Ketosis, Epigenetics, and the Brain

It’s long been understood that ketones, specifically beta-hydroxybutyrate (BHB), are a brain superfuel. It’s easy to explain the evolutionary reasons for this. Hunter-gatherers spent much more time in ketosis. This metabolic state tends to occur during periods of low food access. That happens in winter but also throughout the year, as hunter-gatherers tend toward a feast and fast pattern.

After a period of plenty, it might be a while until the next big kill. Some hunting expeditions could take days or weeks. They needed their brains working in top form for a successful hunt. Many hunter-gatherer tribes purposely fast on a regular basis as a demonstration of their toughness, to show that they can go long periods without food, a very important ability for hunters. Even tribal people living amongst food abundance will fast for no particular reason other than it’s part of their culture.

The Piraha, for example, can procure food easily and yet will go without, sometimes simply because they’d rather socialize around the village or are in the middle of communal dancing that can go on for days. They have better things to do than eat all the time. Besides, on a low-carb diet that is typical among hunter-gatherers, it takes little effort to fast. That is one of the benefits of ketosis, one’s appetite is naturally suppressed and so it effortlessly promotes caloric restriction.

Along with improving brain function, ketosis increases general health, probably including extending lifespan and certainly extending healthspan. Some of this could be explained by creating the conditions necessary for autophagy, although there are many other factors. An interesting example of this was shown in a mouse study.

The researchers exposed the rodents to influenza (E. L. Goldberg et al, Ketogenic diet activates protective γδ T cell responses against influenza virus infection). Most of the mice on a high-carb diet died, whereas most on the keto diet lived. In this case, it wasn’t the ketones themselves but other processes involved. Giving exogenous ketones as a supplement did not have the same effect as the body producing its own ketones. We typically think of ketosis only in terms of ketones, but obviously there is much more going on.

Still, in the case of neurocognitive functioning, the ketones themselves are key. It’s not only that they act as a superfuel but simultaneously alter epigenetic expression of specific genes related to memory. On the opposite side, research shows that feeding people sugar literally makes them dumber. Ketosis also decreases inflammation, including inflammation in the brain. Through multiple causal mechanisms, ketosis has been medically used as an effective treatment for numerous neurocognitive conditions: mood disorders, schizophrenia, autism, ADHD, Alzheimer’s, etc.

If ketosis is a biological indicator of food scarcity, why does the body expend extra energy that is limited? This seems counter-intuitive. Other species deal with food scarcity by shutting the body down and slowing metabolism, some going into full hibernation or semi-hibernation during winter. But humans do the opposite. Food scarcity increases physiological activity. In fact, ketosis is actually inefficient, as it burns more energy than is needed with the excess being put off as heat.

Benjamin Bikman, an insulin researcher, speculates this is because ketosis often happens in winter. Hibernating creatures lower their body temperature, but humans don’t have this capacity. Neither do we have thick fur. Humans need large amounts of heat to survive harsh winters. In ketosis, everything goes into overdrive: metabolism, immune system, and brain. This alters the epigenome itself that can be passed onto following generations.

* * *

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Epigenetics May Provide Relief for Fragile X Syndrome and Intellectual Disorders
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