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

BackgroundKetogenic foods limit digestible carbohydrate but contain high fat, and have antioxidant and anti-inflammatory effects as well as improving mitochondrial function. Beta hydroxybutyrate (BHB), one of the ketone bodies, reduces pro-inflammatory NLRP3 inflammasome, as well as chemokines in cultures.ObjectiveWe assessed the immune-modulating effects of two low carbohydrate (LoCHO) foods varying in protein and fat, and compared their effects to a food replete with carbohydrate (HiCHO) in healthy canines.MethodsDogs were fed control food (HiCHO; ketogenic ratio (KR 0.46) followed by LoCHO_PROT (KR: 0.97), then LoCHO_FAT (KR: 1.63) or LoCHO_FAT followed by LoCHO_PROT. Each food was fed for 5 weeks, with collections in the 5th week; 15 weeks feeding total. Gene expression for circulating inflammatory cytokines from 10 dogs was assessed using Canine RT2 Profiler PCR array and fold changes were calculated using the ΔΔCt method.ResultsLoCHO_FAT significantly increased circulating BHB compared to both HiCHO and LoCHO_PROT When compared to HiCHO there was a significant decrease in several pro-inflammatory cytokines/chemokines in LoCHO_PROT and LoCHO_FAT groups including CCL1, CCL8, CCL13, CCL17, CCL24, CX3CL1, CXCR1, IL-10RA, IL-1RN, IL-5, and SPP1 (all p<0.05). Interestingly, a subset of inflammatory proteins that decreased in LoCHO_PROT, but not in LoCHO_FAT, included IL-33, IL-6R, Il-7, IL-8, NAMPT, and TNFRSF11B. In contrast, the decrease in inflammatory markers in LoCHO_FAT, but not in LoCHO_PROT, included C5, CSF3, IFN-γ, IL-3, IL-10RB, IL-17C, TNFSF13, TNFSF13B, and TNFSF14. Decreased levels of selected cytokines indicate that both low-carbohydrate foods exert an anti-inflammatory effect and provide a strong rationale for testing its efficacy in dogs with inflammatory conditions.ConclusionBoth LoCHO_PROT and LoCHO_FAT foods might be important as part of immune-modulating therapeutic nutritional strategies to reduce inflammation to maintain health in canines. Our study identifies several inflammatory genes that are reduced when fed ketogenic food that were not previously reported.