Death Will Eat Itself (The Enormous Benefits of Autophagy, or Why You Should Stop Eating Once in Awhile)

Martin Berkhan destroys body fat for a living.

About a year ago I became interested in the benefits of intermittent fasting after reading a number of articles on Martin Berkhan’s Leangains site. Martin is a Swedish nutritional consultant/personal trainer/writer. His recommendations run contrary to conventional wisdom among personal trainers, but his ideas are well-researched and accompanied by numerous examples (pictures) of his own physique and the physiques of his clients, who are all very muscular and impressively lean. Martin’s writing style is bombastic, confrontational, and entertaining, but also thorough, persuasive, and rich in citations.

Martin’s main idea is that intermittent fasting can assist with fat loss and muscle growth simultaneously. Most weight-lifters would tell you that both “growth phases” (where muscle and fat are added simultaneously) and “cutting phases” (where calories are restricted and fat is lost) are required. Martin calls B.S. on that idea, and provides ample evidence that restricting eating to an 8-hour daily “window” (only eating between 2pm and 10pm, for example), combined with simple, consistent workouts can allow a person to get leaner and stronger at the same time.

My Own Experience

At this point in my life I’m not looking for a radical change in my physique, but Martin’s posts piqued my curiosity enough to give intermittent fasting a try. I decided I would “dip a toe in” and try not eating until 2pm, one day a week.

I found it to be easier than expected. On my partial fast days, I only drink water and black coffee until 2pm. I rarely experience any hunger pangs (though I do look forward to my first meal more than I would otherwise). Here are a few other subjective observations:

  • I feel a bit colder, during the winter I usually wear an extra layer on fasting days.
  • I feel mentally clear; fasting days are great writing and/or music composition days.
  • I usually double my productivity on fasting days. I think this is a combination of having better concentration and being less vulnerable to distractions, and the extra time from not having to prepare food or clean up after meals.
  • I usually eat two meals on partial fast days, one around 2pm, and dinner around 6 or 7. These meals tend to be larger than normal. I don’t count calories, but I suspect my caloric intake is less than on normal eating days, even though I eat until I’m full.

What Is Autophagy, and Why Is It Good For You?

Autophagy — it sounds like some kind of disease from the Star Trek universe. In fact, autophagy is a normal biological process. During autophagy, organelles called lysosomes break down waste products inside the cells. What’s an organelle? An organelle is a tiny part of your cell, usually with its own membrane, that serves a specific function (like a cellular organ). Lysosomes break down other worn-out organelles, digest food particles, and destroy viruses and bacteria (using hydrolase enzymes). You could think of them as the stomach of the cell, and/or part of the cellular immune system.

Artistic depiction of a lysosome during autophagy.

Autophagy can even extend to include the destruction of the cell itself, a process called autolysis. For this reason, lysosomes are sometimes dubbed “suicide bags.”

Without autophagy, damaged organelles survive, and cells become less efficient. Autophagy may protect against neurodegeneration, viral and bacterial infections, and cancer.

Short-term fasting can induce autophagy. I can’t find any clinical studies in humans showing precisely when autophagy ramps up in response to fasting. Liver glycogen stores are depleted 12-16 hours into a fast, and it follows that autophagy would ramp up soon after (Berkhan recommends a 14-16 hour daily fast as part of the Leangains protocol). If I have my last food of the day around 8pm, then don’t eat until 2pm the next day, that’s an 18 hour fast. So my one-day-a-week half-day fast is probably enough to upregulate this powerful physiological process for at least a couple hours.

My own crude way of thinking about autophagy is that this process “cleans out the gunk.” By inducing autophagy, I allow my body to break down old mitochondria (the “energy producers” of the cell), destroy viruses and bacteria, and suppress chronic infections.

What was that last bit? Chronic infections? How bad is it, J.D.?

We’re All Infected

Well, I have some bad news for you. We all have chronic infections. I’ve been reading The Perfect Health Diet by Paul Jaminet and Shou-Ching Shih Jaminet (thanks Dan Pardi for sending it to me, and thanks Tyler Simmons for recommending it — I’m planning on writing a review post soon). There’s a great section towards the end of the book about chronic infections. Unless you’ve lived in a bubble your whole life, you’ve probably got at least one of the following infections:

  • Cytomegalovirus (CMV) — infection rate among adults in the U.S. is between 50-80%
  • HSV-1 — the virus that causes cold sores is found in about 60% of people in the U.S.
  • Toxoplasmosis — you can pick up this protozoan parasite from handling cat poop or eating undercooked meat. In the U.S. only 10% of the population carries antibodies, but infection rates in other parts of the world are up to 60%

All three of these infections are generally considered “harmless” in the non-immunocompromised, but even people showing no symptoms may suffer long-term effects from these infections. Toxoplasmosis infection may slow reflexes and is associated with a sharply higher rate of car accidents. Long-term HSV-1 infection may be a cause of Alzheimer’s disease. Other extremely common chronic infections include C. pneumoniae (also associated with Alzheimer’s, as well as atherosclerosis, stroke, multiple sclerosis, arthritis, and rosacea) and H. pylori (which causes stomach ulcers). The adenovirus AD-36 is present in about 20% of the population and may contribute to obesity (as well as causing respiratory and eye infections).

The Perfect Health Diet (includes ice cream)

In most cases we’re not even aware of all of our viral and bacterial infections, as many of them start off giving us vague symptoms when we’re first infected, then become asymptomatic in their latent phase. I only became aware that I had picked up CMV after giving blood and losing my CMV-negative status (before, they could give my blood to newborn babies, now they can’t). With hindsight, I realized that I probably got CMV around the time my daughter started preschool. For a couple months around that time I had a slightly swollen submandibular salivary gland. My doctor examined me, shrugged, and said “doesn’t feel like cancer … probably a virus … check back with me in six months if it hasn’t gone away.” Well, the swelling went down, but I later learned that the salivary glands are a common site for CMV infection.

So, we’re all infected. Should we be freaking out, driving to Vegas, and blowing our life savings on one last wild weekend?

Relax, it’s not that bad.

First of all, some chronic infections actually have protective or even positive side effects. H. pylori can cause stomach ulcers, but it is also be protective against GERD (acid reflux), thus protecting against oesophageal cancer. Hookworm infection may protect against symptoms of celiac disease. In some cases parasites have evolved ways to “tamp down” immune responses, thus preventing autoimmune diseases. The basic idea behind the “hygiene hypothesis” is that when our immune systems are underutilized fighting external pathogens (viruses, bacteria, parasites, etc.), the immune system is more likely to malfunction and turn against our own tissues (resulting in more allergies, asthma, and other autoimmune problems).

Still, these infections often prove to be our undoing in the long-run, either by robbing our bodies of resources, causing chronic low-grade inflammation, or slowing invading and damaging internal organs. It’s in our best interest to keep these chronic infections in check.

The Perfect Health Diet recommends eleven ways to enhance immunity and fight chronic infections, but I think that list is too long. Who’s going to do eleven things? I’ve shortened the list to the four most important/effective/doable, IMO:

  1. Get vitamin D levels to within an optimal range (to boost intracellular immunity and increase production of antimicrobial peptides)
  2. Reduce food toxin load (from grains [esp. wheat and other gluten grains], processed vegetable oils, sugar/fructose, bean lectins, etc.)
  3. Get enough sleep (one way to do this is to reduce artificial light in the evening)
  4. Practice intermittent fasting (weekly 16+ hour fasts, optional monthly 36+ hour fasts) to induce autophagy

Other Benefits of Intermittent Fasting (Motivation, Pleasure, Strength)

Short-term moderate food restriction has significant psychological effects. In this study, mice brains were found to remodel in response to food restriction, creating more dopamine (D2) receptors. Adequate dopamine receptors are necessary to allow us to anticipate and respond to rewards, and reduced numbers of dopamine receptors are associated with both aging and obesity. Moderate food restriction may resensitize us, allowing us to experience the same mental rewards from less food, and less palatable food (and other experiences).

This finding syncs with my own experience of intermittent fasting. After not eating for 18 hours, basically any food seems delicious to me — even a bowl of plain oatmeal or a plate of plain raw vegetables.

In addition, if life is feeling a little flat or dull, a short fast somehow alters my perception. Everything seems more colorful, clearer, more vivid, and more exciting.

Can the brain remodel so quickly? Maybe my subjective observations are related to another mechanism, something other than an increase in D2 receptors. Still, something is happening. The mind and body go into a different mode when food scarcity is perceived. Hunting mode, maybe (or gathering, take your pick).

Another benefit of short-term fasting is an increase in growth hormone (which helps to burn fat and build muscle). No wonder Martin Berkhan and his clients are so lean and strong.

Is Intermittent Fasting a Good Idea for Everyone?

I wouldn’t recommend intermittent fasting for everyone, at least right away. If you eat wheat and/or drink milk every day, you might experience exorphin withdrawal soon after skipping a meal. Wheat and milk both contain proteins that mimic endorphins (the pleasure-inducing, pain-relieving chemicals of the brain), and when you cut off the external supply of the chemical mimic, it takes a few days for the brain to ramp up internal endorphin production. In the meantime, you might experience aches, chills, and general grumpiness from cutting out these foods.

Similarly, if your blood sugar regulation is out of whack, intermittent fasting might be less comfortable. If you drink soda or other sweet drinks, eat candy, white bread, etc., then cut these foods out for awhile before you try intermittent fasting. Some supplements and foods may be helpful in regulating blood sugar and restoring insulin sensitivity, including chromium and cinnamon.

Your genetic makeup may also affect your response to intermittent fasting. Many people of Asian and European ancestry (myself included) have a mutation in the SNP rs2291725 that is associated with higher fasting blood glucose. This mutation probably became widespread in some populations thousands of years ago as a response to the inevitable “lean times” that came with a switch to agricultural food production. Women with this mutation were more likely to maintain their pregnancies during times of food scarcity. These days, the same mutation is associated with a higher risk of developing Type 2 diabetes and/or gestational diabetes. I wonder if having this mutation also makes intermittent fasting more comfortable (due to higher fasting blood glucose levels)?

Berkhan has noted that his female clients generally experience negative symptoms of fasting (low blood sugar, poor mood) after a shorter period, and recommends a 14-hour daily fast instead of 16 hours.

Pregnant women probably shouldn’t fast at all, as fasting during pregnancy has been associated with reduced academic performance in the children.

Some fears about shorts fasts are entirely unfounded, like the idea that short fasts will slow down your metabolism, increase cortisol, and force your body to burn muscle for fuel. Berkhan does a good job of debunking these metabolic myths in this post.

If, for whatever reason, you decide that intermittent fasting isn’t for you, fortunately there are other ways to induce autophagy, including exercise (thanks Dan Pardi for the PubMed research).

A Final Thought

I can’t think of a more effective, easier, cheaper anti-aging protocol than my weekly partial fast. The benefits (immunity enhancement, cellular “housecleaning”, growth hormone release, mental clarity, productivity boost) far outweigh the costs (slightly cooler body temperature on fasting days).

There’s also a satisfying kind of mental freedom in knowing you can miss a meal or two and still function normally.

Additional Resources:

46 responses to “Death Will Eat Itself (The Enormous Benefits of Autophagy, or Why You Should Stop Eating Once in Awhile)

  1. Thanks for another fascinating and informative post, JD. The PHD brings a lot of disparate information together. We seem to have covered the same ground, using this “paleo” paradigm (though some times I hate that term) to connect the dots between food, lifestyle, stress, and health.

    2 meals a day, or a very light, late breakfast works for me. Eating a PHD style diet, I just don’t have the same hunger patterns. I recently tried a little “bodyhacking”, starting each day with a coconut/banana/protein shake smoothie. Result? Weight gain, lethargy, morning snacking… I think I’ll quit that experiment.

  2. There’s an interesting study that found intermittent fasting/calorie restriction can increase dopamine receptor levels.

    http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=07-97

    Personally, I do well on weekdays sleeping as late as possible (so no time for breakfast), and taking lunch around 2:30.

    • Yes, same one I linked to above! I wonder how exactly quickly D2 receptors modulate in response to food restriction (in humans).

      • Oops, my face is red! But I would love to see a controlled study of intermittent fasting and correlation with recidivism rates for recovering drug addicts. That would indicate if the results seen in mice are meaningful.

  3. an excellent post with lots to think about. i think i already do this fairly often without really thinking about it. coffee and water and internet…..oh shit where did the time go it’s 2 PM and i haven;t eaten anything.
    one thing your post got me wondering about. lately my breakfast favorite has been oatmeal, coupled with whatever fruit is in the yard (usually bananas or papayas) and some yogurt. what’s your take on oatmeal?

  4. The nytimes article totally had me thinking about this http://well.blogs.nytimes.com/2012/02/01/exercise-as-housecleaning-for-the-body/ and then you blogged about it. sounds like one of those things that seem obvious, evolution-wise, ie not having access to that prime meal all the time, so the body makes use of the ‘downtime’. awesome post

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  6. I have been doing daily IF for 3 months, and it has made an incredible difference in how I feel. I tried it originally to decrease the severity of my annual seasonal affective disorder (depression). IF has been shown to increase BDNF and alleviate depression. IF did improve my seasonal depression to the point that I feel like a different person, but all the other unintended effects combined were miraculous for me. I have gotten rid of most of my routine aches and pains that I had previously accepted as the natural consequence of aging. I sleep much better, have lost about 9 pounds of fat (not muscle), have much more energy, improved mental focus and memory. Now, I know this sounds like the crazy woman has gotten crazier, but it’s all true.
    I began by having a daily window of eating only 5 hours/day per the Fast 5 diet. Over time, I have moderated this recently to a daily 16-18 hour fast. For about the first 3 weeks, I had an incredible high of energy and mood. While this has decreased over the last 6 weeks, it is still much improved from previous levels. Fasting was minimally difficult for the first few days, but the immediate benefits made it worth continuing. After 7-10 days, I rarely thought about food until it time to break my fast. As you stated, food tastes wonderful when you do! I am not unreasonable in my fasting habits. If I am really hungry (now I know what that feels like!), I eat. I try to listen to my body. On heavy exercise days, I break my fast early if I am hungry. And, yes, I exercise while fasting, and I find my fasting exercise more pleasurable than my non-fasting exercise.
    I am a 61 year old female, so I would certainly recommend this to anyone who has seen the changes that aging brings. What a wonderful surprise to find that some of what I felt I had to accept as physical decline can be moderated simply by reducing my calorie consumption and increasing the hours of normal overnight fasting!

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  16. Hi JD, I came across your blog a month ago and have been following it ever since. I would like to commend the effort you’ve put into each article. All of them are well researched with links. Thank you for writing them.
    My reason for writing is with regard to this article on fasting. I am an Indian presently living in India. There is a common practice among Hindus wherein they fast (for religious reasons) for certain days of the week. This would usually be a Tuesday, Thursday or Saturday. The concept of fast varies – some eat a meal only after 6PM, some completely avoid meat on these days (again for religious reasons), some only drink juices, etc.
    Although, for most parts, it may be religious, this practice has scientific roots. (I did not check in detail.)
    So, another suggestion would be – instead of doing a fasts in such a drastic fashion you could try doing them selectively on a regular basis (perhaps consuming juices without artificial sugars on any particular day of the week.)
    Cheers,
    V

    • Hi Vivek! Fasting seems to be a part of almost every religious tradition (I recently fasted for Yom Kippur). Different types of fasting have different benefits. I prefer short water-only fasts because they are comfortable and convey most of the benefits of longer fasts.

      According to the authors of The Perfect Health diet, consuming small amounts of fat or oil during a fast will not disrupt autophagy (if I’m remembering that correctly). Juice fasts, on the other hand, while they might have other benefits, would provide fuel and prevent autophagy.

      I’m not an expert on this topic — I would recommend posts on leansgains.com and marksdailyapple.com for more detail.

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  19. Great article! I’m looking to try Intermittent Fasting, and had a question…
    I saw several research study results on the Internet regarding the benefits of the 5:2 diet (2 days a week of consuming 600 calories only).
    I would like to try the 5:2 diet (which usually allows for 3 low-calorie meals including dinner too on fasting days, but I understand that for autophagy to occur, one needs a 16+ hour fast time).

    So my strategy is on 2 non-consecutive days a week to have breakfast in the morning, and then lunch around 2 PM (keeping the total of breakfast & lunch to 600 calories) and then skip dinner. Then have breakfast the following day in the morning around 8 AM, resulting in a 16 hour fast.
    What do you think of this strategy? Is there any scientific benefit to having most of the fast period during the day rather than at night (e.g. is it better to have dinner, then skip breakfast and have lunch as you do instead?)

    Also, I heard somewhere that one has increased risk of stomach acidity and peptic ulcers if one fasts regularly. Have you seen any evidence for this, and are there any tips for preventing stomach ulcers while fasting (while still inducing autophagy by not eating)?

    Thanks,
    Neil P.

    • Thanks Neil — glad you enjoyed the post. My guess is it probably doesn’t matter if you do a partial fast by skipping dinner or skipping breakfast and having a late lunch … but I’m not aware of any research that compares the two approaches. Try it out and report back!

  20. Thanks, will do!

  21. Does fasting work? Of course it does it,s also known as Ramadan

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  23. i am doing a fast/cleanse today and tomorrow. I love the results of the program i follow.

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  26. Interesting post on fasting, dopamine, ghrelin, and feelings of curiosity and mental focus:

    http://www.startgainingmomentum.com/the-2-day-fast/

    • Hey J.D,
      This is a great article you’ve put together — and a great site you’ve got.

      And thanks for linking to my article in it! :)

      IF (and longer periods of fasting) really changed my life in terms of health, well-being, productivity, and of course getting ripped.

      I was suffering from a rather severe case of candida albicans, but I cured it in a year by cutting out all carbs, fasting, drinking a lot of water and L-glutamine, and coconut fat.

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  28. Hey JD,

    I stumbled upon your post searching for links between IF and some issues I’ve been having since they started shortly after IF.

    I had some symptoms you described and am wondering now if I have CMV. Have had swollen submandibular salivary gland swollen for months, lymph node swollen now for few weeks, and some eustachian tube issues.

    Doctor checked me out and said not to worry about it, but I’m not the type that can let it go without finding a reason. Just wondering how long these symptoms lasted for you before subsiding?

    Thanks

    • Hi Paul. It was a few months at least. Sometimes if you get the OK from a doctor and the symptoms are very minor the trick is to just ignore them until they subside entirely. As long as whatever you are experiencing is decreasing in intensity you should probably not worry. Healing can take a long time. On the other hand if you’re uncomfortable or in pain then get a second opinion. Hope you feel better soon.

      • Did you have any other symptoms or just the salivary gland swelling? Most stuff I see says it goes away in month. None of the stuff is getting worse, just the Eustachian Tube issues are really annoying and worried I even have symptoms.

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