How Intermittent Fasting With Exercise Can Boost Your Brain

From depression to dementia, the benefits are proven.


I like running, but not after midday. I’m a morning person, and like to harness the extra energy that comes with the first half of the day. This routine means that I don’t usually eat anything until 11am. Thus, with no palpable hardship (but with the assistance of some good coffee and plenty of water), I am practising intermittent fasting and fortifying the neurons in my brain.

Most people practise intermittent fasting in order to lose weight, and it is indeed an effective strategy. Less well known are the neurological benefits, which include improved mood and memory, and reduced risk of stroke, Alzheimer’s and Parkinson’s.

Because I usually have my evening meal between 6pm and 7pm, I effectively fast for 16–17 hours. This overnight abstinence is the cheat’s version of intermittent fasting; there are other, more challenging methods for the stronger-willed.

Although there is no official definition of this increasingly popular practice, the IF fundamentals involve a pattern of eating based on extended periods of abstinence. There is ‘time-restricted feeding’, where food is limited to an eating time-frame of around 8 hours — my preferred method. ‘Periodic fasting’ is more extreme, lasting from 2 to 21 days. Another option is to fast for 24 hours twice a week.

I have never attempted any of those more demanding options. I don’t see the need; I like eating and have a healthy relationship with food. I’d like to keep it that way.

Of mice and men

The evidence for the aforementioned neurological benefits of IF first came to light in experiments with laboratory mice and rats. These were followed by human studies, which have had similar results.

How does IF achieve such impressive results? By elevating levels of two key substances in the brain: brain derived neurotrophic factor (BDNF) and ketone bodies.

The role of BDNF

Evolution tells us that the brain performs best when the individual is both hungry and physically active. Hunger primes the brain and sharpens the focus: hunting requires wits as well as stamina.

BDNF is a protein found in the brain and elsewhere in the body. It protects neurons by strengthening resistance to damage, and it encourages the growth of new neurons. BDNF also strengthens synapses (a synapse is the structure between nerves, through which messages are transmitted), and helps form new synapses.

Low levels of BDNF are associated with various neurological disorders, including major depression, epilepsy, Alzheimer’s disease, autism and schizophrenia.

Fasting raises your levels of BDNF, and so too does physical exercise.

BDNF and depression

BDNF levels are reduced in people with depression, anxiety and major depressive disorder, and the lower the BDNF, the more severe the symptoms.

Depression is characterized by “behavioral despair” and the inability to experience pleasure, and both of these are controlled by the brain’s stress and reward system. The “neurotrophin hypothesis of depression” is based on the observation that BDNF exerts a positive effect on this system.

“Based on these studies, the neurotrophin hypothesis of depression was proposed, which suggests that stress and depression is associated with decreased expression of BDNF and that antidepressants alleviate depressive behavior by increasing its level.” (Dwivedi 2009)

Antidepressants raise BDNF levels “up to normal value”, an effect you can also achieve through IF and exercise.

BDNF and memory

BDNF is abundant in the hippocampus, an area of brain that is especially important for memory. Atrophy of the hippocampus is a risk factor for poor cognitive function and dementia.

Do some aerobic exercise, on the other hand, and you can increase the size of your hippocampus.

Combine aerobic exercise with regular intermittent fasting, and expect greater enhancement of cognitive function, whether you be rat or human. Recent studies suggest that together, IF and exercise:

“.. can optimize brain function and may forestall age-related neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases”

A sedentary lifestyle, on the other hand, can have the opposite result, leading to reduced levels of BDNF. So unfortunately it is not enough to sit around doing sudokus and crosswords; intellectual challenges won’t mitigate your vulnerability to neurodegenerative disorders as you age.

Modern Mouse

The ketone effect

When you fast, you do more than raise BDNF; you also increase production of ketone bodies. Ketone bodies are made in the liver from fatty acids stored in body fat.

These ketones provide fuel for the brain in the absence of glucose. This is very, very good news for people at risk of developing dementia, or anyone who just wants to avoid it.

That is because people with Alzheimer’s have impaired brain glucose uptake — deterioration of glucose metabolism in the brain precedes the onset of Alzheimer’s. Research suggests that this deterioration in glucose metabolism is involved in the development of the disease.

That is why type 2 diabetes increases the risk for dementia. Diabetics do not produce enough insulin, or cannot use insulin properly. If you can’t regulate insulin, you can’t regulate glucose. A ketogenic diet neatly side steps this problem — ketones provide an important, non-glucose source of energy to the brain. The liver can produce enough ketones, per day, to meet the brain’s needs.

“In contrast to glucose, brain uptake of ketones appears to still be normal in AD. Hence, ketogenic interventions may help delay AD.” (Cunnane et al 2016)

Ketosis can also be induced on a low carbohydrate diet, as carbohydrates are the body’s main source of glucose. A low carb diet produces a shift to ketone metabolism and is indicated by the presence of ketones in urine. This can occur after several hours of carbohydrate restriction. This is what’s known as the ketogenic diet.

In a study of elderly people with mild cognitive impairment (the pre-dementia stage) who were assigned either a high carbohydrate or very low carbohydrate diet, those on the low carb diet — and therefore producing ketones — performed significantly better in memory tests.

“These findings indicate that very low carbohydrate consumption, even in the short-term, can improve memory function in older adults with increased risk for Alzheimer’s disease.” (Krikorian et al 2012).

It is rare today for most people to arrive at the point where they are producing ketones in the absence of glucose. On the contrary; high glucose is the norm.

High glucose results from eating starchy carbohydrates, and then snacking on carbohydrates, a fairly typical eating pattern in most industrialized countries.

Thus the brain burns glucose all the time. It is said that glucose is the brain’s “preferred” fuel. But glucose can be almost totally replaced by ketone bodies. When ketones are present in the blood, they are used preferentially by the brain over glucose.

“…if the energy needs of the brain are being increasingly met by ketones, glucose uptake decreases accordingly. This decrease in brain glucose uptake when both ketones and glucose are available supports the notion that ketones are the brain’s preferred fuel.” (Cunnane et al 2016)

When fasting occurs for a whole day, glucose remains in the low to normal range, but ketones rise progressively until food is taken. When food is consumed within a 6 hour window, glucose levels rise during the six hours and for several hours after — then they remain low for the following 16 hours, until the next meal the following day. At the same time, ketone levels are elevated during the last 6–8 hours of the 18 hour fasting period.

Combine intermittent fasting with a low carbohydrate diet and you are in ketone central. You will also experience a reduction in appetite, and find you can go for extended periods without feeling hungry. (IF is normally associated with weight loss and its neurological benefits are often overlooked.) Read all about how to achieve this state of nirvana in my article Winning at weight loss, step 2: Lose fat through insulin control.

Calorie restriction versus intermittent fasting

So why not just go on a calorie restricted diet instead of a fast? That way you don’t have to experience extended periods without eating; you just eat less.

It is true that on calorie restricted diets there is significant improvement in cognitive performance. Both intermittent fasting and calorie restriction improve insulin control and lower glucose, which are essential for brain health. However, only intermittent fasting produces ketones.

There is also the issue of compliance. Low calorie diets work in the short term, but rarely in the long term because they are so difficult to adhere to. Ask any veteran dieter. Pity the poor lab rat who has no choice but to endure the torment of food cravings, brought on by low calorie consumption.

Over in the other cage, its lab mate on the intermittent fast experiment is eating plenty of high calorie food, and enjoying the same cognitive benefits but without the suffering.


Isn’t breakfast essential?

Going back to the overnight fast, aka the easy way to commit to intermittent fasting….

Perhaps you’re wondering about the effect of such an apparently long period without eating. After all, “breakfast is the most important meal of the day.”

Says who? Says General Foods, makers of the breakfast cereal Grape Nuts, who coined this dietary dictum in 1944 as part of an advertising campaign, based on no evidence whatsoever.

Oh, the irony. So many people overeat, and snack constantly, yet often have no desire to eat first thing in the morning. So, what are they told? That they must eat breakfast, despite having no inclination to do so. It’s the most important meal of the day!

There is a reason why most people have little or no appetite when they wake up: the human body clock and the production of cortisol. Cortisol is an adrenal hormone produced cyclically: levels start to rise between 3am and 6am, and within thirty to forty minutes after waking most people experience a two- to three-fold surge in circulating cortisol. With cortisol comes energy, in what is termed the ‘awakening cortisol response’. This surge in cortisol, and mobilisation of energy reserves, explains why most of us do not wake up with a ravenous appetite and why so many people manage a pre-breakfast workout in the gym — or go for a run — without passing out.

There are other systems in place to maintain homeostasis: when blood sugar dips, the hormone glucagon, produced by the pancreas, releases stored glucose from your muscles and fatty acids from adipose tissue.

That is not to say that metabolic disturbances do not occur: people with diabetes for example are more likely to suffer from low energy in the morning and may need to eat soon after waking.

IF is an ancient practice, taking on varying formats, for different motives, and practised by populations all over the globe. It is what our hunter-gatherer ancestors did, in the absence of shops and a food industry hell bent on promoting mindless snacking.

They didn’t do it for spiritual or health reasons. They did it because it was the normal human experience.

Challenges in the form of having to find food meant that pre-agricultural humans had to function well when in a fasted state — they had to make critical decisions and move fast. Today, we no longer face the challenge of having to capture our food. With technological advances, there is little requirement to be physically active, and little opportunity to raise those BDNF and ketone levels.

So for body and mind sake, access your inner hunter gatherer and run on an empty stomach.

Source: Article by Maria Cross MSc (

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