The effects of whey protein supplementation on indices of cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials

Introduction: The increasing prevalence of cardiometabolic diseases highlights the urgent need for practical interventions to mitigate their associated public health burden. Whey protein supplementation has emerged as a potential intervention for improving markers of cardiometabolic health. The aim of this systematic review and meta-analysis was to examine the effect of whey protein ingestion on cardiometabolic profile in adults.

Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library from inception until June 2024. Eligible RCTs compared the effect of whey protein supplementation compared to placebo or a carbohydrate-based control on markers of cardiometabolic health. Using the random effects inverse-variance model, we estimated the mean difference (MD) in blood pressure, high- and low-density lipoproteins (HDL-cholesterol, LDL-cholesterol), total cholesterol, triglycerides, and homeostatic model assessment for insulin resistance (HOMA-IR) index.

Results: This meta-analysis included 21 RCTs. Whey protein supplementation had no effect on HDL-cholesterol concentration but did elicit a reduction in LDL-cholesterol in individuals aged <50 years (P < 0.01) and when combined with exercise (MD: -5.38, 95 % confidence interval (95 % CI): -8.87 to -1.88, I² = 0 %, P < 0.01). Total cholesterol was reduced with interventions that combined whey protein supplementation and exercise (MD: -8.58, -14.32 to -2.83, I² = 55 %, P < 0.01), irrespective of age, protein dose, and body mass index ≥25 kg/m² (MD: -6.71, 95 % CI: -11.60 to -1.83, I² = 74 %, P < 0.01). Whey protein supplementation of ≥12 weeks was associated with reduced triglyceride levels (MD: -6.61, 95 % CI: -11.06 to -2.17, I² = 70 %, P < 0.01). There was no clinically relevant effect of whey protein supplementation on blood pressure and HOMA-IR, however, changes pertinent to HDL-cholesterol, total cholesterol, and triglyceride reduction were primarily displayed in healthy adults.

Conclusions: Whey protein supplementation may be an effective intervention for reducing LDL and total cholesterol levels, particularly in healthy, overweight/obese adults aged <50 years, with the greatest benefits observed when combined with exercise. Healthy adults also showed a benefit regarding triglyceride levels.