Curcumin-piperine supplementation modulates inflammation, oxidative stress, and cardiometabolic risk: a systematic review of randomized controlled trials

Background Although curcumin has well-established anti-inflammatory and antioxidant qualities, its low bioavailability limits its therapeutic applicability. Piperine improves systemic exposure and absorption of curcumin. This systematic study aimed to examine the effectiveness and safety of curcumin-piperine supplementation in relation to inflammatory, metabolic, cardiovascular, autoimmune, infectious, and pulmonary disorders. Methods From 2026, a comprehensive search of randomised controlled trials (RCTs) was conducted across the main electronic databases. Studies that assessed oral curcumin in combination with piperine and reported results related to oxidative stress, inflammation, metabolism, cardiovascular disease, or clinical symptoms were considered eligible. Using accepted methodological standards, the risk of bias was evaluated. Results There were 20 RCTs with sample sizes ranging from 8 to 117 individuals and durations ranging from 1 to 12 weeks. Doses of piperine (5–15 mg/day) and curcumin (500–1,500 mg/day) varied. Fifteen out of twenty trials indicated significant decreases in inflammatory biomarkers [C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), and interleukin-6 (IL-6)]. Of 15 studies evaluating these outcomes, 12 showed improvements in oxidative stress markers, including superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Supplementation dramatically decreased fasting blood glucose (FBS), glycated haemoglobin (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in individuals with metabolic syndrome (MetS) and type 2 diabetes. At the same time, 14 out of 18 trials showed reductions in lipid markers (triglycerides (TG), LDL-C, total cholesterol, and HDL-C). After coronary artery bypass grafting and acute myocardial infarction (AMI), cardiovascular populations showed decreases in cardiac damage biomarkers (CK-MB, AST, and ALT). COVID-19, premenstrual syndrome (PMS), dysmenorrhea, and chronic pulmonary illness all showed symptom-based improvements. No significant adverse effects were noted. None of the trials was high risk; 13 had low risk of bias, and 6 had moderate issues. Conclusion In a variety of clinical populations, curcumin-piperine supplementation consistently demonstrates anti-inflammatory, antioxidant, metabolic, and cardioprotective effects, with a good safety profile. Its utility as an adjuvant in metabolic and cardiometabolic illnesses is most strongly supported by evidence. To verify clinical efficacy and improve dosing techniques, larger, longer-term RCTs with standardized objectives are necessary.