Mixture of Arginine, Glutamine, and β-hydroxy-β-methyl Butyrate Enhances the Healing of Ischemic Wounds in Rats

JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):1045-1050. doi: 10.1177/0148607115625221. Epub 2016 Jan 29.


Background: This study investigated the effects of an amino acid mixture containing arginine, glutamine, and β-hydroxy-β-methyl butyrate on secondary healing of ischemic wounds in a rat model (N = 18).

Methods: After the formation of a bipediculated flap on each rat, 2 full-thickness excisional skin wounds (2 × 2 cm) were created on every flap. The rats were then randomized into the control and treatment groups. Every rat received standardized rat food throughout the study. The rats in the treatment group were administered an extra 200 mg/kg of L-arginine, 200 mg/kg of L-glutamine, and 40 mg/kg of β-hydroxy-β-methyl butyrate per day. Wound sizes were measured on days 0, 4, 10, and 14. The rats were sacrificed, and the wounds were excised for biochemical and histologic examination on the 14th day.

Results: As compared with the control group, the treatment group's wound sizes were significantly smaller on days 10 and 14 ( P < .001), as was its inflammatory cell accumulation score ( P = .008). There was no significant difference between the 2 groups in collagen accumulation ( P = .340), granulation tissue maturation ( P = .161), angiogenesis ( P = .387), or reepithelialization ( P = .190) and no significant difference between hydroxyproline concentrations in wounds ( P = .287).

Discussion: This amino acid combination seems to have a positive impact on the secondary healing of experimental ischemic wounds when introduced as a supplement to the standard diet, and the reduction in the inflammatory process appears to play a role in this effect.

Keywords: amino acid; arginine; glutamine; ischemic wound; wound healing; β-hydroxy β-methylbutyrate.

MeSH terms

  • Animals
  • Arginine / pharmacology*
  • Collagen / pharmacology
  • Disease Models, Animal
  • Glutamine / pharmacology*
  • Hydroxyproline / pharmacology*
  • Ischemia / drug therapy*
  • Rats
  • Rats, Wistar
  • Valerates / pharmacology*
  • Wound Healing / drug effects*


  • Valerates
  • Glutamine
  • beta-hydroxyisovaleric acid
  • Collagen
  • Arginine
  • Hydroxyproline