Intermittent Fasting for Brain Health

Intermittent fasting and calorie restriction induce the process of autophagy, the cellular self-cleansing process that rids cells of junk. Autophagy notably declines with age, leading to a decreased ability to clear damage, and since aging just is an increase in damage, the decline in autophagy leads to even more damage in a vicious cycle.

The decline in autophagy has implications for the brain, as brain disorders like Alzheimer’s are characterized by increased amounts of junk molecules, such as beta amyloid and lipofuscin. 1

Fasting and brain function

Could intermittent fasting help protect against a decline in brain function? Yes, it could.

Consider that a drug that induces autophagy is neuroprotective and decreased the accumulation of misfolded, junk proteins.2

But we can get the same or similar results without a drug.

Short-term fasting induces profound neuronal autophagy.3

Disruption of autophagy—a key homeostatic process in which cytosolic components are degraded and recycled through lysosomes—can cause neurodegeneration in tissue culture and in vivo. Up-regulation of this pathway may be neuroprotective, and much effort is being invested in developing drugs that cross the blood brain barrier and increase neuronal autophagy. One well-recognized way of inducing autophagy is by food restriction, which up-regulates autophagy in many organs including the liver; but current dogma holds that the brain escapes this effect, perhaps because it is a metabolically-privileged site. …we show that short-term fasting leads to a dramatic up-regulation in neuronal autophagy…  Our data lead us to speculate that sporadic fasting might represent a simple, safe and inexpensive means to promote this potentially-therapeutic neuronal response.

How does this work? The answer is simple: in the absence of food, the body needs certain constituents to maintain normal function. For energy, it breaks down fat — obviously, since you lose fat when you don’t eat.

The body also requires amino acids, the constituents of protein molecules. Autophagy breaks down proteins to supply amino acids, and in something of a miracle of biological function, it preferentially selects misfolded and non-functional proteins for destruction.

Hence increasing autophagy through fasting leads to better brain health.4

Ghrelin, the hunger hormone

A recent study found that the hormone ghrelin stimulates autophagy in neurons (brain cells).5

Ghrelin is known as the hunger hormone and has a central role in the regulation of feeding.6

This all makes sense: fasting stimulates hunger through the increase in ghrelin, which in turn stimulates autophagy.

Another implication of the role of ghrelin in hunger and autophagy is that if you actually feel hungry, your autophagy rate has likely gone way up — a good thing. So if you get hungry while fasting, just realize that you’re promoting a very healthful process in your body — not to mention the promotion of fat loss.

Insulin, fasting, and autophagy

It turns out that other hormones are important to stimulating autophagy too. A group investigating a cell-culture model of autophagy found that omitting a certain supplemental nutrient formula from the culture potently induced autophagy.7

By a process of elimination, they discovered that the absence of one ingredient in the cell-culture supplement caused a large increase in autophagy, and that ingredient was the hormone insulin.

Insulin is produced in response to carbohydrates and protein in food. (Ingestion of fat causes little or no increase in insulin.) Fasting produces a potent and swift drop in insulin levels.

In our era of high-carb food and 24/7 food availability, most people’s insulin levels never drop much, leading to insulin resistance and obesity. They never go long enough without food, especially carbohydrates, to see much of a drop in insulin.

This has implications for aging. Eating all the time will accelerate the aging process.

The brains of overweight people show much more shrinkage and are functionally ten years older than the brains of lean people.8

This could be due to inflammation caused by excess fat tissue, or through insulin levels that are always high, or some other mechanism(s).

Fasting at least some of the time is necessary for good brain health and slowing the aging process.

My speculation is that even someone who fasts only 12 hours a day, i.e. between dinner and breakfast, would have a dramatically lower chance of brain disorders. These days, most people don’t do that.

You could greatly increase brain health by fasting longer, such as 16 hours or more, say from dinner until lunchtime the next day. Or longer, even 24 hours or more.

Conclusion

  • Autophagy declines with age, leading to accumulation of junk in the neurons of the brain
  • Increased junk is implicated in brain disorders like Alzheimer’s
  • Fasting strongly increases autophagy in neurons
  • Both the presence of ghrelin and the absence of insulin are implicated in increased autophagy
  • Fasting regularly will improve brain health and lessen the risk of cognitive decline and brain disorders

 

PS: Check out my Supplements Buying Guide for Men. Intermittent fasting is an integral part of my anti-aging program in my book, Stop the Clock.

 

  1. Hardy, John, and Dennis J. Selkoe. “The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics.” Science297.5580 (2002): 353-356.
  2.  Tsvetkov, Andrey S., et al. “A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model.” Proceedings of the National Academy of Sciences 107.39 (2010): 16982-16987.
  3.  Alirezaei, Mehrdad, et al. “Short-term fasting induces profound neuronal autophagy.” Autophagy 6.6 (2010): 702-710.
  4.  Anson, R. Michael, et al. “Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake.” Proceedings of the National Academy of Sciences100.10 (2003): 6216-6220.
  5.  Ferreira-Marques, Marisa, et al. “Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation.”Aging 8.7 (2016).
  6.  Nakazato, Masamitsu, et al. “A role for ghrelin in the central regulation of feeding.” Nature 409.6817 (2001): 194-198.
  7.  Young, Jessica E., Refugio A. Martinez, and Albert R. La Spada. “Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation.” Journal of Biological Chemistry 284.4 (2009): 2363-2373.
  8.  https://www.cam.ac.uk/research/news/brains-of-overweight-people-ten-years-older-than-lean-counterparts-at-middle-age
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14 comments
Arren Brandt says August 7, 2016

I suspect that fasting is not mainly about getting nutrients.
At least not early on, probably it’s a part of our programmed lifespan.
The cellular program simply runs on fast forward when there is an abundance of nutrients, shutting down important repair, running the engine at top speed to prevent overpopulation that might kill everyone by starvation the next season.

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Intermittent Fasting for Brain Health – Transhumanism and Longevity Feed says August 8, 2016

[…] Original Article: Intermittent Fasting for Brain Health […]

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Longevity Feed says August 8, 2016

Another excellent article!

I’ve just got caught up on reading “fasting without fasting” and the article about fasting for brain health. The positive impacts of doing it seem to be sky-rocketing. It’s not just great for keeping your weight down.

One thing I still need to cut out of my diet completely is bread, although I do eat far less than I used to.

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Joseph Moroco says August 8, 2016

Fasting is no problem. My only worry is supplements. Most are taken with food, but L-theanine is taken upon waking and still fasting. Curcumin is taken twice, once outside of fasting. I would hate to think such practices ruin a fast.

I need all the brain health possible.

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    Arren Brandt says August 8, 2016

    First of all you don’t need supplements all the time. Fasting is as noted by Mangan excellent on it’s own.
    Secondly you can combine fasting with supplements, coffee and green tea are great when you want something but cannot eat something.
    The research of Valter Longo indicates that the practice of fasting 24-100 hours markedly improves the Differential Cellular Stress respones, making it possible to administer powerful toxic chemicals in larger dosages as a part of chemo-treatment.
    Radiation tolerance is also increased in many animal models.
    So if you worry that supplements will turn toxic worry no more, but maybe you were more concerned about absorption?
    Taking Longos research a bit further it might actually be a very chemo-preventative practice to end a fasting session with a serving of turmeric, garlic, coffee, cacao as the cancer cells possibly in your system will be more vulnerable.

    I should caution that longer fastes (3 Days and forward) should not be ended like this as it might be dangerous. Longer fastes should be ended with careful and slow refeeding to start the stomach and powerful spices have no Place there.

    Reply
ConantheContrarian says August 9, 2016

Fasting and a combination of proper diet after the fast had ended (no processed foods) helped cure my acne. I highly recommend fasting for the various benefits that Mangan (PBUH) mentions.

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Jer says August 17, 2016

Hi PD
Just to say that I’ve been on a fast since Sunday 10pm until 10am today Wednesday morning. All inspired by your inimitable research! I didn’t think it was possible to hold out for that long – I assumed I would be demented with hunger, but in fact the feeling of hunger that I get after not eating for 8 hours (during the day) is worse than the feeling of hunger after 60 hours fasting. My stomach actually feels slightly bloated.

Sure i think about food every now and then, but the thought passes quite easily. I now think I was eating as it’s a passtime.

I’m not slim so there is plenty of “bodily stored resources” to keep me from perishing from hunger. I also have a sedentary desk job and don’t hit the gym – if someone told me that all i needed was 800 calories a day to maintain my weight, i would not be surprised. i generally dont eat that much during the day, but what I do eat is usually unhealthy.

The slightly sad fact is that my hopes of being 6 pounds lighter by today have not come to pass! I think my body is in “starvation mode” and is now operating on fat reserves and it doesn’t seem to need much to operate. Metabolism is now tending towards zero calories per day burnt. Just because i’ve stopped chowing on 2 pounds of food a day doesn’t mean i’ve lost 2 pounds a day.

Thanks for the inspiration. The fast is going to broken this evening with a serious steak. i’ll try a 4 day fast sometime soon!

Best

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    P. D. Mangan says August 17, 2016

    Hey Jer, that’s some serious fasting you’re doing there. After initial water weight loss, which wouldn’t be much if you already eat low in carbs, seems about the most you could expect from total fasting might be 1/2 lb a day. That’s based on burning maybe 1800 calories, which would be the case if no exercise was done.

    Awesome work! I have never done anything like that myself.

    Reply
      jer says August 19, 2016

      Thanks PD

      Here are a few observations for those who may think of doing long fasts (more than 24 hours):
      – it didn’t really interfere with my concentration. Hunger pangs may last a few minutes every now and then, but they are not that bad!
      – I actually felt a little more alert. It was a bit like a feeling of nervousness or mild excitement. It possibly made me more active than usual (although this could be a first time user effect)
      – I had difficulty sleeping – possibly because I felt more excited or alert. I did fall asleep though eventually
      – my body was colder than usual, though that was not a problem per se
      – output from toilet breaks dropped 95%. It seems that if you put nothing in, then not much will come out. I assume that what was produced was the by-product of a “pure” fat burning process. It looks like my body didn’t need to burn that much to survive.
      – I might have felt a bit weaker and tired (though I wasn’t sleeping that well as noted)

      Reply
        P. D. Mangan says August 19, 2016

        Thanks, jer, useful info. I’d like to try one of those longer fasts myself.

        Reply
Joshua says September 16, 2016

“Another implication of the role of ghrelin in hunger and autophagy is that if you actually feel hungry, your autophagy rate has likely gone way up — a good thing.”
This makes me think of something I’ve wondered about for a while. I notice that if I adopt a somewhat consistent fasting routine — say, fasting for 17 hours most days of the week — eventually (over the course of several weeks), my hunger during the fasting period declines significantly. Would that imply, then, that the fasts are doing less good health-wise then they used to? Perhaps it indicates a need to up the ante — i.e. start fasting for longer durations?

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    P. D. Mangan says September 17, 2016

    Interesting question. Despite the ghrelin connection, I’m inclined to say that decreasing hunger does not mean that your fasts are less beneficial. Your insulin has dropped dramatically and blood ketones risen, both are beneficial.

    Reply
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