Enhanced cerebral bioenergetics with dietary ketosis in Mild Cognitive Impairment

Abstract

BACKGROUND: Metabolic disturbance is associated with risk for neurodegeneration, and cerebral glucose hypometabolism is prominent in Alzheimer's disease (AD). Ketone metabolism can compensate for glucose hypometabolism and confers other benefits pertinent to neurodegeneration, among them reduction of oxidative stress and AD pathological factors, suggesting its potential as a therapeutic intervention. In a prior controlled trial, we showed that six weeks' carbohydrate restriction induced ketogenesis and produced improvements in metabolic parameters and memory performance in older adults with Mild Cognitive Impairment (MCI). Those benefits were attributed to the correction of hyperinsulinemia and to the presumed enhancement of cerebral bioenergetic function associated with ketone metabolism. OBJECTIVE: To assess the effect of dietary ketosis on cerebral metabolites in older adults with MCI. METHODS: We enrolled a sample of five MCI participants in a ketogenic dietary regimen and performed pre-and post-intervention proton magnetic resonance spectroscopy to investigate changes in neurochemical metabolites. We also assessed cognitive function and metabolic and anthropometric factors. RESULTS: We observed a significant increase in myo-inositol (p = 0.02) and trends for increases in N-acetyl-aspartate (p = 0.09) and creatine + phosphocreatine (p = 0.11) after six weeks on the ketogenic regimen. Working memory (p = 0.01) and long-term memory (p = 0.07) performances also improved. CONCLUSIONS: This study offers novel, preliminary evidence of cerebral bioenergetic enhancement with mild dietary ketosis in aging humans. Further investigation in controlled trials is warranted to assess the preventive and treatment implications of this intervention for age-related memory decline and dementia.