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Low-protein diet accelerates wound healing in mice post-acute injury

  • Hew, Jonathan J1
  • Parungao, Roxanne J1
  • Mooney, Craig P1
  • Smyth, Julian K1
  • Kim, Sarah2
  • Tsai, Kevin H-Y3
  • Shi, Huaikai1
  • Chong, Cassandra1
  • Chan, Renee C F4
  • Attia, Beba4
  • Nicholls, Caroline5
  • Li, Zhe1, 5
  • Solon-Biet, Samantha M6, 7
  • Le Couteur, David G6
  • Simpson, Stephen J7
  • Jeschke, Marc G8
  • Maitz, Peter K1, 5
  • Wang, Yiwei1, 9
  • 1 Burns Research and Reconstructive Surgery
  • 2 Bone Biology Group
  • 3 Adrenal Steroids Laboratory
  • 4 Electron Microscopy Unit
  • 5 Burns Unit
  • 6 Ageing and Alzheimer Institute and ANZAC Research Institute
  • 7 Charles Perkins Centre and School of Life and Environmental Sciences
  • 8 Sunnybrook Research Institute
  • 9 School of Pharmacy
Published Article
Burns & Trauma
Oxford University Press
Publication Date
Aug 09, 2021
DOI: 10.1093/burnst/tkab010
PMID: 34377708
PMCID: PMC8350350
PubMed Central
  • Research Article


Background Wound healing processes are influenced by macronutrient intake (protein, carbohydrate and fat). The most favourable diet for cutaneous wound healing is not known, although high-protein diets are currently favoured clinically. This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework, a nutrient modelling method, capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake. Methods Two adjacent and identical full-thickness skin excisions (1 cm2) were surgically created on the dorsal area of male C57BL/6 mice. Mice were then allocated to one of 12 high-energy diets that varied in protein, carbohydrate and fat content. In select diets, wound healing processes, cytokine expression, energy expenditure, body composition, muscle and fat reserves were assessed. Results Using the Geometric Framework, we show that a low-protein intake, coupled with a balanced intake of carbohydrate and fat is optimal for wound healing. Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production. These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure, related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots. Conclusions The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.

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