A Moderate‐Protein and Controlled‐Phosphorus Ketogenic Food Improves Lipid Metabolism in Dogs while Preventing Elevations in Circulating Urea and Phosphorus

Abstract

Objective Ketogenic foods (KF) limit digestible carbohydrate (carb) and offer benefits to disease management including cancer, diabetes, renal failure and cognition. While companion dogs are susceptible, their metabolic response to ketogenic foods that vary in protein/fat ratio is not known. We sought to compare metabolic effects of two KF varying in protein/fat, and further compare their effects to a standard adult food (CON). The first KF (KFA) was commercially available and the second (KFB) was developed for this experiment as a moderate protein, controlled phosphorus (Pi) food to make it amenable to at-risk populations. Methods Dogs housed in pairs, with daily group exercise in outdoor grassy runs. All dogs returned to the colony healthy after the study; no invasive procedures. Fasted blood collections under approved protocols. Macronutrients (P/F/C; % energy): CON (21/32/48); KFA (52/42/5); KFB (26/68/5). Food ash, Pi (dry mass, DMB): CON (ash 4.9%, Pi 0.68%), KFA (ash 8.6%; Pi 1.2%), KFB (ash 4.9%, Pi 0.58%). Prospective randomized crossover trial (n = 16). CON the wash-in food followed by KFA then KFB in randomized order (5 wk feeding each). Foods by AOAC methods. Serum beta-hydroxybutyrate (BHB) by enzymatic reaction. Clinical measurements by Cobas. Fatty acid (FA) elongase (ELO) and desaturase (ACD) substrate/product ratios by GC-FID from serum FA. Linear mixed modeling for diet effects. Least-squared means with pooled variance presented. Significance at a = 0.05. Results Ketogenic ratios (KR) of the foods: CON (KR 0.46), KFA (KR 0.97), KFB (KR 1.63). Clinical blood values remained in normal ranges. Despite only 5% carb as energy, the KFA food was not ketogenic; KFA (KFA 101.2 ± 0.09 uM) did not elevate serum BHB above that of the CON food containing 48% starch as energy (CON 93.6 ± 0.09 uM). In contrast, the KFB food was ketogenic; increasing BHB (KFB 143.8 ± 0.09 uM) relative to both KFA and CON. Serum glucose was not different. The KFA elevated insulin and glucagon relative to CON; the KFB food not different from KFA or CON. The KFA increased blood urea and Pi above KFB and CON; KFB food was not different from CON. Liver enzymes ALP and AST were lowest when dogs were fed KFB. Both KFA and KFB decreased serum triglycerides (TG) by 30% compared to the CON food, but increased total cholesterol. The KFB decreased the product/substrate ratios of d-9 (16:1/16:0, 18:1/18:0) and d-5 ACD (20:4n6/20:3n6) but increased that of d-6 ACD (18:3n6/18:2n6, 20:3n6/18:2n6). KFB also increased apparent these ratios for ELOs elov5 (20:3n6/18:3n6) and elov6 (18:0/16:0). Conclusions: A low-carb, moderate protein, controlled Pi ketogenic food increased circulating ketone BHB 40% above that of a low-carb food that contained 80% more protein. Moderating protein and reducing Pi in the KFB prevented elevations in blood urea and Pi that occurred with KFA. Thus, high levels of protein and ash may limit a food's ketogenic potential and it's use in renal patients. The TG-lowering effect of ketogenic foods observed in humans was mirrored in this canine study; we further found that KFB altered fatty acid metabolism. These results will further enable the personalization of nutritional recommendations for ketogenic foods to benefit a broad spectrum of health states.