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Tom Bunn: Good morning, everybody, and welcome to iSelect’s Deep Dive webinar series. My name is Tom Bunn, a principal on the iSelect Ventures team, and I’m excited to walk you through today’s discussion as we have a group of excellent experts and physicians on the call with us. For those new to these webinars, iSelect is a venture capital firm based in St. Louis, focused on companies in food, agriculture, and healthcare. iSelect Invests at the forefront of innovation, seeing emerging problems and technologies at the beginning. And we use these deep dive presentations not only as a way for us to better engage with and understand new science and technology, but also to engage with the experts and entrepreneurs who are driving change and innovation in their respective fields.

One area in which we’ve been interested is personalized health management, field of medicine and wellness that is becoming more accessible, but possibly adding to the broader confusion around what’s healthy and what’s not. What is indisputable is that 6 in 10 Americans suffer from a chronic disease and 4 in 10 have two or more.

What’s more is that an estimated 88 percent of Americans have metabolic syndrome, which is a leading indicator for one’s propensity for chronic disease. On today’s iSelect Deep Dive series, we’ll hear from three experts who are on the front lines of addressing the measurement of the key biomarkers associated with chronic disease and who are using their expertise to figure out what we can do about it. A few process comments. We are not soliciting investment or giving investment advice in any way whatsoever. This presentation is general industry research based on publicly available information. We have invited you to do this because you are technologists, thought leaders, entrepreneurs, industry experts, early adopter customers, or sophisticated investors that are part of our network.

We value your thoughts, questions, and comments. On this topic and would appreciate it if you engage during the presentation there should be a Q and a pain at the bottom of your zoom app. And we will take as many questions as time allows towards the end. So finally, this presentation is being recorded and will be available for replay.

With that, I am pleased to bring you this week’s deep dive on personalized health management.

So we have a great group of guests this morning, this afternoon, depending on where you are. I thought I would give them a moment to introduce themselves before we dive in initially individually on, on each one of them, and then hopefully some time for some collective discussion between all three.

But Dr. Hull, do you mind giving a brief introduction, please?

Allison Hull: Yeah. Thank you so much for having me. So great to be here. I’m Dr. Allison Hall, and I’m a dual board certified and practicing pediatrician and an adult internist. I’ve been in practice for almost 15 years. I’m also the co founder and chief medical officer of Journeys Metabolic, and I’m an associate professor with the University of South Florida, where I conduct research on metabolic disease, utilizing nutritional and behavioral interventions.

Tom Bunn: Thank you, Dr. Hull. And Dr. Lustig.

Robert Lustig: So my name is Rob Lustig.

I am an emeritus professor of pediatrics in the division of endocrinology at the University of California, San Francisco. I have been in this field for a very long time, and I’m starting to see some changes in it, and I’m really, delighted about that.

To sum up my career, I think I can do it in one concept. Have you heard that sugar’s bad for you?

Tom Bunn: Thank you. Thanks, Dr. Lustig.

Robert Lustig: We are doing our best to try to fix the food supply. Yes.

Tom Bunn: Awesome, can’t wait to dive in. And finally, Pranitha Patil, do you mind giving a brief overview, please?

Pranitha Patil: Absolutely. Hello everybody and thanks for having me, Tom. My name is Pranitha. I am the co founder and the COO of Function Health. We are a new company and we’re a new way for people to take control of their ever changing health, which I’ll get into later. Just a very brief history on me. I am not a physician but I am incredibly passionate about health care and how we manage our health.

I’ve had my fair share of health challenges that I’ll get into and my journey began over 15 years ago. I’m very jazzed about the way that our health care industry is moving into because we fundamentally know that we can’t do it the way we’ve done it so far. I’m so really excited to be building a company that’s changing the way that we think about our health.

Tom Bunn: Thanks. Thanks, Pranitha. Excited to learn more about what functions up to. So I thought we’d just go in that order to kick things off. Dr. Hull, maybe a good place to start is if you could give us a background on how you became so focused and passionate around addressing chronic disease and maybe segue that into kind of your toolkit.

Some of your toolkit and some of the low hanging fruit from a measurement perspective.

Allison Hull: Yeah, so about seven years into my practice banging my head against the wall trying to help my patients in my office improve their nutrition and lifestyle and seeing, of course, this rapid obesity diabetes picture.

I said, something that I’ve been preaching and teaching is not right. I did my undergrad at University of Florida Food Science and Human Nutrition, and I was told that sugar is great and fat is evil. That carried through med school and early training and, practice. And I said, this is something.

This is not working. So I took it upon myself to start researching and really looking into what, how should people be eating? What should we change nutritionally? And that was step one in, terms of trying to teach my patients, let’s actually start reducing carbohydrates. Let’s actually eat. more healthy fats.

But I found that that communication, my office was not enough. And even though patients wanted it, they would go home into their home environment and the wheels would fall off and all the habits would come back into play no matter how much they wanted to change. So I said, okay, I need to create a structured incremental, really multifaceted behavior change that incorporates nutrition as a metabolic therapy. So that began seven years ago, and I created a virtual based 12 week protocol that now over 3, 000 patients have gone through. It’s proven to reverse diabetes, fatty liver disease, and And so now we’re implementing that into an application format to integrate with, EHR under the umbrella of journeys, metabolic.

So what did I find in my years of doing this and what’s included in the protocol that is so important? Number one is really focusing on the foundation of behavior change and having people understand the reason why they’re trying to create that behavior change. And then from there, you have to create immediate extrinsic reward mechanisms, data driven to create new habit formation.

So they’ll follow that incremental nutritional change in the protocol. And once I incorporated the behavior components and coupled that with those data driven reward mechanisms, that’s when things really started progressing with the success of the patients. And I’ve had patients who’ve done the protocol back in 2018 who are sustaining their success with their weight loss and remission of diabetes.

Awesome. That answer your question.

Tom Bunn: Yeah, thank you. And so what, looking at biomarkers in particular, what do you think is a good starting point for, example, when you see a new patient when you eagerly say, check out this 12th. week program. What are you looking for?

Allison Hull: So in all patients, even though it’s not guideline recommended, I’m checking an A1C, a fasting insulin level.

We know that insulin is going to rise far before glucose and A1C is going to rise. Of course I do your traditional lipid profile, but also dig deeper looking at able lipoprotein B lipoprotein little a just try to get a more wide picture of their overall metabolic health. And then whether they’re diabetic or not, I want everyone monitoring glucose for the purpose of, it’s a lot of self awareness.

It’s a feedback mechanism, right? So they learn how different. foods affect their glucose. They learn how sleep or lack there of affect their glucose, exercise, et cetera. So, and then it becomes a reward mechanism as well, that when they’re eating the right foods, their glucose levels are improved. Yeah, so a little bit more in depth as far as that, those metabolic markers, insulin, A1C, a greater in depth picture at the lipid profiling, because when people do adopt a low carbohydrate nutritional plan, and those triglycerides come down, there is often then a shift in the LDL cholesterol presentation, and if we’re only looking at the LDL cholesterol then we might be misinformed that’s going up. And in fact, it’s really not. It’s just, there’s a transfer of cholesterol from VLDL to LDL that’s revealed in that standard generic lipid profile, which is why an able label protein B is far more informative.

Tom Bunn: Got it. And so I’m, hearing that you’re doing more than perhaps the standard of care, or perhaps most primary care doctors recommend from a lab point of view.

Do you see that gap? Narrowing. And so to hone in on that a little bit more. So you said ApoB as one sort of demarcation perhaps new or novel or better biomarker that isn’t used as often. Is that one of the main ones? Or can you discuss where, the standard of care ends and where next gen begins?

Allison Hull: So it is not standard of care to do able labor protein B. I will tell you, most of my colleagues have no idea what that is. Nor do they know how to interpret that? No, part of that stems because it’s not the guideline recommendation, of course, right? But guidelines take time, right? It takes years for guidelines to change.

That’s definitely not standard of care, nor is a fasting insulin level, nor is a uric acid level, which is another biomarker I evaluate. And then I actually go into more depth with my patients. I evaluate something called a myelobroxidase level, which is a enzyme produced by white blood cells that are engaging in atherosclerosis and plaque formation and the coronary arteries.

There are definitely things I do that most don’t. And I feel that when you expand that evaluation, you get far more information. You put far more pieces of the puzzle together to make the best decision protocol for your patient moving forward.

Tom Bunn: And so journey’s metabolic. Perhaps you could talk a little bit about that and, how you’re using some of these next gen health metrics in the program. Especially since the idea is, working with health systems. How do you convince some of the health systems you’re working with to use these biomarkers?

Allison Hull: So a great opportunity with Journeys Metabolic, because we will be engaging with health systems, is education. Not just for the patient, but for those health care providers that we’re trying to help supplement that care with. To take a step back, most health care providers just don’t have the time or the bandwidth to spend on this education and nutrition as a metabolic therapy.

I’m still in the trenches of seeing patients every day, all of my partners and colleagues. I know what it’s like. So that’s where we come in to help be that bridge to be that supplement, but we do also need to educate those providers on the utility of these tests, why they’re important, how they’re important, how to interpret these tests and make them meaningful for their patients because with Journeys Metabolic, our goal is not to take over the care of the patient. Our purpose is to supplement and augment that care of the patient to support that provider and that patient. So we’re an avenue of education for those healthcare providers and then in the actual protocol itself.

Another key piece is that we actually measure fat oxidation through the biosense breath ketone analyzer. We are measuring to see if a patient is in a state of fat oxidation, burning their fat through their burning their own body fat as their fuel. And we measure that through breath acetone levels. And so in the protocol, this result of the breath acetone levels is also a customization tool to guide the patient on how to further adjust their macronutrients to ensure they’re in a state of fat oxidation.

So that’s a key component of what we offer in journey’s metabolic too. It’s an immediate reward mechanism. It’s a driver to change their macronutrients as a prescriptive level. And then depending upon that, ace level, the breath acetone level that also dictates are we just in a kind of a mild fat burning mode?

Are we at a level of fat oxidation? That’s going to better reverse diabetes, fatty liver disease. So it will tailor those interventions as well.

Robert Lustig: Got it. And

Tom Bunn: from a more macro perspective obviously physicians are burned out. There’s a shortage. So I can imagine that new movements within the space take a long time.

What do you think the prognosis is to make this more ubiquitous here in the U. S.?

Allison Hull: Well, it’s going to take people like us, right? It’s going to take, it’s local people. It’s going to take both, in my opinion, academia, right? So evidence based research, but it’s also going to take that everyday clinician incorporating this in real clinical practice.

It’s really hard to live in an academic world in the everyday trenches of the practice of medicine. So we have to make sure that we communicate and provide the structure and the protocol that whether you’re in academics or private care, that you have the tools that you need to do this. It takes repetition.

It takes Being vocal over and over again. I mean, I’m in an organization that has over 350 health care providers, and I’ve been doing this for 7 years now, and I have definitely seen a transition with some of my colleagues coming over to my side. But there’s still many who have not. So the work is not done.

It takes a lot to change the dogma of how physicians were trained, especially when they don’t have time in their clinical practice to retrain what they were once taught.

Tom Bunn: Excellent. Thank you. In previous iterations of this deep dive series, we’ve discussed at length with some founders of continuous glucose monitor.

monitor companies. I’m wondering if you can discuss the utility that you see in those and also the data that you’re seeing. I know you’ve done a study using C. G. M. S. Continuous glucose monitors. I’m wondering if you can kind of spell out what you’re seeing from those and where they’re positive and where they may be lacking.

Allison Hull: So it’s interesting. Part of it is based on the individual and their personal preferences. In our protocol, we did point of care glucose monitoring. We didn’t do a CGM and the original protocol. And in Journeys Metabolic, we’ll be utilizing a finger stick point of care. Of course, in this study, we compared the protocol to patients having a CGM and some people really.

Enjoy having that. But admittedly, the feedback over times becomes less useful. It becomes more like white noise to some extent. Also, admittedly, they’re not always the most accurate. So I have a lot of patients. I actually had a patient yesterday who’s a diabetic and she said I, I can’t use this anymore.

It’s so inaccurate. I have to prick my finger anyways, so I might as well just prick my finger. So I also find that when patients have to prick their finger and use a point of care glucose monitor, they’re more intentional when they do that, right? There, there’s a reason they’re, testing.

They want that feedback as opposed to just like constantly. Yeah. swiping. Now, as somebody is trying to make these behavior changes and they’re adopting this kind of new onset of nutrition as a metabolic therapy. Yes. Having something like a CGM is really helpful. It’s immediate. It’s easy. But over time, once people have adopted and they’ve made those changes, it becomes less of a reward mechanism and it becomes less of a driver.

So and I, they’re obviously a lot more expensive. So I have found that just a good old fashioned point of care glucose monitor can be extraordinarily effective and which is really great when we’re talking about helping all walks of life and closing gaps of health equity and health disparity.

Having more affordable mechanisms for patients to take control of their health is really important.

Tom Bunn: Awesome. Thank you. I guess the last question before we move on. What’s low hanging fruit from a dietary intervention perspective that you would, point to to get the patients closer to optimal kind of writ large across biomarkers, if you can give any, advice there.

Allison Hull: Number one as, it’s already been mentioned, get rid of sugar, get rid of processed foods. I, my mantra is always this, I say this every time multiple times every day, we have to eat foods, we grow hunting fish. If we did that and we weren’t counting macros and and just a real food, it would be amazing.

Society would change. So that’s the low hanging fruit, eat fruit. and vegetables and chicken and and fish and vegetables. So eat real food, avoid sugar, avoid processed foods maybe employ some time restricted feeding, right? Closing those gaps of time in which you eat. That also shifts behavior associated with food.

People do naturally caloric restrict when they time restrict feed. So that and eat real food, that’s all we did. It would be a great day.

Tom Bunn: Awesome. Easy enough. Thank you, Dr. Hull. Moving on to Dr. Lustig. Dr. Lustig you’re, a prolific writer, academic physician. Maybe just to set the stage a bit more than, what you did greatly in the in, your intro.

If you could, describe how you came to be a leader in this space, and if perhaps there was an inflection point that made you become more outspoken in the field.

Robert Lustig: Thanks, Tom. First of all, before I start, let me just let people know, I am an advisor to Journeys Metabolic. I am also an advisor to Levels Health.

So I do have, shall we say, skin in the game and vested interest. Bye. Having said that, I did not come at this with an agenda. Basically, the science brought me here. I followed the science where it went. When I went to college, I majored in nutritional biochemistry at MIT, back in the 1970s.

And I learned that different foodstuffs were metabolized in different ways and did different things in the body. Then I went to medical school and they beat it out of me. Basically told me none of that mattered. This is not how we take care of patients. And calories are calories. And I practiced that way for 20 years.

And none of my patients got better. Similar to what Dr. Hull described. And it was only when I started doing research in the field of obesity starting in 1995 that I came to realize that calories were irrelevant and what mattered was the hormone insulin. Now, Dr. Hull mentioned insulin. She mentioned fasting insulin.

And I think that a fasting insulin is probably the single most important lab test that anyone can get. Yet, despite that, the American Diabetes Association tells All the doctors in America don’t draw it. How can it be that I say it’s the single most important test that a doctor can draw and the American Diabetes Association says don’t draw it?

What’s the dichotomy there? Well, that’s part of why I’m so outspoken and vocal about it. The ADA says Two reasons not to draw it, and you need people on this call need to understand why we have this problem and what the, shall we say, the cognoscente are contributing to this problem and why we can’t fix this problem as Dr.

Hull talked about. So I’m playing, riffing off where she took you already. The reason the ADA says don’t draw fasting insulin is twofold. First, different assays give you different results. That’s true. Assays are not standardized across platforms. That is true. For instance, a HPLC will give you a different result than a radio amino assay, which will give you a different result than an ELISA.

That is absolutely true. The reason that this happens is because there is another species. That comes out of the beta cell. When the beta cell is totally taxed, when it is working hard to try to get blood glucose down, it will release anything it’s got in there. And one of the things it’s got in there is a pro hormone, a precursor hormone to insulin, and it’s called pro insulin.

And pro insulin Only has 5 percent of the activity of insulin, but it gets measured in the insulin assay. So, when you measure plasma insulin using a cheap assay, you may not be measuring what you think you are. And that’s why the ADA says don’t do it. Who cares? It’s high. Fix it. That’s, the problem.

ADA is number one. Now the second reason the ADA says don’t draw fasting insulin is fasting insulin does not correlate with obesity. That is also true. It correlates with metabolic health, and there are plenty of thin sick people, as well as plenty of fat healthy people. And the fasting insulin is the thing that tells you whether or not you’ve got mitochondrial dysfunction.

And if you have mitochondrial dysfunction, you have chronic metabolic disease. And what is the single biggest driver of mitochondrial dysfunction in our current environment? There are many, but what’s the single most important? Sugar. Now, there are others. There’s air pollution, there’s environmental obesogens, there’s stuff in the water, there’s stuff in the cosmetics, there’s stuff in the plastic, stuff in the air.

I’ve written several papers on the things that are in our environment that we’ve put there that have basically impacted mitochondrial function. Oh, by the way, one of the things that impacts mitochondrial function, ionizing radiation. We learned that from the International Space Station.

In fact, NASA doesn’t know what we’re going to feed the astronauts going to Mars, because just being in the capsule causes mitochondrial dysfunction. Not just because of the lack of exercise, but because of the ionizing radiation. So these things are all around us. The one we could fix tomorrow, if we had the political will, is sugar.

Because it’s the one that the food industry adds for its own purposes, not for yours. So, that’s why… Dr. Hull said, get rid of the sugar. That’s number one. I say, get rid of the sugar. That’s number one. I totally agree. The question is, how do you do that with our current food supply? Our current food supply, if you go into the grocery store today, okay, 57 percent of the sugar in our diet is in ultra processed foods and 73 percent of the products in the American grocery store are ultra processed foods spiked with added sugar.

Basically, it means getting rid of virtually everything in the grocery store. How do you do that? Can I do a share screen? Says I can’t do it while the other participants are sharing. So somebody has to fix that before I can do it. You should be good to go. No, sorry. Not yet. Not yet.

Ah, now I’ve got it. Okay. There we go. So let me just, I’m going to play you a one minute and 42 seconds video that I made about a company that I am working with that iSelect knows about called Purrfect. And Purrfect is a. Computerized recommendation engine that basically takes your biochemical profile and your grocery store and only offers you the items that will be metabolically healthy to you, no matter what your biochemical profile is.

Because the biggest problem right now, aside from our food, is procurement. People don’t know what healthy is. We’re going to talk about that in a minute. That will be the second part of this, but let me go ahead and play the one minute and 42 seconds, and you will see how this works. Hello, this is Rob Lustig, and I’m going to give you a tutorial on Perfect.

Here we see the store fair for Amazon, Walmart, and Target, and there are a total of 83, 000 products. We’re going to search for those that don’t have diet sweeteners. And you can see we filtered down to 57, 000 products. Now we’re going to just look for those that have one teaspoon of sugar or less. And you can see we’re now down to 12, 000 products.

And if we put no sweeteners in, we are now down to 9, 500 products.

Let’s say you want. No added sugar cookies. So type in cookies, add the no added sugar filter, and you can see that there are only 11 items in the store and you can shop those without even having left your home. And you can see no sugar in this particular item. And you can look for those that have been filtered out.

And you can see that each of those 1800 of them have Sugar, high fructose corn syrup, molasses, or other sweetener that you are trying to avoid. You can do this for virtually any item in the grocery store. You can do this for your biochemical profile, whether you are gluten free or whether you are trying to avoid oxalate, whether you are trying to fix your metabolic syndrome.

This has enormous potential for being able to help you shop the store without having to even get out of bed. Thanks so much for listening. Okay. That’s an example of how one could use technology to be able to advance the concept of metabolic health. Everyone is different. That’s the whole concept of personalized medicine.

So why would you expect that any one diet would work for anybody? And why would you expect that any one grocery store would have what you need? In fact, most people have to go to about five or six grocery stores to buy what they need, which is kind of a problem. So this basically fixes that and also does it in a way that allows people to be able to, because after all, they’re not just shopping for themselves, they’re shopping for their family too.

You know, you’re not just making your meal, you’re making your kid’s meal, and you’re making your husband’s meal. You’ve got a lot of people to have to deal with. And so, being able to mitigate metabolic disease across the board for your family is actually a very difficult thing. Plus, you can’t figure out what has been done to any individual food by looking at the Nutrition Facts label.

The other problem is you can’t just do this with what the USDA give provides. The Economic Research Service database. Because we’ve determined that 44 percent of it is wrong because they get it from the food industry. PERFECT takes all of that into account. We’ve been actually working with the USDA to try to fix their food database.

We need a structured, computerized, accurate food database, and every country needs it, and it needs to be culturally sensitive, and we are doing that. We’re actually working with the American Heart Association on a grant to provide this for the Latino community. So that’s part one of what I want to tell you.

Now I want to tell you about part two, and I’m going to ask to share the screen again. Okay, I’m going to close perfect. Okay. And I want to tell you about a project that we’ve been involved in in the Middle East. So three years ago, this company called Kuwaiti Danish Dairy Company, KDD, came to me. The reason they came to me was because Their CEO and founder, Sir Mohammed Jafar, who was 48 years old, Weighed 350 pounds and had type 2 diabetes and back pain, and he went to his UK physicians who put him on insulin and oral hypoglycemics, and he got worse.

And he said, this isn’t working. So he went to Dr. Google and he found me and Jason Fung, and Jason Fung is an adult nephrologist who does intermittent fasting and he read our stuff. And he decided I’m going to follow what these two guys say. And over the course of the next nine months, he lost a hundred pounds, his type two diabetes resolved and his back pain went away.

And he thinks we hung the moon. Okay, that’s good. And then he has his aha moment, his light bulb, his moment of epiphany. Wait a second. If I did this to myself, eating my own crap, what am I doing to the rest of the Middle East? And so KDD is a privately held company. His Mutser Mohammed and his sister own all the shares.

There’s no Wall Street quarterly reports. There’s no stockholders or stakeholders to have to placate. So they can take the long view. And they came to me and asked me if I would convene a scientific advisory team to work with them over the course of the next three years, which are just completed to make processed food healthy.

Dr. Hull told you get rid of the processed food. That’s right. And the reason is because the processed food that is manufactured today is poison because it in itself is a mitochondrial toxin. And if you are a mitochondrial toxin, it doesn’t matter how much of it you eat, you’re a toxin. Could processed food be made healthy?

That’s the question. Well, in doing this project, we realized that we had to adhere to three principles. And the three principles are here on the slide, called the metabolic matrix. We have published this in Frontiers in Nutrition as of March of this past year. And there are three things you have to do.

Feed the gut, protect the liver, support the brain. Now I’m not going to go into each of these because this would just take too long and then there’ll be no time for Ms. Patil, but the list of what things you have to do are here alongside each of these. Healthy essential fats, you really need omega 3s.

This is about omega 3s. Protect the liver is about sugar and feed the gut is about fiber. So the question is, the science is clear, this is what needs to happen, even to process food, in order to be able to escalate it from its current toxin status to metabolic health status. We need more soluble and insoluble fiber to feed the gut, we need more alpha linolenic acid, EPA, to support the brain, and we need less sugar to protect the liver.

If you could do this to process food, You might actually be able to make improve metabolic health around the world, and at the same time be able to feed 10 billion people by the year 2050. So we need a real food diet. We have a processed food diet. Can the food industry re engineer its current fare to match this?

The answer is, yeah, you can. Okay, but you have to know what you’re doing, and a few people do. Okay, can technology help and turn a profit? You can focus on the ingredient level, these kinds of manipulations, you can focus on the processing level with these kinds of manipulations, you can focus on the packaging level, and you can focus on the data science level.

We are working in all four of these venues. Okay. This is the paper that we published in March in Frontiers in Nutrition called the Metabolic Matrix, re engineering ultra processed food to feed the gut, protect the liver and support the brain. And these are the primary drivers. This is not reformulation.

This is re-engineering. Apologize for that. And we actually submitted every single item that KDD purchases and uses. to biochemical analysis by the chemical company Eurofins to actually determine not just what’s in the food, but what’s been done to the food because the vendors that supply KDD with their products don’t necessarily tell them the truth.

We needed to know actually what was in all the food. And so this was a three quarters of a million dollar project analyzing it all by itself. We then developed the criteria that I just showed you in terms of the matrix. We also developed a tiers criteria on what had to be done to any individual item in their portfolio, and they have 180 items in their portfolio to move it from metabolically toxic.

Too metabolically healthy and all the steps in between, and I won’t bore you with all of that other than to just show you that KDD has taken our advice and 10 percent of their products have now been turned over on the shelf Here’s an example of the original chocolate milk recipe here. This is the re engineered chocolate milk.

Here’s the original chocolate ice cream Here’s the re engineered chocolate ice cream. This continues as we speak the point is that Who tech and medicine and now meet to advance metabolic health. We need public health intervention, which would be one population at a time. We need personalized intervention like we’re talking about today.

One patient at a time, which, for instance, perfect can help with and we need technological in for innovation. One company at a time, which is what Katie D is doing. The good news is other companies. Are starting to get the message that paper in Frontiers of Nutrition is now amongst the most quoted papers in the history of Frontiers of Nutrition, and we are starting to get requests from other companies around the world to talk to converse with them to see what would be necessary for them to be able to undertake a similar exercise.

With that, I’m happy to answer any questions, Tom, that you have or that the audience has.

Tom Bunn: Just one  follow up question, and then we’ll get to Pranitha. But, so, you hear metabolic health, you hear insulin levels too high, but what about the panacea of these GLP 1s? How do those… How do those play in?

What are they helping? What are they just band aiding over?

Robert Lustig: Right,

So I’ve actually written on this. Look, I’m glad GLP 1 analogs exist, but if you think that this is going to solve the obesity epidemic, I got a bridge to sell you. This is not going to work. It’s not going to work for several reasons.

So the first reason is The side effects, one third of people who go on GLP 1 analogs go off them, and it’s not because they lost, didn’t lose weight. It’s because they sick to hell. Okay, it causes nausea, vomiting, causes permanent gastroparesis, causes pancreatitis. Previous versions of GLP 1 analogs, like Exenatide, were associated with pancreatic cancer as well.

Now, why do these all happen? The answer is because GLP 1 analogs bind to receptors in the medulla, in the brainstem, and tell your brain you’ve eaten. Now, that’s good, because you eat less. The problem is, when you try to eat, your body tells you, Hey, I’ve already eaten, I’m sick to my stomach. which is why all of the symptoms are GI.

Basically, what you’ve got is a defect in gastric emptying. This is why these medicines work, is a reduction in gastric emptying. And that is not the best way to do this. And when you look at the GLP 1 analogs, which is done with DEXA scanning, turns out you lose as much… Lean body mass muscle as you do fat mass.

Well, that’s exactly what happens in starvation. So the reason GLP 1 analogs are working is because they are inducing a starvation state. Is that a good thing to do long term? Ask any little old lady who breaks her hip whether she wishes she had a little bit more muscle.

In fact, this is probably not the best way to do this, and certainly not for the people who are sickest. That’s the second problem. And then, of course, the biggest problem is if everyone in America who qualified for a GLP 1 analog got it, that would be 2. 1 trillion dollars to the healthcare 4. 1 trillion.

It would be more than 50 percent increase. In total expenditures, and we can’t afford the health care system we have now. I mean, we’re already bankrupt bankrupting Medicare by 2026. If we actually paid for GLP one analogs for everybody who needed them. Okay, we’d be bankrupt by tomorrow. So this is not the answer.

The question is, does it make sense to take a medicine that will reduce your weight by 16 percent and make you uncomfortable and potentially ill, or does it make more sense to take the sugar out of the food and reduce your body weight by 29 percent and actually be metabolically healthy and fit at the same time and save 3 trillion while we’re at it, which makes more sense.

The answer is easy.

Tom Bunn: Thank you, Dr. Lustig. I appreciate that perspective as always, and I’m sure there’ll be a cascade of questions come through. Should time allow, but want to switch to Pranitha with Function Health. Pranitha, thank you very much for joining us today and would love for you to just kind of give.

Not only the origin story but, also an overview of what, function health is and what it does. Absolutely.

Pranitha Patil: Thank you. It’s been fascinating to hear from both Dr. Lustig and Dr. Hull. So thank you. I, am, as I mentioned, one of the co founders and the COO of Function. And Function is a new way for people to take control of their lifelong health.

And we start with health data, which is. a big topic of today. We have an annual membership and it starts with whole body lab testing. We look at over a hundred markers, including some of the things that were mentioned today, fasting insulin, APOB, uric acid, and so many more. We have a 100 markers that we test that are looking at the state of organs and organ systems like your heart, your home hormones, your liver, and more.

And we start with this as part of the solution. We’re bringing together past datasets so that we have power back into the hands of Individuals and people folks have a misunderstanding of where they are with their health and they ask for testing with their doctors. Many of them are turned away, including myself.

So I’ll share just a very small story of my origin story with function and how it’s all started. We started Function 2 years ago to build against this vision of. putting power back into people’s hands as individuals so they can control their health. And my personal journey began over 15 years ago. I had my fair share of health challenges.

I would track my blood work in a spreadsheet and honestly just ran experiments on how does this food impact my blood work and my body and my overall energy and spent many years doing that on my own independently. And then I worked. With healthcare companies through Accenture’s digital health strategy consulting practice with payers with providers and maternal health in India and Africa.

And then I said, okay, I think I want to work on redesigning and reengineering. the healthcare system in the U.S. So I did what many people do. I went to grad school thinking I would solve my problems going to grad school. And I actually met my co founder, the CEO of Function, Jonathan, while I was at grad school, the Harvard Design Engineering Program.

So you can think design, engineer, new health system, right? And I dropped out of school so I could Function in 2021. And that was when we actually also I joined forces with Dr. Mark Hyman, who is one of the leaders of functional medicine. Many people on this call probably know him. And we built out this entire test of, list of tests of 100 biomarkers that we want folks to get tested.

And this is done twice a year. You get 100 in the first set of tests and you get about 60 to say, okay, here’s some behavior change and lifestyle modifications I’ve made. How has that impacted my biomarkers? So that’s an overview of function as well as my origin story with function. And it’s been two years.

And we’re just getting started.

Tom Bunn: Fantastic. And I should say I’m, a proud user of function, have enjoyed using the product over the last year. I’ve had two blood draws. Done and have been very impressed. One of the things though, Pranitha is I’m, still curious and have some questions around how this ties in with the closed loop of my own health journey as it relates to my, PCP specialists.

Can you talk a little bit about how, your product, how function ties into people’s independent relationships with their other doctors?

Pranitha Patil: Absolutely. So one thing to note is we work with physicians. They’re part of a partnership that we have just to start. So a member comes into function. There’s a physician that’s approving the lab order reviewing their medical history and then providing written commentary based on their medical history as well as the test results.

So that’s just one thing to know. You probably received this as well. The second question is a really important one. The how do we get people across the finish line? And this is an ongoing process. Challenge that we know exists. So we think about this in a couple ways. The first is there is definitely a world in which a member has to go see either their primary care doctor or a specialist.

So how can function connect people with specialists? That’s something that we’re working on. When you do take a list of labs to your physician, you might be turned away. They might say, why’d you get all this stuff done? I don’t know how to answer this. That’s something that we’re looking to say, okay, member, can we arm you with not only information about the biomarker, but what questions to ask, how to get the information you need, how to advocate for yourself in the doctor’s office so that you can get the information you need.

Because everybody on this call knows health is built outside of the doctor’s office, it’s built in the home. So how do we make sure that that information is provided to those folks so that they can cross the finish line? And it’s ongoing again, because you heard this from Dr. Lustig, like, everything is personalized.

You can’t say, hey, Population of 100. Do this. You’re set. Everything has to be on the individual basis and what they need as well as their medical history. So it’s an ongoing challenge that, we’re looking to solve.

Tom Bunn: Fantastic. So currently the product has some component of, nutrition as, a part of it.

Would love to hear plans for future iterations of the product. What other tuck ins you might you’re contemplating from a product point of view, whether that’s more robust nutrition recommendations. microbiome, other tests, et cetera.

Pranitha Patil: Yeah. So our goal is to build a platform that has a 360 degree view of one’s biology and one’s body.

So that means wearable data. That means their nutrition, their diet interest, their biomarker data, how that evolves. And so one of the things you’ve seen also is we test for nutrients. We understand that. Yeah. Where people are at, we test for hormones, we test for heart, and that is a core piece of the product.

The next layer on top of that is how we make connections with information on how this impacts this. And what we can tell an individual as far as next steps to take. So this is if ever evolving and that might come in the form of future meal plans or what ingredients to think about purchasing when you go to the grocery store.

This is all kind of coming soon with function and we’re building that into our product roadmap. But the goal here is to provide access to lab testing, empower people to own their health and. Really just make decisions in the home. When it really matters.

Tom Bunn: Fantastic. And in terms of perhaps risk mitigation on your end if you go in and they have a elevated PSA, for instance, or an abnormal or depressed biomarker.

What’s the, playbook on your end for addressing that and tying in a specialist or, otherwise?

Pranitha Patil: Yeah. So for any critical value, what we, call as critical value our function member gets a call from a clinician. That call with the clinician goes over that biomarker that is critical and they discuss a plan of action so that the individual knows what steps need to be taken to ensure that’s addressed.

So that’s something that we do actively with our members today.

Tom Bunn: Got it. Thank you. We have about 10 minutes left. I do want to get to some questions I know have come in. But also if there are questions among the participants or, commentary that would certainly be okay as well. But we had a anonymous attendee write to Dr. Hull. Are you familiar with novel therapeutics derived from the human microbiome? You mentioned fatty liver disease and recent research has found live biotherapeutics are the most potent known liver cancer chemo chemotherapeutics by a factor of 1000 X and mouse models compared to sore, sorefinib.

Allison Hull: Can you repeat the very first part again? Am I familiar with?

Tom Bunn: Novel therapeutics derived from the human microbiome.

Allison Hull: Oh well, not in that level of detail. I definitely am aware of the impact of the gut microbiome on every component of our health and well being. The 300 trillion micro organisms that dictate so much more than about movement.

So I think the trouble with the gut microbiome is the ability to capture that information. And, make it meaningful. I know there’s so many efforts out there and I 100% the, the healthier food we eat, that fiber that we’re talking about here, that feeds that gut microbiome, you remove that sugar on those processed foods, you increase omega three fatty acid.

So it’s an area that I’m getting more involved in. And I think we’re going to learn so much here in the next few years about the interplay and the use of the gut microbiome as a therapy.

Tom Bunn: Fantastic. Thanks, Dr. Hull.

Robert Lustig: Can I address that real quick? Please. The primary modality that’s microbiome based that’s available today is probiotics.

So I have a question. Has probiotics fixed any disease? Not yet. So here’s the real question. Probiotics are active cultures. You take a probiotic. It’s a bacterium. It should set up shop. You should only have to take it once, and it should pop, repopulate your intestine with the bacteria of choice. But that doesn’t work.

You have to keep taking it. Why do you have to keep taking it? Well, you have to keep taking it for the same reason that the bacteria is not there in the first place. The intestinal milieu is not hospitable to its growth. That’s what killed it off in the first place. So how successful do you think you’re gonna be by adding it back in until you fix the intestinal milieu?

That the bacteria grows in that’s not called probiotics. That’s called prebiotics, making the intestine a fun place for bacteria. And then the bacteria will populate itself. And it’s been shown by Peter Turnbaugh and many other people at UCSF that the microbiome will turn over and change within 48 hours of adding the most important prebiotic to the diet. It’s called fiber. That’s fiber’s job. Fiber is your prebiotic. It is the food for your bacteria. So yes, we have learned a lot about the microbiome. We have learned how important it is. Yes, it is essential to fix, but the best way to fix it is by fixing the food.

Tom Bunn: Agreed. Thanks for that, Dr. Lustig. We also had a question come from Natalie Davis or Pranitha. Does the $500 include initial tests and follow up tests at three to six months?

Pranitha Patil: Yes, it does. So Function is $499 for the year and it includes 100 biomarkers for your initial tests and then follow up tests, about 60 biomarkers. And one thing I didn’t do is actually ask you to go to the next slide, which is just can show folks a quick overview of the Function Health Platform just what it looks like.

If you see this slide. This is kind of what it, what you’ll interact with after you’ve completed your blood work. And then if you go to the next slide, you’ll look at a deep dive on some charts that we have and information for each of the biomarkers, as well as all the physician reviews and lab results of record.

So yes, short answer is that it is included. And what I’ll do right here is send a code to those on this webinar, if they are interested in joining function. So you can skip our wait list in the chat.

Tom Bunn: Fantastic. Definitely check out that that link in the chat. Wanted to go, around or, ask the broader group about kind of the next era of, personalized nutrition and what that entails, whether that’s new biomarkers.

Dr. Lustig, you have the, kind of the eight pathologies underlying a lot of the chronic disease. I’m wondering what as if there is any low hanging fruit on the horizon for important biomarkers that perhaps are just at the precipice of being uncovered. All right. Well

Robert Lustig: Again, I have to do disclosures. I am the chief medical officer of a company. that makes a dietary supplement that promotes autophagy. Now, autophagy is one of the eight, hateful eight in my book, Metabolical. Autophagy is like recycling of defective components of the cell. in order to clear them away. It’s garbage night for the cell.

That’s what autophagy is. Mitochondria burn out, proteins aggregate, lipids peroxidate. You got to get rid of the junk before in order to keep the cell healthy and fresh. Otherwise the cell is going to be burdened and is going to die. Turns out there is a compound in food. It’s actually very high in the Mediterranean diet and maybe one of the reasons the Mediterranean diet has been associated with longevity.

That compound is called spermidine. And spermidine stabilizes DNA during cellular repair. And it also promotes autophagy by inducing an enzyme that binds to an oncogene that basically takes the cell out of cell division. That enzyme is called, that protein is called Beclin 1. We have now done a clinical trial that showed that giving a proprietary formulation which boosts spermidine In people raises Beckman one levels improves cardiovascular parameters and have effects.

And so that’s one potential thing we could be doing to try to improve metabolic health going forward. That company, by the way, is called Kalin Health, K A L I N, which stands for the founders of the company, by the way. Nothing is nothing scientific but in any case that’s one possible option.

The, ultimately, the only thing that’s going to work Is fixing food and I am a great believer in fixing the food so that it is metabolically healthy. And I think there are ways to do that. And we proved that we can do that for a large food company. We need to be able to do that here in the United States.

In order to to be able to mitigate this this pandemic. And that’s not going to really be a personalized intervention. That’s going to be a societal across the board intervention. So there are things individuals can do, but we need society to work too. Dr. Hull any, thoughts there?

Allison Hull: No, I mean, I totally agree.

I mean, I think while we want to kind of investigate the latest and greatest on these biomarkers, I feel like we’re missing the most important point which is. We don’t have to get so fancy sometimes with these investigations if we can do some simple things in providing the right path for patients.

As a pediatrician and an adult internist, I mean I, have pediatric patients. My youngest patient with fatty liver disease is nine. I have multiple kids, 13 and 14 years old that are pre diabetic fatty liver insulin resistance. And. I think the priority needs to be in the public health sector, right?

Population health, empowering individuals. I think too, it could be a social movement. Let’s use TikTok to actually do something good for our kids. And in order to change that child’s behavior, it’s got to start with the parents. So it’s a multi kind of generational problem. But technology is wonderful.

But we as a species it’s… If we do some simple things, we can garner much headway in societal health.

Robert Lustig: Tom, I forgot one other thing. When I was at this meeting in London, I did hear Aaron Siegel, who is a computer scientist epidemiologist at Weizmann in Rehovot, Israel, talk about the Human Metabolome Project, and they are doing some really neat stuff in this space.

They are determining the microbiome of hundreds of thousands of people and then correlating that with their cardiovascular and metabolic status to determine which bugs are missing or which bugs are in excess for which problems in which patients. And then they are designing with CRISPR bugs that will then be given to patients that are missing whatever it is that they need in order to try to improve metabolic health.

That is basically Brave New World. So there is stuff going on and it is personalized and it is technologically savvy. I just think we’ve got a lot of work to do to fix the problems that are on the plate now. Absolutely.

Tom Bunn: Certainly the work is cut out for all of us and particular for all of you at the front lines of this problem.

But with that, I want to thank you all for your time. Dr. Hull, Dr. Lustig, Pranitha, thank you for joining us today. If you’re listening to this retroactively please don’t hesitate to reach out if you have any questions. And we hope to see you next time on the iSelect Deep Dive series.