Effect of a specialized amino acid mixture on human collagen deposition

Ann Surg. 2002 Sep;236(3):369-74; discussion 374-5. doi: 10.1097/00000658-200209000-00013.


Objective: To examine the effect of arginine, beta-hydroxy-beta-methylbutyrate (HMB), and glutamine supplementation on wound collagen accumulation in a double-blind, randomized study.

Summary background data: Control of wound collagen synthesis has been an elusive goal for clinicians and scientists alike. In many clinical instances, it is desired to increase collagen deposition as a means of enhancing wound strength and integrity. Arginine, a semiessential amino acid, has been shown to increase wound collagen accumulation in rodents and humans. HMB, a metabolite of leucine, regulates muscle proteolysis in animals and humans and increases collagen deposition in rodents.

Methods: Thirty-five healthy, nonsmoking human volunteers 70 years or older were enrolled and underwent subcutaneous implantation of two small, sterile polytetrafluoroethylene (PTFE) tubes into the deltoid region under strict aseptic techniques. The tubes were 1 mm in diameter and 6 cm in length with pore size of 90 to 120 microm to allow optimal ingrowth of fibroblasts and the deposition of matrix. Eighteen volunteers (mean age 75.4 years; 2 men, 16 women) were randomized to receive daily supplementation of 14 g arginine, 3 g HMB, and 14 g glutamine (total nitrogen 3.59 g) in two divided doses. The control group (n = 17; mean age 75.3 years; 6 men, 11 women) received an isonitrogenous, isocaloric supplementation of nonessential amino acids. Catheters were removed at 7 and 14 days postimplantation and analyzed for hydroxyproline (OHP, nmol/cm catheter, an index of collagen accumulation) and alpha-amino nitrogen (alpha-AN, mmol/cm, an index of total protein deposition).

Results: Supplements were well tolerated, without any reported side effects. Supplementation with the specialized amino acid mixture led to a significant rise in plasma arginine and ornithine levels. The specialized amino acid supplement led to a significant increase in collagen deposition (as reflected by OHP content) in the PTFE tubes without an effect on total protein accumulation.

Conclusions: Collagen synthesis is significantly enhanced in healthy elderly volunteers by the oral administration of a mixture of arginine, HMB, and glutamine. This provides a safe nutritional means for increasing wound repair in patients.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arginine / administration & dosage
  • Arginine / metabolism*
  • Catheterization
  • Collagen / metabolism*
  • Diet
  • Double-Blind Method
  • Female
  • Glutamine / administration & dosage
  • Glutamine / metabolism*
  • Humans
  • Hydroxyproline / blood
  • Male
  • Polytetrafluoroethylene
  • Valerates / administration & dosage
  • Valerates / metabolism*
  • Wound Healing*


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