PODCAST- Dr. William Hsu – ProLon Diet – How to get the most from fasting

About Our Guest- Dr. William Hsu – ProLon Diet – How to get the most from fasting


After 20 years of a distinguished career as an endocrinologist at Harvard’s Joslin Diabetes Center, Dr. William Hsu joined L-Nutra in 2019 as Chief Medical Officer. In this role, Dr. Hsu leads the clinical development effort at L-Nutra, oversees the Medical Affairs Department, and advances the education and adoption of fasting and Fasting Mimicking Diet as an innovative tool to extend human healthspan. 

Among his prior roles, he served as Vice President at Joslin Diabetes Center, a teaching affiliate of Harvard Medical School, responsible for its international education and healthcare advisory programs. He served on multiple national-level professional committees, including the American Diabetes Association, setting national standards of medical care in diabetes. His previous research interests focused on the pathophysiology of diabetes and the application of digital technology in chronic care.

Dr. Hsu went to Cornell University for college and received his medical degree from Mount Sinai School of Medicine. He completed his Internal Medicine residency training at Yale School of Medicine and completed his fellowship training in Endocrinology and Metabolism at Harvard Medical School. He was Assistant Professor of Medicine at Harvard Medical School.

Full Podcast Transcription

Dr. William Hsu 01:30
So the difference between a prolonged fast and intermittent fast is not only that the amount of calories you\’re going to be sort of not taking in – it goes far beyond simply just not eating. The stress of the fasting causes the cells to respond. And as I mentioned earlier, it\’s so important to a healthy aging process, so important to metabolic stability, that it was awarded the Nobel Prize in 2016.

Diva Nagula 02:02

Hello everyone and welcome to another episode of From Doctor to Patient. Today I am joined with Dr. William Hsu. For 20 years of a distinguished career as an endocrinologist at Harvard\’s Joslin Diabetes Center, Dr. Hsu joined L-Nutra in 2019 as the chief medical officer. In this role, Dr. Hsu leads the clinical development effort at L-Nutra, oversees the medical affairs department, and advances the education and adoption of fasting and fasting mimicking diet as an innovative tool to extend human health span. L-Nutra\’s fasting mimicking diet is called ProLon. Among his prior roles he served as Vice President at Joslin Diabetes Center, a teaching affiliate of Harvard Medical School, responsible for its international education and healthcare advisory programs. He served on multiple national level professional committees, including the American Diabetes Association, setting national standards of medical care and diabetes. His previous research interests focus on the pathophysiology of diabetes, and the application of digital technology in chronic care. He went to Cornell University for college and received his medical degree from Mount Sinai School of Medicine. He completed his internal medicine at Yale University, and completing his fellowship training in Endocrinology and Metabolism at Harvard. He\’s also the assistant professor of medicine at Harvard Medical School. Dr.Hsu, thank you so much for joining us today. How are you?

Dr. William Hsu 03:47
Thank you. It\’s great to be on this show.

Diva Nagula 03:50

I am so looking forward to chatting. This is such great information. And then I really so glad we can share this with everyone. L-Nutra is basically the company that is responsible for the famous product called ProLon which I have actually used on my own. And I have advertisements running on Facebook regularly for ProLon and it\’s very popular among my peers. And so happy to chat with you about this. And I really want to go into more detail as to the benefits and the science of the fasting mimicking diet.

Dr. William Hsu 04:24
Yeah, you know, I was practicing medicine and taking care of patients and doing research. And I came to know the literature around the size of fasting and it really fascinated me. Fasting is one of the most ancient practices across all cultures and all people if you think about it. In fact is part of every every religion around the world, and the science of fasting – really we did not even invent fasting. I mean the fasting has been practiced in nature for millions of years across different species, right? A lion? A tiger? What does it do between hunting, it\’s fasting, right? And so a time really has built in those mechanisms in the body to have fasting as an adaptive mechanism. We often see fasting as an interruption of our feeding, we say, hey, you know, I got to fast I cannot eat. It should be really the other way around, right? Fasting is really the norm interrupted by bouts of feeding. But look at our society today, we\’re dealing with so many different challenges, health challenges, most of them are chronic illnesses in nature, right. And I think fasting could be a new way for us to incorporate into our health and well being.

Diva Nagula 05:52
Absolutely. And there\’s different avenues to fast you can do you know, a regular water fast, you can do the intermittent fasting, you can do a fasting mimicking diet. Can you explain to us the differences between these three?

Dr. William Hsu 06:07
Yeah, I think, you know, as a clinician, that the, the key operating principle has always been do no harm, right. So for every intervention that we introduce into health care, or or into well being, it has to be safe. And so, you know, while fasting has been practiced for 1000s, and 1000s of years, the question for us is, is it safe for everyone? How long is safe, right, especially people with a chronic condition? Is it safe to fast? And that\’s why L-Nutra, after 20 years of research with funding from the National Institutes of Health, the company has invented this product called the fasting mimicking diet. And the intention is to bring the safety of food by giving you the benefits of fasting. And that\’s why it takes so long to scientifically design the ingredients and the composition of the diet to give you that benefits and the safety profile. And so the fasting mimicking diet, or the branding called ProLon is a five day structured meal plan – it\’s a dietary program. In five days, you just consume the food that\’s provided to you without eating any other external food. So it\’s scientifically designed to give you many of the benefitsof a water only fast, except that you\’re now eating so your body sees the food, but the cells in your body actually experience fasting. Now five days is a relatively long time – think about that, if you have to go through water only fast, five days. I think very only very small percent of the population in the world could potentially do it. And it\’s also potentially dangerous for most people to do that water only fast. So you have water only fast as a category, I just introduced ProLon, the fasting mimicking diet, that\’s the concept of fasting with food. And then you have the intermittent fasting. I think most people when we talk about fasting, we\’re really talking about intermittent fasting. And one of the most common ways to intermittent fast is by restricting the number of hours that you eat food to a specific number, like 12 hours, like 14 hours, or 16 hours. And in other words, you will consume all your food in a day within a short period of time, like an eight hour window, and we call that 16/8. If you have fast for 12 hours, then eat 12 hours. That\’s a 12/12 fast. I think that\’s what we\’re talking about.

Diva Nagula 08:44

Exactly. So what are the benefits in terms of choosing, say, the intermittent fasting route, whether it\’s the 16/8, 12/12, or an extended 24-hour fast versus the fasting mimicking diet? Could you elucidate the differences and benefits of each and why would you choose one over the other?

Dr. William Hsu 09:04
Yeah, this is such a common question. It\’s very, very timely. There are more and more studies now being done to look at the effect of intermittent fasting, especially the 16/8 type of fasting. Just remember that it is a relatively short period of fasting time before you break the fast after 16 hours. And studies now are generally smaller in size. It\’s not the hundreds of people studies that we\’re used to seeing the duration of the studies tend to be a little bit shorter, but what these pilot studies are telling us is that many of the weight loss benefits of intermittent fasting is equal to the amount of weight loss you will see if somebody would be on a continuous calorie restriction diet for a number of months. So the the early studies seems to suggest that if you fast or intermittent fast, you\’re going to lose as many pounds of body weight as if you were to be on a low calorie diet for a period of time. So that\’s encouraging, right? Because the way we\’re changing the way we\’re thinking about weight loss is no longer how many calories you\’re eating, or what you\’re eating, although that\’s often important – in the conversation around intermittent fasting is, when do you eat? Right? Without too much restriction on the food you eat, if you\’re able to restricted the amount of time you\’re consuming food, allow the body to do its work during the fasting period, at least some of the early studies are suggesting that we\’re getting a similar benefit as an everyday low calorie diet. So that should be very good news for us.

Diva Nagula 10:49
Absolutely. And besides the the weight loss benefits, what other physiological benefits can we talk about that relates to intermittent fasting, fasting, and the fasting mimicking diet?

Dr. William Hsu 11:02
I think the studies are still sort of ongoing. I mean, early studies are showing that there could be some metabolic health benefits to intermittent fasting. What sets the fasting mimicking diet, the five day fast from intermittent diet, or intermittent fasting is the fact that it\’s five days – five days is a long time. Just remember that the body typically responds to only to stress, right? For example, you think about when you\’re exercising, what are you doing, you\’re actually stressing your muscular skeletal system – the fibers of the muscle gets torn apart a little bit, and then it gets rebuilt and torn apart and rebuilt – that\’s how the body gets strong. Same thing with the idea of fast, you know, if you\’ve fast only for 16 hours and hope to get a lot of benefits, it\’s probably going to take a long time before you see them, right. But a five day fast, you can imagine, you know, the first day the body is using up a lot of glycogen or the strictures stored in your liver. And by the second day or so and so forth, you are now turning to burning fat. So that\’s a good thing. And oftentimes, by second and third day, you trigger a process called autophagy, which is a cellular cleanup. It\’s a process that was awarded the Nobel Prize in 2016 – it describes the recycling of some of the old and worn out cells, organelles or cellular components for something new, right. So it\’s a cellular rejuvenation process that takes place. Unfortunately, that process doesn\’t even begin to take place, you know, until probably 24 hours later, and it doesn\’t hit its peak until likely the second day or third day. So the difference between a prolonged fast and intermittent fast is not only that the amount of calories you\’re going to be sort of not taking in, but additionally on the physiology on a cellular sort of level. It goes far beyond simply just not eating – the stress of a fasting causes the cells to respond. And as I mentioned earlier, so important to the sort of healthy aging process so important to metabolic stability, that he was awarded the Nobel Prize in 2016.

Diva Nagula 14:31

Interesting, I was always under the impression that you could achieve cellular autophagy through doing a 16 hour, 16/8 or even a 24. And so it\’s interesting to hear you describe but the benefits of autophagy don\’t really kick in until after 24 hours and into 36, maybe even to 48 hours. So that\’s very interesting. So then really when we\’re talking about doing this intermittent fasting, whether it\’s 12/12 or 16/8 is really more beneficial for weight loss, because autophagy isn\’t realized during this timeframe. Are there any other benefits that can be seen during this 16/8, 12/12 intermittent fast? Because obviously, we were not able to achieve autophagy during this type of intermittent fasting?

Dr. William Hsu 15:16
Well, I think, certainly on the metabolic aspect, you know – the longer you fast, the less food your body\’s going to see, these nutrients coming in. And think about, you know, today, we have so many health conditions that are associated with an over nutrition, right, a state of over nutrition. So, you know, while we still need larger studies to confirm this, but as I mentioned earlier, just in terms of glucose level, in terms of body\’s sensitivity towards the function of insulin, in early studies, in smaller studies, they do show an improvement, which really, we\’re going to need larger studies to confirm those. But in contrast, when you have a longer period of fast, there are stronger literatures that shows the prolonged fasting, if can be done safely, or can be done with fasting mimicking diet, potentially has more benefits – not only on the weight loss, but I would share with you, for example, in the study that we published a couple years ago, people will go through this five days of fasting mimicking diet and they experienced an improvement in energy. They experienced a mental clarity after five days of fasting. And what\’s also quite amazing, is we see that there is a change in the relationship of the consumer to the food that they consume after five days. Because after five days of fasting, you\’re able to overcome some of those addictions, right, some of those holds that the food has on you. And one of the most common results after five days, or one of the most common questions people often ask is, Dr. what do I eat after five days of fasting? Because now they\’re determined to change their lifestyle, they\’re determined to eat better after five days of fasting. And so we\’re seeing cellular changes, as I mentioned, autophagy, with five days, we\’re seeing mental health changes, because you feel more energetic and have increased, enhanced mental clarity. And you\’ll see behavior changes as well, in addition to the weight loss that we talked about. Now, maybe one interesting fact that a lot of people don\’t realize is, you know, when you lose weight, by low count, by a low calorie diet, you\’re losing both your fat component as well as your lean body mass. Right, because it\’s indiscriminate, but you\’re not eating enough, the body is going to take muscles and break it down as a fuel. So you inevitably you\’re losing weight in many different components, compartments of the body. In an intensive, short fast, you know, a couple of days, you\’re actually sparing these lean body mass, instead, you\’re burning the fat from the belly, we call these visceral fats, right? These are the fat that is bad for you, for your heart health, for your metabolism. So that\’s also a very interesting aspect of fasting, which is very different than simply eating a low calorie diet.

Diva Nagula 18:32

Yeah, you would think that if you\’re restricting your calories, or actually taking part in a fasting mimicking diet, that your consumption of sugar would come from either protein breakdown, or fat breakdown, muscle breakdown. But in this particular case, it\’s designed to be muscle preserving. So it\’s not really catabolic in that in that manner, correct?

Dr. William Hsu 18:55
Yeah. And we see this across animal kingdoms, right? So if you see an animal like a mountain lion – in between the feeding, right, when it\’s going through fasting, if the muscle mass or lean body mass is decreased during that couple of days of fasting, that animal is going to be totally weak, and the species probably would have gone extinct, right? Extinct a long time ago, right? This is part of that survival mechanism that nature has given us.

Diva Nagula 19:31

Excellent. And I\’m assuming there\’s the fasting mimicking diet is structured, where the foods that you\’re eating keeps you in ketosis, because that\’s essentially what fasting is all about. Right? You enter a state of ketosis, which has the primary benefits of reduction in inflammation, and so forth. I mean, we can\’t be eating sugars and things of that nature, because that\’ll take us out of ketosis, so what comprises the fasting mimicking diet that allows us to stay in a ketotic state.

Dr. William Hsu 20:03
And that\’s actually a really interesting question. Because the fasting actually goes beyond ketogenic, or ketosis. Think about it, I mean, you can eat lots of food, and still keep the body in a ketotic state. Just avoiding carbohydrates, you could eat plenty of proteins and fats. But very interestingly, when you consume protein, you\’re actually telling the cells there is food. So, while there\’s many benefits to ketogenic diet, but think about the cells are still getting the signal, hey, there\’s food, we got to grow. Instead of going into rejuvenation, healthy aging, and the pathway, what we call stress-resistant pathways, is pathways that gets turned on when you\’re fasting. So the cells go through those rejuvenation processes. There\’s no energy out there, right. So we\’ve got to we got to make best out of whatever we have left. And that recycling that triggers autophagy only occurs during fasting. Not necessarily, when there is a lot of food coming in with proteins, the nutrients devoid of carbohydrate, yes, causes ketosis yes, but the cells are still getting the signal, hey, it\’s time to grow rather than it\’s time to rejuvenate. So I want to make the difference between the ketogenic process, a generation of ketones, that often contain nutrients – that still tells the cell to grow instead of to rejuvenate, versus a prolonged fast with ProLon, that tells the cells, hey, we\’re fasting, and therefore, we\’ve got to trigger the autophagy, we\’ve got to trigger this cellular cleanup. And so it\’s two different levels of interventions, if you will,

Diva Nagula 21:52
Right. And in this particular case, thank you for explaining that. So what are we talking about that is a composition of the ProLon diet?

Dr. William Hsu 22:00
Yeah, so it took many years of scientific design and testing. Essentially, it is lower in protein components, because as I mentioned earlier, amino acids, proteins can trigger these nutrient sensors, like the cells that have ears and eyes on the surface of the cells that tell the cells hey, are there nutrients or not. So the components of sugar, the component of amino acid is a protein, our major stimulators of these sensors and the nutrient sensors in the body. And so ProLon is designed with low components of proteins, amino acids, and also the way that the carbohydrate is manufactured provides a very slow release of glucose that would be sensed by the cells. And the rest of the calories to nourish the body is provided through a plant-based source of fats. So the entire package, the entire meal plan is plant-sourced. And with lower protein composition, complex carbohydrates, and plant-based fats.

Diva Nagula 23:08

Got it? And I mean, typically, when we\’re talking about entering in a ketotic state, you know, or a ketogenic diet, you\’re typically told that you have to eat a specific percentage of macro-content, so it\’d be 70-80% of fat, 20% would be dedicated to your protein and the rest would be your carbohydrates. Is this a similar composition to what you\’ve designed? In the ProLon?

Dr. William Hsu 23:36
It is not – I think we have even lower protein composition in there. But I think there is certainly more information than what\’s on the surface. It\’s not simply the macro composition, but also the specific composition of foods, the ordering of the food, the fiber contents in there, and clinically tested to give us that fasting mimicking. It\’s difficult to do this on your own, because you might think that\’s the right composition, but you never know, whether this is actually fasting, mimicking or not .You ended up with maybe just a low calorie diet, which is good for you, yes, but you\’re not going to get the cellular rejuvenation benefits.

Diva Nagula 24:26

Right. And that\’s exactly what we\’re trying to achieve. So with this taken into consideration, I\’m assuming….because in general studies have shown preliminary studies anyway, that correspond being in an extended ketotic state with longevity and I presume that with the fasting mimicking diet, we\’re also seeing the same benefits.

Dr. William Hsu 24:51
Yeah, I mean the all the early preclinical studies right, studies done in animals have always shown very positive benefits. For example, if you take little rodents, and you fast them, you think that they probably die of malnutrition, right. But in fact, they will live 30 to 60% longer depending on the mouse strain. And so that\’s why, you know, it really challenged the scientists to try to figure out how does fasting relate to longevity. And that continues to be a topic of tremendous research at L-Nurta. Now, you know, we still have quite a bit of work to do, to convince the regulatory body and to convince the greater world that any research can lead to a prolongation of life. I mean, that is a huge claim – and I think whoever can demonstrate that definitively in the end, will certainly win Nobel Prize – think about the benefits it brings to humanity. But at the moment, we definitely are, that\’s our aspiration. We have over 16 clinical trials done, being conducted at the moment, looking at the benefits of fasting mimicking diet of its various forms, in different conditions and health conditions and even assess its impact on biological age. But these are sort of our commitments at our research and development, by our research development team at L- Nutra that continue to push the envelope to drive the science behind this technology.

Diva Nagula 26:37

Right. And just for further clarification, are there restrictions and activities when on a fasting mimicking diet? Because I mean, a lot of people who might be interested, you know, maybe high performers, when it comes to physical activities, runners, people who like to, you know, pump some iron – is it advisable for them to discontinue these types of activities when doing a fasting mimicking diet?

Dr. William Hsu 27:04
That\’s a very pragmatic question. Because during fast, right, you already have the stress of fasting. So every cell in the body responds to the stress, think about it, right? I mean, it\’s like a universal stress when you fast. And so every cell needs to respond to that in a way, where additional stress from exercise – just remember, exercise itself is also a stress – we often see stress as bad, but physiologically, stress could be very good. But we think that during fasting, one, you\’re not eating very much. Number two, you\’re likely to being a nitrogen negative balance – why are you tearing apart those muscles here, you\’re not giving the nutrients to replenish it – this is probably not the best time to exercise during the fasting period. Okay, when is a good time to exercise? During the refeeding period, right after your five days of fast with ProLon, when you are replenishing your body with nutrients after the five days, those are the times where your body is really primed for growth, because it\’s hungry, it wants to grow now, right, and now the body is clean, the cells are clean. And this is a perfect timing to exercise, to grow, to eat right, to replenish. And so while we talk about many benefits of fasting, a lot of us fail to recognize it\’s really the repeated cycles of fasting and refeeding. Right? It\’s the fasting and the nourishment that completes the cycles of that rejuvenation, you cannot just have one, for example, long term starvation is no good to health, right? Otherwise, humanity, I mean, every time there\’s a starvation, and then people should just live better, longer and healthier. That\’s just simply not true. Right? So it is that repeated cycle, of the cycling of fasting and nourishment. Much like exercise, although it\’s good, you can\’t exercise 24 hours a day – you need to rest, allow the body to rest. So it\’s that repeated cycles of of exercise and rest. That is a form of a formula for for better health. Right? And when you\’re talking about refeeding. And I guess I\’m assuming it\’s going to be really important to understand what you put into your body during this refeeding phase. I mean, we don\’t want to be sitting there going into a fast food restaurant and use that as a means of refeeding – we really want to be able to nourish our bodies with proper amino acids, proper sugars, proper fats. I mean, is there a specific algorithm or a diet that we need to plan for during this refeeding phase? And how long is this refeeding phase? Is it a day or is it a couple days? Yeah, well we generally think of refeeding phases five to seven days after the ProLon fasting The stress of fasting have significantly sort of stressed the body, sort of causes the body to rejuvenate. It takes about five, seven days to really get replenished, we would suggest a plant-based diet for those days. If you must include fish, sort of a pescetarian diet would be really good for the body, but try to avoid as much animals source proteins or animal source fats during this phase. This is like a sponge, you have to picture this right. If you squeeze the sponge out, it\’s totally dry right now – when you pour anything onto the sponge, it\’s going to soak it up. So you\’ve just gone through five days of cleanse here, you don\’t want to to the body to soak up all the all the bad nutrients and ingredients, especially when it\’s most hungry during these refeeding periods.

Diva Nagula 31:01

Right. And I\’m assuming it\’s okay to to ease your way back into exercise during this refeeding phase. I mean, I\’m assuming you don\’t want to go back to your previous activities. And if you\’re a marathon runner, it\’s probably not advisable to start going training for your marathon or running a marathon shortly after the ProLon. So I guess really, in essence, if you\’re going to be doing this or partaking in this, you really want allot five days for the ProLon and probably another week after before really going back into your normal activities and lifestyle and eating, what\’s you were beforehand.

Dr. William Hsu 31:33 That\’s a wise counsel.

Diva Nagula 31:37

Excellent. And in terms of how people can find more information about ProLon and yourself, what is the best way for the listeners of this podcast to do so?

Dr. William Hsu 31:51
For more information, you could go on to prolonfmd.com. You can find a lot of information about the product and there is also a very good resource of information in just on fasting in general with no products. There\’s no mention of any kind of other commercial interest. It\’s fasting.com. That just has a lot of well informed articles and bite- sized information on anything fasting.

Diva Nagula 32:22
Excellent. Well, Dr. Hsu, thanks so much for joining us today. It was pleasure chatting with you. And hopefully one day we\’ll be able to to meet each other in person.

Dr. William Hsu 32:31 Thank you.

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