Ketones, omega-3 fatty acids and the Yin-Yang balance in the brain: insights from infant development and Alzheimer’s disease, and implications for human brain evolution

Abstract

-Optimal brain performance is intimately linked to the brain's Yin and the Yang À the balance between its structure and its energy metabolism. This relationship is clearly exemplified in infant brain development and in Alzheimer's disease, and probably also applies to human brain evolution. In these examples, redundant pathways help achieve this important balance. For instance, the key structural lipid for the brain, docosahexaenoic acid (DHA), is supplied to the infant brain from at last three overlapping sources: (i) milk; (ii) infant's own fat stores and (iii) by some endogenous synthesis from a-linolenic acid (ALA) or eicosapentaenoic acid (EPA). On the energy side, glucose is normally the brain's main fuel but under conditions of prolonged starvation, it can be almost totally replaced by the ketone bodies, acetoacetate and b-hydroxybutyrate. When ketones are present in the blood they spare glucose uptake by the brain because they are actually the brain's preferred fuel and are essential for normal infant brain development. The redundant sources of ketones are long chain fatty acids (including the relatively ketogenic ALA) in infant stores, and medium chain triglycerides (MCT) in milk. Besides infancy, nowhere is the strain on the brain's balance between yin and yang more apparent than in Alzheimer's disease (AD). One of the reasons why attempts to treat AD have largely failed could well be because chronically inadequate glucose supply to some areas of the brain on the order of 10% is present in people at risk of AD long before cognitive decline begins. However, brain ketone uptake is still normal even in moderately advanced AD. Hence, treatments that ignore the brain energy (glucose) deficit in AD would be predicted to fail, but treatments that attempt to rescue brain fuel availability via ketones would be predicted to have a better chance of succeeding. By analogy to ketones sparing glucose for brain energy metabolism, perhaps ALA or EPA entering the brain can help spare (conserve) DHA for its structural role. If so, it would not necessarily be futile to transport ALA and EPA into the brain just to b-oxidize the majority afterwards; DHA sparing as well as ketone production could be important beneficiaries.Keywords: brain / brain development / Alzheimer's disease / glucose / ketones / beta-hydroxybutyrate / aging / omega-3 fatty acids / alpha-linolenic acid / eicosapentaenoic acid / docosahexaneoic acid Résumé -Cétones et acides gras omega-3, la balance du Yin et du Yang au niveau cérébral : apport des données acquises sur le développement de l'enfant à la maladie d'Alzheimer et implications dans l'évolution du cerveau humain. Les performances optimales du cerveau sont intimement liées au Yin/Yang cérébral : l'équilibre entre sa structure et son métabolisme énergétique. Ce phénomène s'applique spécifiquement au cours du développement cérébral du jeune enfant et de la maladie d'Alzheimer et très probablement tout au long de l'évolution du cerveau humain. Dans le cas des exemples précités, des voies ...

Emerging Therapeutic Promise of Ketogenic Diet to Attenuate Neuropathological Alterations in Alzheimer’s Disease

“…The capacity of the brain in glucose utilization seems to be pathologically decreased in AD [93,94]. Neurobiological proofs revealed that the KBs are successful elective energy substrate for the brain [95,96]. Increase in the levels of plasma KBs by medium chain triglycerides (MCTs) oral dose might enhance cognitive function in adult people with memory disorders.…”

Les lipides dans la maladie d’Alzheimer

“…De son côté, Stephen Cunnane (université de Sherbrooke, Canada), récipiendaire de la médaille Chevreul 2017, considère que l'impact du Yin et Yang dans l'équilibre cérébral n'est nulle-part ailleurs plus évident que dans la maladie d'Alzheimer (Cunnane, 2018). Une des raisons pour lesquelles les essais de traitement de cette pathologie ont tous échoué pourrait être, selon lui, que l'apport insuffisant de glucose dans certaines régions du cerveau (de l'ordre de À10 %) précède le déficit cognitif chez les personnes à risques.…”