The Healing Power Of Fasting For Cellular Repair

William Hsu, MD

Dr. Simmons, thank you so much for having me on your show.

Jennifer Simmons, MD

Yes, I am so delighted to have you here, because this audience needs to hear from you, and they need the information that you have at your fingertips. Let us first start with; I talk about all the time that breast cancer is a metabolic disease. Can you talk about what is happening from a metabolic standpoint in terms of cancer promotion, cancer growth, and that thing?

William Hsu, MD

That is an interesting angle. It has not always been this point of view, For many years, the medical community thought cancer had mutations in these cancer cells, so when you think about it, these cells go to grow. Every living thing has to have nutrients. They have to have a signal to grow. So you are right now; pioneering science has begun to look at all cancer types. It has its underpinnings. The mechanism that is inseparable from all the metabolic milieu, all the hormonal influences, the influences that either set the cancer up or promote cancer growth. This is a very timely topic.

Jennifer Simmons, MD

Yes, absolutely. In many ways, the same metabolic dysfunction that is happening in diabetes is happening in people with breast cancer. Often, when I see these people who are not getting flagged as being pre-diabetic, I test them, and their fasting glucose is 95, 100, or 105, and they are fasting insulin. Or even if they are fasting glucose as normal, their fasting insulin is in the 20s and 30s, well above what we would consider healthy. Can you talk a little bit about fasting, glucose, and fasting insulin? Where would you like to see it, and what does it all mean? What does that whole process look like as you approach prediabetes and diabetes?

William Hsu, MD

It is interesting. It is not a surprise. But when you look at people living with type 2 diabetes, that is mainly what we are talking about, and that is the most prevalent form of diabetes in our society. We are talking about maybe around 38 million people with diabetes here living in the U.S. One hallmark of the majority of people with type 2 diabetes is elevated glucose. But also elevated instant, as you mentioned. What that means is that it takes more insulin to do the same amount of work and get rid of the glucose in your body. We have a specific term for that. It is called insulin resistance. 

Let us say, that one unit of insulin generally can move X amount of glucose out of the bloodstream into the tissue. Somebody with insulin resistance now takes one and a half times more insulin to do the same work, twice the amount to do the same work. If you think about it almost in terms of fuel efficiency, when you look at vehicles, big trucks, and big cars, they have terrible fuel efficiency. The same thing that people with our body size get bigger. We call that insulin resistance because it takes more instants to do the same amount of work. 

Now, when you look at people like that—people with type 2 diabetes, obesity, and insulin resistance—very interestingly, they also have a higher level of cancer risk. In other words, people with diabetes. It depends on what cancer it is, but they may have anywhere from 2 to 3 times their risk of developing some form of cancer. That relationship is not coincidental. There is a hard-wired relationship behind them. The link between cancer growth and metabolism.

Jennifer Simmons, MD

Why do you think it is not universally accepted to check people’s fasting insulin? I would think that we would want to know who is becoming insulin-resistant. That is the clinical indicator of who is becoming insulin resistant,?

William Hsu, MD

Yes. I also think it has to do with the division of labor that we have in our healthcare system. By the time you see an oncologist, that means that person is already diagnosed with cancer. The focus is now on getting rid of cancer and killing the cancer cells. The people who ought to be looking for this are not part of that ecosystem. I think it has to do with the fragmented healthcare system we have in our country. The ones that have been taking care of you for many years to help with prevention are thinking about the cancer risk, if you will, with an elevated insulin level.

Jennifer Simmons, MD

They should be thinking about is blood sugar balance; they should be thinking about insulin resistance. That is under the purview of the primary care physician. I feel like, usually, this is a 10-year process, just like breast cancer is a 10-year process. If we had arrested the metabolic dysfunction years ago, we probably would not have gotten to the point where we have a cancer diagnosis.

William Hsu, MD

But I think that that is a very good accusation of how medicine has become more about treating the results than the root cause. Yes, I could not agree with you more. We ought to be spending more of our awareness, our efforts, and our dollars on early detection. That is exactly what an educational session like yours, I think, can help to change.

Jennifer Simmons, MD

Let us talk about fasting. I know that you have looked a lot at fasting and the benefits of fasting in reversing metabolic disease and even in its relationship to cancer. Can you tell us what is happening in the body with fasting and why it helps to reverse metabolic disease?

William Hsu, MD

I think that the relationship between fasting and metabolism is pretty clear. When you fast, you are not giving your body that constant stimulus for growth, and just like a car that is revving up and driving fast on the road, it gets to the destination quicker. What is at stake here? Well, it is your wheel. It is your tire. It is your tire track. Over time, it gets burned up. It gets used up and the same thing with our bodies. If the body is always getting these growth signals, constant growth will occur within 24 hours. Essentially, other than the change in where we are sleeping, our society is inundated with food. That means the body is constantly growing and wearing out, which accelerates our aging process. No wonder, over the last 20 years, we have seen this epidemic of obesity and diabetes all around the country. Partially to blame is all the excessive nutrient consumption that we have. 

Fasting does the opposite. Fasting works almost like a pit stop in a car race, where the engine gets pulled down and the wheels get changed. You can run again. I think if you look at our human natural history, there have always been periods of fasting when the sun goes down. We stop eating. When the sun rises, we start working and eating. But that is changed with refrigeration and light and lighting and knowing. Illumination in the eye, but also the past, there were also periods where there was simply no food. We had to go out and either gather or hunt. Now we have access to food at any time of the day. Our bodies never get time to stop. That is a problem. The constant growth signal pushes us to be biologically older, but at the same time, it sows the seeds for many chronic illnesses to emerge, like obesity, diabetes, and hypertension.

Jennifer Simmons, MD

And cancer.

William Hsu, MD

And cancer, for sure.

Jennifer Simmons, MD

Let us get even more granular about; what is happening when people fast.

William Hsu, MD

Yes, so there are a few things, not all fasts are the same. Let me clarify that a little bit. But one of the most common dietary patterns here in the U.S. is what is called intermittent fasting. A lot of people practice intermittent fasting; about 10% of Americans practice intermittent fasting. That simply means that you are either eating less or fasting for less than two days straight. That could be defined as intermittent fasting. Yet one of the most common things people do is time-restricted eating, as the name implies that at certain times of the day, you are restricting yourself to food consumption. Let us say somebody says 16 a day means 16 hours of fasting and 8 hours of eating. That is very common. 

When people do that intermittent fasting, their metabolism improves. If the glucose level goes down, there is a weight loss. There are a lot of metabolic benefits to intermittent fasting because it allows the body to rest and the liver to rest. It allows the pancreas not to pump up so much insulin. That drives growth. But there is another type of fasting, which I think is very important to differentiate from. That is periodic fasting. That is fasting that is greater than two days or more. This is what nature always prescribes for all the living organisms on earth because not every day there is food around; animals have to go to hunt and gather. So these prolonged fastings do something truly amazing and not only support a healthy metabolism, but because of the stress that is imposed on the cells, which have to survive after two, three, four, five, or six days of no food, the cells say, Hey, where is energy coming from? The cells have to look internally and say, 

Hey, what can I do to burn myself off so that I can survive? 

Now the first thing it burns off is never going to be the brain of this cell, which is the nucleus, because that will be suicide. What it does is begin to look for cellular organelles. These are structures inside the cells that are more disposable. For example, misfolded proteins, dysfunctional mitochondria, and ready things that are older; are more worn out. During that fasting phase, the cells chew these plants up as a source of energy. But the good news comes when food becomes available again. Think about what happened. The cells shrink first in times of starvation. But when food becomes available again, the cells grow those parts better. Now think about what just happened. You have simply replaced those worn-out parts of the cells with new ones. There is a term that describes that process: autophagy. That means self-healing. That process is so important to the survival of all organisms on Earth that it is so pivotal to discover this process that the guy who described it won the Nobel Prize in 2016. Jenn, that was a long description. 

Jennifer Simmons, MD

No, I love that. There is a lot of debate about when autophagy kicks in. What has your research shown you in terms of when autophagy starts?

William Hsu, MD

I think a lot of the literature talks about intermittent fasting, and treating autophagy, I happen to belong to a camp that does not believe in that because, think about that, to eat your cells, to eat, that is that cell. The components I do not think can be triggered with 6 hours of fasting. How could it be? It is not an existential crisis, There is a risk when you begin to digest intracellular organelles. I think it has to be an existential crisis, and that generally takes in humans. I believe it takes probably 3 to 4 days to star in animal models like rodents. It is a little earlier because they are smaller in body size and also because their rhythm is different. But in humans, I believe it probably starts a little sooner than a day or two. then I think it picks up probably three or four days, and therefore there is room for these longer fasts, which is very different and not achievable through intermittent fasting.

Jennifer Simmons, MD

Talk to me about where the research around fasting and breast cancer is.

William Hsu, MD

Yes, it is interesting because it was not so popular, let us say, 10 years ago. When people think about cancer patients, they think about losing weight and their appetite. 

Jennifer Simmons, MD

I do want to expand on that a little bit because we have created a lot of dysfunction around that image now. There is such a thing as wasting in terms of end-stage cancer, but the vast majority of people who are being diagnosed and treated for cancer are not in that phase.

William Hsu, MD

That is why there is always this, almost this, misconception. As we said at the onset of the problem, people who are overweight and have diabetes are generally heavier. They get cancer. That early diagnosis, early treatment—they are not emaciated at all. They are insulin-resistant. They are struggling with something called sarcopenia, where they have less muscle mass, although they have a large amount of adipose tissue in their body.

Jennifer Simmons, MD

Yes. Even those people who are overweight. But sarcopenia means that they just have not preserved their muscle mass. Even those people. Do they benefit from fasting?

William Hsu, MD

I think so. We know fasting does several things to the body. One revealing study that came out in JAMA Oncology a couple of years ago was simply looking at around 2,000 women who had the diagnosis of breast cancer and looking at their rate of, for example, breast cancer recurrence. It was found that people who fasted less than 13 hours a day in a 24-hour cycle have about a 36% higher chance of breast cancer recurrence. Now, it is not a randomized control study, but information like this is very interesting in hypothesizing that not only what you eat but also the timing of when you eat and do not eat could have implications in cancer biology. This opened up many new trials and studies in the field of metabolism in cancer.

Jennifer Simmons, MD

What have you looked at specifically around fasting and breast cancer?

William Hsu, MD

I currently work for a company called L-Nutra, which stands for Longevity through Nutrition. This is a company whose mission is to drive human longevity, or what we call human health span, not just the number of years you live but also the number of years you live healthily. As the Chief Medical Officer. I am tasked with driving the clinical evidence to support not only longevity but also disease reversal. We have about 18 published clinical trials. We have 14 clinical trials ongoing at the moment. I can tell you that some of our studies were on people with cancer and used a very specific nutritional approach called the fasting-mimicking diet, or the FMD. It is a structured meal kit. It is a five-day meal kit, and sometimes it is four days, depending on the conditions. Where we are providing nutrients to people and helping support them through a five-day fast. The first question your listener may have is whether this sounds like an oxymoron. Fasting is just no food for about a year.

Jennifer Simmons, MD

Right.

William Hsu, MD

This is where I wanted to just take a little bit of time explaining that this is what we call neutral technology. It is precision nutrition that gives you the benefits of fasting without the suffering of a fast. It is over 25 years of research funded by the National Institutes of Health. It is possible to provide exact nutrition that falls below the detection threshold of these nutrient sensors in the cells so that you can gain the benefits of fasting without fasting with water.

Jennifer Simmons, MD

That is amazing. I know that Dr. Valter Longo at USC has been looking at fasting through chemotherapy. Can you talk a little bit about that and his work?

William Hsu, MD

I wanted to first address that. This is part of our research and development pipeline now. We do not have a commercially available service or program for this now, but hopefully, we will. But so far, what we have done is tested the FMD in conjunction with standard therapy, and we were able to show that people in the clinical trials who were on the FMD had better outcomes than people who did not. That is because of a very interesting phenomenon called differential stress resistance. What that means is, when you fast when somebody’s going through chemotherapy, what are you doing to the normal cells? What the cells in the normal cells are saying is, Hey, I have no food around. I need to; it is not time for growth. I need to shut down in some way. I need to put my shield out because there is no time for reproduction or growth. That is important during chemotherapy, We know that chemotherapy works on cells during cellular replication cycles. If you arrest or call these normal cells into this enormous stress resistance state, that is protecting the normal cells from the harmful effects of chemotherapy. You are making the normal cells stronger. 

But it is quite the opposite with the cancer cells. The cancer cells cannot regulate whether there is food or not. It is just grow, grow, grow. When you fasted, mimicked, or ate during this process, cancer just continued to grow. It causes even more damage to the cancer cells when they are exposed to fasting in the presence of chemotherapy. Now, during this time of treatment, you have two different pathways. One is to make the normal cells stronger, and one is to make the cancer cells weaker. Our early studies have shown some promising signs of changing the way we think about cancer treatment for a long time. We say, Well, have a new whatever they want. But you think about the very thing we do when we are stimulating insulin production: we are elevating the glucose in the patient’s body. These are growth hormones that drive cancer growth.

Jennifer Simmons, MD

Yes, I think that what everyone needs to know and remember is that insulin is a growth hormone. It is a growth hormone. Someone who already has an issue with growth, which essentially is what cancer is. Why would you give them more growth hormone? We all need to make it a priority to be cognizant of people’s insulin levels and how much growth we are promoting. Someone who already has a growth problem and that message of no matter what you do, do not lose weight. We need to lose that message. That message is very bad and old information.

William Hsu, MD

That is right.

Jennifer Simmons, MD

You did say that people who utilize the fasting-mimicking diet do better when they undergo conventional therapy. I want to talk about what doing better looks like. I also want to talk about what it specifically means to do the fasting-mimicking diet while you are getting chemotherapy.

William Hsu, MD

Well, this is where I wanted to bring caution to our conversation. It is not a clinical program that we have available at the moment, but our research protocol essentially shows they are radiologic evidence of cancer, tumor burden regression with FMD, or fasting-mimicking diet compared to the received chemotherapy. We had a recent paper published that showed that even in negative, triple-negative breast cancer, it is the hardest breast cancer to treat. In this subanalysis of the study, which we published, we found an overall survival of around 30 months versus 17 months without FMD. 

But again, I wanted to just make sure that our listeners were clear about this. This is still under research protocol, but it is promising. It is a different approach to our standard treatment, and we are not saying to do this without going through standard therapy. We are saying that in conjunction with standard therapy, we could see.

Jennifer Simmons, MD

Of course. What does it look like in terms of how long you have to fast before you have chemotherapy for those cells to go into that resting state?

William Hsu, MD

Yes, well, we believe that means since there are over 100 mutations, potential mutations, and mutations with cancer, it is hard to have one broad stroke to cover this. But generally, we think maybe three or four days of fasting and also covering the date of chemotherapy might be an optimal way. It is always best to balance efficacy with safety factors. That is why I think it needs to be tested for different kinds of cancer.

Jennifer Simmons, MD

If someone is already hectic in that they are in that end stage of cancer, that might be someone for whom you are a little more cautious with the fasting. But in general, I would think that the same rules that apply to the general population for autophagy apply to this cancer population. You are going to want seven days of fasting before receiving chemotherapy because you are going to want to get to that state of autophagy that the cancer cells cannot get into.

William Hsu, MD

Yes, the autophagy stories are interesting because different types of cancer can use starvation as an escape mechanism. But what fasting does is it shunts and activates these starvation escape pathways for the cancer cells, which can then be targeted by very specific drugs. I think the story is nuanced. The mechanism of action is complex. But then I worry, saying that instead of ignoring metabolism as part of your cancer support, now there is evidence, emerging evidence, and even more credible research being done day by day, with more publications showing the intricate relationship between metabolic health and cancer health.

I will just say one more mechanism of action that I think may be of interest to your listeners: fasting. We also found in our publication that through FMD, we also found recruitment of these defensive cells called T cells. These are the ways the antitumor immunity gets activated. You have recruited T cells into the cancer cells and begun to help destroy the cancer cells activated by the FMD. That is also very interesting because it is not simply just insulin levels coming down or glucose levels coming down, but there is a huge recruitment of these immunity cells in the fight against cancer through activation through FMD. That is truly amazing.

Jennifer Simmons, MD

Yes, that is very interesting.

William Hsu, MD

Yes. Fasting has both a cure effect and longer growth-modulating effects. It has truly just opened our eyes to new areas of therapeutic potential.

Jennifer Simmons, MD

I am curious as to whether or not you guys looked at other side effects of treatment and whether or not fasting had any relevance in the area of immunity. Do people get the same white count drops if they have fasted that they do with conventional chemotherapy, fatigue, or nausea? Does it change any of these other known side effects of chemotherapy?

William Hsu, MD

Yes, it is very interesting because that is the other side of the treatment outcomes that we are looking for. One is a cure or treatment. The other side is tolerance. We have seen this in our animal studies, where a fasting or fasting-mimicking diet in animal models certainly protects the animal from the side effects of chemotherapy. I think we are in the process of demonstrating and testing if that is the same with humans, especially not only for chemotherapy but also the more popular immunotherapy as well. I think the jury’s still out there, but we are closely looking into it. It makes sense because of the resistance, the differential stress resistance factor that I mentioned earlier.

Jennifer Simmons, MD

Yes. What about fasting in terms of preventing recurrence? We all know that people after breast cancer treatment—I call it the quiet after the storm. It is like they have surgery, some people have chemotherapy, and some people have radiation. People get on extended endocrine therapy. But when that acute period of treatment ends, everyone’s like, Okay, bye, see you in six months. People are left wondering, Oh my God, what do I do now? Why is it so quiet? I feel like I am not actively doing anything anymore. Is there a role for fasting in terms of preventing recurrence?

William Hsu, MD

I am so glad you brought up the whole issue of survivorship. I think what is more powerful are the therapeutics that we have known. That means people are living longer, and people have options now. I think absolutely. At the onset of the program, I quoted a study in JAMA Oncology talking about intermittent fasting helping prevent recurrence. I think that that story clearly shows that we need more studies. But think about what the downside could be. When you, instead of these long fasting periods associated with acute chemotherapy, once you have gone through those periods and into survival, I think this is when you keep your insulin level down and your glucose level down. 

There is another important marker called the IGF, which is an insulin-like growth factor at a reasonable level. That tells the body, Hey, do not grow so fast. Take your time; do not overdo it; do not put your growth engine into overdrive. It was in my mind, and as shown by some of the studies, that had to be one of the key strategies to keep you healthy. Why give your body a chance to grow again and put your growth pattern into overdrive with high insulin, high IGF-1, and hypophysis? I would certainly recommend getting a more plant-based approach, lowering the install level, watching your carb intake, and certainly managing it the way it is. It is great for your overall health, but maybe specifically also for your cancer health.

Jennifer Simmons, MD

Yes. You did bring it up; is it safe? because I know that people inherently have things in their heads like, I need food for fuel; I need food for energy. Are there any safety concerns with fasting? In the long term, how frequently should people be doing these extended fasts?

William Hsu, MD

I think there are two different conversations when it comes to time-restricted eating. I think everybody ought to be, whether you have cancer or not or whether you are a survivor or not, at least 12. Which means 12 hours of eating and at least 12 hours of a window that has no food in your body. I think that is very reasonable.

Jennifer Simmons, MD

Yes. I want to say that if you cannot go 12 hours without food, you have big problems. Yes, it is just not healthy. At least 12/12.

William Hsu, MD

Yes, I think 12/12 is the basic. Then if you could push up the hours from time to time, I think that, depending on your unique body, this extended period of periodic fasting may maybe a different story. Everybody’s health condition is different, and I do not want to generalize, but it is something that you probably ought to discuss with your healthcare provider, whether you can do like this. FMD was specifically designed to mitigate some of these burdens with prolonged fasting. But again, I would advise that you speak to your healthcare provider to make sure that a five-day fast, even with some precision nutrition, such as in the FMD, is for you.

Jennifer Simmons, MD

Then, in terms of assuming that it is, ideally, how many times a year in survivorship, would you be recommending doing these five-day FMDs?

William Hsu, MD

Yes, we do not yet have the exact data to show how many psychological years of extended life extension. But I could cite some general ideas. If someone is looking to extend their healthy lifespan for healthy aging purposes, which is meant three times a year, so three times a five-day fast with FMD. That is for healthy longevity. For somebody with very specific metabolic needs to drive down, for example, a body weight, or visceral fat, we are talking about more frequently, and that is often a monthly cycle for a couple of months. Then for disease reversal, such as the diabetes remission program that we have currently commercially available call, L-Nutra Health for Diabetes Program, which generally involves six monthly cycles. Now sounds like a lot, but you are talking about five days of fasting per month for the rest of 25 days. You go back to living and eating normally. For six months, you are talking about 30 days of effort.

Jennifer Simmons, MD

Although it is eating normally that got you in that position in the first place, I think we need to be far more mindful about what is normal.

William Hsu, MD

I was just maybe saying some of the findings with this monthly approach. We published a paper about two years ago on people with type 2 diabetes. That was truly a result. The results were truly astounding. Five days per month for six months, we show that people lost about 22 pounds with the preservation of lean body mass, without a loss of muscle. At the same time, we saw a 1.4 drop in A1c, which is a marker for glycemic control for your glucose level. Then, mostly, what is most amazing was that two-thirds of the people—about 67% of the people—were able to reduce their diabetes medicine at the same time. I think overall, it just shows you the power of extending fasting, or these periodic fastings, on our metabolism. Hopefully, we will be able to show how approaches like this can be a standard practice for people with cancer.

Jennifer Simmons, MD

Yes. That is amazing considering that when you look at one of the GOP inhibitors, they look like Ozempic or Wegovy or whatever. When you look at those people, they are having a 40% reduction in their lean body mass along with their weight loss, and this is going to lead, and we are going to see it. It is going to lead to huge metabolic problems because, as we lose that lean body mass, that is the center of our metabolism. These people, even though they are losing weight, are losing the part of them that maintains health and longevity.

William Hsu, MD

That is exactly right. There are only two options: Either you continue to take that medicine the minute you stop, or your weight rebounds, and the worst of all is that when it rebounds, it is all fat. You do not gain muscle fat. It is either that or a lifelong dependence on medicine, which, I do not know, is a definition of health.

Jennifer Simmons, MD

Well, it is; there is no way that their system can sustain it. I think I heard Mark Hyman’s podcast where he talked about how, if we were only to put the diabetes population on Medicare for that drug, the cost would be like 280 billion and the budget is 140. It is impossible and not sustainable. The studies are too short, and we are only now seeing the real implications of putting people on these medicines. Between pancreatitis, bowel obstruction, and gastroparesis, these have huge implications. I know that this is not about that. We will move on from that, but only to say that we have to come up with real healthy solutions. Fasting appears to be one of them.

William Hsu, MD

Unless you think that fasting is very fast and very unfamiliar, I just wanted to say that everybody fasts every day.

Jennifer Simmons, MD

Yes.

William Hsu, MD

This is not a foreign concept. We fast when we sleep.

Jennifer Simmons, MD

Yes, absolutely.

William Hsu, MD

If you just take a look around nature, every other living thing changes from time to time.

Jennifer Simmons, MD

Absolutely. Without question. We can just take the example of our children. When our children get sick, they do not eat. Because they intuitively know that that is not what their body needs. Their body needs rest and repair. That is not happening when you are eating. Once a baby gets to be six or seven weeks old, they do not even wake up at night to feed anymore. If they do, that is on mom and not the baby. We need to get out of this mentality that we need to feed ourselves constantly because it is killing us. It is aging. 

I am so grateful for the work that your company is doing and for the information that it is providing to our society because it is necessary and it is needed. What is old is new. Again, every single religion has passed. We are historically beings that were meant to have periods of starvation, and everyone alive today is alive because they can tolerate periods of starvation. We need to get back to that because it is that time when healing is happening in the body, and we all need more healing.

William Hsu, MD

Very well said. I think this is a time-tested message from every culture, every religion, and every religion. Now it is supported more than ever by science. It is time that we bring this practice back to humanity.

Jennifer Simmons, MD

Absolutely. Dr. Hsu, thank you so much for joining us today and for providing us with all this information. I look forward to the time when this information is readily available and routinely practiced. I know that you and your company are going to make a huge difference in this space and the world. I thank you so much for the work that you do.

William Hsu, MD

Thank you, Dr. Simmons.

Jennifer Simmons, MD

It is Dr. Jenn. Bye for now.