Addressing Methodological Gaps: A Systematic Review and Meta-Analysis of Beetroot Juice and Exercise Capacity in Chronic Obstructive Pulmonary Disease

BACKGROUND: Despite numerous meta-analyses examining the effects of beetroot juice (BJ) supplementation on exercise capacity in patients with chronic obstructive pulmonary disease (COPD), significant methodological shortcomings persist, including failure to stratify findings by study design. OBJECTIVE: In this meta-analysis we aimed to assess the effects of BJ supplementation on exercise capacity and cardiovascular parameters in COPD patients, identifying methodological gaps by stratifying the results of parallel and crossover randomized clinical trials (RCTs). DATA SOURCES: We conducted a systematic search in Scopus, Lilacs, PubMed, Embase, Web of Science, CENTRAL, and Science Direct from database inception until December 30, 2024. We identified studies of the effects on of nitrate-rich BJ supplementation on exercise capacity and cardiovascular parameters in COPD patients. DATA EXTRACTION: Data extraction was performed independently by 2 reviewers, who collected information on participant characteristics, supplementation protocol, exercise capacity outcomes, and cardiovascular parameters. Data synthesis included subgroup and sensitivity analyses, meta-regression, and stratified random effects meta-analyses. Bias risk was assessed using the revised tool to assess risk of bias in randomized trials (RoB2), and evidence certainty was evaluated via Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. DATA ANALYSIS: The data extraction yielded 12 studies (357 participants) that were included in this study. Supplementation with BJ significantly improved the exercise capacity (standardized mean difference [SMD], 0.31; 95% CI, 0.10-0.53; I2 = 0%). Stratified analyses revealed greater benefits in parallel RCTs (standardized mean difference [SMD], 0.52; 95% CI, 0.23-0.81; I2 = 0%) compared with crossover trials (SMD, 0.06; 95% CI, -0.25 to 0.38; I2 = 0%). Beetroot juice (BJ) reduced systolic (mean difference [MD], -5.33 mmHg; 95% CI, -6.45 to -4.21) and diastolic blood pressure (MD, -3.01 mmHg; 95% CI, -4.39 to -1.63; I2 = 0%). CONCLUSION: This meta-analysis provides robust evidence that BJ improves exercise capacity and key cardiovascular parameters in COPD patients. By addressing critical methodological limitations and stratifying the results by study design, this study established a reliable foundation for clinical application. Standardized long-term studies are essential to confirm these findings and elucidate dose-response relationships. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. [CRD42024540181].