Background: Metabolic syndrome (MetS) is a cluster of central obesity, hypertension, hyperglycemia, and dyslipidemia. It is a global health issue with an increased risk of cardiovascular disease. Recently, a few natural products have been reported with promising anti-inflammatory and antioxidative effects. We aimed to evaluate the impact of δ-tocotrienol and resveratrol mixture (TRM) supplementation on cardiometabolic risk factors and biomarkers in patients with MetS. Methods: A randomized controlled trial was conducted at the hospitals of National University of Medical Sciences Rawalpindi, Pakistan. A total of 82 patients with MetS aged 18-60 years were enrolled based on International Diabetes Federation-2005 diagnostic criteria and randomly grouped into TRM (n = 41) and placebo (n = 41). Patients in the TRM group were given a 400 mg capsule (δ-tocotrienol 250 mg; resveratrol 150 mg), and a placebo (cellulose 400 mg) twice daily for 24 weeks. The biochemical tests were analyzed on ADVIA 1800 Chemistry^® analyzer and inflammatory biomarkers by ELISA methods. Results: In the TRM group, a significant reduction in waist circumference, blood pressure, mean (95% confidence interval) of fasting plasma glucose -0.15 mmol/L (-0.22 to -0.08), serum triglyceride -0.32 mmol/L (-0.47 to -0.17), and increment in high-density lipoprotein cholesterol were observed as compared with placebo. TRM supplementation also improved biomarkers: high-sensitive C-reactive protein -0.61 mg/L (-0.89 to -0.33), interleukin-6-1.99 pg/mL (-2.50 to -1.48), tumor necrosis factor-α -2.19 pg/mL (-2.55 to -1.83), malondialdehyde -0.48 μmol/L (-0.65 to -0.30), and total antioxidant capacity 1.71 U/mL (1.29 to 2.13). Conclusion: TRM supplementations improved cardiometabolic risk factors and biomarkers of inflammation and oxidative stress without any significant side effects in the patients with MetS. Clinical Trials Registry: The clinical trial was registered in Sri Lanka Clinical Trials Registry (https://slctr.lk/trials/slctr-2019-021).

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