Effect of l-arginine supplementation on C-reactive protein and other inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials

Complement Ther Med. 2019 Dec;47:102226. doi: 10.1016/j.ctim.2019.102226. Epub 2019 Oct 31.


Objectives: We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of L-arginine on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6) and TNFα.

Methods: A systematic search was carried out in PubMed, Embase, Scopus, Cochrane library databases and ISI web of sciences to retrieve the RCTs which examined the effect of L-arginine supplementation on inflammatory biomarkers up to October 2019, with no language and time restriction. Meta-analysis was performed using a random effects model, and I2 index was used to evaluate the heterogeneity.

Results: Search yielded 2452 publications. Eleven RCTs were eligible. Results indicated that L-arginine supplementation had no significant effect on inflammatory biomarkers including CRP, IL-6 and TNFα. However, when subgroup analysis was performed, we found that L-arginine supplementation increased CRP levels in subjects with ages >60 years old, participants with baseline circulating CRP levels >3 mg/dl, patients with cancer and when used in enteral formula.

Conclusion: Results of the present meta-analysis indicated that L-arginine supplementation increased the circulating concentrations of CRP in subjects with ages >60 years old, subjects with higher levels of CRP, patients with cancer and when used in enteral formula. Therefore, L-arginine should be used with caution in these subjects. However, further well designed, large-scale studies are needed.

Keywords: C-reactive protein; Inflammatory biomarkers; Meta-analysis; TNFα; interleukin-6; l-arginine.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Arginine / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis*
  • Dietary Supplements*
  • Humans
  • Inflammation / drug therapy*
  • Interleukin-6 / blood
  • Randomized Controlled Trials as Topic
  • Tumor Necrosis Factor-alpha / blood


  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Arginine