Primary components of MCT ketogenic diet are detrimental to bone loss associated with accelerated aging and age-related neurotoxicity in mice

Abstract

Medium chained triglycerides (MCT) ketogenic diet is being extensively investigated for its neuroprotective effects against adverse effects associated with aging and neurodegenerative disorders. Aging is a common risk factor for the development of both osteoporosis and neurological disorders. Hence, suppression of aging and age-related neurodegeneration might contribute to delaying skeletal aging. The present study was designed to investigate the effects of the primary components of the MCT diet, against bone resorption associated with D-gal-induced accelerated aging and D-gal /AlCl₃-induced age-related toxicity. We report bone loss in accelerated aged mice and age-related neurotoxic mice through declined Sirtuin1 (SIRT1) expression, depleted bone turnover markers, (P1NP and β-CTX-1), low bone mineral density (BMD), and deterioration of trabecular bone microarchitecture in both the distal femur and proximal tibia bones. Administration of MCT dietary components decanoic acid and octanoic acid, led to a decrease in body weight and only octanoic acid increased serum levels of ketone body, β-hydroxybutyrate (β-HB), but both of them failed to reverse the diminishing effects on bone health associated with aging and age-related neurotoxicity. Surprisingly, decanoic acid, octanoic acid, and their combination also exhibited negative effects on trabecular bone microarchitecture and BMD in the distal femur and proximal tibia bones of healthy mice. The findings from this study provide supporting evidence on the deterioration of bone health associated with aging and age-related neurotoxicity, and the bone resorption potential of MCT dietary supplements that are being prescribed in healthy older populations and elderly persons diagnosed with neurological disorders.