ALS is an adult-onset neurodegenerative disorder in which spinal and cortical motor neurons die causing relentlessly progressive weakness and wasting of skeletal muscles through the body.
“ALS is such a devastating disease for those individuals diagnosed with the disorder,” said Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at The Mount Sinai School of Medicine and lead author of this study. ”The findings assert the significance of certain high caloric dietary intake in the prevention of ALS. In view of any available therapeutic application for the disease, this new evidence might bring hope to those affected.”
The cause of neuronal death in ALS is uncertain but study researchers say mitochondrial dysfunction plays an important role. Ketones promote mitochondrial energy production and membrane stabilization. Mitochondiral membrane dysfunction, loss of oxidative stress control, generation of excessive free radicals, neurofilament accumulation, and excitotoxicity are all implicated in the onset of ALS.
About the Study Mount Sinai School of Medicine investigators used a mouse model to examine the affects of a ketogenic diet (KD) on the progression of ALS. ALS mice were fed a high caloric – ketogenic diet (KD) and motor performance, longevity, and motor neuron counts were measured in treated and diseased mice. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, the effect that the principal ketone body, D-?-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection were studied.
Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than the disease controls. The interaction between diet and change in weight was significant; KD mice weighed 4.6g more than the disease control group at study endpoint. In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals. DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in spinal cord motorneuron was also inhibited by DBH.
The Conclusions This is the first study showing that diet, specifically a high caloric - KD, may slow the progression of the clinical and biological manifestations of ALS in a mouse model. This may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.