Effect of a ketogenic food on canine hypertriglyceridemia

Abstract

Canine hypertriglyceridemia (HTG) is a metabolic disorder that can present as a transient postprandial state, a primary idiopathic condition, or secondary to other endocrine diseases (Xenoulis, 2015). Traditional nutritional management of hyperlipidemia relies on strict dietary fat restriction to decrease circulating lipids (Ford & Ludlow, 2010b; Xenoulis, 2015); however, emerging evidence suggests that modulating other macronutrients, particularly carbohydrates, may offer a more comprehensive mechanism for improving systemic lipid metabolism (Clifton & Keogh, 2007). Chapter 1 explores the literature on canine dietary preferences and the physiological basis for an alternative nutritional strategy: replacing dietary carbohydrates with protein and fat to formulate a ketogenic, low-carbohydrate food that addresses metabolic dysfunction. Chapters 2 and 3 detail the first study, to the best of the author’s knowledge, to evaluate the clinical and metabolic impacts of this novel ketogenic food. Nineteen adult dogs with confirmed HTG were randomly assigned to receive either a traditional low-fat (Control) food or the experimental ketogenic (Test) food. Over the 10-week treatment period, a significant diet x day interaction was observed in caloric intake (Kcal/day, P = 0.03). Additionally, diet had an effect on average caloric intake (P < 0.01). Specifically, dogs fed the Test food maintained adequate caloric intake, while the Control group exhibited transient fluctuations in daily caloric intake, before stabilizing by week 10. Body weight demonstrated a significant effect dependent of day (P < 0.01), with no overall difference between the treatments. Although the Control group experienced a temporary within-group fluctuation in body weight (P = 0.03), both groups concluded the study with stable weights (P > 0.05). Analysis of serum triglyceride concentrations demonstrated a significant effect of day (P = 0.03). Importantly the Test food performed similar to the nutritional standard of care Control food, with both foods achieving a mean reduction from baseline (Test:-161 mg/dL and Control: -112 mg/dL). The macronutrient shift in the Test food induced ketosis, evidenced by a significant diet x day (P < 0.01) interaction, as well as an effect of day (P < 0.01), and diet (P = 0.01) for [beta]-hydroxybutyrate (BHBA). Dogs in both groups started the study with similar B-HBA concentrations (Test: 0.93, and Control: 0.88, mg/dL; P = 0.52). However, by end of study dogs on the Test food continued to increase B-HBA concentrations while the Control group remained unchanged (Test: 1.4, and Control: 0.85, mg/dL; P < 0.01), when compared to baseline. Driven by the replacement of carbohydrates with fat and protein, the Test food increased proteolytic fecal short-chain fatty acids (SCFAs) including 2-methylbutyric acid (P = 0.03) and isobutyric acid (P < 0.01) and decreased saccharolytic SCFAs including propionic acid (P < 0.01). Conversely, the Control group demonstrated an increase in saccharolytic SCFAs including propionic acid (P < 0.01), and acetic acid (P < 0.01) when compared to baseline and demonstrated no changes in proteolytic SCFAs including 2-methylbutyric acid (P= 0.67), isobutyric acid (P= 0.93), and isovaleric acid (P= 0.24). Additionally, both foods modulated hormones involved in appetite regulation; circulating ghrelin exhibited a diet x day interaction (P = 0.04 ), with final concentrations remaining stable between dietary groups (P = 0.04 ). However, the Test food induced an increase in ghrelin at week 5 (P = 0.04) through study end when compared to baseline, whereas the control group exhibited no change (P = 0.78). Leptin and peptide YY (PYY) demonstrated no diet x day interactions (P > 0.05) and were influenced solely by time (P < 0.05). Finally circulating glucose-dependent insulinotropic polypeptide (GIP) and pancreatic polypeptide (PP) remained stable throughout the study, showing no significant variations (P > 0.05). Collectively, this research is the first study to evaluate the potential clinical efficacy of a ketogenic food in managing canine HTG, by maintaining body weight and intake, and improving systemic lipid metabolism. More research is needed to determine the full potential a ketogenic food could represent as a therapeutic alternative to traditional low-fat dietary interventions for certain chronic endocrine disease management in dogs.