Whey Protein Intervention and Inflammatory Factors and Oxidative Stress: Systematic Review and Meta-analysis of Randomized Controlled Trials

Nutr Rev. 2025 Apr 1;83(4):609-621. doi: 10.1093/nutrit/nuae100.

Abstract

Context: Whey protein (WP), a high-biological-value protein contained in milk, may have anti-inflammatory properties and can reduce proinflammatory cytokines; however, the current evidence is inconclusive.

Objective: The aim of this study was to further investigate the effects of whey protein supplementation on inflammatory factors and oxidative stress in adults.

Data sources: We conducted a comprehensive search up to March 2022 using relevant key words in databases such as PubMed, Scopus, Embase, and the Cochrane Central Register of Controlled Trials, focusing on randomized controlled trials (RCTs).

Data extraction: RCTs that examined the impact of WP on C-reactive protein, tumor necrosis factor alpha, interleukin-6, glutathione, malondialdehyde, and total antioxidant capacity were selected independently by 2 authors. Results were pooled using a random-effects model as weighted mean differences and 95% CIs.

Data analysis: The results of the present study demonstrated that WP supplementation had no significant effect on the modulation of inflammation and oxidative stress compared with the control. None of the predefined subgroup analyses explained the differences in the effects of WP supplementation on inflammatory factors and oxidative stress.

Conclusion: This research suggests that WP supplementation had no significant effect on inflammatory factors and oxidative stress.

Systematic review registration: PROSPERO registration no. CRD42022325855.

Keywords: inflammatory factors; meta-analysis; oxidative stress; systematic review; whey protein.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Adult
  • Anti-Inflammatory Agents* / pharmacology
  • Antioxidants
  • C-Reactive Protein / metabolism
  • Dietary Supplements*
  • Humans
  • Inflammation Mediators*
  • Inflammation*
  • Interleukin-6 / blood
  • Oxidative Stress* / drug effects
  • Randomized Controlled Trials as Topic
  • Tumor Necrosis Factor-alpha / blood
  • Whey Proteins* / administration & dosage
  • Whey Proteins* / pharmacology

Substances

  • Whey Proteins
  • C-Reactive Protein
  • Antioxidants
  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Anti-Inflammatory Agents