Autophagy and Fasting – The Best Thing About Intermittent Fasting

Siim Land

Want to know what the BEST THING about intermittent fasting is? It’s AUTOPHAGY. This article is about autophagy and fasting.

The Best Thing About Fasting

There are many reasons why people do intermittent fasting, starting from weight loss and ending with convenience.

Although restricting your eating window within a certain time frame makes it very easy to create a caloric deficit, using IF for fat loss is just the superficial benefit.

The best thing about intermittent fasting is autophagy.

I did some research, and in this article, I’m going to tell you what I learned about autophagy and how you can benefit from it when doing intermittent fasting.

What is Autophagy

Autophagy or autophagocytosis in fancy science language translates from the Ancient Greek word autóphagos which means self-digestion or -devouring.

Autophagy is a natural process by which our cells disassemble and remove their dysfunctional components[i]. It’s basically the recycling of cellular waste and taking out the trash.

Autophagy puts you into a catabolic state, which breaks down your own tissue, as opposed to an anabolic one, which is about building up.

There are a ton of benefits to autophagy:

  • Reduction in inflammation
  • Improved immune system
  • Slows down the aging process [ii]
  • Eats up cancerous cells and tumors
  • Kills infectious particles and toxins[iii]
  • Inability to cause autophagy makes rats fatter, less active, have higher cholesterol and impaired brain function[iv]

How Does Autophagy Work?

When you trigger autophagy, you allow the organelles of your healthy cells to hunt out dead or diseased cells and then eat them.

This involves forming a double membrane around the cell that’s going to be eaten called an autophagosome. The autophagosome then dissolves the sick cell or the toxic protein and creates energy.

What regulates autophagy?

The main signallers of autophagy are two protein kinases mTOR and AMPK[v][vi].

  • mTOR or mammalian target of rapamycin is responsible for cell growth, protein synthesis, and anabolism. It promotes the activation of insulin receptors and will make the body build new tissue.
  • AMPK or AMP-activated protein kinase is a fuel sensor that is involved with balancing energy deprived states

MTOR inhibits autophagy because it makes your body grow, which requires conserving energy and upregulating the metabolism, whereas AMPK supports autophagy due to the energy deprived state.

Autophagy and Caloric Restriction

The reason intermittent fasting induces autophagy has to do with caloric deprivation.

Nutrient starvation allows unneeded proteins to be broken down and recycled into amino acids that are essential for survival[vii][viii].

Research has shown that consuming fewer calories prolong your lifespan. HOWEVER, to get the lifespan-prolonging benefits of caloric restriction you need autophagy.

In one study on mice and flies, they found out that if you inhibited autophagy but still fed the animals fewer calories, they didn’t live longer, but the ones who were proficient at causing autophagy did[ix].

This is a very important point – it means just going on a weight loss diet while not allowing autophagy to do its work will actually be bad for your longevity and health. Long-term caloric restriction leads to micronutrient deficiencies and more oxidative stress.

The reason you get kicked out of autophagy, even when eating fewer calories, is eating too frequently. If you consume protein or carbohydrates, you trigger mTOR. Even as little as 50 calories or just 2 grams of leucine will shift you from a fasted state into a fed one and makes you suppress autophagy[x].

You Need to Fast to Trigger Autophagy

You would be better off by consuming no calories at all and doing intermittent fasting, rather than breaking your fast with a small amount of calories and stopping autophagy.

That’s the reason I believe everyone should practice some form of intermittent fasting. If not daily then at least periodically throughout the week.

Imagine if you’re eating breakfast, lunch, and dinner

  • You stop eating at 8 PM, you fast throughout the night, and you consume your first bit of calories at 8 AM.
  • There’s a 12-hour space between your meals, but it takes about 6-8 hours for your body to first digest the food and then enter a fasted state.
  • You really only start fasting in the middle of the night and you’ve done so for maybe 6 hours by the time of breakfast.

When you’re in a fed state, autophagy is low because of mTOR and insulin. As these fuel sensors drop, autophagy rises.

How Long Does It Take to Trigger Autophagy?

I tried searching for an answer in studies but it seems there is no clear answer to this. Autophagy happens in varying degrees in varying tissues.

Generally speaking, as soon as your blood sugar levels get low and you suppress mTOR and insulin, you’ll begin to show some signs of autophagy.

You would have to be in a mild ketotic state with depleted liver glycogen to let these processes take place. This can happen already within 16-24 hours.

However, this is a very mild response and autophagy starts to really ramp up after the first 48 hours. To get a really good effect from autophagy, you’d have to fast for 3-5 days.

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How to Do Intermittent Fasting for Autophagy

With that being said, I believe it’s not optimal to be eating food only after every 5 days because you wouldn’t be able to sustain other healthy activities like exercise.

Fasting won’t make you lose muscle because of increased growth hormone and ketone body production. Autophagy itself is actually needed for maintaining muscle mass[xi], which means that if you’re constantly staying in a fed state, then you’re becoming more susceptible for unnecessary catabolism because your body doesn’t know how to use its own stored fat for fuel.

Here are a few ways of doing intermittent fasting for getting autophagy and improving your health.

  • Fast for at least 16 hours every day to even enter a fasted state. This will allow your liver glycogen to get depleted and keeps you in mild ketosis for the majority of the day.
  • Keep your insulin and blood sugar levels low. If you eat carbs or protein, you’re going to suppress autophagy. But if you consume more fats then you’re going to blunt the insulin response, which will then prolong the effects of fasting. It’s still going to stop autophagy but you’ll still keep your body in a ketotic state. Ketosis has great anti-inflammatory and longevity-boosting benefits, which promotes autophagy indirectly. Funny enough, a recent 2017 study found that rats who were fed more olive oil in addition to their regular diet had better memory scores and higher levels of autophagy compared to the ones who just ate their regular chow[xii].
  • Don’t eat too much protein or carbs – whatever diet you’re on because it’s g going to trigger mTOR and insulin, which accelerate aging and creation of cancer cells. However, it’s not that black and white – mTOR also makes you build muscle, which can improve your health. You definitely don’t want to be in an anabolic state all day every day because you’re going to die sooner. That’s why I believe this feast-famine cycle is optimal for getting the best of both worlds – you fast to get the life-span prolonging benefits of fasting and when you do eat you eat enough to promote recovery.
  • Exercise can also stimulate autophagy. However, you’d have to do it in a fat burning state whether through carbohydrate restriction of in a fasted state. Doing cardio on an empty stomach will put you into ketosis faster and will increase fat oxidation.
  • Have extended fasts for 3-5 days a few times per year. It should be mandatory if you want to get any significant benefit from autophagy. 36 hours and beyond should be the minimum if you want to clean your body and promote longevity. I’ve already had a 100 hour fast this year and a few 48-hour ones but I’m planning to have another 3-5 day one quite soon so stay tuned for that because I’ll definitely be making a video about it.

Self-Destruction Leads to Empowerment

As you can see, stress and self-destruction are needed for your body to maintain its healthy functioning.

But you know, us at Team Empowerment aren’t about just being adequately healthy or well-off. We’re about transcending and going beyond that.

Fasting and autophagy are great ways of improving your body’s inner physiological functioning, which is going to make you fitter, live longer, acuter in your cognition and more empowered.

What I’ve learned about autophagy so far is that you need to be very mindful with how you control mTOR and insulin as the two directly stop autophagy and can speed up aging as well as cancer cell growth.

That’s why I doing the ketogenic diet as it’s a moderate protein, low carb and high fat diet – perfect for sustaining autophagy throughout the day and improving your entire cellular functioning. Check out my KETO//IF program that combines intermittent fasting with keto.


Stay Empowered







[v] C. A. Lamb, T. Yoshimori, and S. A. Tooze, ‘The Autophagosome: Origins Unknown, Biogenesis Complex’, Nat Rev Mol Cell Biol, 14 (2013), 759-74

[vi] R. C. Russell, H. X. Yuan, and K. L. Guan, ‘Autophagy Regulation by Nutrient Signaling’, Cell Res, 24 (2014), 42-57