Autophagy: what’s all the fuss about?

Written by Liz Withyman
October 10, 2023

What is autophagy?

In 2016 Dr Yoshinori Ohsumi won the Nobel Prize for Medicine for his groundbreaking research on the process of autophagy. The term “autophagy” comes from the Greek words “auto,” meaning self, and “phagein,” meaning to eat, so it literally translates as “eating yourself”. Doesn’t sound great, but in fact it may hold the key to longevity.

The concept initially emerged in the 1960s when researchers observed that a cell could destroy its own contents by enclosing them in its membranes, and then recycle them.

Another phrase used to describe the process is ‘cellular spring cleaning’.

Why is it important?

Thirty years later Dr Ohsumi began to experiment and showed that disrupted autophagy is linked to many diseases, for example Parkinson’s, Alzheimer’s, Type 2 diabetes, heart disease and cancer. And it’s linked to the ageing process itself. He recognised its fundamental importance in physiology and medicine.

Intense research is ongoing to develop drugs that can result in targeted autophagy for various diseases, but an intermittent fasting practice stimulates autophagy without drugs.

How does autophagy work?

So how exactly does autophagy work? A top scientist in the fasting world, who explains things really clearly, is Dr Jason Fung. He explains that autophagy is the body’s mechanism for breaking down all the old cells when they’re no longer needed or they’re not functioning well. The process of autophagy takes proteins to the liver and there they are broken into component amino acids.

His analogy is that it’s like taking a messy pile of lego (the amino acids), sorting it out and then building something new from it (a new protein).

Autophagy is one of the body’s means of survival when faced with stress, including the stress produced by fasting. Dr Fung explains the different types of autophagy – lipophagy, aggrephagy, xenophagy and mitophagy which each target different types of poorly functioning or harmful cells.

Lipophagy

Lipophagy is a process by which cells break down and recycle fat. It’s like a “clean-up” process that helps cells get rid of excess or damaged fat molecules and uses them for energy, which also suppresses inflammation.

Aggrephagy

Aggrephagy is a process by which cells break down and recycle clumps of misfolded or damaged proteins, which are associated with neurodegenerative diseases like Alzheimer’s. It’s like a “garbage disposal” system that helps cells get rid of unwanted or harmful proteins.

Xenophagy

Xenophagy is a process by which cells engulf and break down invading pathogens (like bacteria or viruses) that have entered the cell. It’s a “defence mechanism” that helps cells protect themselves from harmful intruders.

Mitophagy

Mitophagy is a process by which cells selectively remove and break down damaged or dysfunctional mitochondria, which are linked to the development and progression of cancer. It’s like a “quality control” process that helps cells maintain healthy mitochondria and avoid oxidative stress.

Fasting induces autophagy

Dr Fung explains that one key for activating autophagy is nutrient deprivation ie fasting, including intermittent fasting.

When you eat carbohydrates, insulin signals to the body that food is available; and when you eat protein, a hormone called mTOR does the same. When you fast, these hormones are absent, so the body gets the signal that no food is available, and this activates the body’s maintenance mode.

Autophagy happens to some degree all the time in our cells but when we’re fasting, autophagy is enhanced to ensure our survival in the absence of food intake.

So you get the benefit of autophagy when you fast, and fasting also primes your body for the growth of new, youthful healthy cells when you eat again: Dr Fung calls this process ‘rejuvenation’.

He reminds us that people have fasted for this reason – and for mental acuity – for thousands of years, from the Greek philosophers to Buddha.

It is now understood that a reason for the mental clarity and high levels of energy experienced by fasters is the ketones that are produced during fasting. Science is just catching up!

Other ways to get autophagy

Other activities that can induce autophagy are endurance exercise, and exposure to stressors such as heat or cold by way of saunas and cold water immersion.

How do you know when you’re in a state of autophagy?

While there aren’t immediate, perceivable signs that show you’re in a state of autophagy, the benefits may manifest over time. For example, Gin Stephens, author of ‘Feast, Fast, Repeat’ refers to some ‘non-scale benefits’ (ie benefits beyond weight-loss) of intermittent fasting such as having smoother skin on your feet and elbows. And Dr Mindy Pelz talks about the alleviation of musculoskeletal pain and stiffness resulting from fasting.

Dr Jason Fung says that, by contrast with people who lose large amounts of weight through calorie restriction, he’s never had to send a patient to a plastic surgeon for skin removal, even if they’ve lost more than 7 stone. Dr Fung’s theory is that autophagy breaks down the old skin tissue and recycles it.

How long do you have to fast to get into a state of autophagy?

You might be wondering how long you have to fast to get into autophagy. There is no simple answer to this question because it depends on all sorts of factors, like the type of fast (water-only vs other kinds of fasting for example); individual metabolism; and your glycogen stores before you started the fast.

Autophagy is like a dimmer switch

Because it can’t be measured in the way that, for example, being in ketosis can, there is debate about how long you need to fast to get into autophagy. Some scientists say it begins at 24 hours of fasting. Fasting expert Dr Mindy Pelz advises us to think of autophagy as a dimmer switch, increasing the light gradually the longer you fast & she says that more intense autophagy starts to kick in around 17 hours of fasting.

Diabetes expert Professor George Cahill puts increased autophagy at 16 hours of fasting on the basis that that’s typically when stored glucose tends to run out.

It depends on many factors

Dr Fung describes how “when we fast, insulin goes down and glucagon goes up. This increase in glucagon stimulates the process of autophagy…in fact provides the greatest known boost to autophagy”. But it seems that exactly when this metabolic switch happens in a given individual, on a given day, will depend not only on when, but also what and how much they last ate and on how much energy they’ve used since they last fuelled up. So as usual, it’s complex and will depend on many factors.

The science is developing in this area.

Many of the studies so far are in animals, but human studies are underway and no doubt the messages will become clearer in time.

A daily dose of rejuvenation, anti-ageing and healing magic

Personally, I move a lot and fast for anything between 18 and 20 hours most days, so I’m giving my body a dose of powerful cellular spring cleaning, rejuvenation, anti-ageing and healing magic on a daily basis.

This is the style of Intermittent Fasting I focus on in my coached IF program, 7 Habits for a Vibrant Life: Time Restricted Eating (TRE) as a daily practice.

My clients shrink their eating windows in tiny increments, eating the right foods to make fasting easy, with accountability from me and from the group, so that they build up their metabolic flexibility comfortably.

It’s a winning combination (check out the testimonials on my website here: https://coachingforavibrantlife.com/).

24-hour fasts

Personally, I’ll also throw in occasional longer fasts and a weekly 24 hour fast – which for me looks like fasting from dinner one day until dinner the next.

Why?

Because following the dimmer switch analogy, the longer you fast between 17 and 72 hours, the brighter the autophagy light; and I’ve found that once I had the right mindset and had built up my habits in small increments, it became easy to do…and so worth it for the DNA repair, metabolic resilience, cognitive benefits, weight maintenance, clarity of mind and the increased energy, as well as the knowledge that I’m giving my insides a spa treatment!

36-hour fasts

It’s been in the news that Rishi Sunak’s approach is to do a weekly 36-hour fast, consuming only water, tea, or black coffee from 5pm Sunday to 5am Tuesday. This is a form of intermittent fasting, offering all the benefits mentioned above, including autophagy.

Some critics claim adverse cognitive effects as a potential drawback (& suggest that his decision making on Mondays is flawed), but whilst I’m not revealing my political leanings here, I’d suggest they consult the history books on this point! That was NOT the experience of the Greek philosophers.

A 36-hour fast is definitely tougher than a 24-hour fast because you go to bed without having eaten that day…which I find quite a challenge, but from time to time I treat my body to a longer fast.

Health effects of prolonged fasts

Prolonged fasts such as the 3-day fasts Dr Pelz leads in her programs can be fantastically healing, providing all the health effects of fasting to a an even greater degree, but these are beyond the scope of my program, 7 Habits for a Vibrant Life.

For longer fasts she suggests an autophagy hack (if you are struggling to get beyond 17 hours of fasting) which is to break your fast at 17 hours with fat which will not affect your blood glucose or your level of autophagy.

However, if one of your reasons for intermittent fasting is to lose weight (burn fat), then as Gin Stephens says in her book, you are better off burning your own body fat than introducing an external source of it, so I keep it simple and stick to Gin’s Clean Fast principles and that’s what I recommend for my clients.

Fasting is not for everyone

I am a regular intermittent faster so my body is trained to become ‘metabolically flexible’ or ‘flip the metabolic switch’ into fat-burning, and the knowledge that while I’m fasting all this magic is happening in my body is a huge motivation.

But Intermittent Fasting is not for everyone, for example it is not recommended for pregnant or breastfeeding mothers; or teens; or anyone who has or has had an eating disorder; likewise if you have diabetes, this is not recommended without medical supervision.

And of course we’re all different: some people are challenged by the feeling of hunger that naturally arises from time to time during fasting; some feel irritable; some (particularly if their body isn’t metabolically flexible yet) may feel tired or unwell. In this case, it may just not be for you.

Or, it may not have worked for you YET, and with more support, perhaps you’d get the benefits.

Please note that none of what is written here is medical advice and if you have any doubts about intermittent fasting, you should consult your doctor.

Liz Withyman

Liz Withyman is an ICF-registered ACC (Associate Certified Coach) who trained with the Coaches Training Institute, the most rigorous and respected coach training in the industry. She runs her online Coached Intermittent Fasting Program 7 Habits for a Vibrant Life several times a year. 

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