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Enhancement of Wound Healing with Dietary Ketosis: in vivo and in vitro Experiments
Author(s) -
Kesl Shan,
Jung Michelle,
Sherwood Jacob,
Wu Mack,
Gould Lisa,
D'Agostino Dominic
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.876.4
Subject(s) - ketone bodies , ketosis , wound healing , medicine , ketone , reactive oxygen species , in vivo , physiology , endocrinology , chemistry , surgery , biochemistry , metabolism , biology , diabetes mellitus , microbiology and biotechnology , organic chemistry
Chronic wounds create a substantial burden to patients and health care professionals, affecting 1.8 million new patients per year and costing $25 billion annually. The majority of chronic wounds occur in the elderly. Key features associated with age‐related impairment of wound healing include limited energy and nutrient exchange, increased reactive oxygen species (ROS), and diminished blood flow. Ketone bodies, including β‐Hydroxybutyrate (βHB), are naturally occurring energy substrates. We previously reported that oral ketone supplementation without dietary restriction enhanced wound closure and increased blood flow in young and aged Fisher rats. We hypothesized that improved wound closure was due to a ketone‐induced favorable shift in metabolic parameters and a decrease in ROS production. Following a 28‐day administration of oral ketone supplements in young rats, serum was analyzed by Metabolon using GC/MS. Ketone supplementation significantly increased TCA cycle intermediates, antioxidants carnosine and anserine and significantly increased adenosine. Experiments in vitro with young and aged primary human dermal fibroblasts supplemented with 5mM βHB for 72 hours prior to an oxidative stimulus (100mM tert‐butyl‐hydrogen peroxide), resulted in a significant decrease in cytosolic (young and aged (p=<0.0001)) and mitochondrial (young and aged (p<0.0001)) ROS production and significantly enhanced cell migration. We conclude that ketone supplementation given in vivo and in vitro alters antioxidant status and blood metabolites associated with enhanced wound closure.