence certainty was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework and a risk-of-bias assessment. Meta-analysis was not performed due to clinical and methodological heterogeneity across studies and lack of comparable effect sizes. Current evidence suggests that ubiquinol may improve functional status, selected biomarkers, and patient-reported QoL when used as an adjunct to standard therapy in specific cardiovascular populations. Ubiquinol supplementation significantly improved EF in patients with systolic heart failure and enhanced NYHA class and QoL in advanced heart failure and post-surgical recovery. Reductions in BNP levels indicated decreased cardiac stress, while benefits in HF with preserved EF were less pronounced. Mortality and hospitalization outcomes varied. Larger, rigorously designed trials powered for guideline-relevant outcomes and cost-effectiveness are needed before integrating ubiquinol into health policy and reimbursement frameworks.