Autophagy and fasting.
Unless you’ve been hiding in a cave for the past few years you would certainly have heard the word “autophagy” thrown around the keto world, and to a lesser extent, the world in general.
In the past few years the word Autophagy has left the scientific arena and has entered, if not mainstream thinking, then at least the thoughts of a great many people interested in diet and healthy living.
It seems that as buzz words go, autophagy is now up there with the superstars and I can see why.
The word has actually been around for longer than you’d think. It was first used by the Frenchman M. Anselmier all the way back in 1860. He presented a paper to the Academy Of Medicine detailing his rather dodgy (in my opinion) experiment where he starved two animals. One was bled regularly and given its own blood to drink. It lasted a few days longer than its unfortunate friend, who died without being given anything to eat or drink. 1
From this, Anselmier proposed that man was designed to “eat himself” when facing starvation and that this was a natural process that increased the chances of him being saved.
More recently the Belgium biochemist Christian De Du Duve provided biochemical proof of the involvement of Lysosomes in the process of Autophagy 2. Other scientists began to uncover more about the processes of autophagy and eventually one scientist, the Japanese researcher Yoshinori Ohsumi, won the Nobel prize in Physiology or Medicine in 2016.
In 1999 an important link between Autophagy and Cancer was discovered by Beth Levine’s group 3 and set the path of current research which is mainly concerned with this link.
Since then, the connection between Autophagy and neurodegeneration and immune defense has received a lot of interest, and it has now also been noted that fragmentation in cell lines can be induced by Autophagy (Carol Mercer 2008).
There are three main types of Autophagy, and each is in involved in the eradication or engulfment of damaged cells or proteins, engulfment of cytoplasmic material, eradication of pathogens and dealing with misfolded proteins.
As our bodies contain both damaged cells, and senescent cells its easy for even a non-scientist to understand that Autophagy is not only a natural, but a necessary process to clean out all these damaged cells that are accumulated over time. These cells trigger inflammation which is now implicated in the development of numerous diseases, if not all of them 4 .
This includes Cancers and autoimmune and neurodegenerative diseases.
“Molecules that can regulate autophagy seem to have great potential to modulate the clinical course of neurodegenerative diseases” (Sarkar et al. 2007). This isn’t just interesting, it has massive implications for the millions of people at risk of the two most common neurodegenerative diseases, Parkinson and Alzheimer disease.
There have been several studies showing the link between chronic inflammation and the development of malignant tumors. One study even suggests that inflammation is essential for the development of all cancers. You can read the study here 5 .
Autophagy and the immune system are now known to be linked and the immune system uses Autophagy to regulate many of its systems. Autophagy is involved in seeking out pathogens, and has a role in the fields of vaccines and aging 6
In 2015 a scientific paper “Essential role for autophagy in life span extension” 9 was published in the Journal of Clinical Investigation (Frank Madeo, Andreas Zimmermann, Maria Chiara Maiuri and Guido Kroemer).
In this paper they describe aging as a process whereby there is a gradual accumulation of cellular damage and neurodegeneration. They suggest that the future of combating aging will be in finding a way to stop this occurring, rather than new ways to treat the symptoms as they arise.
They are of the opinion that one of the most promising causal treatments of aging is Autophagy. Importantly, they go further by stating that a lack of Autophagy can accelerate aging. As several studies have now concluded that the process of Autophagy decreases with age, its a short step to see how this is so vital in the study of longevity.
Given all this evidence, it’s difficult to overstate the importance of Autophagy and the role it plays in keeping us healthy and our immune system working efficiently.
It is now evident that Autophagy is a process that is necessary for us to remain in the best possible physical condition and to minimize our chances of developing some very serious diseases and becoming ill or disabled as we age.
Why isn’t autophagy happening enough
As Autophagy is a natural and healthy process, why does it seem that it is not happening enough to keep us as healthy as we could be? I am going to discuss what we need to know to induce autophagy but shouldn’t it happen without us having to give it any thought?
Actually it can happen automatically, and it does a lot the time. Unfortunately, the fact is that in our distant past it happened a lot more often than it does now. The biggest problem for so many people in today’s world is that they have a pattern of eating that doesn’t allow Autophagy to take place often enough.
The biggest single factor that stops the signal for the process of autophagy to begin is when our body senses that there is an abundance of nutrition.
We are simply not designed to graze, we are meant to eat a meal and then wait for the next one. We evolved at a time when the wait between meals could be several days, or at the very least many hours.
Our bodies developed a system for using that period of going without food to clear out any damage to cells, clear out pathogens and sharpen our thinking. Not only was this good for our health but it also for gave us an important cognitive edge at a time when we needed to be working out how to get our next meal.
By contrast, modern man is rarely not eating. Meals are frequent, and often there are snacks in between. We are seldom if ever hungry. In the fed state we cannot enter Autophagy.
Add to that a lack of exercise and epidemic levels of weight gain – which also gets in the way of Autophagy – and you can see that many people are simply not going through this vital process often enough to maintain their health and to prevent the development of future disease.
As we age so the frequency of autophagy is naturally reduced. This is a time of life when people need to be taking extra care to eat in a way that promotes health. Unfortunately the opposite is often true, it is frequently a time when years of poor nutrition coupled with insufficient exercise add to the natural slowing down of this important process.
The result? According to many scientists, it is an explosion in the incidence of neurodegenerative diseases, cancers and as already suggested, quite possibly most other diseases too.
All fairly depressing stuff, but the good news is that the latest science is not just showing us how important autophagy is, we are also being given several ways of ensuring that we can control the amount of time we spend in autophagy.
The following section will discuss some of the most important of those methods.
The single most important trigger for Autophagy is a complete lack of all nutrients.
Due to the fact that not every cell in your body would be able to note a lack of nutrients it was thought that the system that controls the onset of Autophagy would have to be a general body system. It is now accepted that it is the endocrine system, in particular Insulin, that controls the switch to Autophagy.
Mortimore and Pösö 1987 showed that Autophagy is suppressed by Insulin and enhanced by glucogen. 6
In other words, fasting lowers Insulin and forces the body to use its glucogen stores. The lack of Insulin together with the use of glucogen is the signal for your body to begin the process of Autophagy.
This means that not only long fasts, but intermittent fasts too will begin this important process. Read more about the importance of intermittent fasting and not eating all the time, and fasting’s ability to induce Autophagy in greater detail in this article here .
Congcong He, Rhea Sumpter, Jr., and Beth Levine published the findings of their study into the ability of exercise to induce autophagy. “Exercise induces autophagy in peripheral tissues and in the brain” 10
This study certainly caught my interest, and it should catch yours too.
They discovered that exercise induced autophagy in multiple organs such as muscle, liver, pancreas and adipose tissue. They realized that this suggests that the already known metabolic effects of exercise could be caused because exercise induces autophagy.
They also concluded that exercise induces autophagy in the cerebral cortex of the brain. You know, that important part that determines your intelligence, personality, motor function, touch, planning and organization, processing sensory input and language development.
Aerobic exercise is especially beneficial and it has been shown that Aerobic exercise alone can induce Autophagy, especially in the brain 7 .
Older adults- above age 69 where shown to be able to increase the amount of time they spent in autophagy by resistance training.
One study concluded that people who had regularly played a sport not only had more frequent times in autophagy, but were biologically younger than people who did not. Intense exercise also brings about autophagy in the muscles.
This definitely puts exercise right up at the top with nutrition when it comes to being healthy and preventing disease.
The keto diet
This very low carbohydrate way of eating helps get Autophagy underway. The keto diet activates many of the same pathways to autophagy as fasting.
There is scientific evidence that ketosis plays an important role in autophagy.
What is the optimal time to benefit from autophagy?
Short term fasting will give all the benefits
Fasting is a normal and natural thing to do, we all fast every night while we sleep, hence the meaning of breakfast which means literally to break fast. Some people are worried about the health effects of fasting but here is no reason why short term fasting should negatively affect your health.
A healthy adult will be able to fast for at least three days without any worries. By fasting, I mean no food but plenty of water, tea or black coffee. If you do have a health issue, you should talk it over with your doctor before you begin. If you’re taking any medication, this could be affected by fasting so again, seek medical advice.
As you have read, there are now many studies that support the fact that short term fasting will promote autophagy.
Mehrdad Alirezaei et al. in their paper “Short-term fasting induces profound neuronal autophagy” found that short term fasting promoted Autophagy and had a profound effect on neurons. They went on to state that ” short-term food restriction may represent an attractive alternative to the prophylaxis and treatment of diseases in which candidate drugs are currently being sought.”
In other words, short term (or intermittent) fasting which produces autophagy could be of even greater benefit than the drugs currently being developed for the treatment of neurodegenerative conditions.
More than enough reason to give some serious consideration to making intermittent fasting a part of your regular routine.
So, what is the best length of time to fast?
Just an overnight sleep is enough to get Autophagy started, and there is some evidence that a 12-hour fast is enough. Other studies have demonstrated that between 18 and 24 hours there is the greatest drop in insulin levels which is implicated as a signaler for autophagy.
It has to be said that there are many differing opinions about the ideal time to reap the most benefit from Autophagy. Most of the evidence suggests times that range from 12 hours or more. In my opinion, it seems that a fast of 16 -36 hours is optimal to gain all the benefits of Autophagy.
Certainly, the 16-hour fasting/ 8 hour eating schedule is one of the most popular ways of intermittent fasting. This is normally done a few times a week, although many practise this way of eating every day.
Personally I don’t recommend that you fast for longer than three days, although some have suggested up to five days, done once every four or five months. I don’t see any compelling evidence to suggest that this is necessary. If more studies are done in the future, then I will be updating my information to take account of any new findings.
Too long on a fast changes the fast from being healthy to being in a state of starvation which is dangerous. it’s important to make sure that you eat extra on the times that you’ve set aside for eating. Your average intake over an entire week should be enough to maintain your weight, or at the very least to stay within your weight loss goals.
See my article here which goes into detail about intermittent fasting.
It could be useful to weigh yourself once at the beginning of your fast to ensure that you are reaching your daily nutritional needs.
What stops autophagy?
In a single word, food. Here’s why:
The main regulator of Autophagy is mammalian Tor (mTOR). This protein is vital to all living organisms and it is a nutrient sensor. mTor increases in response to dietary amino acids, aka proteins. When mTor goes up it stops Autophagy.
There is also a system in your body that registers the amount of energy that is stored in cells. When energy is low, autophagy is activated and old or damaged material is used for fuel. When energy levels are high autophagy stops and cell growth can continue.
Autophagy is a naturally occurring process, and is the common name for several related but separate pathways that each are crucial for the eradication or engulfment of damaged cells or proteins, engulfment of cytoplasmic material, eradication of pathogens and dealing with misfolded proteins.
In addition, autophagy also plays an important part within the immune system and in the regulation of cellular processes such as insulin sensitivity.
Autophagy as a process developed during our evolution as a self- cleansing system that provides protection against many diseases such as cancer, cardiac disease, infections and aging.
Autophagy is induced by fasting, the keto diet and exercise.
Continual eating slows down the occurrences of autophagy, as does aging. By fasting, following the keto diet and / or exercising regularly we can increase the amount of time autophagy can take place, with huge implications for our health and protection against disease.
Older people, who experience a natural slowing of autophagy, can compensate for this by the same means – intermittent fasting and exercise.
There is ongoing and increasing interest in autophagy within the scientific community, and although more work still needs to be done, there is already more than enough evidence to support the idea that ensuring that we induce autophagy regularly is one of the most important things we can do for our health and the prevention of disease.