BACKGROUND: Increasing protein intake (above the recommended dietary amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov identifier NCT02912130) of 100 community-dwelling older adults (mean age 68.73 +/- 5.80 years, body mass index 27.06 +/- 5.18 kg/m2 (52% women)) who were randomized to four independent groups (control (C), exercise (E), exercise plus protein (EP), protein (P)). E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers (glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, and ferritin), insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. RESULTS: Total protein intake (habitual diet plus supplementation) increased to 1.55 +/- 0.69 g/kg/day in EP and to 1.93 +/- 0.72 g/kg/day in P, and remained significantly lower (p < 0.001) in unsupplemented groups (E: 1.08 +/- 0.33 g/kg/day, C: 1.00 +/- 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP (mean difference -0.79 mmol/L, 95% confidence interval (CI) -1.29, -0.28, p = 0.002) and P (mean difference -0.76 mmol/L, 95% CI -1.26 to -0.26, p = 0.003) versus C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference -0.40, 95% CI -0.65 to -0.16, p = 0.001) and P (mean difference -0.32, 95% CI -0.56 to -0.08, p = 0.009) versus C, and fold changes in HOMA-IR improved in EP (mean difference -0.37, 95% CI -0.64 to -0.10, p = 0.007) and P (mean difference -0.27, 95% CI -0.53 to -0.00, p = 0.048) versus C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: p = 0.009). No other interactions were observed in outcome measures (p > 0.05), and kidney function (eGFR) remained unaltered. CONCLUSIONS: Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults.

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