Dear Ben, I just giving you my overall view whatever I learnt from my research area and knowledge. There is a direct relation between calorie uptake and aging that means that during fasting oxidative stress inside the body slows down and when it persist for a long time it bring dynamic changes inside body. It was seen that people who are going on fasting improves their mood/behavior, general appetite, control blood pressure and many more. I am not a huge spiritual person but in Vedic literature fasting is mandatory to control your mind and improves concentration for studying. One day of fasting really works, I saw these results on myself because I am doing one day fasting in a week from last 7 years.

Go through with this link:

https://www.scientificamerican.com/article/the-hunger-gains-extreme-calorie-restriction-diet-shows-anti-aging-results/

Thank you for the answer and the link. The negative impacts of extreme fasting such as in anorexia is, of course, an important reminder of extremism. Having just said that, I also realize that many of us often do things in extreme way. We tend not to tolerate inconvenience or a little aberration from what we call "normal". We actually invent our own normalcy to suit our own perception of what normal is. Most animals living in nature out there have to constantly struggle to find food. We are the only animals that always have food ready to satisfy our desire at any time, hungry or not. Don't get me wrong. I love food and I love eating. As a clinician, I believe the over-consumption and sedentary lifestyle of modern people are the main reason of the increase in many diseases we're facing right now. Some moderation and a more balanced way of consuming food may offer some solution to the problem. We are so accustomed to instant gratification. When the stomach is growling, we instantly look for something to satisfy the feeling. Is it really good to do that? Nature goes through extreme conditions such as in season of plenty and drought . Is there anything that we can learn from nature? Maybe, instead of extremism, we can just find a good balance between the instantly satisfying the desire and the delayed gratification at later time.

Ben, I agreed with your every aspect of observation and study. Hunger is now more psychological (mind) related than actual hunger (required). A little urge makes us to eat without struggling in nature, definitely it affects our body and may be the prime reason of most of the diseases in this present time. I want to share you a serious fact, biology of animals including us are same, there are some monks, spiritual people in Himalayas who take so little amount of raw vegetables and water and having age of about 80-90 years having not even a single disease. Such mysteries are still not solved. Indian military scientists are studying an 82-year-old who claims he has not had any food or drink for 70 years. Hope so someday we discover this mystery behind food and survival, when no one will feel hunger and finally live peacefully.

The answer to your mystery is complex. Our lives depend heavily on the expressions of our genes. Not only the way we look is the product of our genetic expression, but more importantly, the diseases that we develop and how we fight diseases depend on the genes that get turned on or off or mutated. Whether it's miracle or curse, we can see the whole spectrum of opposite extremes in life and nature. We're often tempted to imitate or emulate others that we perceive to have it better than us. Do this, do that, don't eat this, eat that, etc are excellent examples of how confused we are regarding what 's really good for our health. Medicine is not yet an exact science. I'm not sure that it will ever be. What works for the monk in Himalaya may not work for someone in New York. The problem with many medical studies and research is that they are not repeatable everywhere or can be applied to everyone due to the the abundant variability. In exact sciences such us physics and mathematics, one plus one is always equal two no matters what or where. It is definitely not the case with medical science. Diet is definitely a very important aspect of our lives and health. Food gives energy and nutrients. But, how does food or lack of food alter or control the genetic expressions of the genes that we inherit? Which genes that will get turned on or off? And, what will trigger the macrophages or our immune system to kill the mutation or harmful cells?

I have seen study that shows the state of under-nutrition without being malnourished when the caloric intake is significantly reduced which result in moderate weight loss may prolong survival in animals. The weight loss is the key. One study shows intermittent fasting without weight loss due to overeating in between periods has no survival benefit or improvement. The benefit is seen only in the group that restrict the caloric intake overall.

There's a study done at the University of Southern California that shows moderate calorie restriction for a few days a month can have some health benefit that may occur during the regenerative process after fasting. Aging is unpredictable because people vary greatly from their dietary requirements to our own genetic expressions, our own individual behaviors and the unique circumstances that we all experience. However, I think we may be able to control our behavior and what we eat. We can at least change the factors that are well within our control and help to keep our healthy body last a little bit longer. Conversely, we can not ignore the fact that long term, continuous fasting will have deleterious effects and cause severe malnutrition such as seen in "marasmus" and "kwashiorkor".

Since people vary greatly in what they eat, maybe the question should be " how much food and how often do people need to consume to stay healthy?" Is breakfast really that important? What happens to the extra calories from the dinner that we eat last night? Why can't the body use up the stored energy first before storing it up again? Why do we have to eat breakfast if the body has enough fuel already stored and ready to be used in the beginning of day? Maybe, it's all about custom, culture, and commerce, and not about health or what the body needs. Just food for thought!

I think our body is like a factory. So, during metabolising the food, body loose some essential components that needs for a perfect breakdown and assimilation of nutrients. To recover the degraded part body requires more food consisting recovery nutrients, to do so a consistent need of food is required even when we did not feel any urge of hunger. I am also agreed with the fact that customs changed our view of taking food when need and when not. But it may be possible that previous customs also linked with some hidden science that we are not know till right now

Maybe, we need to learn from our bones. Bones require to be stressed and exercised to stay healthy. Our bones start to degenerate early in life. We rely on the process of osteoclast and osteoblast . We have to have a good balance of destruction and regeneration. I think that's the key to healthy body and life, BALANCE.

Another key aspect of maintaining a healthy body and achieving longevity is through our complex immune system such as the cellular immunity mediated by the T lymphocytes and the humoral immunity mediated by the antibodies. We know that our immune system is pretty much responsible for many common illnesses or diseases we know outside the inherited genetic errors that cause rare diseases and the diseases caused by poor lifestyle choice. Mutated cells such as in many cancers should be able to be eliminated by a healthy and intact immune system. What is the relationship between the food we eat in our diet and the immune system? What is the relationship between an active body such as in regular moderate exercises and the immune system? Most of us lead a sedentary lifestyle that makes exercise a requirement instead of part of our daily life.

I think a combination of both the diet and an active body will keep us healthy for a long time through many mechanisms that the body is very well equipped, one of them is the immune system.

According to the definition, "hunger" is the discomfort, pain, or weakness caused by a need for food. In the research article by Longo and Mattson, hunger as an adaptive response to food deprivation and which causes changes in our sensory, cognition, and neuroendocrine system to make us look for food could also play very important role on aging and disease susceptibility. In that research article, it is noted that when the mice' hypothalamic "hunger peptide" is selectively ablated, the ability of "caloric restriction" diet to suppress tumor growth is abolished (Shi et all..2012). From their research, it could be concluded that the normal hunger response by the brain plays very significant role in the positive effect of calorie restriction and/or fasting. The hunger feeling could be seen as an important signal that the body produces to signify some changes that could be beneficial and protective in the molecular level to help fight disease and to stay healthy.

Ben Martinez Nice update. Now a days I am discussed about a new topic that is ''psychological hunger''. I think during the depression and fear, humans were tend to move toward over eating or sometime no eating. Final consequences are weight loss, obesity, gastric disorders and sometime memory loss. It was seen that yoga or meditation actually smoother the nerve impulses and bring peace and calmness. these people are very selective to food. Recent study about the change in the structure of water molecules due to the emotional changes.

Imagine our whole body consist maximum amount of water. For all metabolic activities water act as mobile carrier to transport all sort of biomolecule. Its should be a matter of debate how psychological changes can effect our daily food demand and finally leads to factors causing diseases.

Psychology, i.e the mind, is the biggest elephant in the room implying that there's so little known about the mind in comparison to the rest of the body. There are numerous anecdotal evidence that positive thinking and having good attitude produce results that are beyond what the current conventional medical science can explain. The recent incidence in Thailand regarding the trapped young soccer players and the coach could be seen as yet another example of the mind. The coach taught the children to meditate to calm the fear and decrease the oxygen consumption in such deprived and dangerous surrounding.

Ben Martinez Scientists are now describing the brain as quantum field. Millions of brain cell club together and creates the sense of smelling, listening, taste. And triggers the hunger as a need or the greed. By controlling the mind with maintained diet a human can increase the lifespan or can prevent from different diseases. As per my observation cancer was one of the rare disease that we listen nearby. But now a vast variety of cancers are present in the society. All because of poor diet, huge gaps between the meals, work pressure, anxiety n many more. peaceful meditated mind and fasting can bring a significant good results in the society.

I recently read a commentary by a physician who approaches diet and fasting in a very pragmatic way. The thinking is that "food" is the essential fuel to stay alive and an essential component of a happy life where food becomes the core life pleasure and should be savored with others. I can't agree more with this very pragmatic view of the food that we consume in our diet. The good doctor further explains how he's able to skip meals Mondays through Thursdays by staying busy and using various ingenious methods to consume very little calories until dinner time which he also restricts the amount of calories consumed by choosing healthier source of protein such as fish in addition to vegetables and salads. On Fridays and weekends, the good doctor doesn't fast. He and his family enjoy good healthy food prepared by themselves using whole food ingredients found in local farmers' and fish markets. They often enjoy and treasure their family tradition of long prepared meal which is shared together with nostalgia and comfort on Sundays. I really appreciate this pragmatic point of view toward food and diet because food must be both treasured and enjoyed. The problem is to find a balance where food can still be enjoyed and shared without causing detrimental effects on our health and life.

What goes in must come out. Matter can neither be destroyed nor created according to the law of physics. Whether you want to lose weight through diet, exercise, or the combination of both, you're required to be discipline and to follow the regimen from start to end. If you take in 1000 calories a day and burn 1200, according to the law of physics, you should lose the weight in the form of heat through routine daily activities. The problem is not the exercise. The problem is sticking to the routine to do the exercise. It is without question that exercise is important in maintaining health. "What you don't use, you will lose" can be seen routinely in our bone and muscle cells. I recently read that "the lack of exercise" is more common risk problem in women in the development of cardiovascular diseases than obesity and smoking. Exercise, not only will it help to lose weight, but it will definitely improve how one feels and even improve how one looks if it's done correctly and part of the lifestyle. It promotes the feeling of well being by forcing the release of feel-good hormone such as endorphin in addition to keep the muscles strong and in good tone to keep us fit and looking "good". Even though the jury is still out regarding the relationship between exercise and telomere length, more studies have shown positive effects than otherwise. How about "fasting"? Why don't physicians recommend moderate or light form of fasting to the routine? What's wrong with fasting? What's wrong with holding back food once in awhile especially if there's no contraindication in obese patients? We hold back many other unhealthy desires in life. Why can't we hold back from eating once in awhile? I think fasting should be included in the regimen for weight loss if there's no contraindication.

Completely agreed with you Ben, there is also one think that I want to discuss as I am not a completely religious person and try to find the link between science of religious practices. As per religious prospective people moves towards starvation for a particular of season (months) and duration (time). If you read about it, you will find that in this season changes and time, a variety of diseases like cold, allergies were become common. I think our ancestors were highly aware about it hence created the concept of fasting to get less exposure of non-veg food (as these animal food could suffering from any disease) and plants getting deteriorated nutrient content.

Now a days, people forget what really hunger means because of un-mannered consumption of food. Hunger help them to consume food wisely as well.

You will not lose weight if the consumption is equal or more than what is spent. It is a simple equation. What goes on metabolically is, of course, very complicated and complex and is not an easy mathematics equation. The energy expenditure or the amount of calories used during a typical 30-60 minute exercise is not really that much in the context of the total daily calories used just to stay alive. If we look at our evolutionary history, we have evolved to be the way we are because it must be the most efficient way for us to stay alive. We have big brain and long limbs. We use our brain to think and to take advantage for a better life. What do we use with our long limbs? We no longer run and hunt for our food. So if we no longer use our limbs to do the work, and instead, most of us just sit behind a desk for the most part of our lives to do the typical requirement of our modern jobs, I dare to extrapolate that we will eventually evolve to have short limbs and very big head that will contain even bigger brain in addition to very large trunk to accommodate the large food consumption that seems to be endless

The DAF-2 gene is responsible to encode the insulin-like growth factor 1 (IGF-1) receptor in the worm called Caenorhabditis elegans. DAF-2 essentially works by regulating the amount of nutrients the body will absorb. It has been shown that mutation of this gene, DAF-2, has a wide range of effects on the regulation of the rate of aging, resistance to oxidative stress and pathogens, and reproductive development among others. Work by Cynthia Kenyon and others have shown that mutations in DAF-2 gene double the lifespan of the worms. It has been theorized that by regulating this insulin growth factor, the organism can control the amount of nutrients the body will absorb. If the insulin growth factor doesn't work as well, the body will absorb much less nutrient, essentially tricking the body into FASTING mode. The worm will enter into less active metabolic state during food scarcity or overcrowding causing the delay in development. When DAF-2 is disabled, development is delayed, effectively increases longevity. Insulin and its effects are required for the organism to absorb nutrients. If insulin is regulated in such a way that the body thinks that it already has enough food and forces itself to go into "protective" mode by taking better care of everything, "fasting" is a very natural way to induce this effect that is discovered in the mutated DAF-2 gene.

As previously mentioned, the amount of calories the body uses during a typical one hour of physical exercise is small in comparison to the total calories used in our daily living. Therefore, exercise alone is hardly enough to cause any significant weight loss. The question probably is not that "exercise is overrated" but "is exercise alone enough to lose weight?" The resounding answer is NO. There's still so much we don't know and understand about the body's cellular metabolism. Studies have shown that most of our energy or calories are spent just to stay alive in the form of basal metabolic rate. Basal metabolic rate is not precisely the same for everybody. The older we get, the rate tends to slow down. The body is amazingly efficient and complicated machine. I like to use automobiles as analogy to metabolic rate. Some cars are very fuel efficient and some aren't. It is much easier for the body to decrease its metabolic rate than to increase due to the body survival instinct. To spend more energy will cause more stress to the body and is much harder than to conserve. Studies and many evidences have shown that after a period of significant weight loss, the metabolic rate will also decrease. Therefore, unless there's a proportionately significant caloric restriction being adapted, the body will eventually gain the weight back, and probably even more because the metabolic rate decreases while the consumption remains. While currently there's no dispute in regard to the health benefit of exercise, the effect of exercise metabolically and the overall impact on the body adaptation to the overall change in the calorie expenditure is still debated. The body has been shown to produce a metabolic compensation in response to calorie reduction and increased activities by lowering its basal metabolic rate. Exercise may induce the body to seek more food to compensate for the calories spent, thus effectively negate the calories spent during exercise. The body may also choose to be less active after exercise, therefore, effectively compensate for the increased activities during exercise. Since basal metabolic rate varies greatly among individuals, this could be one reason why some people can stay lean and others have such difficulty to shed the pounds they have gained through the years. I think the most important factor in staying lean and healthy or in losing weight for obese people is to "adapt to healthier lifestyle" in which the caloric consumption is moderate and derived from natural and healthier form of food with less animal fat in addition to staying physically active.

Nice explanation Ben, I think that's what a dietitian is doing now a days. He/she analyze our daily workout details, age and diet, finally built a complete chart containing daily protein, carbs, vitamins, minerals and water requirements. I used to here this all the time that a dietitians prescribe a diet but its not working any more. I think it vary from person to person as you also said. We are really don't know anything much about our body metabolism. And it is highly affected by our enzyme system. Weather it control nutrition update or hormonal. I think hormones are actually energy channels inside our body. An healthy diet controls our hormonal base and also control whole metabolism. People using simple food low fat, protein but access amount of vitamin and minerals were sustain their cellular life and control aging.

A very interesting terminology that I recently stumbled upon was "Calorie Restriction Mimetic". Basically, scientists and researchers are looking to find compounds whether they are drugs or dietary supplements that can mimic the significant beneficial health and anti-aging effects that calorie restriction has been shown to have on both animals and humans. One very notable such compound or drug is Metformin, the very popular drug that treats Diabetes. There are currently many ongoing research studies to learn more regarding the possible wide range benefits of Metformin from cardiovascular disease and cancer to Alzheimer and longevity. If the science and the studies can confirm the speculations and can be translated into clinical practice, Metformin will be the wonder drug. Having said that, I find it very ironic that we are looking for some miracle dug to mimic or copy what we already can do without taking any drug at all simply by REDUCING our calorie intake. Is it in our nature to "have the cake and eat it too", to injure ourselves first and then try to find a cure after? Another food for thought.

Dear Dr.

i think this link will help you

Regards,

https://www.lifehack.org/articles/lifestyle/10-benefits-of-fasting-that-will-surprise-you.html

Ismail,

Thank you for reading my writing. There are a lot of claims out there such as the link you posted above. Claims without proof or having any scientific evidence that can be repeated faithfully are just hoaxes. Thanks again for your interest.

Ben

Some small studies have shown that fasting or time restricted food consumption improved control of DM and weight loss.

Fasting also help to improve mind's concentration because there is no rush to digest or assimilate the nutrients that consumed a lots of energy (secretion of dopamine showed feel good behavior while fasting as well). whole body on fasting consume stored bio-molecules (fatty acids, proteins, carbs) and also balance the enzyme to substrate ratio results good digestion on very next day.

William and Vikas, thank you for the contributions.

The long term effects of moderate calorie restriction diet of about 20 to 40% has been studied extensively for a long time on cancer progression. It has been known to cause changes in glucose and IGF-1 levels in addition to persistent weight loss in both laboratory animals and humans.

Calorie Restriction diet made national news on major network television yesterday 11/25/18. NBC put up a story regarding the possible benefits of calorie restriction and the ongoing research by various institutions.

The Japanese cell biologist, Yoshinori Ohsumi, won the Nobel Prize in Medicine/Physiology in 2016 for his discoveries of how cells recycle their contents or "autophagy". Autophagy is a Greek term for "self-eating". Autophagy is process of recycling and degrading to balance the energy sources and to keep cells healthy by destroying damaged structures and invading foreign organisms such as as viruses and bacteria. Autophagy plays important role as the housekeeping and cleaning mechanism within the cells by clearing damaged mitochondria, endoplasmic reticulum and peroxisomes for examples. Autophagy is also very important in eliminating and destroying intracellular pathogens. The process of "self-eating" is critical for cells to survive and is a key homeostatic mechanism for preservation of the organisms from yeast to mammals. Autophagy has been recognized as a very important mechanism to defend against malignancy, infection, neurodegenerative diseases, cardiomyopathy, and autoimmune diseases to name a few. Autophagy works by balancing the sources of energy in response to "nutrient stress". During starvation, cells will break down proteins and other nonessential components to reuse them for energy. It has been known that food restriction induces autophagy in many organs and tissues. Autophagy is strongly induced by starvation and becomes an important adaptive response to nutrient deprivation for the organisms to stay alive until nutrients become available.

There exists now the "Fasting Mimicking Diet" or FMD. The diet program is called ProLon and is a 5 day program that is supposed to mimic intermittent fasting without actually fasting or stop eating. It sounds contradictory. But in the age of all things short-cut and convenience, anything is possible. Why not, right? We're still looking and waiting for the fountain of youth and the magic pill that can stop and alter the process of nature.

Recently, there was yet another study that promotes eating breakfast as a way to keep cardiovascular health. The study compared the breakfast skippers to breakfast eaters and found that the breakfast skippers had a higher risk of cardiovascular mortality. In my opinion, this is yet another example of a casual association of "cause and effect" without being able to explain the scientific mechanism of the "cause". What is the underlying science of eating breakfast? Why is eating breakfast good for health? What is the difference between breakfast and lunch or dinner? Couldn't it be that breakfast eaters are generally healthier individuals who tend to take care of themselves better? And, couldn't it be that the breakfast skippers are generally riskier individuals who tend to overindulge and engage in unhealthy lifestyle such as smoking and drinking too much and don't really care when or what they eat as long as they satisfy their hunger, and not to mention the lack of exercise. I don't believe such casual association in many studies should be emphasized since the underlying scientific mechanism is not yet revealed. I would much prefer that this particular study would emphasize more on the riskier and unhealthy lifestyle of the breakfast skippers than the "breakfast" itself. There is too much unfounded beliefs, fads, and hysteria out there in public regarding diets and health in general. Everybody seems to want the magic cure that by taking this recipe, supplement, or doing certain thing will give us the fountain of youth or longevity that only the wise and lucky have achieved.

We all know that sleep is just as important as food to keep good health. Seven to eight hours of sleep seems to be the consensus belief to be the right amount we should have when we sleep. I would like to know whether it matters or not what time of day the sleep is obtained. Is there a difference between the early sleepers compared to late sleepers? What about people that have to work at night and sleep during the day? Are there studies that investigate these questions? I would like and welcome some insight in this regard.

Back to the breakfast issue, why do we have to eat breakfast if we're not hungry? Since we have so much stored glycogen and fat, when are we going to ever use and burn that energy so they can be replenished later? What happens to the stored energy if it never gets used because we constantly stuff our body with new energy every time we feel hungry?

It's a known tradition since ancient in India and do believe that it is very good for your health especially for digestive system.

Regards

We can have a good argument or debate regarding what food is good for the body and our health. Everybody has his or her own personal likes and dislikes including our own personal beliefs whether they're supported by real science or not. We won't find any shortage of opinions regarding the foods we should eat, that's for sure because we enjoy our food too much. What about the thoughts that go into our mind, how important are the thoughts that go into the mind? Are there good and bad thoughts that can influence the body and our health in general? Can restricting the thoughts that go into our mind such as during "meditation" improve our overall wellbeing? It seems there is a parallel or even eerie similarity between the thought restriction in "meditation" and calorie restriction in "fasting" . What do you think?

The U.S military is proposing the implementation of ketogenic diet as a way to improve the soldiers' physical and mental performance. This recommendation is based on studies done at Ohio State University that shows weight loss and improvement in insulin sensitivity. Furthermore, the ketosis state is shown to change the way the body handles oxygen deprivation which enables divers to stay underwater for longer periods which could be very beneficial for Navy SEALS. While this study is exciting and adding more light to the effects of the food we eat, it is still not known what the long term effects on such extreme diet rich in fat and protein with very little carbohydrates. An easier way to be in ketosis is "not to eat too much" while fasting in moderation. A little feeling of "hunger" in the belly may do the soul and body good.

I was recently being made aware of the 15th century Venetian nobleman, Luigi Cornaro, who wrote books regarding "secrets to living long and well" by a another fellow research gate participant, Ligen Yu. After falling ill at the age of around 40 years old, Luigi Cornaro adhered to "calorie restriction" diet and continued to follow the same diet for decades until he died at least at the age of 98 years old. What's so amazing to me is the fact that even centuries ago, some people have already realized that excessive consumption is the cause of unhealthy life and illnesses.

Dear Ben

Thank you for mentioning me here in this discussion about fasting. Yet I need to correct you that Luigi Cornaro is actually anorexia nervosa, not fasting nor calorie restriction. One should not follow his diet if one's body condition is not ready for it. The biggest difference between anorexia nervosa and fasting or calorie restriction is one's attitude to food. In anorexia nervosa, stavation is anxiolytic, and normal eating is very stressful. So Luigi Cornaro is forced to eat very little, is not by his free will. He would fall ill if he eat a little more.

We have hypothesized that Luigi Cornaro had a very rare physiological condition of sustained up-regulated autophagy (SUA) without anorexia:

Article Sustained upregulated autophagy (SUA) without anorexia-Aetio...

This condition is mainly as result our body's fighting to sever illness, chronic infection and inflammation, or chronic injury. Fasting and calorie restriction along is not able to trigger a fully developed SUA without anorexia.

Ordinary people who can eat normally should not try the Luigi Cornaro diet. They can eat less, but not so less as Luigi Cornaro. What Nietzsche said is correct: "I have no doubt that hardly any book (with the exception of the Bible, as is only fair) has done as much damage, has shortened as many lives as this curiosity which was so well-meaning. "

(http://www.faculty.umb.edu/gary_zabel/Phil_100/Nietzsche_files/Friedrich-Nietzsche-Twilight-of-the-Idols-or-How-to-Philosophize-With-the-Hammer-Translated-by-Richard-Polt.pdf)

Thank you very much again, Ligen Yu. You seem to be the authority regarding Luigi Cornaro. I didn't know much about him until you mentioned in your reply on one of the subjects I'm writing, "the placebo effect". I've learned in medical school that "anorexia" is an illness and definitely does not promote health. "Fasting" in calorie restriction diet is not an illness, as a matter of fact, is done to promote health. In anorexia, patient lacks or even loses the appetite for food and possesses extremely disturbed body image with a constant fear of being fat. The difference here, as you already mentioned, is intention or attitude toward food. (I will use this example to continue my discussion regarding the placebo effect because the effect of the "mind" seems to occur everywhere). In fasting, autophagy is only one of the important processes that take place and not the only one that's important. An appetite for food and the feeling of hunger are usually normal signs the body produces in healthy individuals. I mentioned in my earlier writing on fasting some studies that show the feeling of hunger is actually beneficial, and when the "hunger peptide" produced by the hypothalamus is eliminated, some of the benefits from fasting is not seen. There is still too much to learn in medical science, and there's no silver bullet to kill all or one magic pill for all men's illnesses.

Dear Ben Martinez

Thank you for your reply. Anorexia is an alarming symptom of sever physiological disorder in the body. But itself, like fever, hypertension, is not an illness. Actually, it is our body's defense strategy against the underlying sever physiological disorder. Our body is trying to eliminate the illness by starving itself. Even Cachexia in cancer is a 'Last Ditch' Mechanism of Host Defence against cancer:

Article Cachexia: A 'Last ditch' mechanism of host defence?

Anorexia has different forms like illness-induced anorexia, anorexia nervosa, anorexia of ageing. All these anorexia are closely related, as there are the indication of up-regulated autophagy.

In anorexia nervosa and anorexia of ageing, there is actually no "anorexia" (loss of appetite as a physiological symptom), the persons fear of eating more or being fat is a real physiological fear, as they really have the potential of growing into morbid obesity.

Thank you for your response, Ligen Yu. In the U.S, Anorexia Nervosa is classified as a "psychiatric or mental" disorder or illness. It's an emotional disorder and not physiological disorder of the body. Anorexia as a symptom of no appetite for food due to illnesses is indeed alarming. But, the concept of anorexia as the body's own self defense mechanism is very intriguing. I will look into the article you mentioned above regarding "cachexia" and anorexia due to other illnesses. It's indeed a very interesting and provocative idea to think that the loss of appetite which will cause calorie restriction is actually the body natural defense mechanism. Excellent! But, how do you apply this knowledge into everyday clinical practice with real patients and real diseases? When is the right time to intervene if any if your theory is right? When do we know that the up-regulatory mechanism in autophagy is not helping patient with the disease?

Dear Ben Martinez

As I am not a medical professional by training, I haven't thought about how to apply the knowledge into practice with patients yet. I publish these things in hoping that the medical community can do further study so that eventually these knowledge can benefit the patients.

Before I myself accidentally developed anorexia nervosa, I also thought that it is an psychiatric or mental problem. But after I had anorexia nervosa myself and recovered from it by adopting the Luigi Cornaro diet, I realize that there is something much deeper beneath the anorexia nervosa symptom than labeling it as a mental problem. You may read the following tragic story about Prof Rosemary Pope:

http://news.bbc.co.uk/2/hi/uk_news/england/dorset/7360470.stm

Please note that Prof Pope has a background in health and psychology. It is so unfortunate that her specialty was in psychology, not in gastroenterology. If she were an expert in gastroenterology, she would have found that her problem is within her gastrointestinal tract in her 30 years of anorexia nervosa.

And if we read Luigi Cornaro's description of his 8-day overeating trial which almost killed him, we may realize that this almost fatal experience was not because of over nutrition, but because of injury to the weak gastrointestinal tract by the excessive food.

So the problem with anorexia nervosa is very complicated, and we may not simply say it is a mental problem.

Thank you again, Ligen yu, for your insight. I'm not a psychiatrist, but I respectfully disagree with you regarding Anorexia Nervosa which I firmly believe is the product of the mind. Having said that, I'm actually very interested in the concept that the lack of interest in food or lack of appetite during illness is the body self-defense mechanism to fight the disease. If that were the case, it must be within certain parameter and time during the disease process. However, the body will ultimately perish if this process fails. I'm having difficulty in trying to understand this concept. During illness, the body is under attack and is being stressed. So, the body is already being forced to use all of its resources to fight the disease which will require many more calories and demand more input from outside in term of food intake. When the body needs more calories to fight the disease, why would restricting food intake be a defense mechanism? The body generates immune system to fight infection naturally. However, before the discovery of antibiotic or penicillin in the beginning of the 20th century, the life expectancy at birth was only 47 years. People were dying of infectious diseases. Now after the discovery and development of antibiotic, the life expectancy at birth is around 78-79 years. The body is equipped to survive many years but often needs a little "outside" help or even encouragement. The body is an amazing thing, but even amazing thing when abused will eventually falter. From the studies I've seen, moderate fasting or calorie restriction on "healthy" subjects when done properly is beneficial for health. In my opinion, people are overeating and over-consuming everything. Some restriction or reduction in what we put inside our body makes perfect sense. Feeling hungry every now and then may be good for the body.

Dear Ben Martinez

Understand that it is hard to convince the medical community that anorexia nervosa is a symptom of sever physiological disorder in the body, rather than a mental disorder by itself, although no one knows the exact etiology, or the cause of anorexia nervosa.

Yet everyone agrees that anorexia nervosa has serious physiological consequences like malnutrition, dysfunction in gastrointestinal tract, and so on. Is there any chance that the medical community is actually “mistaking the consequence for the cause”, as what Friedrich Nietzsche criticized the Luigi Cornaro diet?

For illness induce anorexia as our body's defense strategy, it is well documented. You may interested the following references:

Article Sickness-Associated Anorexia: Mother Nature’s Idea of Immunonutrition?

Article Autophagy-A free meal in sickness-associated anorexia

Article Roles of Autophagy in Elimination of Intracellular Bacterial Pathogens

Article PKR-Dependent Xenophagic Degradation of Herpes Simplex Virus Type 1

Article Infection-Induced Anorexia: Active Host Defence Strategy

Article Cytokine mediators of malnutrition: clinical implications. T...

These articles may answer your question: " When the body needs more calories to fight the disease, why would restricting food intake be a defense mechanism? "

Thank you for your reply, Ligen Yu. The definition of anorexia is "lack or loss of the appetite for food". The definition comes straight from the dictionary. I'm not a linguist and am not interested in debating about definition. Nervosa means nervous in Latin. Anybody can draw their own conclusion what the combination of those two words are supposed to mean.

I am not disputing anorexia as a symptom and the result of physiological condition as you cleverly mentioned already. There are too many physiological conditions occurring in the body that will cause "anorexia", but will not cause "anorexia nervosa". I worked and played too hard yesterday, and as a result, I was too tired and lost my appetite to eat. Numerous medical conditions from cancer, heart disease, and infection may cause anorexia, not to mention "depression".

This discussion regarding anorexia nervosa has actually helped me think of another angle that is related to my original question regarding our diet and food intake that ultimately ends up in our "gut" or gastrointestinal (GI) system which digests the food we eat. The enteric nervous system from esophagus to rectum contains more than 100 million nerve cells and has been considered by many as our "second brain". The connection between the brain and the gut is underappreciated and often ignored but plays important role in our well-being. When the "gut" is not feeling well, the rest of the body won't feel well. Anxiety and depression are often translated into significant change in our eating habit. The feelings that we feel in our gut whether it's "butterflies" or "the gut feeling" are examples that the gut is communicating with the brain. My grandfather used to tell me that he would have a good day if he had a good bowel movement in the morning. If no bowel movement occurred, he would suffer the rest of the day. This is just an anecdotal personal story , but I will go with my "gut feeling" that his GI system played a significant role in his well-being.

Dear Ben Martinez

I really appreciate your reading of my post and reply to me. Your perception about anorexia nervosa (AN) is typical in medical community: AN is a serious psychiatric illness, and the patient o AN is suffering. I'm not questioning the seriousness of this fatal illness, and if the patient himself or herself has the same perception like the medical community, then AN can be easily treated.

Now, the problem with AN is, the patient actually value their anorexia nervosa, and is reluctant to recover. This is the most difficult part in treating this illness, as the AN patient perceives AN in a completely different way.

Article Reluctance to Recover in Anorexia Nervosa

Article The Egosyntonic Nature of Anorexia: An Impediment to Recover...

The AN patients do suffering from depression, but this happens when after they eat a normal meal, not when they are starving themselves. The happiness expressed in Luigi Cornaro's discourses is the typical happy feeling of an anorexia nervosa patient after their restrictive eating or starvation. For normal person, fasting or calorie restriction will leads to negative feelings, and the person in fasting or calorie restriction cannot stop their temptation of normal eating. Only the AN patients starve themselves in a willing way. And this is most dangerous, as everyone knows the disastrous consequence of starvation.

Here is a provocative question for everybody. Does anyone out there ever think that we humans are just a bunch of "lab rats"? Yes, "laboratory rats or animals" like in science experiment. The only animals that are fat and obese are animals that humans feed whether they're the beloved pets at home or the guinea pigs in some science laboratory. Has anyone ever seen a fat wild animal living in its natural element and environment? I have never been on an African safari or been on Amazon adventure, but I have been a big fan of nature shows since I was a little kid. I have never seen an obese lion in the Serengeti or a big fat monkey on the tree living naturally in their environments and not being fed by humans. When the foods are plenty, they look well fed but not fat and obese. Why is that??? They become fat and obese only after human intervention.

Thank you, Ligen Yu, for those articles you referenced in your previous writings. It is indeed against the conventional wisdom to think that "anorexia" is the body's own self defense mechanism by up-regulating "autophagy" and mobilizing the immune system. You should write more and enlighten us, ignorant clinicians. You seem to know and understand more regarding this subject. You know, when you really think about it, it actually makes sense. If the body requires more nutrients in term of food for the calorie burden during severe illness, why wouldn't the body naturally requests its demand by increasing the appetite for more food? I would now argue that the body does not require such intervention. Therefore, we could argue that the lack of appetite in illness is natural and should be tolerated.

Dear Ben, your understanding is correct. The lack of appetite in illness is natural and should be tolerated. anorexia induced by illness or injury is totally different from starvation. because of the up-regulated autophagy, the energy and nutrition balance in our body is well maintained. Aggressive food intervention will disturb the up-regulated autophagy, and slow down the recovery. But minimum easily digestible food consumption is still necessary to keep the gastrointestinal tract well functioning.

My personal experience also shows that maintain a slight hungry feeling by eat less can greatly speed up my recovery from catching cold or back injury (due to fall), and it is really amazing.

While the lack of appetite may be one of the early signs and ways the body is responding to some illnesses, prolonged anorexia in severe illnesses such as advanced cancers especially in the gastrointestinal organs or lungs will lead to cachexia which is one of the strongest predictors that death is imminent. It is important to understand the difference between starvation due to the simple lack of appetite in "anorexia" and "cachexia" that's due to advance cancer or even heart failure. In cachexia due to advanced severe illnesses, the weight loss is due to the breakdown of both fat and muscle cells. In starvation, ketone bodies are being used as fuel instead of glucose from the metabolism of fat cells and very little from muscles. When the proteins from muscles are being used for fuel, the body is essentially wasting away and will be unable to fight to survive. It is also important to note that the state of cachexia in cancers will not be reversed by nutritional supplement and is irreversible. There are currently some studies to find therapies to fight cachexia, but it most likely requires several different modalities. This is yet another example of how complex the human biology is and the importance of achieving homeostasis.

Dear Ben

Fully agree with you on your comments on cachexia. Although "anorexia" can be viewed as manifestation of the powerful self-healing capacity of our body, "cachexia" shows that this self-healing capacity has its limitations. One cannot presume that he can rely on this self-healing capacity to recover from any illness, so he can do whatever he can do to harm his body without taking care of his health carefully. This also apply to physical exercise. Autophagy can help one to recover from injury, but constant vigorous exercise may create injuries to body that exceed the capacity of autophagy, so should also be avoided.

Sorry, I have not read all the replays, but regarding the main question, two major mechanism that are at play when fasting.

1) Fasting result in a decrease in various growth factors. As an example, insulin is released following a meal, so fasting would supress insulin levels. Longer term fasting will also impact on the release of growth hormones.

Now, a decrease in growth factors like insulin will have two major effects.

Firstly, fasting-induced suppression of growth factor would result in lower cell anabolism (bio synthesis of cellar products) and proliferation. This is because growth factors promote, as their name implies, ‘growth’. Mechanistically, these types of hormones tend to activate canonical anabolic pathways such as mTOR/PI3K/AKT signalling pathways.

Cancer is uncontrolled cell proliferation. Cancer cells evolve a more autonomous phenotype (they proliferate despite the absence of growth factors –they are truly disobedient cells).

Now see what happens:

a) If in a fasting state, serum growth factors levels will decline.

b) Normal/healthy cells will stop proliferation (their metabolism is more catabolic instead of anabolic).

c) Cancer cells, however, are ‘autonomous’ (‘disobedient’) and continue on proliferating despite the decline in growth factors.

d) So, while healthy cells are more catabolic in a fasting state, cancer cells maintain high levels of anabolism.

Notice that this situation provide a differential target for cancer cells: because cancer cells are proliferating despite the absence of growth factors, they are more susceptible to certain chemotherapeutic (remember, healthy cell only proliferate if they receive the signal (i.e., growth factors) to do so, but because you are fasting they will tend not to proliferate). While cell proliferate, they are more sensitive to radiation therapy and chemotherapies that disrupt processes of cell proliferation. So cancer cell that proliferate while your cells are more quiescent will be ‘harder hit’ by the chemo or radiation therapy.

Secondly, fasting will result in higher levels of autophagy. “Under normal circumstances the cells in your body use autophagy (a kind of cellular 'recycling process plant') to clear the garbage generated by the wear and tear of the parts in a cell. Through autophagy, the cell is able to recycle the debris or junk that could otherwise have caused damage to the cell.” [1] So, in a fasting state, autophagy is upregulated to that the cell can better ‘recycle’ as there are limited resources available during a fast. But having elevated levels of autophagy also has a key benefit: cells will be better able to removed damaged cellar machinery. This is critical, as damaged proteins can easily aggregate and precipitate, leading to cell death. Similar, autophagy help removed damaged mitochondrial (cellar ‘power station’). This is critical, because damaged mitochondrial can ‘leak’ free radicals and cause cell death. So, fasting would result in the mobilisation of the autophagic machinery, rendering cells more able to deal with cellar insults (e.g. chemo). In fact, upregulating autophagy renders numerous organism (mice, yeast, flies etc.) more resilient against a wide range of stresses (from poisons to radiation).

[1] Layperson explanation for autophagy: http://www.sun.ac.za/english/Lists/news/DispForm.aspx?ID=3784

Fasting and its effect on anti-neoplastic therapies: https://www.frontiersin.org/articles/10.3389/fonc.2016.00242/full

2) Fasting will prevent the increase in secondary bile acids (which act like hormones) that occurs after a meal.

Bile acids (BA) are released fooling a meal and help to emulsify fats droplets (it helps forming smaller fat droplets that increase the surface area and thereby rendering it easier for lipase enzymes to digest the fats/oil in a meal). Importantly, the BA are metabolised by bacteria into secondary BA (Briefly, bile acid consist of a cholesterol moiety conjugated to either an amino acid like glycine, or to taurine. The gut biota ‘snip off’ the amino acids: this is probably a strategy of the bacteria to prevent the BA from killing them since BA can ‘dissolving’ their membranes). Anyway, the secondary BA (i.e. the bile acid that was metabolised by intestinal biota) is very efficiently reabsorbed in the small intestine (~95% of all your bile acids are ‘recycled’ because of this very efficient reabsorption).

Now, when these secondary BA enter circulation (following the effective reabsorption form the gut) they act exactly like a hormone! (I.e., they act as a signalling molecule and actually have dedicated receptors that can detect their presence and solicit various cellular effects). One of the key effects of secondary BA is to inhibit autophagy, there are other effects as well.

Read more about secondary bile acids and their hormonal function: https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2160-4

Just a quick note on anorexia nervosa: Anorexia nervosa (AN) is not the same as sickens associated anorexia (SAA).

SAA forms part of a constellation of behavioral modifications following an infection: these behavioral changes are collectively referred to as sickens behavior (SB). They are induced by cytokines (‘hormones of the immune system’) like Il-1b and TNF. Literally, injecting these cytokines into a healthy person (i.e. no infection of tissue trauma) will solicit these SB -including SAA. You might also have noted that certain vaccines (which are in effect a ‘simulated infection’) may make you feel sick –this is sickens behavior as a result of immune activation. But critically, once the inflammatory insult is removed (i.e. once the cytokines levels returned to normal) SB also becomes suppressed and your appetite will return.

AN in contrast, is NOT dependent on immune system activation. In fact, severe nutritional stress (i.e. once you have lost a lot of weight) is actually immunosuppressive! If SAA and AN operated with the same goal, they would both be responsive to the immune system –but AN is not. AN is also associated with other psychological issues (e.g. ‘purging behavior’ such as excessive exercise and the use of laxatives) that does not feature in SB. In short, people with AN have real psychological issues, whereas SAA is 100% immune-mediated.

Also see this: “Finally, it is worth noting that inflammatory mediators antagonise the digestive process. Cytokines such as IL-1β, IL-6 and TNF-α, through various mechanisms, decrease bile flow (reviewed in [2]). Also, TNF suppresses gastric motility through its action on the dorsal vagal complex [3]. This illustrates that inflammatory mediators enact a range of physiological responses intended to limit the intake of food, strongly supporting the notion that a decrease in feeding represents a dedicated response to inflammatory mediators.” (https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2160-4) Notice that AN is an immune suppressed state, so they will not have these inflammatory mediates to induce SAA or SB.

Old, but beautiful manuscript on sickness behaviour: https://www.ncbi.nlm.nih.gov/pubmed/3050629

Excellent insights and explanation! Thank you, Gustav. I enjoy reading what you wrote above including the referenced articles you mentioned. Obviously, you have done tremendous work in the field of autophagy and cancer where "fasting" can be used to promote up-regulation in autophagy to fight certain cancers. In your responses above and the articles you referenced, I didn't see any mention regarding the energy sources being used by the cells such as glucose versus ketone bodies. I would like your insight regarding ketone bodies as the energy source in cancer cells and the role of fat metabolism in fasting.

Dear Ben

Gustav is an expert on autophagy and sickness associated anorexia (SAA). I have learnt a lot from his publications, and really appreciate these knowledges.

The problem with fasting is that, fasting is not an sustainable lifestyle, one have to "break" the fasting, and eat normally, especially after a long time (say a few days or a few months) fasting. Also fasting will place a great stress on the gastrointestinal tract (GIT), and lead to the atrophy and dysfunction of GIT mucosa. So I would suggest time-restricted eating, which is more practical for general people:

Article Time-Restricted Eating to Prevent and Manage Chronic Metabol...

As a veteran of anorexia nervosa (AN) who have recovered from this suffering, I would like to provide my understanding about this condition.

The name “anorexia nervosa” is misleading. Anorexia nervosa neither have the symptom of “anorexia” (loss of appetite, the persons in AN are actually has very good appetite, they are simply afraid of eating), nor “nervosa” (meaning that this condition is controlled by metal disorder. On the contrary, it is actually resulted from physiological disorder, and the mind has to follow the paradoxical instructions from the biological body).

It is true that sickness associated anorexia (SAA) is not the same as AN, yet they are related. A person prone to AN normally had a weak body condition in early childhood, and they had a long history of chronic infection/inflammation which triggered upregulated autophagy/SAA repeatedly. Eventually, up-regulated autophagy becomes persist, and SAA disappears. Because this persisting up-regulated autophagy can provide the host with plenty of recycled nutrition and energy, normal eating soon make the person overweight or obese. So they start to eat restrictively. For normal persons, restrictive eating creates so much negative feelings that forces them to quit. But for persons with persisting upregulated autophagy, restrictive eating is anxiolytic, meaning that they feel very comfortable with restrictive eating and fasting. And this is the starting point of AN, even without the awareness of the person themselves.

The fear of eating of AN patients come from two aspects, one is from the fear of become morbid obesity (because of the persisting upregulated autophagy, they are prone to morbid obesity); the other is from the injury of food to the atrophied weak GIT mucosa.

Eat-but-little is an effective practical way for AN patient to recover from AN.

Dear Lingen Yu

Thank you for the interesting feedback –it seems like a truly fascinating article! And you are right: persistent fasting is not effective. The “time-restricted eating” is, I think, similar to the idea of “intermittent fasting”–an idea that I try and implement in my daily routines. In general, I believe that we should try and ‘simulate’ our Palaeolithic ancestors’ way of eating (i.e. avoid processed food and induce/promote longer periods in a ‘catabolic’ state). Specifically, I strongly suspect that the ‘3 meals a day’ paradigm is wrong. My strategy is to only eat sometime only after 11:00 in the mornings. This mean that I have placed my body in a fasted state for about 16 hours.

There is something else also: I exercise first ting in the morning on an empty stomach. Exercise, like fasting, also induce autophagy (exercise place your body in a catabolic state). This maximises the extent to which I can place my body in a catabolic state, while also minimising the amount of time I spent not eating.

But anabolism and catabolism is sort of a ‘Yin and yang’ relationship: like you correctly pointed out, prolonged fasting is not sustainable and actually detrimental. So, what I do is to eat a wholesome meal at night, so that I maximise the extent to which my body enter an anabolic state at night. So, in the day, I try and be catabolic: at night, I maximise my anabolism.

I simply don’t know enough about AN to make any comments on it. When I was an undergraduate, we were taught in psychology that AN is about control –not food or appetite. Individuals exhibiting AN often have other social ills and often feel powerless/frustrated. Controlling their weight gives them a sense of agency as it is something they can control in a world where they feel powerless. Sometime they feel it is the only thing they can control in their lives. AN is thus a way of assuring yourself, by exercising extrema control over your food intake. This seems plausible psychological explanation, but I simply do not know. And in all honesty, I am skeptical of the psychology field, and extremely suspicions of my university’s psychology department, so I don’t have a strong opinion on this. But, I suspect you might like to read some of the literature on “Darwinian medicine”-a field that try and understand ‘pathology’ form an evolutionary perspective. (I do this all the time!) There is a guy called Randolph Nesse –he is a psychiatrist that is very involved in Darwinian Medicine. If you are interested in AN, I would encourage you to maybe have a look and see what he and his colleges think about AN (see, e.g., Anorexia: A perverse effect of attempting to control the starvation response).

With regards to the effect of fasting on the gut biota, there is evidence that it might actually be beneficial on the short term! Here is some notes that I made a while ago:

When the host is in a fasted state, the composition of bacteria populations can be manipulated by the host’s secretion of O-linked glycans to “intentionally influence this ecosystem for better health and nutrition” [4]. Interestingly, there is evidence that at least part of the change in microbiota in response to fasting might be evolutionary conserved. In a group of 5 different tetrapods (tilapia, toads, geckos, quail, and mice), all exhibited a decrease in Coprobacillus and Ruminococcus during fasting [5]. It is tempting to speculate that SAA, which is itself also an evolutionarily conserved response, may represent a strategy to optimize the microbiome for enduring an infection. There are various mechanisms that could be at play. As an example, perhaps by selecting for a more diverse microbiome, host causes more ‘infighting’ between bacteria strains (a ‘divide and conquer’ strategy that renders the microbiome less of a threat during an infection). Alternatively, host-fed (with glycans) bacteria may be more ‘domesticated’ than some other pathobiont: in this scenario, fasting may actively select for more ‘docile’ bacteria. If true, nutritional support may be detrimental, as it denies the host the ability to modulate the intestinal environment.

There is also evidence to suggest that nutritional support may act as a fast-acting ‘phenotypic switch’ in the microbiota, soliciting a change in microbiome physiology independent of altered population composition. As an example, during sepsis, higher ethanol levels were observed in the urine of patients with poor prognosis [6]. Since ethanol is only derived from fermentation by gut biota (patients nutrition was controlled for 24 hours), it suggests that microbiome may impact on sepsis. Specifically, if the patients had not received nutritional support, there would not be the substrate for bacteria to ferment. So nutritional support can alt@er both the ‘phenotype’ of bacteria (e.g. allow them to ferment sugars if is available) and alter the intestinal ecosystem.

References

[4] N.M. Koropatkin, E.A. Cameron, E.C. Martens, How glycan metabolism shapes the human gut microbiota, Nat. Rev. Microbiol. (2012). doi:10.1038/nrmicro2746.

[5] K.D. Kohl, J. Amaya, C.A. Passement, M.D. Dearing, M.D. Mccue, Unique and shared responses of the gut microbiota to prolonged fasting: A comparative study across five classes of vertebrate hosts, FEMS Microbiol. Ecol. (2014). doi:10.1111/1574-6941.12442.

[6] M. Garcia-Simon, J.M. Morales, V. Modesto-Alapont, V. Gonzalez-Marrachelli, R. Vento-Rehues, A. Jorda-Miñana, J. Blanquer-Olivas, D. Monleon, Prognosis biomarkers of severe sepsis and septic shock by 1h NMR urine metabolomics in the intensive care unit, PLoS One. 10 (2015). doi:10.1371/journal.pone.0140993.

Dear Ben Martinez

Thank you for the kind word. I am going to be honest here: I don’t know enough of ketone bodies to have a very strong opinion about there role in cancer.

I suspect that cancer cells will probably be less able to utilise ketone bodies. This is because cancer cells often use aerobic glycolysis (i.e. ‘Warburg effect’) which use glucose. This glucose-dependant aerobic glycolysis is typical of cells that are in an anabolic state. (As an example, proliferating immune cells, as well as the developing foetus uses aerobic glycolysis).

But I am not sure enough to make any good claim. And cancer cells exhibit much more metabolic heterogeneity than the ‘Warburg effect’ so I don’t know.

It is an interesting question and I am planning on doing more intensive reading on ketone bodies some day. Fasting impact on so many things.

Thank you both, Ligen and Gustav, for the well thought and passionate discussion and science based explanation on the subject. Ligen Yu, your own experience and explanation regarding Anorexia Nervosa (AN) is definitely unorthodox in medical community and teaching that I am aware of and remember as a student. Like Gustav, I don't know enough regarding AN to make meaningful contribution in the subject. I've never treated AN patient before. Your latest explanation of AN makes a lot of sense and adds merit to the physiologic cause instead of psychological. Many diseases are multi-factorial and do not have clear-cut etiology which make treating them also require multiple disciplines. The "gut" as our second brain deserves more scrutiny and should be included when we think of our well-being. I'm of the camp who thinks that the mind has much more significant influence on us as human being as a whole which composes of both body and mind. We all are very similar biologically. What differentiate us is the way we think and the translation of what we think into our actions which have tremendous influence on our biology in terms of how we develop diseases. The placebo effects, in my opinion, is only one example of how the mind exerts control or at least shows connection with our physiology.

Thank you, Gustav van Niekerk. I'm thrilled to read your explanation regarding intermittent fasting. That's exactly the idea behind this whole "fasting" discussion. I have the same opinion and strategy as you described. I like your explanation and it makes perfect sense. Personally, I simply believe that most of our modern ailments are due to "over consumption" and "over indulgence". Some reduction and restriction would do both the body and the mind some good. I highly recommend your daily routine. It makes sense and practical. Thank you.

Dear Ben and Gustav

Thank you for reading my posts and your reply. As I am not a medical person by training, my knowledge on medical issues are limited. So my interpretation about AN may be wrong, or at least is not complete. Yet my experience of AN and my recovery from AN does tell me that there is some special physiological process controlling the AN patients, which I temporarily call it as sustained upregulated autophagy (SUA).

What fascinates me is that, in this dreadfull illness of AN, it might hides the solution for most of the medical conditions we are facing today. The physiological process (SUA?) that caused AN might also the ultimate solution of most of the infectious diseases, metabolic syndromes, degradation of organs, and some types of cancers. And what we are discussing now like fasting or restrictive eating are based on the development of this physiological process in our body. The full exploration of this physiological process can ensure everyone of us as human being to live an illness-free happy long (150-200 years?) life. And yes, protect our gut in good condition, as Ben pointed out, and regular restrictive eating, only eats the food that are necessary to maintain homeostasis of our body and our gut according to the requirement of this physiological process, might be the way leading all of us to such an illness-free long life.

Dear Gustav:

Thanks for recommending Randolph Nesse’s paper to me. I have also found one of his recent interesting book: “Good Reasons for Bad Feelings: Insights from the Frontier of Evolutionary Psychiatry”:

Book Good Reasons for Bad Feelings: Insights from the Frontier of...

I find that there is a lot of knowledge I need to learn, and I think our body and mind really have a lot of latent capacities need to be explored, so that we may use these latent capacity in a constructive way to benefit us.

I like the provocative proposal you mentioned regarding SUA, Ligen Yu.

Here are my questions that come to mind now:

-Can sustained upregulated autophagy (SUA) be achieved by intermittent fasting?

-What is the most efficient and practical regimen to do intermittent fasting? It may vary greatly depending on each individual preference and custom.

-Does any type of calorie restrictive (CR) diet or regimen being implemented in intermittent fasting cause the same result in autophagy as long as there's calorie restriction? In other words, does the source of energy matter whether it's from carbohydrates, proteins, or fats?

Dear Ben:

For your first question, the answer is no. SUA has to be coming naturally (my understanding). There is around 1% of the population have AN in young people, yet the percentage increases to 25% for people at the age of 65-75 (anorexia of aging):

Article Anorexia of Aging - An Updated Short Review

Anorexia of aging has the same detrimental effect like AN, but it will be even worse if the old people is force-feeding. They should eat-but-little like AN patients to maintain the homeostasis in the GIT mucosa and in the body.

The most efficient trigger of SUA is illness, which is inevitable for young people. Starvation is also one of the trigger of SUA, but it is not the stronger one. With the development of SUA, one becomes healthier if one eat the amount of food according to the requirement of SUA.

For IF, different people have different strategy, based on their daily life. I think it doesn't mater what we eat, as long as eating just enough food to support our body's needs, and has some time of serum starvation (autophagy) to remove all the ectopic fats from our organs. In the CR state, we are harvesting our nutrition and energy from the microbes like bacteria and virus by xenophagy, so it really doesn't matter if we are vegetarian or carnivorous, as our food is mainly feeding the microbes.

Thank you for your reply, Ligen Yu. I need to clarify my intention and purpose of my interest in discussing "fasting" as part of a healthy lifestyle such as sleep and exercise. We need food both for nutrition and enjoyment. So, prolonged fasting is neither achievable nor desirable. Fasting in a form of skipping a meal once in awhile such as breakfast as mentioned by Gustav which I personally would recommend is very achievable and tolerable. Maybe, instead of having the goal of living to be 150-200 years old to be achieved by "sustained up-regulated autophagy" (SUA), we should just aim to live to be 100-110 years old by "intermittent upregulated autophagy" created by "intermittent fasting". That way we still live longer and enjoy our food and life. Extremism usually has dire consequences and is very difficult to adapt. As a fellow human being and a physician, I always attempt to look at another person as a whole, both body and mind. Many times we only have the opportunity to see the outside of a person or the outcome and yet become arrogant enough to pass judgement. As an example, let's look at the population you mention, 65-75 years old, who develop anorexia of aging and become malnourished. The first reaction is to feed them properly to gain some nourishment. But, not many people would take the time and try to find out their "state of mind" because the mind stays hidden and can not be quantified. For many people, their mind will speak out through their body. It's great that we can study cells under microscope and learn everything there is to know about the cells. But, human beings are much more complex than those cells under microscope. We have "feelings" that occur in real life situations which can not be studied in the laboratory nor under microscope.

Regarding what we eat, of course, what we eat matters. We have evolved to be "omnivores". We can eat pretty much anything. But, through science and legitimate research, we now know enough how individual food category such as carbohydrate, fat, and protein gets digested in our body. So it's not just a matter of the amount of calories being consumed for our energy expenditure but more of how the energy is being supplied and in what form. In ketogenic diet for example where higher fat and animal protein are consumed, the body will rely some of its energy requirement from ketone bodies instead of glucose. The body's requirements for vitamins and minerals can't be neglected either. Very strict diets that avoid certain group of food may cause deficient in essential components that the body needs. One good example is vitamin B12. This is a very common clinical condition that can be a result from a poor diet alone. I like the saying "you are what you eat".

I believe intermittent upregulated autophagy can be achieved by intermittent fasting which is a very reasonable approach to a healthier lifestyle.

Dear Ben, You are right. Never go extreme. Moderate is always the right way. This is why I mention that SUA should be reached in a natural way, and don't try to push it. And IF is sufficient to keep away diseases and live a healthy and enjoyable life. I also agree with you that mind and body has very close interactions, but mind is more or less hidden.

Dear all

I am under extreme time contains and will not be able to contribute to this very interesting disusing. But a final note about extending the life span with food…

It is critical to distinguish between maximum and average life expectancy. It is comparatively easy to increase the average life span of a population: just prevent the death of people who would have died young (lifestyle, infection, drugs, accidents, homicide etc.). But it is much more difficult to increase the maximum life pan! This entail actually preventing the aging process (as appose to preventing death from disease or violent crime, accidents etc. which are challenges we actually already know how to address).

In fact, there is evidence that we have approach the limit of how long we can live (i.e. maximum life span): https://www.nature.com/articles/nature19793?draft=collection

The reason for this is because of there is very evolutionary pressure to life beyond ~40 years and almost non to life beyond 60. (I will explain why in the next paragraph). So, because there is no selective pressure to live for, say, 200 years, the phenotype “live for 200 years” is vestigial trait. Consequently, it is lost, just like we have lost the ability to synthesise vitamin C. (Briefly, our ancestors got enough vitamin C from their diet that they no longer needed to synthetises vitamin C, so there was no selective pressure to maintain the biosynthetic pathway. This is how some pseudogenes are formed). Another reason for a limit to our maximum lifespan is pleiotropic trade-offs between genes that make us life longer, and genes that make us have more offspring. As an example, a genetic network that causes you to be strong, healthy and appear physically attractive may predispose you to cancer.

Why do I claim there is no selective pressure to life beyond 60 years? The reason is because of the external mortality rate (EMR): our ancestors got infected with pathogens, eaten up by lion, fall of cliffs and killed each other in conflicts (anthropological studies have repeatedly shown that humans males are extremely violent – Steven Pinker eloquently point this out in Blank Slate: The Modern Denial of Human Nature). In short, stuff out side of our body kills us. So, there is no point in having the ability to life for 200 years, because virtually no one in our evolutionary history would live this long –because of the EMR. We also observe this in other animals. As an example, flight is amazing way of limiting your external mortality rate because it helps you escape predators effectively: consequently, birds tend to life rather long lives (compared to other animals). Mice on the other hand face really high level of ‘external mortality’ and also have short lives.

*Also see “disposable soma theory of aging”

*Any form of caloric restriction must not ever induce micronutrient depletion –supplement if you have.

*Yes, we are omnivores, but keep in mind that the daily minimum requirement for carbohydrates is exactly zero. We don’t need sugar/starch in our diet!

*There is more to living long than just rejuvenating your body through cycles of catabolism and anabolism. Highly processed food are poison! But I don’t have time to explain…

Fascinating and very sobering explanation about our evolutionary lifespan. Very well done and well thought! Thank you very much for your contribution in this discussion, Gustav van Niekerk. Obviously, you're a scientist with great mind who uses science not only to print textbooks but rather to apply the good knowledge into everyday practical application that all of us can learn and follow.

I agree with your analysis regarding human lifespan. The average human lifespan can be increased by all of those things you already mentioned including interventions by governments. The maximum lifespan, however, relies on the body's own aging process. Excellent point, Gustav. In the U.S, some people in their 30s have already shown some signs of wear and tear and already required medical intervention. By the time in their 40s and 50s, many will already have established medical diagnosis that require lifelong intervention to stay alive. Modern medicine has afforded the temporary artificial prolongation of life. We have discovered and invented many formulas and ways to combat diseases but not the aging process itself. People are now living with deadly diseases such as cancers, HIV and hepatitis infections, heart and neurological diseases etc because of our modern medical knowledge which may contribute to the pervasive "cure" attitude instead of "prevention". We want to cure diseases instead of wanting to learn to avoid getting diseases.

Yes, processed food is not good for health. Having said that, unfortunately, processed food has become the new mutated DNA in our human culture. Modern life can not and will not eliminate processed food. It is ingrained in the fabric of modern life both economically and culturally. Even though it's impossible to eliminate processed food in our life, "knowledge is still king and moderation can be the rule". A good diet is diet that derives all of its ingredients naturally using whole foods.

Dear Gustav, Thank you for joining the discussion, and hope that you can visit this discussion again when you have spare time. You posts are all very knowledgeable, and I have really learned a lot from your posts. Although we might have different views about some issue, I will say that it is normal, as I fully believes in that our bodies are quite adaptive and can accommodate different, even controversial practices and still get the same healthy result.

Yet, I might respectfully disagree with your attitude to carbohydrates. Our body may don't need carbohydrates, but don't forget that the mucosa in our gastrointestinal tract consists mainly glycoproteins, and they are replaced and regenerated every 3-5 days because of the wear and tear of food digestion. So minimum amount of carbohydrates are essential for the homeostasis of our GIT mucosa.

If I'm not mistaken, agriculture has only been around for the last 10,000 years or so. Agriculture was invented as an alternative and more convenient food source. Prior to agriculture, humans were mainly hunters and gatherers for millions of years. Agriculture comes with very heavy price tag and burden to mother nature and earth as a whole. Adaptation has always been the key to survival. Humans have adapted to very heavy carbohydrate diet ever since the invention of agriculture and the recent commercialization of processed food heavy in carbs. Organic animal fat and protein are much more expensive than plant based food. It's much cheaper to feed the explosion in population growth with carbohydrates. The body can get its energy source purely from animal fat and protein. The body may need some micronutrients such as vitamins and minerals from other source but not its energy requirement.

Dear Ben, thank you for your explanation of the hunters and gatherers diet. I have no knowledge about this. I think you are right. Our gastric acid is designed to digest proteins, this means that the hunters and gatherers diet is more suitable for us, and high carbohydrates may not good for us.

Yet the GIT mucosa is special. It is a barrier between our stomach wall and the gastric acid. Without it, the gastric acid will digest our stomach (protein), just as what happened when one has gut ulcers.

So no matter what diet we adopt, minimal amount of carbohydrates are essential for GIT mucosa.

The key thing here, Ligen, is moderation and to know what's good and what's not. There's too much hype and commercialization out there not to mention "lies" that are being told through bogus research. Remember a few decades ago about "margarine" ? Well, that's just one example of the hype that turns out to be bad for you. I couldn't a agree more with Gustav regarding the 3 meal a day concept. Who started the idea that we had to eat 3 meals a day? Why do we have to eat before we start the day? Instead, we should use up the stored energy before we eat again. When we constantly eat, our body is also being put in constant anabolic state which easily explains the obesity epidemic. We constantly eat throughout the day and don't exercise. As Gustav mentioned, the anabolic and catabolic states should compliment each other and work in harmony. I always remember the bone metabolism from my student days. To keep the bone strong and healthy, "it has to be destroyed (catabolic state)" by means of exercises so it can be rebuilt (anabolic state). Without exercises, the aging process will dominate and rebuilding will not occur.

Dear Ben, I like your example of bone metabolism. To me, it is a good example of the self-healing capacity of our body. By destroy-rebuilt, our bone can be kept strong and healthy. During the process, up-regulated autophagy is involved. Not only our bone, virtually all our organ has this self-healing capacity. All illness will trigger up-regulated autophagy, and by triggering up-regulated autophagy, Our body means that it can cure its illness by itself.

Back to your previous saying that "in the U.S, some people in their 30s have already shown some signs of wear and tear and already required medical intervention. By the time in their 40s and 50s, many will already have established medical diagnosis that require lifelong intervention to stay alive." To be ill is a bad news for everybody. But, it is actually a good chance for the person to make change, and change to the good. Any sign of wear and tear is a clear sign that this person is over-eating, as the illness induced anorexia, or up-regulated autophagy already provide enough nutrition to that person, and by reducing the food intake according to the degree of his up-regulated autophagy (or SUA, as I put it), this person should be able to recover from the illness, and become stronger and healthier. And he should not develop his illness into lifelong one that need medical intervention, if he eat properly. To my understanding, one person should be much healthier when he is aging, as SUA will naturally develop with aging (because we cannot avoid illness like infection and inflammation, as our environment has plenty of bacteria and viruses, which is strong trigger of SUA, and SUA will naturally bring us back to health). This is our body's destroy-rebuilt mode of keeping us in health.

You are right, the key point is doing everything in moderation and to know what's good and what's not. Yet, this point of moderation is rather very difficult to find, try and error is necessary. And as researcher, we need to understand the value of "multiple hypotheses", as proposed by T.C. Chamberlain in 1897:

http://www.mantleplumes.org/WebDocuments/Chamberlin1897.pdf

we should never assume that we have found the final answer. So always remain open to the possibility that we may wrong, and be prepared (and happy) to hear an alternative theory.

For overweight and obese, the situation is rather very complicated. We may not simply label it as an epidemic. I have started a new discussion:

https://www.researchgate.net/post/Obesity_is_an_overblown_epidemic_What_is_your_opinion

You may have a look if you are interested.

Thank you, Ligen. You've always managed to arouse my curiosity by expressing your opinion and thought. I neither have the intelligence nor the confidence to ever claim that I have the answer for anything. However, I'd rather learn from other people's mistakes than make the mistakes myself. There's no final answer that will fit and satisfy everyone for truth is nothing but one's own illusion or perception. My truth may be completely different from your truth.

Back to the subject of being ill. Yes, I agree. Common sense would dictate that when you make a mistake or when something goes wrong in life such as falling ill, you would learn from your mistake and try to change the way you do things or at least learn not to repeat the same mistake. Common sense would do as you say when you fall ill, i.e, it's the chance to change your life for the better. You would be very surprised if I tell you, that in reality not very many people choose to follow common sense. Why is that? The answer to that is very complex because this is when the mind will take control and rationalize your action. It's back to the mind again. Children that are born healthy should also grow old healthy. Healthy lion cubs will most likely grow old healthy unless they're injured or killed by external force. Why do we have so many human diseases as we grow older. Part of the answer is the many options that the brain has to choose in how to live our lives. We all have the same biology, but as you can see all around you, the results vary tremendously. Why? It's because our mind is not uniform. I know it's a difficult concept to visualize, but the mind is what differentiate us all and not our phenotypical appearances. It's the mind that defines us as individuals. The appearance is the cover-up. This is why I'm interested in the placebo effects as the result of our mind.

Ye, I will look forward to your discussion regarding obesity. Thanks.

Dear Ben, I gradually understand what you mean by saying that mind controls body. There is something deep in my mind which become my subconscious and which is irrational, I think health is a faith. Put it in simple words, if one think he is healthy, he will be healthy. Saint Augustine had a good saying: "Faith is to believe what you do not see; the reward of this faith is to see what you believe".

I firmly believe in that I am healthy, and any illness is temporary, and my body will somehow bring me back to health when illness does occur. Because of this belief, my attitude to medicine is negative. Although I will visit a doctor when I fell ill, I only ask the doctor to see how serious my illness is, but not really follow all the instructions from the doctor. You may find the following news report interesting:

https://cityroom.blogs.nytimes.com/2012/09/24/lessons-of-107-birthdays-dont-exercise-avoid-medicine-and-never-look-back/

This report shows that how important to think positively.

Thank you, Ligen Yu. I think you got me all wrong, or at least, you misunderstood me. I agree that positive thinking is beneficial compared to negative thinking. Health and faith are two completely different things. Health is tangible and is not a "belief". Faith is unquestioning belief which doesn't require any proof or evidence. I'm not here to change anybody's belief or faith. I'm here to discuss science based proof that intermittent fasting has many health benefits and may be considered as a healthy lifestyle. The brain or the mind does indeed have a very significant impact on the human body, but it's very far fetched if not a complete sham to think that the mind has some telepathic power to control anything outside the neuroendocrine system or the psycho-physiological process. Medicine has done wonders to relieve human suffering and to increase the quality of life. If anybody doesn't think that, well it's his or her prerogative. There are too many anecdotal stories and evidences out there about almost any subject. Exceptions and unusual occurrences are not science. Science is when things can be faithfully repeated over and over again with the same result regardless. I've known and seen smokers that lived into their eighties. I've seen people that drink moderate alcohol every single day in their adult life and hardly ever get sick. I have witnessed a poor person in his late eighties with very poor diet consisting mainly of processed foods, and the only thing that's wrong with him is his increased cholesterol. And so on and so on.... Let's discuss science and not anecdotal stories.

What are humans left with without the mind? We're left with pretty much nothing. The mind defines of who we are as individuals. How to use the mind depends on each individual person for better or worse depending on the outcome of the decision made. As this discussion has revealed, intermittent fasting is based on science and not "belief" or "faith" as some people may suggest. The science behind autophagy is probably one of the most compelling reasons to support the practice. It is important to keep in mind that I don't think this is the "magic bullet" or the "fountain of youth" many people are hoping. As Gustav has already pointed out that the maximum human lifespan is nearing its limit and the natural aging process will ultimately triumph and put a lid to our maximum longevity. Intermittent fasting can be used as a simple tool in conjunction with a healthy mind through positive attitude to increase the quality and enjoyment of life with fewer setback due illness.

Dear Ben:

Thank you very much for your frankness in presenting your opinion. Obviously, we have different views on some topics. And it is such dispute that helps me think more and learn more. So I really appreciate your views which are different from that of mine.

Now for Faith and Science, I don't see any conflict between two of them. Maybe I can explain my view a bit more on the power of faith. When one firmly and irrationally believes in something, such faith will give the person a peaceful and calm mind. According to Dr David R Hawkins, our human consciousness has 17 levels, and everyone of us is staying in one level of them: shame, guilt, apathy, grief, fear, desire, anger, pride, courage, neutrality, willingness, acceptance, reason, love, joy, peace, enlightenment:

https://karendevine.co.uk/2497-2/

It really doesn't matter if the faith itself is right or wrong, the faith will bring the person directly from any level to the level of peace. When one feels safe and relax in peace, his body will automatically perform the self-healing capacity. And with peace of mind, one will make more correct decisions, which is also beneficial to one's health.

But we cannot take science as a belief or faith, as scientific skepticism is the spirit of science. Falsifiability, according to Karl Popper, defines the inherent testability of any scientific hypothesis, and science advances itself by falsification of old theories.

Also, there are so many different and controversial theories about the same topic. Take fasting and dieting as an example, "fasting is good", "fasting will not help to loss weight in long term", "dieting is good for health", "dieting makes you fat", ... All these claims are supported by scientific research, and if one follows all these claims, he will soon be totally lost.

Thank you, Ligen Yu, for your openness and tolerance. Like yourself, I too welcome different opinions and thoughts for they will enrich my knowledge and maybe even add a grain of wisdom to the life journey.

"Science" is the only thing I know that ever comes close the "absolute truth" that exists in our world without too much interference or adulteration due to other motives such as political or prejudices. There are too many claims, theories, hypothesis, etc that are not backed by real science. A lot of medical information such as being mentioned in your response above ("fasting is good", dieting makes you fat", etc) is merely the result of meta analysis and is hardly science at all. It is, however, attention grabber and sells a lot of newspapers and magazines. The result of the meta analysis should just be the beginning of a theory that needs to be proven and repeated to make it valid. Unfortunately, too many of the claims and meta analysis are just that, bunch of claims without scientific proof or able to be faithfully repeated when tested. Real science is not based on faith, but it's based on "facts" alone. However, even "facts" and "truth" could be different for different people. Truth could be viewed as merely the perception that a person interprets in his mind. To most adults, a magic trick is just a magic trick and not real. To young innocent children, the magic trick is as real and true as anything they've ever seen or experienced. So who is right? The adults know better because of the memory and experience in their mind. The children's mind, however, really believes that the magic trick is indeed real because their brain can only interpret what it perceives as being real and true. It's the same with countless things in life. The truth is only as true as the person's perception that his or her brain allows him or her to think.

Relax and peaceful mind has some healing capacity is mentioned in your response above. This is interesting because I've brought up the subject regarding the placebo effects and effects of positive thinking and attitude on the body's healing process. However, the validity and practical application of this mind bending idea is still yet to be explained and proven.

This is a response to Ligen Yu's "human consciousness" according to Dr. Hawkins. I have proposed a discussion regarding the effects of the mind through the placebo effects which could be seen as an example of the connection between the mind and body. Though the connection with no doubt exists, the details and how the connection works and how it can benefit and improve our overall health are worth more scrutiny and deserve more study. It's not enough to have the "faith" that "peaceful" mind has healing capacity. Real life is not that simple. What is peaceful mind anyway? No worries? That's impossible.

In dementia, the data that's stored in our brain is being lost or erased. If the data in our memory cells in the brain is completely wiped out, what will happen? We're left with a body with no brain which basically translates into nonexistence as far as being a human being is concerned.

Artificial Intelligence is currently still in its infancy in its evolution. The infant will soon have more data and and more memory cells to process more complex situation similar to a human baby accumulates more information and grows his brain capacity. The baby will grow and continue to accumulate, and to process, and to learn as time passes together with his level of cognition and intelligence. The consciousness being mentioned by Ligen from shame, guilt...to love, joy and peace is the result of our cognition and intelligence in using an digesting all of the data and information stored in our brain. Maybe, it's too far-fetched to imagine a robot to feel apathy and love, but why not if the robot is equipped with the same brain. Currently, the robot does not have enough data and capacity to act like human, but how does a person with severe dementia act? Like a robot? The significant difference between human and robot is the data and memory cells that each has. If artificial intelligence in a robot can posses the same amount of data and memory cells as a human brain, why can't a robot possess the same kind of consciousness and experience apathy, love, peace, etc? Medical practice will soon change rather drastically. According to one estimate as an example, images from Xrays to MRI etc being read by radiologists have about 30% rate of errors compared to 1% read by artificial intelligence or computer. If a human baby can grow to experience apathy and love through the memory stored in the brain, why can't artificial intelligence do the same?

Dear Ben, thank you for your reply. I'm thinking how to define our "mind". It is obvious that our mind is not constrained within our brain. Some of our skills like bicycle riding and swimming are remembered by our body and muscles. Besides the conscious, subconscious and unconscious part of our mind, we may also include the spontaneous adaptation and self-organisation of our cells into our mind in a broad way. Or at least regard them as a primitive form of "mind", as these adaptation abilities are directly linked to our body and its well-being.

Yet, even if we have a clear idea of what our mind is, given the complexity nature of our body, we may not able to find out how mind interact with body, as there are so many known or unknown varying parameters besides our mind contributing our health, and we are not able to isolate them.

So as what I have proposed in the other post, it is more practical to find out what are the essential conditions for our health, then just focus on these essential conditions, and leave all other matter to our body itself.

In my own case, as my body has already adapted to the Luigi Cornaro diet, I can make sure that my gastrointestinal tract is protected in good condition, and my body can take care of itself with the help of SUA. So I don't need to worry about illness anymore.

Thank you, Ligen Yu. I agree with the notion that we need to look at health in a big picture before the individual problem could be tackled. The cross current and complex interaction among all the parts in a person are the reasons of "replication crisis" which causes treatment failure. As much as I like the idea of intermittent fasting as a healthy lifestyle, I am sure intermittent fasting can not be applied to everybody.

Here's an anonymous email I received to be added to this discussion. Thank you for the contribution.

Dear Ben,

Based upon my experience, Western people depend on science which has hypothesis or theories that prove visible.  I have no doubt that Western people develop science that enhances people’s lives through scientific means.  Moreover, I agree with you that "Science is the only thing I know that ever comes close to the ‘absolute truth’ that exists in our world without too much interference or adulteration due to other motives such as political or prejudices.”  However, science is a very small part in the universe.  For example, the terminal cancer patient you mentioned in your other writing about a "miracle" in making a full recovery from the terminal cancer was a "miracle" which cannot be proved by science because no one builds any theory or hypothesis yet.  If there is not any scientific proof, shall we deny the miracle? 

Dr. Ligen Yu says, “any illness is temporary, and my body will somehow bring me back to health when illness does occur. Because of this belief, my attitude to medicine is negative.”  I heard people’s talks like Dr. Yu’s when I was young.  I felt fatalism of Asian culture instead of his negative mind against medicine.  Many Asian people accept the four phases of life (birth, old age, sickness, and death) as an unavoidable fate in human being’s life.  Thus, if a person has the fate of a long life, he/she will recover his/her health from a serious illness, and vice versa.

Anyway, I found an exciting answer that, “Gustav has already pointed out that the maximum human lifespan is nearing its limit and the natural aging process will ultimately triumph and put a lid to our maximum longevity.”  Today, medical teams replace some parts of patients’ bodies to treat illnesses then finally extend patients’ lives.  However, people will be completely defeated by the natural aging process, Gustav says.  My idea is that people can live forever if people invent technology of which people’s memories can be copied and transferred.  Think how to define a figure as "I"!  After "I" undergoes plastic surgeries and changes all clothes to wear, the figure is still "I" because of memories.  Even though "I" was a trans-gendered prior to the surgeries, the new figure is still "I" because of the memories.  If so, the memories can be copied then pasted in another young healthy figure.  The figure will become "I"; it will be the veritable biotechnology.  How do you think about my idea as a doctor?

Dear Ben, thank you for posting the email from one of the readers. Appreciate that he read my post in such a detail. He is right that my thoughts has big influence from Buddism, yet, my attitude is more close to therapeutic nihilism, not fatalism:

https://en.m.wikipedia.org/wiki/Therapeutic_nihilism

The difference is that, in my opinion, one phase of life stated in Buddism, the sickness, can be eliminated by our efforts, everyone of us as human being can live an illness-free happy long life with the help of our own self-healing capacity in our body, and medicine is not a necessity for human being.

That may be too extreme to think that no medicine or no intervention is needed. Human beings are too weak not to have medicine man with his "super natural" power and his special concoction to heal illnesses. How about spirituality and its healing power? Can the belief alone heal the body? Is it placebo effect?

Dear Ben, yes, your are right. My opinion may go to the extreme. We need to consider that everyone is different. Although all of us potentially have this self-healing capacity (with up-regulated autophagy as its main component), this evolutionarily conserved biological mechanism is not coming naturally, and needs some proper stimulation for it to come into functioning. Spirituality may play some limited role, but eventually it is the physiological mechanism that works. Without the substantial biological existence, mind can do nothing.

Dear Ben, I think I have my answer for the placebo effect: it shows the negative effect of our mind to our health.

Human being are irrational, and our reasoning is only a very small part of our minds. As the book of Randolph Nesse says:

Book Good Reasons for Bad Feelings: Insights from the Frontier of...

our minds have a negative bias:

https://www.psychologytoday.com/us/blog/changepower/201610/8-things-you-didnt-know-about-your-mind

Such negative bias is good for us to survive in harsh environment, as optimists are more easily captured by predators, but is detrimental to our health.

We tend to not believe ourselves, but have great faith about hospital and doctors. In hospitals, the patients feel more safe and can be more relax, so the negative effect of our mind is minimum, and the placebo effect works.

That's exactly the point that everybody is different and that "extremism" does not work for the average. If you look at the bell curve, the overwhelming majority fall outside the two opposite extremes. Spirituality actually plays a very important role in most people's lives. In extreme cases, there are numerous examples that clearly show and prove that the state of mind in spirituality does exert control over the body. In many religious ceremonies or events, the obsession that is the result of spiritual belief is transformed into mind boggling feats or acts. How does a person walk on burning coals without being burnt? How does the skin and flesh being penetrated by sharp metals not bleed and endure the pain, etc, etc? The body is obviously producing some counteract measures such as the release of hormones, chemicals, etc to produce such tremendous result but is being controlled and directed by the brain and mind.

Dear Ben, you are right. Life is full of miracles that may not easy to be explained by the limited current scientific theories. Yet in the future we may find the scientific answer to these miracles.

If we pay attention, we may find such miracles in daily life. When cooked seeds will decay in few days at room temperature, living seeds can survive for years in room temperature, some of them can survive over a thousand years under cold dry environment, which is much long-living than any human beings. What make it a miracle is that, a seed is an open system, and it is "communicating" with its environment in every seconds, and it will germinate when the environmental condition permits!

Science is just it, science. Science can not and will not explain everything that occurs in nature. Science may be able to explain certain aspect of spirituality such as how the mind may influence the body as what I have been trying to articulate here. However, science should not be used indiscriminately to force or to change the natural world according to what we want or desire. On the other hand, we should use and learn from nature to enhance our understanding of science and its proper application. Instead of trying to completely change or force nature, we should work in harmony with nature only to modify for life adaptation. Things that occur harmoniously in nature usually follow certain rules such as can be seen in Fibonacci number, sequence, and ratio which occur abundantly in our natural world, and it's just the way things are. So to try to change what's naturally occurring could be futile.

I'm fond of numbers and mathematics for many things in nature can be formulated into mathematical equations. Numbers can be used to explain many things in nature. I know it's not the exact topic of the discussion, but knowledge is indiscriminate and should be applied accordingly and when appropriate. The Fibonacci number that occurs in biological setting can be used as an example of how some things in nature can work so harmoniously without any detail scientific explanation. They're just like that and they work according to the original creation.

There are certain things in life that just happen. Humans have evolved to learn and gain knowledge to conquer nature. We should instead learn and work together with nature. Obesity from over-consumption could become a health problem when the homeostasis within the body's organ system is not maintained, but this could happen to anybody, thin or fat. Obesity is a multi-factorial problem that needs to be addressed accordingly and individually. The key thing in treating any disease successfully is to find what works for that certain individual. To try to change what seems natural in someone who has the natural tendency to be obese either behaviorally or biologically will be almost impossible without severe setbacks or side effects. Just like the Fibonacci number that occurs in nature, obesity within certain parameter could be part of our natural modern world and should not always be corrected to fit the so called norm. What is normal anyway? Who defines normal?

Agree that we can only follow the natural laws, not do anything aginst it. Any effort to conquer nature will not be successful. In stead, we need to learn to live harmonically with nature. And yes, obesity is a very complicated medical condition which has no easy solution.

For obesity, there are both protective and destructive features associated with it. So it is important to find a balance between these features and avoid the destructive consequences, but not try to eliminate all these features.

What I was implying was that there may be nothing wrong with some obese people. The same can be said with some people with "ideal" weight who could actually be sick underneath the all perfect appearance. We like to label and generalize everything. "Fat people" don't look good and healthy, therefore, there must be something wrong with "fat people". People that look "fit" look good and healthy, therefore, there's nothing wrong with them. Biology and nature are not that simple and do not work that way.

I received some email asking me the best intermittent fasting regimen that they can follow.

I don't think there's one best or correct way to do intermittent fasting (IF). I've seen and heard many different variations. Here are some that I've seen and thought :

- fast for 15-16 hours a day simply by skipping breakfast everyday, every other day, or every day except the weekend.

- normal breakfast and lunch but no dinner or very little dinner.

-24-36 hour fasting once or twice a month.

-24 hour fasting once a week.

-etc....

The most important key takeaway is to learn about your body and system and to know which one that works and which one doesn't. Remember that everybody is different. We should learn and know about our own system. People that are living with certain conditions such as diabetes or heart diseases need to pay very special attention and should be under the supervision of their physicians before they decide to alter their diets. Some condition such as diabetes, for example, requires very close monitoring of the glucose level to avoid very bad consequences or even death. Intermittent fasting could be a healthy lifestyle to certain people, but like everything in life, IF may not be good for everybody.

Another important key takeaway from the discussion so far, and I would like to thank everybody for participating and reading my discussion, is that there's some real science and evidence to show that "fasting" triggers many beneficial biological processes that are unique and innate to our system. Intermittent fasting may be one of the answers to our modern disease epidemic derived from over-consumption. Intermittent fasting may unlock the mystery behind longevity.

Dear Ben, I just came across the following paper dealing with complexity science and homeopathy by Prof Paolo Bellavite:

Article Complexity science and homeopathy: A synthetic overview

I suspect that medical science is much more complex than any theory in complex science can describe.

Thank you, everybody, for participating and reading this very interesting topic of discussion. I have learned a lot and gained some knowledge by interacting with everybody and by always keeping an open mind to any theory or possibility. Science is indeed vast and does not always have to be exact especially medical science where real people's lives are at stakes. I would like to continue to be engaged in any medical science topic and hope that we can live life with optimal health and highest quality.

I now would like to summarize what has been discussed so far. It may take me some time, but I will start now.

1) Calorie restriction in the form of Intermittent Fasting (IF) may reduce oxidative stress from free radicals and inflammation by switching the body energy source from glucose to fatty acids through the utilization of body's own fat cells. This switch to fatty acids have many beneficial health benefits from weight loss in overweight individuals to better glucose control in people with metabolic syndrome such as diabetes.

2) Although it is not uniformly and scientifically explained, fasting has been practiced and a part of the way we live since ancient civilizations and religious practices from the Mayan and the Greek to the Hindu and the modern day Muslim and Christian.

3) Hunger or "feeling hungry" may not all be due to physiological response to the need for more food to generate more energy, but "feeling hungry" is the result of the brain's, specifically the hypothalamus, interpretation of very complex computation of our own behavior and habits. Why do we get hungry at certain times of the day? Is it really that the body needs more fuel? Or is it because of habitual behavior which alerts the body's complex and sophisticated neurocircuitry to sense everything from an empty stomach to the taste of food which lead to anticipation of food? Maybe, the hypothalamus is wrong in triggering the hunger feeling because it is more psychological need than physiological need for more food to nourish the body. In healthy people, skipping a meal will cause an acute sensation or feeling of great desire for food. However as time passes, the hunger feeling will dissipate and eventually disappear without any adverse consequences to the body. From this simple argument, I would like to conclude that eating 3 meals a day is not necessarily a physiological response, and intermittent fasting by skipping a meal from time to time is a good practice both for the body and mind by controlling the amount of calories being consumed and controlling our desire for food psychologically. After all, we're able to control many other desires, why not the desire for food every now and then?