Over-eating, Fasting and Brain Health

Hobbits eat seven times a day: breakfast, second breakfast, elevenses, luncheon, afternoon tea, dinner and supper. For the pampered Hobbits, eating one fruit-based meal a day was something to get used to when the fated few who, by an unusual combination of circumstances, left the Shire and waded into the great war of Middle Earth against the evils of Sauron. This seemingly overindulgent life-style of the average hobbits, in fact, epitomizes the life-style of the average modern people.

Source: The Lord of the Rings: The Fellowship of the Ring (2001)

We are no longer hunters and gathers like our forebears who, driven by the primitive signal of hunger, navigated through complex natural environments and engaged in strenuous physical activities to get limited amount of food; presumably, back in the prehistoric time, people did not eat on a fixed three-meal-a-day schedule with snacks and coffee breaks in between.

Source: ThoughtCo

Nowadays, the feeling of hunger is alien to many people in the younger generations; and the only navigation that one has to do in order to get food is probably just crossing the kitchen to get to the fridge or walking downstairs to get on some form of transportation bound for supermarkets and restaurants. The evolutionarily selected responses that we’ve inherited from prehistoric hunters and gatherers, which sustained cognitive functioning during food deprivation, have become rusty under the modern environment (reviewed by Mattson, 2019). This begs the intriguing question of whether there is a cost to living a life that we are not evolutionarily adapted for. Judging from what I’ve read, I would say that the answer is YES.

Source: Michigan Health Blog

First, let’s look at the consequences of energy overconsumption. One study conducted in 2008 found that rats fed on a high-glucose and high-fat diet supplemented with 30% fructose corn syrup in the water suffered from memory deficits. More specifically, compared to the control rats, rats with this high caloric diet (HCD) were generally underperformers in locating and navigating the way to the hidden platform in a water maze, which is a task that is dependent on memory. An examination of the HCD rats’ hippocampi, which are brain structures critical for memory and learning, revealed decreased dendritic spine density and reduced long-term potentiation in the synapses. These results loosely translate to this: the high-fat, high-glucose diet prevalent in the Western world changed the structure and function of rats’ hippocampus for the worse. So, what about in humans? In an 8-year study that traced and assessed the hippocampus of 420 volunteers aged 60-64, it was found that hippocampus atrophy was greater in those who had greater body mass (Stranahan et al., 2008). Although direct evidence is lacking (probably due to ethics reasons), it is highly suspected that this high caloric diet, which is closely associated to obesity, could do just about the same to human brains (reviewed by Mattson, 2019).

So, it seems that our brain is burdened by an excess of energy, which our ancestors were not used to. Some researchers therefore suggested that maybe, if we plunge ourselves back into a situation of food deprivation in good prehistoric fashion, we might tap into the evolutionarily conserved pathways that ensure cognitive functioning in face of hunger and reap some cognitive benefits.

Source: Huntington’s Disease News

This proposition is supported by many studies which showed that, compared to fellow rats who had unlimited access to food, rats on an intermittent fasting regime (fed every other day), demonstrated better brain functioning that ran the entire gamut from having stronger spatial learning abilities and less age-related memory deficits to resistance to seizure-induced damage of the hippocampus (Reviewed by Mattson, Moehl, Ghena, Schmaedick, & Cheng, 2018). Intermittent fasting, an artificial production of food scarcity, seems capable of promoting brain health, supporting the idea that a brain unchallenged by food scarcity as in the old times works only sub-optimally. The molecular mechanism by which intermittent fasting works further demonstrates an evolutionary root to the cognitive benefits associated with fasting.

The key difference between intermittent fasting and eating all the time lies in how we metabolize fuels. The brain’s primary fuel is glucose, which, besides the free glucose carried around by the blood, is stored in the form of glycogen in our liver and released when our blood sugar is low. The liver glycogen store is usually depleted within 14 hours after a meal, which can be achieved by fasting as well as getting a really long night of sleep. When glucose is not available, our body would switch to metabolizing fats, which are broken down into ketone bodies to feed the brain. Therefore, intermittent fasting means, on the molecular level, the frequent switching between utilizing glucose and utilizing ketone bodies as fuel, whereas an unrestricted diet, which replenishes the glycogen store before it runs out, would mean a monotonous metabolism dominated by glucose.

Source: Ruled.me

The switch from metabolizing the primary fuel glucose to fats represents a major adaptation to food deprivation (reviewed by Mattson, Moehl, Ghena, Schmaedick, & Cheng, 2018). It was in situations where there was not enough food that humans particularly needed decent cognitive functioning to navigate through creeks and forests to find shrubberies laden with berries or to come up with a good scheme to catch a prey— indeed, being active when hungry and sedentary when full is a conserved trait in mammals (Longo & Mattson, 2014).

And how is cognitive functioning related to the fasting state? Many studies have suggested ketones to be the active ingredient in the dose of cognitive enhancer (I made this name up) that is produced by intermittent fasting. For example, one study found that the ketone beta-hydroxybutyrate could upregulate the expression of brain-derived neurotrophic factor (BDNF), which is a signaling molecule that plays a pivotal role in memory and learning processes by facilitating long-term potentiation, a process which strengthens the connection between neurons (Autry & Monteggia, 2012).

Source: Archeologické 3D virtuální muzeum

The logic is now complete. Loads of evidence point to the idea that evolution has selected those who could have a clear mind under food deprivation, possibly by evolving pathways signaled by molecules that are signatures of the food-deprived metabolic state to enhance cognitive functions for purposes of efficient foraging and hunting. And living in the modern world, we are deprived of, instead of food, opportunities to let our brain exercise the pathways that once made us better at surviving.

There is a Chinese folk saying used to comment on people who have done something stupid: “you must have stuffed your stomach too full”. There is a grain of truth to this saying after all. Even if we have used our great intellect to leave the days of hunger behind, we still need to be wary of our evolutionary heritage. While we are building environments for ourselves and changing the environment to ease our survival, the subtle differences in brain function still reflects how the environment has changed us since prehistoric times.


Autry, A. E., & Monteggia, L. M. (2012). Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacological Reviews, 64(2), 238–258. https://doi.org/10.1124/pr.111.005108

Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular Mechanisms and Clinical Applications. Cell Metabolism, 19(2), 181–192. https://doi.org/https://doi.org/10.1016/j.cmet.2013.12.008

Mattson, M. P. (2019). An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition. Trends in Cognitive Sciences, 23(3), 200–212. https://doi.org/10.1016/j.tics.2019.01.003

Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018). Intermittent metabolic switching, neuroplasticity and brain health. Nature Reviews Neuroscience, 19, 63. Retrieved from https://doi.org/10.1038/nrn.2017.156

Stranahan, A. M., Norman, E. D., Lee, K., Cutler, R. G., Telljohann, R. S., Egan, J. M., & Mattson, M. P. (2008). Diet-Induced Insulin Resistance Impairs Hippocampal Synaptic Plasticity and Cognition in Middle-Aged Rats, Hippocampus, 18, 1085–1088. https://doi.org/10.1002/hipo.20470

Source of featured image: The National Lifestyle

3 thoughts on “Over-eating, Fasting and Brain Health

  1. It’s interesting to learn that “evolution has selected those who could have a clear mind under food deprivation,” since nowadays it seems that those who are hungry often are irritable and unable to focus. Perhaps this is the effect of under-using or under-developing the pathways that allowed us to switch from glucose and fat metabolization. Interestingly enough, because we consistently eat, allowing for replenished glucose, we don’t metabolize our fat, and the extra glucose is stored as fat. But if we don’t eat (or don’t eat enough), our body naturally tends to go into ‘survival mode’ where we use only a portion of the glucose taken in and store the rest as extra fat in order to ensure we have energy for later. So the question now would be: How we can start implementing methods in our daily lives that naturally allow us to utilize fat metabolization without triggering excess storage of fat for ‘later use’?


  2. “Intermittent fasting” is a phrase that seems to have come up a lot in today’s media. Recently, Jack Dorsey (Twitter’s CEO) talked about his relationship with intermittent fasting in which he only eats dinner during the week and then fasts from Friday night to Sunday night. With extreme cases of intermittent fasting like this gaining a lot of media attention comes the potential for people to want to follow suit: “if Jack Dorsey can do it, I should too!” While intermittent fasting can lead to health benefits, I think it’s also important to talk with your doctor before you start because each person has a different body and should make a cohesive plan before doing anything too crazy. Thank you for this article!


  3. I am really stuck on this “intermittent fasting” concept. One would think that being starved would deprive the brain of essential energy, but in fact, it does the opposite. It would be interesting to perform studies on why this happens. Also, I think that you have an interesting take on the subject relating it back to prehistoric times when people weren’t on the breakfast, lunch and dinner schedules. How do you think this “intermittent fasting” interacts with people’s circadian rhythms?


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