FASTING AND HUMAN BRAIN

As many of you know, as people are getting older, there have been advances in the cancer research cardiovascular disease research many people who would have died in their 50s and 60s from those diseases are living in the danger zone for Alzheimer's and Parkinson's disease. It is projected that by 2050 the number of people with Alzheimer's disease will triple from what it is today. It is 5 million today and it will be 15 million by 2050. In Mark Mattson's lab who is the chief of the laboratory of Neuroscience at National Institute on Aging and he is also a professor of neuroscience at the Johns Hopkins University, they use a number of different animal models that are relevant to age-related neurodegenerative disorders. They have mice that accumulate amyloid in their brain as they get older and they have learning and memory problems. They also have mice that have damage to dopamine-producing neurons that control body movements that is Mylo -Parkinson's disease. They also have models of stroke, which is again another major-rat problem and cause of death. It has been known for a long time that one way to extend the life Spain of laboratory animals is simply to reduce their energy intake. In rats and mice, one can increase there lifespan by 30 or 40 %. Through Mark Mattson's research, I started looking at the effect of energy restriction on the brain in the context of age-related neurodegenerative disorders and found that we could slow down, for example, the abnormal accumulation of amyloid or the degeneration of dopamine neurons in the Alzheimer's and Parkinson's may by reducing energy intake. Now there are a number of ways you can reduce energy intake. You can simply eat less at each meal or you can do what we call intermittent fasting, So reduce the frequency of the meals. What I am going to tell you now is that fasting does good things for the brain. In the animals, researchers have insight into a lot of the neurochemical changes that are occurring in the brain that I think explain why fasting is good for the brain. But I am going to start out and talk a little bit about anecdotal evidence that fasting is good for the brain and also evolutionary perspective on why fasting might be good for the brain. Everybody knows that in Islamic religion people will fast periodically, down through history many famous people with good brains have fasted regularly like Plato, he fast for greater physical and mental efficiency.

Upon the top here Is a quote from Plato, he fasted for grater physical and mental efficiency. There are few quotes in the picture including one from about 6000 years ago an Egyptian pyramid inscription that says " Humans live on one-quarter of what they eat and on the other three-quarters live there doctors". In the present time as you know being overweight is a big problem. It is not only a risk factor for cardiovascular disease and diabetes, certain cancers but emerging evidence suggests that it is also a risk factor for age-related cognitive impairment and possibly Alzheimer's disease, in the lower right of above picture there is a reference to a book written over a hundred years ago by Upton Sinclair. Many of you may know Upton Sinclair is the author of " The Jungle "a book on meat packing industry but he also wrote and published the book that you can find in the full text online called " The Fasting Cure". In that book he interviews 250 people who had some ailment and went on fast for various lengths of time and expect in a handful of cases, their health condition improved.

Before I focus on the brain which will be main part of my talk, I just want to point out that there is evidence not just from animals but from humans as well that fasting is good for body.

It will reduce inflammation , it will reduce oxidative stress in organ system throughout the body and one thing that happens when you fast that does not happen when you eat three meals a day, is that your energy metabolism shifts so that you start burning fats. Every time you eat a meal the energy goes into liver and it's stored in the form of glycogen and that is always tapped into first. It takes about 10 -12 hours before you deplete the glycogen stores in your liver. So if you eat three meals a day you never deplete the glycogen stores in your liver although If you exercise you can. Once you deplete the glycogen stores in your liver then you start burning fats and you produce what are called ketone bodies. It turns out ketone bodies are very good for your brain and I will talk about in a bit. Researchers like Mark Mattson have done a lot of work on animals in the 90s between 15 and 20 year ago showing that intermittent fasting was good for the brain. Then they started collaborating with some investigators did some human studies looking at effects on the body. Then a producer at the BCC named Michael Mosley made a program on intermittent fasting that was aired on the BBC, it has been aired on PBS he wrote a book called "The Fast Diet ". Just in the last two years, there has been a flurry of books on intermittent fasting for health and it is becoming what I think some people may think its a fad. What do I mean by intermittent fasting and intermittent energy restriction? there is a lot of variations that there've been on used on this. One sorta harsh one is every other day only eat 500 calories. In human studies, researchers have been doing what's called the 5:2 diet.

Where two days a week you only eat 500 calories, the other 5 days you eat normally, Eat healthy if you can. The book called "Eight-hour diet ", there is evidence that if you restrict the time window that you eat each day to eight or less hours. It will have health benefits again that is long enough to shift the energy metabolism. Why does fasting bolster brain power?

During the development of your brain, but also in the adult neurons are generated from stem cells. They grow out there axons and dendrites they form connections with each other -synapses and communication with each other. During Aging many people their brain ages successfully, they stay cognitively intact, whereas unfortunately others develop a disease. We think the reason the main take-home message of this talk is that fasting is a challenge to your brain and your brain responds to that challenge of not having food by activating adaptive stress response pathways that help your brain cope with stress and resist disease. Anything we talk about in Biology we always have to ask the questions, why is it that way? Why when we take animals and put them on an intermittent fasting diet are there neurons protected in mice of Alzheimer's and Parkinson's disease? Why do they perform better when researchers test their learning and memory? it amazes, well if you're hungry and haven't found food you better figure out how to find food. You don't want your brain to shut down if you're Hungary.In fact, that is what researchers find in the animals. Nerve cell circuits are more active. Some of the changes that occur with intermitting fasting also occur with vigorous exercise. When we start looking at what are the changes in the brain with intermittent fasting, they are very similar to exercise. Exercise and intermittent fasting both increase the production of proteins in the pain that are called neurotrophic factors. Researchers discovered this many years ago back they found that neurotrophic factors such as FGF and one called BDNF-brain-derived neurotrophic factors promote the growth of neurons, promote the condition of the neurons and the strengthening in synapses.Now here is the idea,

  Challenges to your brain whether it is intermittent fasting, vigorous exercise or what you are doing now hopefully if you haven't fallen asleep while reading my blog, is cognitive challenges, When this happened neurocircuits are activated levels of neurotrophic factors such as BNF increases that promote the growth of the. Neurons, the formation, and strengthening of synapses. It turns out both exercise and intermittent fasting and using your neurons, using your brain can increase the production of new nerve cells from stem cells at least in one region of your brain called the hippocampus which is shown in the picture above. I mentioned ketones which come from burning fat and that happens during fasting. The Romans discovered ketones even though they had no idea, they haven't taken any chemistry course or didn't know what it was. People with epileptic seizures back then, they thought they were possessed by demons and they found if they take these people and shut them in a room and don't feed them the demons will go away. What is happening is ketones go up and it is well-known fact that ketenes suppress seizures and in fact, ketogenic diets are used to treat, even today patients with severe epilepsy. By Studying researches and books , trying to understand why ketones are good for neurons. One reason is they provide an alternative fuel for the neurons, they boost the energy levels in neurons. Recently Mark Mattson and his group discovered that fasting, by increasing BDNF levels in the brain as a neurotrophic factor can increase the number of mitochondria in your nerve cells.

I am not going to go in details of this slide here but the mechanism is very similar to the mechanism whereby exercising your muscles increase the number of mitochondria in your muscles. The fasting is a mild energetic stress and the neurons respond adaptively by increasing mitochondria which helps them produce more energy. researchers have recently shown that by increasing the number of mitochondria in neurons can increase the ability of the neurons to form and maintain synapses and thereby increase learning and memory ability. In addition to the increasing neurotrophic factors and increasing neuronal bioenergetics researchers have found that intermittent fasting will enhance the ability of your never cells to repair DNA,

so right now and also probably exercise and also intellectual challenges, again what is happening in this case when you are using your neurons, exercising your neurons it causes a mild oxidative stress, at the same time that there is increased oxidative stress the cells are enhancing their ability to repair oxidative damages to DNA. Why is that a normal diet is three meals a day plus snacks? It isn't that it is the healthiest way eating pattern and that is my opinion, but I think there's a lot of evidence to support that. There are a lot of pressures to have that eating pattern. There is a lot of money involved. The food industry are they going to make money from skipping breakfast , no they are going to lose money .if people fasts the food industry loses money .what about the pharmaceutical industries ?what if people do some intermittent fasting and exercise periodically and they are very healthy ?is the farm acoustical industry going to make any money on healthy people ? So one challenge for society is that communication is the way to improve health. People understanding what they can do to improve their health and then taking action. So I would urge to communicate and spread the word that there are ways for people to be healthy. Try it out ...what I found in the human studies though is, it is kind of exercise , if you never exercise before and you go and run 3 miles you are not going to feel good, if you eat three meals a day and of a sudden you go all day not eating anything that day you are going to feel irritable and ornery and so on..but it turns out if you can kind of force yourself to do that , maybe one day a week for a month and then two days a week , you get used to it and after a month or two many people can adapt to that kind of diet with no problem and you will find that on the days when you don't eat so much you are more productive .