Sustaining dietary ketosis to improve blood flow and wound healing in young and aged Fisher rats (734.7)

Abstract

Increasing evidence shows that limited energy and nutrient exchange is associated with age‐related impairment of wound healing. Ketone bodies, including β‐Hydroxybutyrate (βHB), are naturally occurring energy substrates, which may augment wound healing. We hypothesized that oral ketone supplementation without dietary restriction would enhance wound closure in young and aged Fisher rats by improving blood flow and supplying an alternative energy substrate. In our preliminary studies, we measured the magnitude and duration of ketosis following administration of a single 6.5g/kg dose of ketone precursors: R,S‐1,3‐Butanediol (KS1), Na+/K+ βHB salt and medium chain triglyceride (MCT) oil 1:1 mixture (KS2), or water in young and aged fisher 344 rats (n=6). Substances were administered through an intragastric gavage and whole blood samples (10 μl) were acquired for analysis of glucose and βHB at 0, 0.5, 1, 1.5, 2, 4, 8, and 12 hours following administration. Using an ischemic wound‐healing model, the ketogenic supplements were added to a standard diet fed ad libitum for 28 days. Laser Doppler imaging of the ischemic peri‐wound tissue every 7 days demonstrated significantly increased blood flow in young rats (n=10) fed KS1 at day 14 and 28 (p<0.001) and KS2 at day 7, 14, and 28 (p<0.01). In aged rats, blood flow was significantly increased in KS1‐fed at day 14 and KS2‐fed at days 7 and 14 (p<0.05). Wound size was significantly smaller in young rats fed KS1 and KS2 at 11 and 14 days following wound creation (p<0.05). In aged rats, KS1‐fed wounds were significantly smaller at days 11 and 14 (p<0.05) and in KS2‐fed at days 11, 14, and 28 (p<0.05). Wound healing improved by 3 days in aged KS1‐fed, 7 days in young KS2‐fed, and 10 days in aged KS2‐fed. Grant Funding Source: Funded by the Office of Naval Research