Macronutrient Proportions and Fat Type Impact Ketogenicity and Shape the Circulating Lipidome in Dogs

Abstract

Many physiological processes including ketogenesis are similar in dogs and humans, but there is little information available on the effect of carbohydrate restriction in dogs. Here, the ketogenicity and serum metabolic profiles of dogs were assessed after they had consumed high carbohydrate (HiCHO); high protein, low carbohydrate (PROT_LoCHO); or high fat, low carbohydrate (FAT_LoCHO) foods. Thirty-six dogs were fed HiCHO for 4 weeks, then randomized to PROT_LoCHO or FAT_LoCHO for 5 weeks. Dogs then crossed over to the other food for an additional 5 weeks. Generally, reduction of dietary carbohydrate by replacement with either protein or fat increased the energy required to maintain body weight, and fat had a greater effect. Postabsorptive energy availability derived mainly from glucose and triglycerides with HiCHO, from gluconeogenic amino acids and fatty acids with PROT_LoCHO, and from fatty acids and β-hydroxybutyrate with FAT_LoCHO. This study demonstrated that the reduction of carbohydrate in canine foods is potentially beneficial to dogs based on improvements in metabolism and supports the use of low-carbohydrate foods as safe and effective for healthy adult dogs.

Immune-Modulating Effects of Low-Carbohydrate Ketogenic Foods in Healthy Canines

“…The results show that in addition to effects on circulating leukocytes, both LoCHO_PROT and LoCHO_FAT foods decrease several proinflammatory cytokines/chemokines. Taken alongside the metabolic effects previously reported from this trial [ 5 ], the results of the current report indicate that nutritional ketosis may link immunologic and metabolic phenomena in dogs to modulate immunometabolism.…”

“…Human subjects consuming LoCHO diets and ketogenic fats [e.g., those containing triglycerides of medium-chain (MCT) fatty acids] undergo a “metabolic switch,” resulting in an increased reliance on fat catabolism for energy metabolism [ 4 ]. The same phenomenon has recently been demonstrated in dogs [ 5 ]. In the context of acute viral infection, reduced capacity for metabolic switching to ketogenic metabolism results in impaired immune cell function, and the predominant ketone body β-hydroxybutyrate (BHB) restores cytokine production and endogenous antioxidant status of T-cells [ 6 ].…”

“…For PCR analyses reported here, 10 canine subjects were randomly selected from a larger population ( n = 35) that enrolled in a previously reported trial [ 5 ]. The trial was performed under approval by the Institutional Animal Care and Use Committee (Protocol #: FP885.1.1.0-A-C-D-ADH-MULTI-112-MULTI), as well as Hill’s Pet Nutrition Animal Welfare Committee.…”

“…Although several of the studies on the beneficial effects of ketogenic foods have been reported in humans and rodent models, the immunologic response of dogs to ketogenic foods is not well characterized, particularly in the context of reducing dietary carbohydrates by replacing carbohydrate energy with protein (LoCHO_PROT) compared with fat (LoCHO_FAT). We recently reported that LoCHO_PROT and LoCHO_FAT are not equivalent in the degree to which they induce metabolic switching to ketogenesis in dogs; nutritional ketosis is induced to a greater extent from carbohydrate restriction with replacement by fat energy [ 5 ]. Ketogenesis is qualitatively similar between humans and canines, with a similar acetoacetate:BHB ratio and urinary ketone body excretion profile [ 25 ] as well as similar patterns of BHB use as fuel by the brain, heart, and kidney [ [26] , [27] , [28] ].…”

“…Although there is evidence to support the anti-inflammatory effects of ketogenic foods, studies investigating the effects of ketogenic foods on the cytokine and chemokine profile in canines are scarce. To gain insight on this topic, a pilot study analyzing the immunomodulatory potential of LoCHO foods relative to a standard canine adult food replete with carbohydrates was assessed from a subset of samples in the aforementioned trial [ 5 ] in which each subject was fed each food in a crossover design. The results show that in addition to effects on circulating leukocytes, both LoCHO_PROT and LoCHO_FAT foods decrease several proinflammatory cytokines/chemokines.…”