Fasting and Autophagy – Fasting 25

posted in: Fasting, Health and Nutrition | 129

What is autophagy? The word derives from the Greek auto (self) and phagein (to eat). So the word literally means to eat oneself. Essentially, this is the body’s mechanism of getting rid of all the broken down, old cell machinery (organelles, proteins and cell membranes) when there’s no longer enough energy to sustain it. It is a regulated, orderly process to degrade and recycle cellular components. junker_sot_up

There is a similar, better known process called apoptosis also known as programmed cell death. Cells, after a certain number of division, are programmed to die. While this may sound kind of macabre at first, realize that this process is essential in maintaining good health. For example, suppose you own a car. You love this car. You have great memories in it. You love to ride it.

But after a few years, it starts to look kind of beat up. After a few more, it’s not looking so great. The car is costing you thousands of dollars every year to maintain. It’s breaking down all the time. Is it better to keep it around when it’s nothing but a hunk of junk? Obviously not. So you get rid of it and buy a snazzy new car.

The same thing happens in the body. Cells become old and junky. It is better that they be programmed to die when their useful life is done. It sounds really cruel, but that’s life. That’s the process of apoptosis, where cells are pre-destined to die after a certain amount of time. It’s like leasing a car. After a certain amount of time, you get rid of the car, whether it’s still working or not. Then you get a new car. You don’t have to worry about it breaking down at the worst possible time.

The same process also happens at a sub-cellular level. You don’t necessarily need to replace the entire car. Sometimes, you just need to replace the battery, throw out the old one and get a new one. This also happens in the cells. Instead of killing off the entire cell (apoptosis), you only want to replace some cell parts. That is the process of autophagy, where sub-cellular organelles are destroyed and new ones are rebuilt to replace it. Old cell membranes, organelles and other cellular debris can be removed. This is done by sending it to the lysosome which is a specialized organelle containing enzymes to degrade proteins.zh10080957560005

Autophagy was first described in 1962 when researchers noted an increase in the number of lysosomes (the part of the cell that destroys stuff) in rat liver cells after infusing glucagon. The Nobel prize winning scientist Christian de Duve coined the term autophagy. Damaged sub cellular parts and unused proteins become marked for destruction and then sent to the lysosomes to finish the job.

One of the key regulators of autophagy is the kinase called mammalian target of rapamycin (mTOR). When mTOR is activated, it suppresses autophagy, and when dormant, it promotes it.

Nutrient deprivation is the key activator of autophagy. Remember that glucagon is kind of the opposite hormone to insulin. It’s like the game we played as kids – ‘opposite day’. If insulin goes up, glucagon goes down. If insulin goes down, glucagon goes up. As we eat insulin goes up and glucagon goes down. When we don’t eat (fast) insulin goes down and glucagon goes up. This increase in glucagon stimulates the process of autophagy. In fact, fasting (raises glucagon) provides the greatest known boost to autophagy.

This is in essence a form of cellular cleansing. The body identifies old and substandard cellular equipment and marks it for destruction. It is the accumulation of all this junk that may be responsible for many of the effects of aging.

Fasting is actually far more beneficial than just stimulating autophagy. It does two good things. By stimulating autophagy, we are clearing out all our old, junky proteins and cellular parts. At the same time, fasting also stimulates growth hormone, which tells our body to start producing some new snazzy parts for the body. We are really giving our bodies the complete renovation.

You need to get rid of the old stuff before you can put in new stuff. Think about renovating your kitchen. If you have old, crappy 1970s style lime green cabinets sitting around, you need to junk them before putting in some new ones. So the process of destruction (removal) is just as important as the process of creation. If you simply tried to put in new cabinets without taking out the old ones, it would be pretty fugly. So fasting may actually reverse the entire aging process by getting rid of old cellular junk and replacing it with new parts.

Autophagy is a highly regulated process. If it runs amok, out of control, this would be detrimental, so it must be carefully controlled. In mammalian cells, total depletion of amino acids is a strong signal for autophagy, but the role of individual amino acids is more variable. However, the plasma amino acid levels vary only a little. Amino acid signals and growth factor/ insulin signals are thought to converge on the mTOR pathway – sometimes called the master regulator of nutrient signalling.

So, during autophagy, old junky cell components are broken down into the component amino acids (the building block of proteins). What happens to these amino acids? In the early stages of starvation, amino acid levels start to increase. It is thought that these amino acids derived from autophagy are delivered to the liver for gluconeogenesis. They can also be broken down into glucose through the tricarboxylic acid (TCA) cycle. The third potential fate of amino acids is to be incorporated into new proteins.

The consequences of accumulating old junky proteins all over the place can be seen in two main conditions – Alzheimer’s Disease (AD) and cancer. Alzheimer’s Disease involves the accumulation of abnormal protein – either amyloid beta or Tau protein which gums up the brain system. It would make sense that a process like autophagy that has the ability to clear out old protein could prevent the development of AD.

What turns off autophagy? Eating. Glucose, insulin (or decreased glucagon) and proteins all turn off this self-cleaning process. And it doesn’t take much. Even a small amount of amino acid (leucine) could stop autophagy cold. So this process of autophagy is unique to fasting – something not found in simple caloric restriction or dieting.

There is a balance here, of course. You get sick from too much autophagy as well as too little. Which gets us back to the natural cycle of life – feast and fast. Not constant dieting. This allows for cell growth during eating, and cellular cleansing during fasting – balance. Life is all about balance.

129 Responses

  1. How long do you need to fast to get this result?

    • Brad Pillion’s Eat Stop Eat goes into this a little more. He suggests that autophagy peaks in the 16 to 24 hour range of a water only fast. Hence his recommended 24 hour fast, once or twice a week.

      • Hi Robert,

        Will coffee (without sugar, milk, cream or butter) cause the autophagy to stop? Any pointers on this? Black coffee helps stop my hunger pangs and hence I do have 2-3 cups of black coffee while fasting for 24 hours.

        Thanks,
        Sarah

    • I,ve been using intermittent fasting for about 7 years and have noticed amazing results. I am a 51 year old natural bodybuilder and I have watched people in my age group get older at such fast rate and yet I ( or so I have been told ) don’t look older than my early 40’s. I have investigated nutritional practices for the last two decades and this process has been the most profound I yet to come across.

    • Rubana Manzur

      Just follow the us, the Muslim ( you don’t have to do it all 30 days) and do it from sun up to sun down starting tomorrow the 6th June

      • Muslims don’t fast. You gorge yourself on all kinds of food at night and don’t eat during the day. That isn’t a fast.

        • Ahmed, a simple muslim

          The good Islam practitioner will follow the teachings of Islam about fasting. It looks however that you have come across many Muslims who don’t live those good practices.
          Fasting goes like this: fast fom dawn to sun-set, breakfast at sunset over few dates (ideally seven) and some water, go do sun-set prayers, you can later eat after prayers under the condition that you only eat a maximum of one third of your stomach and drink another one third and one third is empty. You should take “Sohour” which is the meal before dawn which should be at minimum to drink some water and preferably dates or a meal to the maximum of the three thirds rule. It is also prohibited to have marital intimate relation during the fasting time (Dawn to Sunset), one must be particularly careful about his manners and temper during fasting, and should not commit sins during the evenings after he breaks fast. Fasting is mandatory to males and females beyond puberty. Pregnant women, old persons, very ill persons, and persons on travel are exempted from fasting; and according to case would have either to compensate the days later after the exemption reason is cleared out, or to give charity money to the poor for every days missed in some cases.
          Fasting is mandatory for 30 straight days in the moon-calendar month of Ramadan, and optional throughout the year, recommended two days per week, which are preferably Monday and Thursday, and to the maximum recommendation of the Profit David which is to fast every other day.
          Millions of god Muslims practice fasting in the right way, while other millions make bad mistakes. Very few would however argue about what the right practice is.
          Muslims believe that fasting is a deeply routed ritual in the history of Islam and that it has been practiced by all Muslim profits included Jesus Crist, Saints including Saint Mary his mother, Profit Kind David, and all Israliete profits among others.
          Hope that gives you a clearer view of what fasting is in the religion of Islam.

          • Yes a Muslim cannot eat until full, Prophet Saw said “Stop eating before your stomach full”,

            Dude, I was wondering is honey suppress autophagy? honey contain zero protein.

            Does anybody know what prophet SAW eat daily from morning when not fasting?

            Thanks

          • If you eat before sunrise and then after sunset (as during Ramadan then I wonder whether you will get the benefits of autophagy which requires fasting of 16-24 hours.

          • The beauty of fasting in Islam is, Who said U “have to” eat before Sunrise? Its not mandatory, You can just sip a water, then U fast, so I think more than 18 hour from last dinner. But for women, just google it, fasting cannot to long like men, also when a person have arrythmia cannot extend to long to fast. And during fasting, we cannot say bad to other ppl, or commit sin, there are different level of fast, the highest fast is beside eat drink, sins, is his mind is must focus to God. So moslem 24 hours must be for God, and serve his ppl with good deed.

            OOT: The Prophet saw said ” If someone do bad thing to others (non moslem) because of their religion, I (Prophet Saw) will be his enemy at akhirat (afterlife). So a Moslem cannot hate someone of their religion. Even during war, (after attempted murder and 43 times the peace agreement is broken so became war), One cannot harm plant, trees, women and children, and person who work in their field. Moslem only attack if their attack. Just google Zakir Naik in youtube.

          • That was very kind of you to take the time to describe Muslim fasting in the manner in which you did. Thank you

        • Looking for the bad in others and then spewing back at them in anger doesn’t seem terribly Christian to me.

        • Jeanmarie

          Dear “servant of Jesus Christ”:
          It’s inappropriate for you to tell someone from a different faith tradition that their mode of fasting is not true fasting. That’s not your place to judge. Why don’t you just concentrate on being more Christ-like instead?

  2. margy waugh

    Once again a great explanation Dr. Fung. I am a follower of both you and the Diet Doctor!
    In August 015 my husband had a wake-up call, ending in the ER with what we thought, a cardiac problem, turning out to be a hyper-glycemic state. Having been privileged to accompany brilliant individuals with paradigm shifting concepts in the healthcare environment, simplifying, their brilliant ideas, when I came across one of your first presentations regarding DT2 and carbohydrates, immediately applied the strategy without discussing it with his physicians. (having dealt with the community for over 3 decades …. and totally respecting them, also know – that the ‘earth is not flat anymore’ takes forever…….)
    The results were amazing lost 20 kgs in 8 weeks, from 125 kgs to 105 kgs, glucose levels to almost normal with lowest dose of metformin (not having increased it as prescribed). His physician was amazed but continued to suggest several small meals a day, including 4 slices of bread, etc.etc.etc. Today March 016, stablized at 95 kgs from NCH to LCH but have not been able to convince to intermittent fasting…. My husband is 1m92.

    • Andrea Chang

      Hello, I’m trying to help my mom stop or reduce her meds. But we need to do it on our own because here (Lima, Peru) doctors don’t want her to stop eating and just keep telling her she needs to eat carbs. Can you please tell me what your husband did? For how many days did he fast? Didn’t his blood sugar level dropped too low at some point? Did he fast drinking just water or fuits and veggies juice? I’d be really greateful if you can help me

      • Hello Andrea.
        If having her fasting is an idea stretched too far I suggest that you silently cut down the carbs and replace it with lot of fat and proteins. Maybe it will be unnoticed. Carbs is the worst of all because it triggers the insulin spikes and consequently prevents any autophagy. Have her replace rice, potatoes and quinoa (since you live in Peru I suppose you have lots of it) by caudiflower with full of cheese spread on it. Give her also lots of green vegetables, advocatoes, eggs, and again cheese. Fish and meat are good too.
        Last thing: go to dietdoctor.com which is the best blog and ressource for LCHF. You will also find lots of wonderful receipes to be inspired from.

        • My nutritional list told me that quinoa is not a grain. It is a seed. It is high in protein low in carbs.

          • Yes, technically a seed not a grain and higher in protein than most other grains and seeds but still too high in carbs….

  3. Victoria West

    I was wondering how long also. I eat 500 calories on my fast days; does that stop autophagy? Also does not eating any calories for 15-16 hours each day give enough time for autophagy?

    • Bernard P.

      In the above post, Dr. Fung explains that eating even a little stops autophagy. See next-to-last paragraph.

      If you eat 500 calories on a given day, you are not truly fasting. You are restricting calories. Why not go all the way and try a true 24-hour fast, with only water, tea, or coffee (no sugar)? Believe me, it’s easier than you think, and it gets easier as you get used to it.

      Dr. Fung’s approach is based on true intermittent fasting.

      • Brian Ralston

        I personally suspect that fasting means what it says: – not DIETING. FASTING = NOT EATING. To me, that means ANY calorie intake whatsoever during a ‘fast’. Otherwise you are turning ‘fast’ into a ‘diet’. It’s seems that is very hard for some people to get one’s head around NOT EATING. Apparently, for centuries, we all have been ‘programmed’ to EAT, EAT, EAT. Fasting, to me is a form of ‘controlled eating’, which translates into a health exercise – NOT starvation or self abnegation.

        • Valeria

          Dr. Fung does suggest that if one were to eat purely fat, and no protein that they could actually take in hundreds of calories and not interfere with autophagy as MTOR is the regulator of autophagy and a protein sensor, so protein is the turn off for that. If you ate zero carbs, zero protein and a pure fat, you could get all the benefits of fasting without actually fasting. https://www.youtube.com/watch?v=v9Aw0P7GjHE Around 30 min mark. This is what I was looking at as I want to do a water fast for the benefit of autophagy, but I have daily medication that requires fat for bioavailability, and I can’t NOT take the medication as it has really bad sudden withdrawal symptoms that I’m not willing to risk.

    • In order for autophagy to kick in, you need to have a break of at least 16 hours between meals. One easy solution would be to eat in an “eating window” such as 2 p.m. till 10 p.m., then fast between 10 p.m. and 2 p.m. (16 hours of fasting)

      This would give you four hours of autophagy per day.

  4. Madeline Winter

    Are there any studies on adding MCT oil, coconut oil or exogenous keytones to fasting ?
    Thank you for this post.

    • any caloric foodstuff or beverage you put in your mouth breaks the fast. why use oil and other fats to increase ketosis when most folks have more than enough on their own bodyfat for that purpose?

  5. I”m so glad you wrote about this. I was also wondering how long one needs to fast before autophagy starts. 😀

    • The scientific studies I’ve read suggest that autophagy STARTS after 12 hours of fasting. So it’s recommended that you fast for 16 hours a day. This gives you 4 hours of autophagy. It’s also good to, once in a while, spend an entire day or day and a half (24 to 36 hours) fasting. This allows for a “deep cleaning.”

      • Nils, could you post references to studies that show the levels of autophagy in humans 12 or more hours after a fast begins?

        • Glycogenolysis and gluconeogenesis are partly under the control of glucagon, a hormone produced in the α-cells of the pancreas. During the first 8–12 hours of fasting, glycogenolysis is the primary mechanism by which glucose is made available (Figure 1A). Glucagon facilitates this process and thus promotes glucose appearance in the circulation. Over longer periods of fasting, glucose, produced by gluconeogenesis, is released from the liver.

          Figure 1.
          Download figureOpen in new tabDownload powerpoint
          Figure 1.
          Glucose homeostasis: roles of insulin and glucagon. 1A. For nondiabetic individuals in the fasting state, plasma glucose is derived from glycogenolysis under the direction of glucagon (1). Basal levels of insulin control glucose disposal (2). Insulin’s role in suppressing gluconeogenesis and glycogenolysis is minimal due to low insulin secretion in the fasting state (3). 1B. For nondiabetic individuals in the fed state, plasma glucose is derived from ingestion of nutrients (1). In the bi-hormonal model, glucagon secretion is suppressed through the action of endogenous insulin secretion (2). This action is facilitated through the paracrine route (communication within the islet cells) (3). Additionally, in the fed state, insulin suppresses gluconeogenesis and glycogenolysis in the liver (4) and promotes glucose disposal in the periphery (5). 1C. For individuals with diabetes in the fasting state, plasma glucose is derived from glycogenolysis and gluconeogenesis (1) under the direction of glucagon (2). Exogenous insulin (3) influences the rate of peripheral glucose disappearance (4) and, because of its deficiency in the portal circulation, does not properly regulate the degree to which hepatic gluconeogenesis and glycogenolysis occur (5). 1D. For individuals with diabetes in the fed state, exogenous insulin (1) is ineffective in suppressing glucagon secretion through the physiological paracrine route (2), resulting in elevated hepatic glucose production (3). As a result, the appearance of glucose in the circulation exceeds the rate of glucose disappearance (4). The net effect is postprandial hyperglycemia (5).

  6. @Misty – This paper (http://spectrum.diabetesjournals.org/content/17/3/183.full) states “During the first 8–12 hours of fasting, glycogenolysis is the primary mechanism by which glucose is made available…Over longer periods of fasting, glucose, produced by gluconeogenesis, is released from the liver.” This seems to suggest one would need to fast longer than 12 hours to get this effect.

  7. What about the concentration of Leucine found in bone broths? Is this amount negligible? Long Cooked Chicken Bone Broth
    serving Size 8 fl. oz.= ~276.33 mg

    • I looked it up and the most abundant amino acid in bone broth is Glutamic Acid- I wonder if that amino acid does not interfere with autophagy?

  8. I usually will take some essential amino acid supplements when fasting to prevent muscle loss. I am trying to lose about 40 lbs and have started two 24-hour fasts per week. If I understand the post, Leucine stops autophagy…I take supplements that are 30 calories and have 410 MG of leucine. (8 capsules of Now Sports Amino Complete before and after exercise) I do not want to lose muscle while fasting but want all the benefits of autophagy. Any clarification and advice would be helpful. Thanks

    • Kevin, I don’t take any protein while fasting and have gained strength while fasting. In fact, I’ve gained so much strength that I re-injured an old shoulder injury to the point where I had to stop lifting weights. I also had to stop doing leg presses with machines, as I got to the point where I could lift the entire stack for too many reps.

      • BobM, how do you time your weight workouts relative to the fasting period? You fast how many hours per day?

      • Stuart Mather

        You won’t lose any muscle at all up to the 36 hr period of water fasting. and only negligble amounts daily thereafter. So 24 hr non caloric fasting is ideal to get the cellular benefits of autophagy if done a couple of times a week. Even the tiny amounts of muscle you lose on slightly longer total caloric fasts is probably a good thing anyway. Because in my experience you put it back on more efficiently than before you fasted.
        Think about this. Humans are the ONLY species on earth that does not thrive on Eat Stop Eat automatically. Even herbivores (in the wild) go for long stretches without food. And early hominids did too. And we wonder why the human race is getting sicker as the standard of living improves. We never stop eating or looking a few hours ahead to the next oh so delicious piece of food.
        Stop eating regularly for at least 24 hrs. LCHF, Protein ‘sparing – all those too clever by half ways humans try to manage macronutrient ratios/ intake’. It’s all completely missing the point. Just learn to enjoy hunger.
        It’s hardly going to kill you. Particularly at night. Fasting during the day and then eating in the evening as in Ramadan or the ‘Warrior’ diet is just the WORST way to fast. Slightly better than not fasting at all? No question. But eating in the evening is just sub optimal. If you are going to fast at all, why not get the best bang for your buck?

        • Why do you say Warrior diet is the worst way to fast? It really makes sense to follow circadian rythm regarding to food intake. Also, it makes sense that ancestors hunted or collected food all day and ate at night only. Also, food intake relates to sympathetic and parasympathetic nervous system. I think if you are going to fast for 24h, ie. eat only one meal per day, then you should be eating it at night.

          • MachineGhost

            I suspect it’s because the insulin response is substantially higher at night than daytime. And stuffing an entire’s day worth of calories into one meal or meals over a four hour period doesn’t seem too healthy from a post-prandial perspective. And it’s also how Sumo wrestlers eat.

          • Gerald

            Eating at night or after sunset doesn’t seem healthy cause of circadian Rhythms, in my view your body clocks are out of whack and disease can begin, by sunset your brain is telling your body to slow down and switch off … but your body clocks (liver etc) are saying no I can’t cause Ive just had a meal and have to start working, so your brain clock – the major clock is saying sleep and calm down, relax, slow down but you eat and start the digestive process and your peripheral clocks HAVE to work, they have no choice and so they are in conflict and go against the main command of the brain clock.

        • I just read last night in ‘The complete guide to fasting’ that you don’t loose muscle until ALL the fat has been used.

    • Bernard P.

      Dr. Fung has at leat one post on this web site where he explains why fasting doesn’t cause loss of muscle mass. Therefore, you don’t need to take supplements for that, especially with a comparatively short 24-hour fast.

      • I’ve been taking L-arginine (amino acid) with the hope that it would lower my BP without meds. Is this supplement detrimental to my fasting? Thank you!

        • Arvin Aquio

          Fasting itself will help regulates your BP. In fact, its one of the major effect of IF along with decreased of triglycerides and maintenance of blood sugar to an optimal level.

  9. How do you switch from fasts to feasts? – With “e” s 🙂

  10. hmm… talk about fortuitous timing! mercola’s site just published this article about autophagy and other ways to boost autophagy, other than intermittent fasting.

    http://fitness.mercola.com/sites/fitness/archive/2016/03/11/autophagy.aspx?e_cid=20160311Z3_DNL_art_1&utm_source=dnl&utm_medium=email&utm_content=art1&utm_campaign=20160311Z3&et_cid=DM99804&et_rid=1395113384

  11. Wenchypoo

    Does autophagy happen in the brain too…as in beyond the post-menopausal blood-brain barrier? If so, how does the waste matter get OUT of the brain (through the post-menopausal blood-brain barrier)? Is there any sort of supplement help we can give to speed up the cleanout of our aging brains?

    • sten Bjorsell

      A lot of the debris is reformed to energy and useful amino acids according to the post. Maybe some of that takes place “in situ”, and some conversions are made in the liver. The “Blood brain barrier” is in essence blood vessel capillaries as in other tissues, although they may have special filters in the brain, but nutrients and wastes need to exchange well also there! If I am wrong please correct!
      Regarding the frequent question on how long before autophagy is initiated, it must depend on the amount of activity in the fasted state, activity the day before and the amount of calories consumed at last meal meaning it could take anywhere from maybe 8 to 20 hours. Adding 500 calories in the middle of a “fast” would break the fast more or less. Better to add fat at last meal before fast to avoid bloodsugar triggered hunger pangs. I am doing “one meal per day” fast for the last week now and it is going better and better. A 30 minute walk after 20 hours seem to do something as bloodsugar below 4 before it rose to around 5 just after walk. Could that be conversion of some of the cleaned out debris to glucose ? 30 minutes later BG was down near 4 again! Anyway I enjoy the energy this fasting is giving me! Thanks Jason!

  12. P.E. Descoteaux

    Does fasting and autophagy increase the probability of ADN mutations?

    • Achromatic

      I would reason that it lowers the chance as mutations are more frequent in damaged/not perfectly functioning cells. As autophagy gives the body the opportunity to clean out old or damaged cells, the occurrence of those is reduced. Hence this would result in a better relation between healthy and damaged cells and therefore indicate a lesser probability of mutations.
      But that is only based on logical reasoning, i dont know of any studies regarding the question…

    • sten Bjorsell

      Here is what a UK professor in immunology says about autophagy and DNA mutations in short:
      “.. Our models show that the lack of autophagy, particularly in white blood cells, leads to an accumulation of toxic waste, which then leads to DNA mutation transforming these white blood cells, for example into a leukemic cells.”
      A one page interview about autophagy here: http://www.ndm.ox.ac.uk/katja-simon-autophagy

  13. Lol…”fugly”… You must have grown up in the 80s like me :0)

    Great reading, as usual!

  14. https://www.bulletproofexec.com/what-is-protein-fasting-bulletproof-diet/

    Interesting article on doing protein fasting to bring about autophagy.

    • sten Bjorsell

      Jeff, in the article you linked to Dave Asprey claims carbs are neutral for autophagy! That is in direct contradiction to what Dr Jason says here, that glucose and insulin turns autophagy down.
      This study http://www.jbc.org/content/284/45/31484.full (on mice !) supports Dr Jason that high insulin as in insulin resistance turns off autophagy, while lower insulin also promotes it. Hence carbs could be neutral only when insulin is kept low but never with even slight insulin resistance. Hence best avoided in “protein fasting” if any health issues at all, as most today are related to metabolic syndrome, the common denominator in most modern disease. Water fasting is simpler and reliable.
      Notes: When I posted a comment to similar effect on the blog it was not published/approved !!!

      (Side note of interest to many: Irrespective of the mice study results, the study says that the mice were made insulin resistant on a “high fat diet” (HFD. I checked the mice chow declaration and it contained 36 grams fat and same weight carbohydrates. The carbs were cornstarch and maltodextrin, both high fructose corn syrup in slightly different forms but 55% fructose and 42% glucose. That explains why the mice became insulin resistant, but hardly due to a HFD as the researches wrongly advise. But such wrong labels are common and large parts of “our” research community therefore still believe that fat causes insulin resistance! A check with the supplier by a different researcher gave the reply that ” without the sugars the mice/rats wont eat the “high fat diet” at all ” )

      • What Dave Asprey doesn’t explain all that well, perhaps because he’s not familiar with the latest research. is that there are several types of autophagy, triggered by different dietary protocols. Here’s an easy way to understand it:

        1) The simplest way to go to into autophagy is to simply stop eating all nutrients for a few days, and having only liquids like coffee and green tea and water. However, there are some dangers in doing so, including electrolyte depletion.

        2) For this reason, some people try to induce autophagy by restricting CARBS (i.e., a period of fasting followed by eating ample protein and fat, but no more than 20 grams of carbs a day. This works but is not as comprehensive as just drinking liquids. But it’s a way of experiencing a moderate level of autophagy.

        3) Others try to induce autophagy by restricting PROTEIN (i.e., a period of fasting followed by eating some carbs and fats, but no more than 20 grams of protein a day). This works on a deeper level than restricting carbs. But both types of autophagy are useful (though both are partial, compared to a water-only fast).

        Asprey recommends doing “restricted carbs” on most weekdays, and a “restricted protein” regimen one or two days a week, based on the advice of Josh Whiton (author of the Whiton Protocol). But many specialists who have really studied it recommend doing a five day restricted protein regimen, followed by a re-feed on the remaining 25 days each month. (See Valter Longo’s work). (Longo feels that it takes 5 days to do a deep cleaning that clears the body or senescent cells and can overcome autoimmune conditions.)

  15. Does adding lemon or lime to your water break the fast? I have been trying to figure this one out, but can’t find any info.

    • I don’t think so. Correct me if I’m wrong but I thought the acid was good for you? Or is that only if you are about the eat a meal that your insulin response to that meal will be lower if you have acid (i.e. lemon/vinegar) before a meal?
      I have a thick slice of lime in a large glass of water about 4 times a day when I am fasting. I have fasted from 3-7 days at a time over the last month using fizzy water with a thick slice of lime and sprinklings of sea salt… and am losing weight. I also drink a little black tea or watered down coffee but I stopped the coffee although I may return to it in future….
      I already weigh less than I have for many years. Anyone interested in my story can read my ramblings (sorry?!) in the comments here:
      https://intensivedietarymanagement.com/the-ancient-secret-of-weight-loss-fasting-part-8

  16. Hi Petra…from what I’ve seen, both personally and from others, a squirt or two per glass of water is OK. My ketones stay above 3.0 on extended fasting (after three days) when I take 2-4 squirts of lemon juice in my water throughout the day. Dr. Fungs Long Distance Program guidelines allows for use of lemon in water.

    • I am dabbling with 16:8 intermittent fasting and have done one 24hr fast. I find that coffee keeps hunger pangs at bay.

      I have added butter to my coffee instead of milk, in case the lactose in milk (added to coffee) induces an insulin response and hence “breaks” the fast? Will a small amount of milk do this? Should I just go with black coffee?

      Steve, what (machine presumably) do you use to measure ketones?

      • sten Bjorsell

        Best keeping high calories like butter,cream and milk out of fasting period and staying with water and squirts of lemon. Reserve the goodies to eating periods for minimum insulin spikes and hunger pangs during following fast, is my take.

      • I use the Precision xtra blood glucose/ ketone meter. The machine is very accurate when I compare it against lab test results. NOTE: the ketone test strips can be VERY expensive when you buy in the States ($3-5/ each). I recommend using sparingly! Glucose strips are much cheaper. I also have a Ketonix breath ketone tester with pretty good results. Take care.

    • Steve, I would love to hear how your glucose and ketone readings change over the first 48 hours of your fast, and how many hours into the fast are ketones at 80% of their maximum value? When do you hit that max value?

      As soon as I exhaust glycogen – around hour 18 of a fast – I feel horrible and have no energy. My ketones only come up to about 0.3 to 0.5 mmol/L. I really seem to lack metabolic flexibility to shift rapidly into ketosis.

      I would greatly appreciate learning as much as possible about how glucose and ketones change – hour by hour – during the critical period when you convert to ketosis.

      Haven’t you read that fasts that are three days or longer are potentially harmful to autophagy because when you refeed the body actually turns off autophagy completely for a while, thus allowing pathogens to grow back (assuming you were using autophagy to fight systemic, intracellular, parasitically-entrenched bacteria and viruses).

  17. Andrea Chang

    Does juicing stop the fast? I juice fruits and veggies to get the nutrients and also drink 2l of water. Am I doing it wrong? I mean, I take the fiber out the fruits and veggies and just keep the water they contain.

    • King Chiam

      Juicing is a big no no. The juice is all the sugar. To juice one glass of say apple juice, you probably need at least five apples. Try to eat five apples at one go, can you do it? You actually want the fiber in fruit as it is like antidote to the sugar. Juicing does the opposite!

    • It depends on the nature of your fast, and which juices you’re using. If you’re doing a 5 day “protein resticted fast,” juices are allowed, as long as they contain minimal protein. Parsley juice, celery juice and cucumber juices work well on this type of fast. They are also, incidentally, low in protein. But if you’re simply trying to lose weight by skipping meals, don’t juice during the times when you’re skipping meals…. juice later in the day and have the juice with your meal.

  18. Anyone wonder why Dr. Fung recommends All Bran to help increase fiber? The 2nd and 3rd ingredients are sugar and HFCS. I don’t get it.

    • Kat Lakie

      Hi Jana,
      Does he recommend the brand ‘All Bran’? or is he recommending to eat (all bran) meaning bran which has not been de-nuded of it’s fibre………..which is a way to get more fiber?

  19. Following a calorimetry test, I was told by my physician that my REE was very low (its 1250, he estimated that it would be over 1600 based on my weight and height). My question: could fasting cause my metabolism or REE to go even lower? I am a 58 year old female, about 50 lbs overweight. I exercise 3-4 days a week (bootcamp) and follow a low carb diet. I didn’t lose any weight until I started fasting 2X a week. Thanks!

    • If you have done low calorie diets in oast it could have slowed you down. Doing the fasting should reset your metabolism as you fix insulin resistance n lose weight.

    • Michele, if you listen to Dr Fung’s videos, one of his main points is that when you cut total calories, the body responds by lowering resting metabolism, thus negating the value of dieting.

      The whole point of his approach is to use intermittent fasting to lower insulin while NOT lowering total calories more than a few hundred calories below your metabolic need.

  20. Does eating a sandwich stop the fast?
    Just joking.
    I’m having trouble understanding why people are having trouble understanding.
    Fasting means fasting – as in no calories. None. As in zero.

    • Lil' Edgy

      Yes Ermias, it will stop the fast unless you are merely eating the sand, which is there. Very old joke

  21. Does diet coke stop the fasting process since it has zero carbs/calories? Does the artificial sweetener cause an insulin spike?

    • Kat Lakie

      Connie,
      as a T2D I cannot eat any sort of artificial sweetener without getting a bs spike……..does that answer your question?

  22. […] process until I came across it on Dr. Fung’s Intensive Dietary Management blog in the post Fasting and Autophagy – Fasting 25. He has several posts tagged autophagy. He describes the […]

  23. Melinda Pfeiffer

    Question: When you say amino acids stop autophagy, does that mean calories = amino acids?

  24. Is there any citation or link to discussion about the idea that autophagy is started when glucagon goes high?

  25. Is there any biochemical marker – particularly one that can be ordered today at a commercial lab – that would signal the body is in autophagy?

  26. This article is claiming that new research is finding that Metformin may lower blood sugar by lowering Glucagon:
    http://www.healthcentral.com/diabetes/c/5068/158478/metformin/

    If Dr Fung’s claim that high glucagon is the biochemical trigger for autophagy is true, then it might follow that Metformin will slow or stop autophagy.

    • Just to add to my comment on Metformin: Metformin has been shown in lots of studies to increase autophagy. The method of action for this is to increase AMPK, which then in turn downregulates MTOR. This upregulates autophagy.

      Since Metformin – independently – appears to downregulate glucagon, then one would assume that autophagy is not upregulated by rising glucagon? Because if autophagy increases when glucagon increases, then you wouldn’t be able to explain how Metformin manages to increase autophagy.

  27. Wait- a small amount of amino acid will stop the process, I’ve been fasting three days with lots of lemon in my water- like 3 lemons a day. Lemons contain amino acid? Does this mean I’ve just wiped out all my effort?

  28. ok, I looked it up and lemons do not contain amino acid. but they do contain 4 carbs, so the question is the same, would 3 lemons a day, negate the autophagy on a fast?

    • Christian

      Im wondering the same question, I drink 3 cups of thin coffee and a lemon diluted into three glasses, but if this retards the autophagy itd be nice to know so were not waisting our time.

      • thanks for seconding, I also wonder about cucumber water and bone broth. Both are said to be ok by Dr. Fung but he does not specifically state that it does not affect autophagy. Neither cause insulin spike and that is what he is talking about I believe. this is my 4th day of my fast and I’m want to stop insulin resistance as well as clean up my system. At the same time I read that bone broth helps skin- and as a 47 year old female, I’d love to include it. But not if it hinders the process. So hard to know what to do for optimal results.

  29. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580722/

    this is an article that is very technical about amino acid and autophagy, maybe someone smarter than me can tell if Glutamic Acid (bone broth) is included in the amino acids that stop autophagy?

    I’m on day 5 of a planned 28 day fast. I’m including both lemon and cucumber infused water and mineral water, as well as coffee and tea. I’m considering adding bone broth on my last week. It would be great if someone could say more definitively if bone broth stopped autophagy or not. Thank you.

  30. also please tell me if a long term fast is detrimental to your metabolism. Is doing several shorter term fasts better for metabolism? sorry to be a pest, it just seems that this is the only place to find answers.

  31. ok- I am scouring Dr. Fungs blogs and found one that said fasting metabolism stays relatively the same during a 30 day fast. It was only a sentence, and I guess I’d like more reassurance than that. There was a chart, but I could not fully comprehend it. So anyway, Thank you Dr, Fung, you have answered my question. Also I have started adding bone broth to my fast (day 10) partly because I read your blog that talked about how you included it many times because it counters the re feeding syndrome, so you answered that too : )

    I am so grateful for all the information I am getting here!!! I am technically no longer diabetic and no longer on blood pressure pills! I’m fasting to get rid of my remaining insulin resistance which would have stayed forever if I had not found out about fasting. You have significantly improved my quality of life for the rest of my life.

  32. Richard S Stone

    If you read some of the medical and research literature regarding autophagy it seems obvious that the main trigger available to start autophagy is “nutrient deprivation.” Taken simply, that would mean no calories, as in no food. (This would, as I see it, mean eating no fats or cream or other sources of calories.)

    Reading the various literature seems to suggest that autophagy is in some senses well understood, and in others not so much. A failure of autophagy appears to allow or create cancer cells. And yet there is, as I read it, some sense that cancer cells should be one target of autophagy, and so they may have mechanisms to resist it. What I find amusing is the “testing” of autophagy by giving drugs that simulate or stimulate autophagy: But why not just see how well basic nutrient deprivation works first? That might be a baseline? Or maybe even successful? (That may not be research drug companies want to fund.)

    There is also the sense that immune system disorders, essentially destructive inflammation, may be reduced (or cured, as in the sense of curing diabetes) by enhancing autophagy. Maybe it would be nice to have a pill to start autophagy for such a purpose, but why not just try fasting? What I have noticed is that my thumb joints, damaged by competitive college gymnastics many (like 50…) years ago, seem to be much less painful after the IF I have been doing for the last months. Very interesting. The idea of removing damaged cells and cellular structures, as well as the creation of growth hormone, as well as some other hormones, seems a potent mix. Best of all, it costs nothing. No special equipment is required.

    • Maybe intake of fat does not negate autophagy in the way intake of proteins or carbohydrates do. Considering that fats give very little insulin response, and it is the anabolic effect of insulin that promotes protein synthesis (often used by body builders for that reason) and inhibits proteolysis. Could it be simply the lowered insulin levels that allow for protein breakdown? Of course, little response is still different from no response, but a little heavy cream or bone broth is not likely to be too disruptive.

      • Jennifer

        For autophagy: no bone broth,no cream, no coconut oil – Dr. Fung has stated in his blog that even bone broth will halt autophagy

        • Thank you, good to know!

          • Although, the science he has shared so far only implicates carbs and protein… I need to hunt for more evidence.

      • Do a search for “fasting mimicking diet”. I am a 3 day per month (most months) water only faster myself but found the research to be interesting. It seems mostly that the protein restriction is the magic although their diet was only 40-50% of normal calories.

  33. Could this also explain the link between insulin use or hyperinsulinemia and cancer? You should do a blog post about data on insulin as a growth factor.

    It may also explain the link between insulin resistance and neuro-degenerative disease. Check out this interesting experiment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/

  34. I have been following a 16 to 18 hour fast 2 times per week for the last 2 1/2 years. I still wonder if it is initiating autophagy. Also how long does a single cell take to move through an autophagy event. Once initiated, does it go to completion once I begin eating. Also, does this apply to all types of cells? Are there some cell that take longer than the 16 to 24 hours for them to initiate autophagy due to the body providing nutrients and proteins to that set of cells? The concept of fasting and autophagy is simple to understand, but I have yet to find answers to these type of questions.

    I’m sure I have benefited from the fasting. I’m very healthy and the life insurance industry has acknowledged it with at the age of 62 giving me the highest rating for the price of my policy. A surprise to my agent. Anyway, I feel great and will continue what I am doing. I just want to know if there are other areas I may need to focus on because autophagy fails in those specific areas.

    Anyone have source studies or documents to provide answers?

  35. Stephen Gordon

    I have been doing IF for 1,193 straight days. Eating every 16 to 20 hours but mostly 18. I also exercise heavily. I’m 67 & have never felt better. Also have been on a Paleo diet for 6 years.

    The results have been that I’ve lost a 100 pounds & got rid of a host of metabolic syndromes without any medications. I started seriously taking care of my poor health at 57 & the point is is that it’s never too late to turn your health around…

  36. Mary Cameron

    I am doing my first water fast. I take water and green tea. It took 60 hours for ketones to rise above glucose. I test both twice per day. My ketones are now in the 5-7 range and glucose usually hovers between 4 and 5. I am now on day 9 and feeling good, but do have some fatigue. I am due for surgery in 2 weeks time to remove ovaries and fallopian tubes (suspicious neoplasm 3 cm found on ovary) and I went on the water fast in a bid to do everything I could to put the odds of survival in my favour. A dear mate of mine died of ovarian cancer. It is truly a silent killer.
    Does anyone have an opinion on how long before surgery to break the fast? Thanks.
    I am astounded that I can go without food and remain okay.

  37. Jackie Friend

    Dr. Fung, I’m wondering if you have had issues with patients developing a type of skin rash as a result of ketosis or rapid weight loss. After a time of using fasting for a period of time I noticed that I start to itch and break out in something like hives. After searching the internet to see if others had experienced this, I found that many people had experienced this same thing and the research tends to indicate that it is relatively common amongst people that are in a deep state of ketosis. The medical term for this is prurigo pigmentosa and the resolution to the problem seems to be suspending fasting, adding carbohydrates, or taking antibiotics. Have you seen this and is there an explanation and/or a better solution?

  38. […] ja korvataan uusilla (kierrätetään). Havainnollinen selvitys autofagiasta löytyy esim. tältä sivulta, josta myös ao. kuva on […]

  39. […] REAL research confirms how and why fasting is path to health. […]

  40. R.Srinivasan

    I am a hindu brahmin observing full fast for a day once in 15 days , that day is called as Ekadhashi .

    Next day early moring we break the fast & take light food after doing puja .

    So with this autophagy will work out better .

    R.Srinivasan ( India )

  41. Dr. Jason Fung’s new book, THE COMPLETE GUIDE TO FASTING, answers all these questions. It works.
    I also take Serrapeptase and Nattokinase while fasting. I usually go for 5 days and eat moderate protein and lots of fat on 6th day and then repeat 5 day fast.
    Instead of becoming a carb calculator, check out this site by a retired US Army doctor, Dr. Paul Mabry – the transformation will amaze you http://www.borntoeatmeat.com

  42. Jane Morris

    Hi
    I have been doing 22:2 fasting for the last 5 days and have noticed an amazing increase in my energy levels.
    I was diagnosed with ME about a year ago and have really been struggling to do more that 30 mins activity before I needed a rest.
    Today I was active from 9 am till 3 pm without a break!!!
    I’m really hoping this isn’t just a fluke.. can someone tell me what’s going on?

  43. […] Fasting and Autophagy – Fasting 25 […]

  44. Jason this is all fascinating, you are doing phenomenal work! (Although I see now watching your youtube videos why they told me when I did my MFA thesis I was going into too much detail…you are like me in this respect, sometimes.) The blog above about autophagy includes an important reference on how taking a single amino acid can bring autophagy to a halt. I have fasted up to 4 days at a time since the early 1990s after reading Fuhrman’s book. Previous to that, I had tried fasting up to 3 days since learning about fasting as a health promoting strategy in around 1979. In recent years, my wife has joined me and we have done much longer fasts (up to 10 days) water only because she has an ovarian tumor and read in Fuhrman’s book about shrinking these by fasting. Hers went down in size from 444 cubic centimeters to 195 in 10 days! But we have found it nearly impossible to fast completely without using some supplements, mainly vitamin C and some minerals, which help us sleep during the fasts (otherwise we have a very hard time sleeping more than a few hours per night). We have sometimes added amino acids with reputations for helping detoxification or tissue repair (taurine, lysine/proline especially) but after reading this we will try to go without anything (perhaps only the vitamin C) for a few of the days if possible. I know Dr. Alan Goldhamer, who has supervised many fasts, always opposes using any supplements. Perhaps you could do a blog on this topic for those of us who are into the supplements and wonder whether this is more helpful or not with fasting. Thanks! I just ordered your book btw.

  45. Hi everyone
    Trying a fast for autophagy of my skin, I wonder if I can still take Ltyrosine at dawn and ltryptophane at night as i do since years. Could they breaks the autophagy process ? Sorry for my struggling english I’m French

  46. Can Autophagy help me get rid of Gallbladder polyps (Cholesterolosis)? I have to have these checked every 6 months to make sure they don’t grow more than 1cm, in that case they can become malignant and so Id have to have the gallbladder taken out, I don’t want to have this operation if I can avoid it, I have 3 tiny ones and 2 at 0.6cm.
    I reasoned that by getting my body to go into a state of Autophagy then this state could help ‘munch’ away unwanted tissue, my idea was that Glycogen stores deplete, then fat is used as fuel and this autophagy happens but would this be enough to eat away those polyps made of cholesterol I assume? A self cannibilsm I mean of tissue that isn’t needed or crucial, the body does this naturally by not munching its own muscle because first fat reserves are used when dietary glucose from carbs aren’t available and then adipose/visceral fat etc then muscle. Some people have fasted to heal themselves from cancer but did more prolonged fasts of water which I can’t do cause I’ve been taking meds for 20yrs and trying to taper off but can’t just stop and can’t fast longer than a day or two, I have read people doing veg/juice fasts to heal from cancer but don’t understand how they did this seeing as Glucose from carrot/apples etc are being ingested so autophagy doesn’t happen, right? Most of these diets do remove meat and animal foods from their diets which may increase IGF1, heme iron etc which may be linked to cancer, also they use digestive enzymes like papaya/pineapple which may help fight cancer as well. Its really confusing, I wonder if for cancer or shrinking tumors Intermittent fasting which stimulates autophagy is better than eating throughout the day cancer fighting foods?

  47. Anne-Marie

    Can fasting reduce the number of fat cells ? Was that ever tested ?

  48. Anne-Marie

    Does autophagy affect the number of fat cells ? Can the number of fat cells be reduced in any way ?

  49. Sarah Lou

    Hi Dr Fung

    Does apple cider vinegar stop autophagy?
    I keep seeing articles saying it contains amino acids but not on any credible sources.

  50. I’ve been intermittent fasting as a lifestyle for over seven years and didn’t know what it was called or the benefits of it. I just didn’t want to think about food and when I ate I wanted to eat whatever I wanted, which surprisingly wasn’t sweets. I would regularly have huge cheese laden pasta dinners and not gain weight. I never felt deprived, but I really didn’t eat vegetables or fruits which left me, you guessed it, constipated. I’m now eating more veggies, but usually cover them in butter, cheese and bacon. Thank you for the info!

  51. prettybrilliant

    Best and easiest plan of all is not 24 hours, but at least 4-5 days a week of 16-20 hour fasts.
    Add in cup or two of bulletproof coffee (butter plus pure heavy cream) to increase efficacy.

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