The Wound Healing Diet
You Are What You Eat
It’s no secret that nutrition is a cornerstone of health. For our bodies to maintain a physiological state of homeostasis, a diet of properly adjusted nutrients-both macro and micro- is required. This becomes especially important when faced with the issue of a non-healing wound. It is our job to educate patients on proper nutrition in order to facilitate wound healing. Of the three macronutrients, protein is most often in the spotlight as a key nutrient for the promotion of wound healing. A 2018 study investigated the effects of protein malnutrition on the chemical composition of wound fluid during the wound healing process (Yamane, Shimura, Konno, Iwatsuki, & Oishi, 2018). Wound fluid is a cocktail of many bioactive molecules including cytokines, chemokines, growth-factors, protein degrading enzymes, and inflammatory cells, and has been shown to stimulate both keratinocytes and fibroblasts- aiding in epithelization and the formation of granulation tissue at the wound base. “Conversely, wound fluid can also have a negative effect on wound healing. For example, wound fluid collected from chronic wounds has been shown to contain many inflammatory cells, including macrophages and neutrophils, and inflammatory factors such as matrix metalloproteinases, which inhibit wound healing by maintaining inflammation” (Yamane et al., 2018).
Diet vs. Wound Care — The Big Picture
Speaking more specifically to the effects of protein on wound healing, the previously mentioned study indicates that its purpose in wound healing is served predominantly in the proliferative phase. In the group being fed a protein-free diet, there was a significant reduction in wound contraction on days 4,5,6, and 7 after the initial wound, which corresponds to the aforementioned phase of healing (Yamane et al., 2018). The same group showed reduced thickness of granulation tissue and a lesser number of Ki67-positive cells present within granulation tissue (Yamane et al., 2018). Taken together, these results show protein malnutrition in wound patients can delay wound healing through a decrease in cell proliferation in granulation tissue during the proliferative phase (Yamane et al., 2018). Wound fluid obtained from the same patients being fed a protein-free diet also showed suppressed dermal fibroblast proliferation. This may be due to a suppression in IGF-IR and ERK (1/2) activation (Yamane et al., 2018). The study summarized these results stating that wound fluid in test subjects fed a protein-free diet may ultimately disrupt the healing process by inhibiting granulation tissue formation through the suppression of IGF-I/ERK signaling pathway (Yamane et al., 2018).
With protein malnutrition being such a common occurrence in wound care, it begs the following question: Where are these patients getting their calories from? Often, the demographic of patients we see are consuming large amounts of processed foods rich in fats. In order to investigate the effects of this type of dietary consumption I dug a little deeper into the direct effects of high-fat consumption on wound healing. A 2019 study investigated the effects of a high-fat diet (wherein 60% of calories came from fat) on cutaneous wound healing, and it found that a high-fat diet, even for a short period of time, impairs wound healing, affects the inflammatory phase, and disturbs neovascularization and matrix organization (Schanuel, Romana-Souza, Monte-Alto-Costa, 2019). During the early phases of wound healing, neutrophils arrive at the wound site within minutes of injury and are responsible for cleaning out the debridement and contaminating bacteria, and after a few days, they are replaced by macrophages, and the number of neutrophils in the wound diminishes. The test group showed increased levels of macrophages and neutrophils 10 days after initial wounding, indicating the inflammatory phase had been affected (Schanuel, Romana-Souza, Monte-Alto-Costa, 2019).
“Under normal conditions, the function of the inflammatory phase is to prepare the wound bed for healing by removing debris and bacteria and recruit and activate fibroblasts (Menke et al., 2007). Our results presented an alteration in the inflammatory phase and an increased myofibroblast density in the HFC group 10 days after wounding, so the impaired wound contraction induced by high-fat diet may be related to this interference in the inflammatory phase that leads to delayed myofibroblastic differentiation” (Schanuel, Romana-Souza, Monte-Alto-Costa, 2019).
Those in the test group also showed an impaired ability to convert type III collagen into type I as a normal part of the remodeling phase of wound healing. It can be deduced from this study that high-fat diets can lead to a prolonged inflammatory phase. Based on conversations I’ve had with both patients and providers alike, chronic wound patients are often consuming diets that are high in fat and low in protein, and because of this, they are more susceptible to a prolonged inflammatory phase from the onset of their wound. When I think of wounds stalled in the inflammatory phase, the first thing that comes to mind is biofilm; however, after reading this study, I will begin to look at malnutrition as another possible source for this issue.
The last of the macronutrients is carbohydrates. The role of carbohydrates in wound healing is most closely related to the provision of energy substrates to fuel the body to allow re-epithelization and recovery (Molnar, 2007).
“Immune cells, nerves, keratinocytes and fibroblasts are particularly dependent on glucose as an energy source. Adequate intake is essential, as dietary carbohydrates suppress hepatic gluconeogenesis. In the context of wound healing, carbohydrates minimise the consumption of protein for gluconeogenesis, and therefore has a protein sparing effect that increases the availability of protein for wound healing. Carbohydrates are also the substrate for the production of glycoproteins which are fundamental components of the cell membrane” (Hew, 2019).
In the context of wound healing, simple nutritional intervention can make an important difference. Finding the proper proportions of macronutrients is essential in facilitating the wound healing process. Most current research supports a high-protein diet as the most optimal for wound healing. However, a 2019 study has revealed that there may be a better way. Contrary to common practice, response surfaces showed wound healing was fastest with a low-protein intake, that non-protein energy should come from a balanced intake of fat and carbohydrates and very-high fat intakes should be avoided (Hew, 2019.) Accelerated local wound healing in this group was associated with increased mRNA expression of essential cytokines. IL-6 facilitates increases in leukocyte infiltration, re-epithelialization, and collagen accumulation (Hew, 2019). TNF-α is essential for inflammatory cell migration, fibroblast proliferation and angiogenesis (Hew, 2019). TGF-β1 is important as it has a predominant role in accelerating epithelial migration and promoting the progressive replacement of immature collagen III with mature collagen I (Hew, 2019).
“Systemically, response surfaces showed body weight loss occurred with high carbohydrate and high-fat intakes. High-protein intakes generally prevented body weight loss. Further analysis of body composition showed significant lean body mass loss with high-fat intakes, moderate amount of lean body mass loss with high carbohydrate intakes and preserved lean body mass with high-protein intake. The ability of protein to preserve lean body mass is a well-known and studied phenomena. Preventing loss of lean body mass is important because considerable lean body mass loss delays functional recovery after injury. An interesting finding in this study was that mice with a low-protein intake, although losing some lean body mass, had accelerated wound healing. This suggested that a degree of metabolism of protein from lean body mass rather than enteral protein is well tolerated and perhaps beneficial for wound healing” (Hew, 2019).
The low-protein diet also showed an earlier and greater systemic inflammatory response as determined by systemic cytokine expression profiles (Hew, 2019). These results suggest that low-protein intakes are associated with an early inflammatory response that contributes to lean body mass catabolism while wound healing progresses optimally (Hew, 2019). A possible mechanism responsible for this surprising finding is the nutrient sensitive autophagy pathway (Hew, 2019). The wound healing processes may also be accelerated by low-protein diet induced thermogenesis as heat improves circulation, tissue oxygenation and accelerates local enzymatic processes (Hew, 2019).
“The main finding from this study was that a low-protein intake paired with a balanced carbohydrate and fat intake is the most effective nutritional intervention for supporting acute cutaneous wound healing processes. Whether this diet is optimal in the context of a chronic wound, such as a pressure ulcer, remains to be confirmed and requires further investigation with a mouse model of chronic wound healing. Investigating the possible benefits of low-protein diets for healing of acute wounds in humans can be facilitated by the fact that nutritional therapy is an essential component of enhanced recovery after surgery (ERAS) protocols” (Hew, 2019).
The Wrap Up
Proper nutritional protocol is a vital part of the wound healing process, reiterating once again the theme that is described throughout this article. Each of the respective macronutrients has an array of effects across the different phases of healing. Keeping this in mind, it could be beneficial to patients to cater their nutritional protocol based on the phase of healing in which their wound presents itself. Rather than jumping straight to a protein-rich diet, consider creating a nutritional protocol that first caters to the enablement of the inflammatory phase- the phase that wounds most often find themselves stalled in. After successful progression into the proliferative phase, the patient’s diet can then be altered to aid in the formation of new granulation tissue and epithelialization. Finally, once the wound is healed, the patient’s diet could be altered a final time to promote efficient conversion of type III collagen into type I during the remodeling phase. As more research is conducted on nutrition and wound healing, I have no doubt that new information will come to light and we again will see a shift in what is considered the most optimal. As we continue to move forward, continue to treat patients, and continue to heal wounds, it is important to keep proper nutrition as the foundation that supports it all.
If you found this article interesting or have experience with this topic that you would like to share, please feel free to reach out to me or leave a comment below!
References:
Yamane, Takumi, et al. “Wound Fluid of Rats Fed Protein-Free Diets Delays Wound Healing through the Suppression of the IGF-1/ERK(1/2) Signaling Pathway.” Molecular and Cellular Biochemistry, vol. 452, no. 1–2, 2018, pp. 177–185., doi:10.1007/s11010–018–3423–8.
Schanuel, Fernanda S., et al. “Short‐Term Administration of a High‐Fat Diet Impairs Wound Repair in Mice.” Lipids, vol. 55, no. 1, 2019, pp. 23–33., doi:10.1002/lipd.12189.
Molnar, Joseph. Nutrition and Wound Healing. CRC, 2007.
Hew, Jonathan. “1 Optimising Dietary Macronutrient Intake for Cutaneous and Burn Wound Healing Using The.” The University of Sydney, Burns Research Group, ANZAC Research Institute, Sydney Medical School, The University of Sydney, 2019, pp. 1–197.
