title: Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.
abstract: The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature) as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.
authors.affiliation: Department of Psychology and Neuroscience Program, Trinity College, Hartford, Connecticut, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Ruskin
authors.forename: Masahito
authors.initials: M
authors.lastname: Kawamura
authors.forename: Susan A
authors.initials: SA
authors.lastname: Masino
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D055423:Diet, Ketogenic; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000178:diet therapy / Q000473:pathology; D005247:Feeding Behavior; D005620:Freund's Adjuvant; D048788:Growth and Development; D007249:Inflammation / Q000150:complications* / Q000178:diet therapy* / Q000473:pathology; D007662:Ketosis / Q000178:diet therapy; D008297:Male; D009619:Nociceptors / Q000378:metabolism; D010146:Pain / Q000150:complications* / Q000178:diet therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005620:Freund's Adjuvant