A Focus on: Brain Health, Metabolism and Homeostatis



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Regulation of the “milieu intérieur” as the “condition for the free and independent life” was proposed by French physiologist Claude Bernard over 150 years ago and later termed homeostasis by American physiologist Walter Cannon. Not surprisingly, maintaining homeostasis in a dynamic and adaptable brain [1] is expensive: it demands more energy than other tissues. In parallel, metabolic dysfunction is associated with diverse neurological disorders, including autismbrain injuryParkinson’s disease and Alzheimer’s disease


Although often unknown whether a neurologic or metabolic problem came first, we have decades of evidence that a metabolic therapy can treat – and sometimes cure – a neurological disorder. For example, epileptic seizures can be reduced or eliminated by a ketogenic diet. Established nearly 100 years ago, this high-fat, low-carbohydrate, restricted protein diet promotes using ketones for cell energy while maintaining a low, stable blood glucose. The ketogenic diet improves mitochondrial function, and can stop seizures in children and adults - even when all other therapies fail [2].


Based on proven success, diverse mechanisms, and evidence for improved metabolic function, there is growing resurgence of interest and research into ketogenic diet and analogous strategies for many indications [3]. For example, recent evidence suggests that ketone administration can restore cognitive function and reverse hypometabolism found in early Alzheimer’s and mild cognitive impairment [4]. Dozens of ongoing clinical trials aim to determine the impact of ketone-based metabolic approaches on general health and fitness and on conditions such as brain cancer (glioblastoma multiforme), brain injury, autism spectrum disorder and diabetes [5].


Chronic neurological conditions are costly in many ways, with limited treatments and some with no cures. We are just beginning to appreciate gut-brain-immune interactions and impacts of the microbiome on brain health [6] and able to quantify the significant influence of lifestyle and environment on brain function. An integrative approach that leverages fundamental metabolic strategies could herald a new era in preventing, treating or delaying diverse disorders – and thus support a “free and independent life.”

Dr Susan A. Masino is Vernon Roosa Professor of Applied Science at Trinity College, Hartford, Connecticut. She is the author of Homeostatic Control of Brain Function, available in print and online, and the forthcoming Ketogenic Diet and Metabolic Therapies which will be available to purchase in October 2016.

References and further reading

[1] Masino, SA (2016) Homeostatic Control of Brain Function, Oxford University Press.

[2] Gano, L., Patel, M. and Rho, J. (2014) ‘Ketogenic diets, mitochondria, and neurological diseases’, Journal of lipid research., 55(11), pp. 2211–28.

[3] Masino, SA (2016) Ketogenic Diet and Metabolic Therapies, Oxford University Press.

[4] Cunnane, S.C., Courchesne-Loyer, A., Vandenberghe, C., St-Pierre, V., et al. (2016) ‘Can Ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer’s disease’, Frontiers in Molecular Neuroscience, 9. doi: 10.3389/fnmol.2016.00053.

[5] www.clinicaltrials.gov

[6] Dinan, T. and Cryan, J. (2016) ‘Microbes, immunity, and behavior: Psychoneuroimmunology meets the Microbiome’, Neuropsychopharmacology [Epub ahead of print]. doi: 10.1038/npp.2016.103.