Exogenous Ketones for Wound Healing


Well-known member
May 24, 2021
Metabolic Therapy for Age-Dependent Impaired Wound Healing

This is a very interesting study completed by a PhD student working under the guidance of arguably the leading researcher of the ketogenic diet and exogenous ketones in the world, Dr. Dominic D’Agostino at the University of South Florida. This dissertation was completed in pursuit of a Doctor of Philosophy and examined the use of exogenous ketones as a “novel method of inducing therapeutic ketosis via exogenous ketone supplementation to promote enhanced ischemic wound healing in young and aged Fischer 344 rats.”

The author highlights a largely unknown problem of chronic wounds affecting a large group of patients in the United States that places a significant stress on the health care system with costs approaching $25 billion per year. This cost is said to be steadily and rapidly increasing “due to a disproportionate occurrence in the ever-aging population.” The growing problem of chronic wounds is exasperated by the fact that normal wound closure is complicated and unfortunately current treatments are “minimally effective”.

The paper lists four main features of age-related impairment of wound healing that were targeted in the proposed exogenous ketone therapeutic treatment:
  1. unresolved inflammation
  2. increased reactive oxygen species (ROS)
  3. diminished blood flow
  4. decreased metabolism and ATP production
The rationale for the use of exogenous ketones to treat impaired wound healing lies in the fact that “ketones have been shown to decrease inflammation, decrease ROS levels, increase blood flow, and increase ATP hydrolysis and increase metabolism.” To test this hypothesis, the researchers chose to examen the effects of exogenous ketones “in vivo using an ischemic wound model in young and aged Fischer 344 rats and in vitro using patient-derived primary human dermal fibroblasts isolated from discarded skin.”

The dissertation included the examination of five ketogenic agents to test the established hypothesis:
  1. 1, 3- butanediol (BD)
  2. medium chain triglyceride oil (MCT)
  3. sodium/potassium-βHB mineral salt (BMS)
  4. combination of BMS+MCT
  5. 1,3-butanediol acetoacetate diester/ ketone ester (KE)
The effects of these five oral ketone supplements on blood ketones, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats were measured over a 28-day period. In summary, it was found that: “though each ketogenic precursor had a distinctive effect on each of the parameters, overall oral ketone supplementation rapidly elevated blood ketone levels and suppressed blood glucose levels without significantly affecting heart health biomarkers. Additionally, we sent serum and hippocampal samples from KE (5 g/kg) and BMS+MCT (10 g/kg) supplemented rats to Metabolon Inc. to determine the effects that oral ketone supplementation would have on the metabolome. Ketone supplements increased Kreb’s cycle intermediates, antioxidants, and adenosine, which supports our hypothesis that oral ketone supplementation, will enhance wound healing.”

Major Findings of the Study

  1. Dietary Ketone Supplementation Increases Blood Flow and Wound Closure in an Ischemic Wound Model in Young and Aged Fischer Rats
  2. Aged rats metabolize exogenous ketone supplements differently than young rats
  3. Hypoglycemic effect of hyperketonemia attenuated with age
  4. Ketone supplementation increases blood flow in both young and aged rats
  5. Ketone supplementation accelerates wound closure in young and aged rats
  6. Food- integrated ketone supplementation did not elicit weight loss in young and aged rats
The researchers found the exogenous ketones used in the study (BD and BMS+MCT) had similar wound healing effects, but the analysis of how the effects were achieved revealed they do so via distinct mechanisms. Of note was the fact that the ketone ester supplement was not analyzed for its potential wounding healing effects due to the unpalatability of the supplement to the rats. In other words, the rats refused to eat it! Anyone that has tried a ketone ester supplement will understand the rat’s attitudes about the taste. The authors remarked that the palatability of KE will need to be improved and/or a capsule created for it to be used in future studies. Yeah, it tastes that bad.

This study concluded that exogenous ketones do indeed enhance wound healing
though calling for additional studies to fully flush out the mechanisms involved and further clarification of the best combinations of exogenous ketones, their method of delivery and how ageing impacts the mechanisms involved. The author suggests that a combination of the ketogenic diet and exogenous ketones may provide potential benefits for certain patients and it was also suggested that topical ketones may be a unique and valuable application for wound healing.

From the author:
“Preliminary mechanistic studies demonstrated that exogenous ketone supplementation enhanced wound healing via increasing proliferation and migration, decreasing lactate production, and decreasing ROS production as well as affecting inflammatory cytokines and growth factors. We conclude that exogenous ketone supplementation will be an effective, cost efficient, low toxicity therapy to promote enhancement of wound healing in an aged population.”