What is the role of arginine (L-arginine) in wound healing?

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From the Guidelines

Arginine supplementation, particularly when combined with other nutrients like glutamine and antioxidants, has been shown to improve wound healing by enhancing collagen synthesis, promoting blood flow, and supporting immune function, as evidenced by a recent study published in 2024 1.

Key Mechanisms of Arginine in Wound Healing

  • Arginine serves as a precursor for collagen synthesis, which is crucial for wound closure and tissue repair.
  • It promotes blood flow to injured tissues by converting to nitric oxide, which dilates blood vessels and increases oxygen and nutrient delivery to wounds.
  • Arginine enhances immune function by supporting T-cell activity and macrophage function, which are essential for fighting infection and clearing debris from wounds.
  • It stimulates the release of growth hormone and insulin-like growth factor, which accelerate tissue repair.

Recommended Supplementation and Dietary Sources

  • Typical supplemental doses of arginine for wound healing support range from 3-6 grams daily, divided into multiple doses.
  • Food sources of arginine include meat, dairy, nuts (especially walnuts), seeds, and legumes.
  • People with herpes infections should use caution with arginine supplements as they may trigger outbreaks.
  • Those with kidney or liver disease should consult healthcare providers before supplementing.
  • Arginine works best when combined with adequate protein intake, vitamin C, and zinc, which are all essential nutrients for proper wound healing, as supported by a study published in 2022 1.

Clinical Evidence and Guidelines

  • A study published in 2024 found that an arginine/glutamine/bHMB mixture improved the healing of pressure ulcers in polymorbid patients 1.
  • The American College of Physicians recommends using protein or amino acid supplementation, including arginine, in patients with pressure ulcers to reduce wound size, based on moderate-quality evidence 1.
  • Another study published in 2022 found that supplementation with an oral nutritional formula enriched with arginine, zinc, and antioxidants improved pressure ulcer healing in malnourished patients 1.

From the Research

Arginine and Wound Healing

  • Arginine is a bioactive component that has been studied for its excellent biosafety, antimicrobial properties, and therapeutic effects on wound healing 2.
  • Arginine-based therapy can be separated into two categories: direct supplemental approaches of free arginine and indirect approaches based on arginine derivatives 2.
  • The beneficial role of arginine supplementation in wound healing is mediated, at least in part, through nitric oxide (NO), which mediates processes involved in tissue repair, including angiogenesis, epithelialization, and collagen formation 3.

Mechanisms of Arginine in Wound Healing

  • Arginine metabolism plays a crucial role in wound healing, with increased levels of citrulline, ornithine, and NOx observed in wound fluid compared to plasma 3.
  • Arginase-1 and arginase-2 are expressed in various cells, including neutrophils, macrophages, fibroblasts, keratinocytes, and endothelial cells, upon wounding 3.
  • iNOS is expressed by neutrophils, macrophages, fibroblasts, keratinocytes, and endothelial cells, while eNOS reactivity is observed in endothelial cells and fibroblasts 3.

Effectiveness of Arginine Supplementation

  • Current evidence suggests that arginine supplementation, in conjunction with oral nutrition supplementation, may promote wound healing in older adult patients in acute care and long-term care settings 4.
  • Arginine supplementation has been shown to enhance wound strength and collagen deposition in artificial incisional wounds in rodents and humans 5, 6.
  • However, the therapeutic effect of arginine supplementation on chronic wound healing in humans is still undetermined and requires further objective evidence 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Advances and impact of arginine-based materials in wound healing.

Journal of materials chemistry. B, 2021

Research

Role of arginine in superficial wound healing in man.

Nitric oxide : biology and chemistry, 2009

Research

Arginine physiology and its implication for wound healing.

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2003

Research

Arginine supplementation and wound healing.

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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