The effect of red pepper/capsaicin on cardiovascular risk factors: a systematic review, meta-analysis, and GRADE...

Cardiovascular disease (CVD) is a leading global cause of mortality. Capsaicinoids, the active compounds in red pepper, act as agonists of the transient receptor potential vanilloid 1 (TRPV1) and may offer cardioprotective benefits by modulating lipid metabolism, glucose homeostasis, and vascular function. This systematic review and meta-analysis aimed to evaluate the effect of red pepper/capsaicin supplementation on cardiovascular risk factors.

A comprehensive search of MEDLINE/PubMed, and Scopus was conducted from inception until May 2025, following PRISMA guidelines. The conducted systematic review and meta-analysis adhered to the pre-specified protocol registered in PROSPERO (CRD420251119445). In order to avoid missing an article, a manual search was finally conducted in Google Scholar. Randomized controlled trials (RCTs) in adults supplementing with capsaicin, red pepper, or related compounds versus a placebo were included. Outcomes of interest included lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoprotein [LDL], high-density lipoprotein [HDL]), blood pressure (systolic [SBP] and diastolic [DBP]), and glycemic indices (glucose, insulin, HOMA-IR, HbA1c). Data were pooled using a random-effects model and expressed as weighted mean difference (WMD) with 95% confidence intervals (CI). Thirteen RCTs (n = 821 participants) were included. However, the findings were marked by substantial heterogeneity and a limited total sample size, which necessitate cautious interpretation. Red pepper/capsaicin supplementation was associated with small, statistically unstable reductions in total cholesterol and diastolic blood pressure; however, these effects were not robust to sensitivity analyses and should be interpreted as low-confidence estimates. However, no significant effects were observed on TG, LDL, HDL, SBP, glucose, insulin, HOMA-IR, or HbA1c. Significant heterogeneity was observed for most outcomes (I² > 50%). Subgroup analyses suggested that longer intervention durations (≥8 weeks) might be more effective for improving TC and HDL. The overall certainty of evidence, assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE), was low to very low for most outcomes.

Red pepper/capsaicin supplementation may yield modest benefits in reducing total cholesterol and diastolic blood pressure. However, sensitivity analysis demonstrated that the significant results for TC and DBP were dependent on a single study; their exclusion rendered the results non-significant. Due to significant heterogeneity, the limited number of studies, low sample sizes, and the instability of results upon sensitivity analysis, these findings must be interpreted with caution. Larger, well-designed, long-term RCTs are necessary to confirm these potential cardiometabolic benefits. PROSPERO registration number: (CRD420251119445).