Advances in Nutritional Science
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Tom Bunn: good morning everybody and welcome to IS Select’s Industry Overview webinar series. My name is Tom Bun, I’m an associate on the IS Select Fund Ventures team, and I’m excited to walk you through today’s presentation and findings for those new to these webinars. I Select is an early stage venture capital firm in St. Louis, Missouri. Focused primarily on early stage companies in healthcare and ag. AT IS Select, we are privileged to live at the forefront of innovation, seeing emerging problems, solutions, trends at their beginning, before they make their way into popular culture. We use these webinars 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 such topic is nutrition. I select invests at the nexus of food and health, and many of the most disruptive technologies in this field have and will continue to have nutritional science at their core. Is select is mapping towards what we call food system C, which offers affordable, nutritious, healthy, and tasty food at scale, and a price parody or discount to junk food, for lack of a better term.

This is in contrast to what we call food sy Food System a. Which is a proxy for the food system, which developed in the post-war boom and is a product of the, Green Revolution, which brought calorically dense food to the masses. It’s also in contrast to food system B, which is what we call the very fresh, tasty, but very expensive food often found at whole foods and the like and is price or geographically prohibitive to the masses.

So a lot of our thesis in, this area is really bridging food systems A and food systems B, to bring the cost of healthy, nutritious food down. So for this reason and many others, which we’ll cover in today’s webinar, advances in Nutritional Science are up Utmost Interest to select. Before we get started, 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. Secondly, we have invited you to this because you are technologists, thought leaders, entrepreneurs, industry experts, early adopter customers.

Or sophisticated investors that are part of our network at isec, we value your thoughts and questions. So please do feel free to type questions into the chat, pain or q and a pain. We will have hopefully some dedicated time at the end for a broader q and a time as well. However, that being said, we do ask you to put yourself on mute for the time being given some background noises.

I’m contending with some construction on the floor above me, so hopefully that doesn’t become too distracting. But again, feel free to unmute yourself or ask a question if the spirit moves you. Finally, this presentation is being recorded and will be available for replay. So with that, I’m pleased to bring you this week’s deep dive on advances in nutritional science.

So what we’re gonna do today, we’re gonna begin with some introductions, some speaker introductions. In the interest of time, I will introduce the panelists. Then I will impart a short background on the landscape, nutrition and chronic disease. And then I’ll hand it over to the, researchers we have here get their perspectives on some of the cutting edge work they’re working on.

In this field, and we have a couple entrepreneurs as well, showcasing their nutritional or nutritionally based startups. Again, we will have some time at the end for considerations going forward. Questions, hopefully this is a cross pollination event. Questions are encouraged in and among the the panelists as well as for the, broader attendees and all the folks at I select.

Huge thank you to our experts and panelists. Thanks so much for joining us. This morning I’d like to introduce Dr. Keith Barr. Keith is a professor at uc Davis and the head of the Functional Molecular Biology Lab there, where he studies how the musculoskeletal system functions, including how diet and physical activity affect muscle growth and how tendons and ligaments respond to the stresses of exercise.

He pursued a master’s degree at. Uc, Berkeley and a PhD at the University of Illinois where he discovered the molecular mechanism’s underlying muscle growth in response to exercise. In addition, over the last 15 years, Dr. Barr has worked with elite athletes as the scientific advisor to Chelsea Football Club, U s a, track and Field, Paris Saint Germain Football Club, British Cycling, the English Institute of Sport, Lester Tigers Rugby, and the Denver Broncos.

Next we have Susan Bratton. Susan is the founder and c e O of Saver Health, a startup that harnesses the power of health and nutrition data to provide personalized nutritional services to those suffering from chronic disease. Susan left her career on Wall Street and spent two years researching the scientific literature regarding the symptoms and side effects experienced by cancer patients and interviewing cancer patients, caregivers, and the medical professionals who treat them so that she could create a solution to address these unmet needs.

In a scientific and clinically appropriate way. We also have Dr. Ellen Gross. Dr. Gross is the c e O and CS O of Keto Swiss, which is a Swiss biotech startup that develops highly potent therapeutic ketones for neurological disease prevention. She holds a Master’s of Science and Neuroscience from the University of Oxford and a PhD in clinical research from University of Basel in Switzerland, a former migraine sufferer.

She has used her research to target exogenous ketones. For migraines and other neurological disorders. Next we have Doc Dr. Robert Lustig. Dr. Lustig is a pediatric endocrinologist. He’s a professor of pediatrics in the division of endocrinology at the University of California San Francisco, where he specializes in neuroendocrinology in childhood obesity.

He’s the author of the 2013 book, fat Chance Beating the Odds Against Sugar, processed Food, obesity and Disease, and his upcoming book is called Metabolical. The lure and lives of processed food, nutrition, and modern medicine, which is scheduled for release in May of this year, I believe. Finally, we have Dr.

Darsh Moza. Farian. Darsh. Moosa. Farian is a cardiologist, Dean and Gene mayor, professor at the Tufts Friedman School of Nutrition, science and Policy, and Professor of Medicine at Tufts Medical School. Dr. Moza Farian has authored more than 400 scientific publications on dietary priorities for obesity, diabetes, and cardiovascular disease.

On evidence-based policy approaches and innovations to reduce these burdens in the US and globally. He has served in numerous advisory roles, including for the US and Canadian governments, American Heart Association, W H O, and United Nations. His work has been featured in a wide variety of media outlets, New York Times, wall Street Journal.

To name, but a couple. And Thompson Reuters has named him one of the world’s most influential scientific minds. Additionally and close to home. He is also an advisor to Eye Select Portfolio Company, bright Seeded Bio which has a discovery platform for plant-based phytonutrients and bioactive ingredients that can be used in the fight against chronic disease.

So with that, let’s get into it. So a couple background and trend slides just to set the stage so to, to lay the groundwork of the importance of this issue. This slide shows the economic toll of some major chronic diseases for which nutrition is a leading cause. You can see cancer up at the top costs roughly 80 billion annually, and a recent study shows that 5% of new cancer cases have nutrition as their cause.

That study actually was partially contributed to by, by Dr. Moza Farian would love to touch on that in a bit. Diabetes, obviously a huge chronic disease and, one that’s obviously come to the fore in terms of healthcare costs. Costing 327 billion annually and one in four healthcare dollars significantly is going towards diabetes.

Important to note that this is not just us. There is, as far as we can tell, not a single country in the world who has stable or decreasing rates of, diabetes. So while this slide is focused on the US these, problems are obviously global in nature. Cardiovascular accounts for 351 billion annually in costs and it is the leading cause of death and accounts for one in four deaths in the us.

Finally, obesity. You can see the 1.7 trillion number here, which is a staggering, figure. So that accounts for total indirect economic impact due to loss, productivity and all the accompanying costs around that as far as direct healthcare costs, it’s estimated at about 480 billion, which still trumps.

The three preceding disease indications I’ve just listed here, and we will hopefully be talking about Alzheimer’s a little bit, but in the interest of time and space here Alzheimer’s isn’t listed, but it’s estimated at 300 billion in, total cost in, 2020. And it’s been implicated in a lot of nutritional science and in some cases it’s referred to as type three diabetes.

In some studies have shown that people with type two diabetes may be twice as likely to get Alzheimer’s disease. Hopefully, when we get to Dr. Gross and some of her work around exogenous ketones, we can touch on that a little bit more.

This slide here is from a presentation I viewed that was put on by Dr. Mo Farian. And it shows that, this is a comparative risk assessment, basically, that it attempts to model the causes of disease from different risk factors. So you can see the number of deaths on the x-axis and the causes on the Y axis, and then the colors are the types of death.

So you can see the kind of the blue is more on the chronic disease scale of diseases. So the conclusion here is really that food is the single biggest cause of poor health in the us. Trumping tobacco, smoking, high blood pressure, high body mass index, and all other causes of death, which is astounding and and, important.

So these last two slides and some were very sick and nutrition is seemingly the smoking gun here. So what do we do about it? What what’s the takeaway from what we just said? Obviously, Simplistically, we should get smarter on nutrition. But as you have probably all seen on Google searches, good Morning America, et cetera, it is very hard to wade through a lot of the noise going on in this market with headlines like these contradictory headlines all the time.

It’s impossible to understand what’s true and what’s not. Seemingly every day there’s a new shocking. Or contradictory study that contradicts the study from, last week or even the day before. Examples of this, is keto good or bad plant-based diets are they the best or are they in, in the podcast fear, the carnivore diet seems to be making the round, making the rounds.

But an equal number of studies show the kind of the dangers of eating meat. Intermittent fasting. Is that good or bad? In short, people are. Simply bombarded by reports, studies, bloggers, influencers, you name it, that, that make figuring out what, true nutrition is.

And optimal nutrition is incredibly difficult in today’s day and age. So with that I will get right into it. Would love to, to feature Dr. Moosa Farian first. Dr. Moosa Farian. How, do you wade through? How do we get to something that is less confusing for the public around what to eat given what we know about the increasing contradictory headlines?

How do you think about showcasing what’s true?

Dr. Darius Mozaffarian: That, that was an excellent overview. Tom, you covered a lot of the, crucial issues and I think that just to again, emphasize if we care about health, this is the top cause of poor health in, our country and the top cause on the planet.

And so we’re not gonna address health. Or rising healthcare spending until we fix fixed food. And and there’s billions of dollars being left on the table, billions of dollars being left on the table in preventable healthcare spending. And so the, companies that capture that, whether it’s ag retail restaurants personalized nutrition wellness should be rewarded.

And we need to create way ways for companies to be directly rewarded. And I hope we can talk, about that too. I, think for the, confusion. You, highlighted the Green Revolution and the goals of the Green Revolution in the fifties and sixties, which was to prevent a planet from, starving, and also to get a handful of vitamins and minerals that we had knew about then into the population.

And so if you walk down the cereal aisle today, that cereal aisle was, a very consciously created set of products to meet a need to provide vitamins and starchy calories to the world. And it was successful. So I really, this I, don’t think we should be bashing industry. Because industry did what we told them to do.

They made starchy staple foods that were fortified with a handful of vitamins. That’s what we told them for 60 years to do. And so I think the, first point about the confusion, one of the reasons there’s confusion is that this is a very, young field. Nutrition, science. The first vitamin ever isolated and synthesized was 1932, right?

That’s, less than 90 years ago. And then the, next 70 years focused on nutrient deficiency, diseases and calories. And so it’s really only been 20 or 30 years that we’ve started to, really think about and understand in, a meaningful way, diet and chronic diseases, cardiovascular diseases, brain health and micro, the gut microbiome headaches and neurologic diseases.

All these issues. So, I think the reason there’s confusion is this a very young field and we don’t have enough science to answer many questions. Now that doesn’t mean we can’t say anything. And so there are broad, truths. But we don’t have kind of an authoritative, credible voice speaking about science, and the public doesn’t trust the government.

The public doesn’t trust business. And, so I think it’s a very challenging situation. You know what, we try to do is direct people to a academic, reliable, science-based sources of news, but those are really overwhelmed by the cacophony of other voices. Often for profit voices trying to make a, buck off of saying something.

That’s, more controversial. So I think it’s very challenging. I, think that universities and businesses and nonprofits and government need to get together and, say that we, have to create a better way to communicate to the public. And one thing that we’ve proposed is that the n I h create a new National Institute of Nutrition.

As I mentioned, this is the top cause of poor health. We’re not investing nearly enough in the science and innovation to spur all of the, great discoveries. Think about Isec and, your portfolio companies. If the federal government was spending a couple billion a year, two, 3 billion a year, which is pennies compared to the healthcare spending on advancing nutrition science, it would help all of your, businesses.

So, we think a National Institute of Nutrition at nih. With significant new funding could advance the science and be a trusted communicator of the science of the public. And we’ve also recommended for a federal leadership office on food and nutrition in the cabinet at the White House. And cuz there’s really no leadership in the White House on food and nutrition structurally.

And so, I think it’s a real challenge. But I think for now we’re gonna be for the next 10 years, I think. Until those things happen. Unless those things happen, we’re going to be stuck because. There’s many, voices who have a, buck to a, quick buck to make by having a, startling headline about some new discovery.

Tom Bunn: And, yesterday I was listening to a, conversation that you had with Sanjay Gupta from Mindy Bao. And I, think a highlighted section for me there was. When you said we don’t have enough knowledge to outline what the major causes are with quantitative certainty for obesity, type two diabetes, cancer, and heart disease.

So first of all, I wanna say I, I respect the humility there from, someone of your research stature. But I guess, what can we say with quantitative certainty at this point? What are you certain about?

Dr. Darius Mozaffarian: We know even if with big, broad, rough averages, it’s, we know diets a single leading cause for health.

We know it’s largely driven through metabolic illness. Diabetes, obesity heart disease, stroke are, the top, drivers and much learning much, more about g gut health and brain health and cancer. It’s not gonna be. As big for those diseases compared to some other risks but very, important.

And so we know it’s the biggest cause. And from one estimate we, you mentioned in a paper we published recently that 5% of cancers are due to, poor diet. And we estimated when it comes to cardiovascular diseases heart, attack, strokes and, diabetes. 45% of those are directly due to poor diet.

Almost half. Of all of the cardiovascular disease and diabetes in our country could be prevented if we had a healthier diet. And then I think there are big picture things we know about what, foods are healthy for us. And I, put foods in three buckets. I think it’s. Wrong to say eat everything in moderation.

That’s not the right approach. That’s eat all the terrible food in moderation. That’s actually absolutely not what we want. That would be like you as a investor saying, I’m just gonna invest in all startups in moderation. No, You wanna pick the winners and drop the losers, right?

And so similarly for food, there’s winners and losers. So I think there’s three buckets. There’s foods that are really good for us, foods that are neutral. And neutral is, okay. We can eat neutral and there’s foods that are really bad for us. And, so foods that are really good for us, Are fruits, beans, vegetables, most of which are actually fruits, nuts, seeds, minimally processed whole grains, yogurt and fish.

And if you look at that list, the things they have in common mostly are, they’re phenolic, phenolically rich. They have thousands of bioactives that we’re still just barely starting to, understand. They have fiber, which are really really think of as prebiotics for your microbiome. They’re slowly digesting and.

Fish has omega-3 S yogurt has probiotics, so there’s other benefits. I think those are the, top beneficial foods, and I think we know that starch and sugar and salt are really bad for us. And over the last 10 or 20 years, one of the mantras became fat, sugar, and salt. And I’m really trying to change that to start sugar and salt cuz most fat is actually good for us.

And so start sugar and salt is really what’s, terrible and, starch and sugar is about 40 to 50% of calories in the food supply. So that’s a big, chunk of the food we have to avoid. And then everything else is the stuff we should probably be eating in moderation. Butter, cheese, unprocessed red meats the food poultry foods that aren’t really.

Incredibly bioactive or positive or aren’t incredibly negative. So that’s, I think, the big picture, what we know, but there’s so much uncertainty and, unanswered questions after that.

Tom Bunn: Sure. Curious about your research on fatty acids. So when I mentioned you did Dr. Lustig you mentioned that you’re the best in the big leagues on, this subject.

How would you distill your research on that subject down to action advice?

Dr. Darius Mozaffarian: This is what got me into the field 25 years ago as a training physician I, realized that food was, killing and harming my patients more than anything else, and yet I wasn’t learning anything about it.

In, in I did 19 years of training from college through to my PhD, 19 years. And until I got to the public health, I hadn’t learned anything about food and nutrition. So I wanted to learn about it myself. And so in the mid nineties, I started reading the science myself to understand. Why we were recommending low fat, low saturated fat, low cholesterol diets to our patients.

Cuz that was the recommendation, right? You had a low fat diet and even in the nineties, the science didn’t support those recommendations. There was no strong evidence to support a low fat diet in the, even in the nineties. And so that, those two things. Hit me. If I wanna make a difference in, in, people’s lives, I have to better understand food and nutrition and translate it to the public and policy makers and, the business community.

So, I started researching fats because if fats aren’t bad for you, we have to understand them. And so I think I would distill it as top, take home messages first. We should stop thinking about. Nutrients generally, and we should really think about foods. There’s foods that are good for us.

And so I think plant foods in particular that are rich in unsaturated fats or the oils from those plants are very, good for us. And so we really should be maximizing and increasing oils from, plants and from seafood and whether it’s as the food or as the oil. And there’s a lot of misinformation on this.

On, on, so on, on social media. Somehow the keto, paleo. Group that is right about avoiding starch and sugar has also latched onto avoiding seed oils, which is crazy, like soybean oil, safflower oil peanut oil these are really healthy oils and somehow there’s this very strange social, media that these seed oils are, unhealthy.

So that’s one. Take a message. Fats are your friend. You really gotta eat a lot of healthy fats. And then secondly, saturated fat, I think is, has been a big distraction because, Cheese is not, yogurt is are not nuts or not, bacon is not a fresh steak and all of us have saturated fat.

So you can’t tell someone to lower saturated fat. It doesn’t have any real meaning cuz it depends on the food and the source that it’s coming from. So I think those are two big take home messages to not count grams of fat or grams of carb even, and just eat, healthy foods. And then lastly for the investors in the science and thinking about a company like Bright Seeded, which you mentioned.

Fatty acids are among the most bioactive and bio biologically interesting nutrients out there, right? They’re not just calories of calories. They affect your genetic function. They make up our cell membranes and affect how our cells communicate with each other. They turn into things like interleukins and maurin and protectins and all these incredible bioactive molecules that at that, at Picogram quantities.

Alter inflammation and, cell signaling. So, I think fats, carbs are pretty inert and most proteins are actually pretty inert. Fat, fats are not inert. Fats are really biologically interesting. So, I think that’s also really a, key take home message.

Tom Bunn: Great. Just a couple shots from the Foodist Medicine.

Key facts from Tufts University. One of the studies that you were part of around the association between dietary factors and mortality you focused on 10 foods with health, impact. I found that that very interesting. Can you walk through the, methods there and, what you team is most important from, the infographic on the left.

Dr. Darius Mozaffarian: Yeah. So you know, whenever you hear anybody say this, many people are dying from smoking, or this many people are dying from air pollution or, so on you have to model that using all the best available data. And so we did this for diet. We said using the best knowledge that we have about how these suites affect health, their current intake levels, the current rates of disease what are our best estimates of how these are directly affecting health.

And that chart you show there is the numbers of. Heart disease, stroke, and diabetes deaths. That we, found due to these factors that we thought had the strongest evidence for, harms or benefits. And I think that one one key take on message, like I said, is the green bars.

And that to me is where we should be focusing. In the business community. There’s a lot of good, there’s a lot of good that we’re eating too little of, and so nuts and seeds, seafood, vegetables, fruits, whole grains and, healthy fats. Like we’re, that’s actually causing similar or more disease than the bad.

And I think our policy, measures and our approach to business in the public health community has been to attack food companies for the bad. I think we need to celebrate the good and, encourage the good. And reward the good. So I think the green bars, there are the foods and ingredients that we should be getting more into the food supply.

Tom Bunn: Great. On the right is I think some, research interests from, your lab and, your institution. I’m excited to, to see what comes next. As you have been a prolific author we can get back to that if time allows. But one question I’d like to ask everybody is if you have a bill, if you could put anything on a billboard for you, Dr.

Zafar, and let’s stay in, in Kendall Square or on mass on the Mass Turnpike. What would your billboard say? Health. Health related,

Dr. Darius Mozaffarian: ideally. Yeah. For now, right now, given Covid 19 COVID 19 is a fast pandemic on a slow pandemic of obesity and type two diabetes. And if we didn’t have the slow pandemic of obesity and diabetes, which has killed many, more people, then Covid will.

COVID 19 would be much, less severe. Far less severe. We would have already been probably through it like, like India is now. So I think what drives me crazy is the public is hearing about wearing masks and, hand washing and social distancing and vaccines, but nobody’s talking about metabolic health and better nutrition and, physical activity.

We should have just, we have a, an incredible missed opportunity the last year and since. Since we’re not through covid yet, and since more pandemics are gonna come, my billboard would say eat some more healthy foods and move a little bit more, cuz it’ll save your life.

Tom Bunn: Awesome. Thank you. Moving on to Dr.

Rustic. I took a liberty here. My, my guess about his billboard might be protect the liver, feed the gut. But I don’t want to, I don’t wanna speak for him. But Dr. Las, can you explain what you mean when you say protect the liver? Feed the gut? I’ve heard you say it a number of times.

Dr. Robert Lustig: All right. So the question first of all, d I couldn’t agree with you more. I’ve totally endorse and second, every single thing you said, except that food is medicine. Because food is medicine, only when it’s real food, processed food. Is not food processed. Food is poison, but we think of it as food.

And the reason processed food is poison is what I’m interested in. So when we talk about processed food what are we talking about? It’s not what’s in the food that matters, it’s what’s been done to the food. That makes a difference, and I’ll try to elaborate on that as we go. So my concern is that we have missed the what the elephant staring in front of us.

The diseases that Darius ticked off diabetes, heart disease, cancer all the chronic metabolic diseases. They are not diseases. They are the symptoms of the underlying pathologies that actually belie all chronic disease. Right now we are treating the symptoms, got a high blood glucose lower the glucoses.

You got a high LDL, lower the LDL. So we do this with drugs. The fact of the matter is, The drugs really don’t work, and the reason they don’t work is because they’re only treating the symptoms of the pathology, not the cause. If you want to fix a problem, you have to go upstream and you have to fix the cause.

And we’re not fixing the cause. We are fixing the result. And that’s why healthcare is going on in this ever ending now downward vortex. And we are not getting anywhere and we spend more money than any other country on the planet by far. And we get less healthcare for it is because we have attacked the wrong problems and the problems are because of what’s been done to the food.

Rather than what’s in the food. And that’s why the nutrition label is useless, is because it doesn’t tell you what’s been done to the food. And I’ll try to make that clear as I go. Next slide. Okay. The, point is that people think that those metabolic diseases, the diabetes, the heart disease, the cancer, the dementia, the fatty liver disease, et cetera, these are all due to obesity.

These are all downstream manifestations of obesity, therefore eat less. That’s been the mantra, the charge for the last 50 years, and it hasn’t worked, and there are a lot of biochemical reasons why it will never work. The point is, Those diseases are all mitochondrial diseases. Those diseases are all diseases of energy utilization, and very specifically, those diseases are all driven by eight.

Count eight, chronic pathologies, which are listed on this slide. B, oxidative stress, mitochondrial dysfunction, insulin resistance, membrane instability, inflammation, methylation, and autophagy. These are what I call the hateful or actually grateful eight because if you subserve those, You can be 110 playing tennis, and if you don’t, you’ll be in a wheelchair on dialysis at age 40, nursing your stroke and waiting for the grim reaper.

And turns out none of those have an I C D 11 code. None of those have a drug treatment, but not, drugable, but they’re all suitable. And the question is, how. Do you food them? And the answer is every single one of those is made worse by some aspect of food processing in terms of glycation.

It’s the addition of sugar and starch in terms of reactive oxygen species. It’s the removal of antioxidants. In terms of mitochondrial dysfunction. It’s the lack of omega-3 S in terms of insulin resistance. Again, it’s the addition of sugar and starch in terms of membrane instability. It is the trans fats and the lack of omega-3 S in terms of inflammation.

And, I could go on. Okay. In terms of methylation, it’s folate and the B-vitamins in terms of lack of autophagy. It has to do with very specific amino acids and also sleep. Bottom line is that we are poisoning ourselves. The food that we eat is poisoning us because it is basically driving and aggravating these eight separate pathologies, and it has nothing to do with obesity because 40%.

Of the normal weight population, get the exact same diseases as do the obese or normal weight. People get hypertension cardiovascular disease, type two diabetes lipid problems, cancer and dementia. And those thin sick people are calling the fat sick people the problem. So to me, The important thing is to address the problem.

The problem is what we do to the food, not what’s in the food. And unfortunately that’s not what we’re taught. That’s not what’s on the food label. And in fact, doctors aren’t taught anything about nutrition. Darius himself said he didn’t learn any nutrition in medical school. Guess what? Neither did i. I actually learned it in college cuz I majored in nutritional biochemistry and then when I got to medical school, they beat it out of me.

And perhaps that’s why I’m so passionate about this problem is because I knew in 1975 what the issues were. And then I went to medical school and they told me, nah, it’s just about calories. And it only w occurred because of the research that I was doing that I even came back to this issue. So I think that we’ve made a terrible mistake.

We’ve made a real wrong term in terms of medical knowledge, and it goes back to the Flexner report because Flexner did not believe in nutrition. In fact, it was dissed in the Flexner report of 1910, which is what all of modern medicine and how modern medical schools developed after that. Nutrition was relegated to the dregs.

Ultimately, the dieticians picked it up because the doctors didn’t. So don’t go to a doctor expecting any nutritional advice cuz they don’t know any. And so I think that a National Institute of Nutrition would be a absolutely wonderful idea, provided of course, it’s not co-opted by the food industry. And I think that getting nutrition into medical schools because, Ter.

Currently today, only 28% of medical schools actually have a nutrition curriculum. I think these things are absolutely essential if we’re going to turn this around and we have to deal with the process food problem, and we have to deal with it upfront. Terrific.

Tom Bunn: Couple co questions, we’ll come back to you, Dr.

Thank you very much for, that perspective. Moving on to, to. Dr. Keith Barr, who has done some fascinating research on, lifespan and healthspan with the ketogenic diet. For, mice. Dr. Barr, can you walk us through what you’ve been working on at uc Davis? Yeah, so thanks

Dr. Keith Baar: Tom. I’m happy to do it.

So again what, Darius was talking about is absolutely spectacular because really what we’re looking at and, even as we go through what we just heard, a lot of what we’re, what we look at is, how our decisions, how our behaviors are changing our lifespan. These are studies that you can’t really do in humans

Tom Bunn: very much because again, we’re starting.

Dr. Keith Baar: These mice on, a diet at, midlife. So they’re, starting halfway through their life, and then they’re gonna go and we’re gonna measure how long they lived. And, that’s not something you can do with a, 40 year old to 50 year old in, in human years because that study’s gonna take you 40 to 50 years to complete.

And so what we’re doing is we’re using this model, it’s not a perfect model, but we, try and take advantage of the model. And so what we’ve done is a couple of different things, and here it’s important to realize that we’re using. Again, as we talk about it, we’re using a processed food for these animals.

They’re gonna be held iso caloric, so that means the diets that we’re giving them are exactly the same calories for the control

Tom Bunn: diet. As for the low, we did a, low fat,

Dr. Keith Baar: sorry a, low carbohydrate diet, but was non ketogenic. And we did a ketogenic diet in these animals.

Tom Bunn: And what we

Dr. Keith Baar: found is that the. The low fat, or sorry, the low carbohydrate diet, it increased lifespan non significantly, about 6%.

And the ketogenic diet increased lifespan in these animals by

Tom Bunn: 13.6%.

Dr. Keith Baar: So they, increased their lifespan over that period, over the period that they were fed a ketogenic diet. And the reason that we look at this and that we’re interested in this is because It’s, what’s been said by the first two speakers is we’re, eating the wrong things and we’re not moving enough.

And so what we think is happening is it’s a combination of what happens when you exercise. Can you model any of those things by the food that you eat? And one of the things that happens as you shift towards towards a diet that has less carbohydrate is that you’re more dependent on maintaining mitochondrial function.

And as we just heard, mitochondrial function is one of the, key parameters in keeping cells healthy. So if you are going to use fats as a fuel, because you have to use fats as a fuel. You have to use your mitochondria in order to break down those fats. So those fatty acids can only really be used if you’re going to use mitochondria in order to do that.

Tom Bunn: And what we’ve shown happens is it that

Dr. Keith Baar: on a ketogenic diet, you can take a sedentary individual and you can actually change their muscles so that it looks like they’re doing. A little bit of endurance exercise. And what we showed in these animals is that not only did they live 13.6% longer, but their health span was actually increased.

Their grip strength was maintained at their middle-aged at their middle-aged levels. Their endurance, so their ability to use that muscle for time was improved and it was actually maintained at 26 months. Basically into their equivalent of 75 to 80 years old. It was maintained at the same level as they had at the equivalency of 40 years old, and the muscle mass was maintained as well, and we were

And, so the reason that we think that this is important, Is that we think that it’s doing very similar things to what exercise is doing.

So exercise is giving us this and we know that exercise also increases lifespan through, through animal studies.

Dr. Keith Baar: And what we think is happening is there’s this shared, there’s this shared mechanistic component of it. And that means that if we can increase the functionality of the mitochondria, if we can maintain those mitochondria for longer, we can increase the, Lifespan and the health span of the animals. One of the most interesting things that we found was this last piece here at the bottom, which is that the ketogenic diet that we were using was actually. Able to preserve learning and memory in these older animals. And what we think is actually happening is, that, and it’s this, again, it’s very similar to what happens with endurance exercise.

So when we do a lot of endurance exercise, even in humans, we see that learning in memory is improved. In the animal studies we show that the, or we’ve seen.

Tom Bunn: The, research has shown that, when you do endurance exercise,

Dr. Keith Baar: it increases the number of neurons in the brain, specifically in the hippocampus and other areas that are important for learning and memory.

And we see the exact same thing that’s happening with the ketogenic diet. And we think that mechanistically, the reason that’s happening is because, There are certain metabolites that circulate through the body that are basically breakdown products from amino acid metabolism. And one of them is a, product called Cain.

And when Cain gets across the blood brain barrier, it gets converted into quinlin acid. And that quinlin acid causes neurotoxicity.

Dr. Robert Lustig: And so one of the

Tom Bunn: interesting things

Dr. Keith Baar: that happens when you have more muscle and more mitochondria in your muscle is that you can convert that cain into something that can’t get into the brain.

So you prevent this neurotoxin from getting into the brain. So one of the things that we think is happening, And why we think the muscle is important in this is that the ketogenic diet, the exercise that you do is improving the mitochondrial function within all of that huge amount of muscle masks, 45% of our body mass.

And what that does is that’s preventing the this, neurotoxin from getting into the brain and having this neurotoxic effect which we know is important in, depression and Alzheimer’s.

Tom Bunn: Great. Thanks, Dr. Barr. That’s a great segue into, our entrepreneur showcase. But in some, from the, three researchers we’ve heard one of the things we’re wondering about is what what, say three things would you like to better be able to measure or monitor either in the food we eat or going on in our bodies that either can’t be or is too inconvenient or invasive to do today.

Measurement methodology in relation to a lot of this groundbreaking research. I would open that question to, to any of the three of you.

Dr. Robert Lustig: I’ll, take a stab first. Everyone and his brother are currently using continuous glucose monitoring as a modality for being able to try to limit glycemic excursion, which to be honest with you, is a very good thing to do.

And I’m not a against it. I’m for it. It’s become a cottage industry. Of biohackers running around with CGMs on their arm in an attempt to try to determine what foods limit glycemic excursion the most and more power to them. However, I do believe that this modality of just monitoring glucose only gives us about 10% of the equation.

I think it’s a small amount in the grand scheme cuz it’s not actually getting to where the real problem is. The real issue, and it’s related to glucose, is the insulin level. The postprandial insulin level dictates a lot of the processes that Dr. Barr just discussed. And so how high that insulin goes, which of course is subservient to the glucose excursion.

I’m not saying it’s not, but it is by, but it is way more complicated than that, including the amino acids, including the fatty acids, including. The insulin suppressive activity of soluble fiber that gets turned into short chain fatty acids in the colon. So that insulin response to food, I think is even more important.

And what we have also learned from our research at U C S F and Touro University is that the postprandial triglyceride rises, which has thus far been completely ignored. Because number one, it changes. Yes. That’s the whole point. It changes. Everyone measures fasting, triglyceride. Turns out what your intestine does to process carbohydrate into postprandial, triglyceride.

And that triglyceride has very specific and detrimental effects of its own. So being able to know what happens to your triglyceride level after you eat will end up being an extremely important piece of the, shall we say, personalized nutrition puzzle. People are working on wearables. That will be able to do these three measurements and actually a fourth measurement of C peptide cuz that you need the, C peptide to determine whether the insulin’s really insulin or pro insulin.

But those four channels, glucose, insulin, C peptide, triglyceride, people are working on wearables that would do those in real time and give you that information. And instead of just dumping the data, would actually interpret it for you so that you could actually monitor yourself and make. Changes on the fly.

Tom Bunn: Darius or Keith? Any, other thoughts there? I’ll let Darius go

Dr. Keith Baar: first, or I can go in. So, I would actually say that one of the things that, that we actually look for is we, do a, measure of endurance. Because for us, again, There’s, there are going to be genetic things that are going

Tom Bunn: to

Dr. Keith Baar: predispose people to diabetes, but if we can say that you have really strong endurance function, that’s going to give us a sense as to.

Your cardiovascular risk, it’ll give you, give us a sense as to a lot of your insulin sensitivity. It’ll give us a sense of a lot of

Tom Bunn: other components. And that’s

Dr. Keith Baar: something that we can do relatively straightforwardly that you don’t need any, any too much specialized equipment to do. You can just do a very simple endurance based test to actually see how people perform and how that’s going to be predictive of what their long-term performance

Tom Bunn: is gonna be.

Great.

Dr. Darius Mozaffarian: Yeah I, think my comments are more broad about kind of the, concept of personalized nutrition. I think that personalized nutrition personalized on many, factors as has been mentioned. Is interesting, but it’s gonna be a relatively minority solution to get us out of this mess.

We need public health. If you look at all the advances in human health, all the advances in any aspect of humanity, o over our, evolution, it’s been population-wide. Things that are, good changes in housing, changes in infection control, changes in water. So personalization will be interesting.

It will be important. It does have promise. We need to, pursue it. But big picture we, there are gonna be solutions that are true. We’re all humans. We all share the same biology and the big picture solutions are gonna be common. And that’s actually a positive message. Cuz if you were a business and you had to create a completely different product for every single person, a completely different way of changing behavior, a completely different approach, right?

We’d, never get anywhere. And I think of it like a seatbelt. We could go through and personalize, create personalized algorithms that, that predict and examine and understand exactly when you are gonna be at risk and when you need to wear a seatbelt and when you don’t. Or we could just have everybody wear seat belts and, do better.

So I think that I, I don’t wanna over, over get overexcited about personalized nutrition, but I will say that we have a the, Tufts Food and Nutrition Innovation Institute, which brings together investment groups. Businesses, nonprofits across pharma, food, a ag healthcare and personalized nutrition is one of our four areas of focus.

And so our four areas of focus are sustainable nutrition, personalized nutrition, food is medicine and nutrition security. So I think those are the four really interesting areas for, more science. But again, as a person who straddles the world between kind of medicine and, public health there are big picture solutions, which will help the population and I think that’s what we need to also focus on.

Thank

Tom Bunn: you, appreciate that. Those perspectives. So this is these are some of the some of the data from Dr. Barr’s work. Feel free to dive into that when you get the recording or the, presentation. But moving on. These are Dr. Barr’s acknowledgements and disclosures. Dr. Barr, I don’t know if you wanna speak to these briefly.

And also

Dr. Keith Baar: these are just the people who have supported our research. Most of the research is done by publicly funded organizations. The PepsiCo is, things that I didn’t talk about, keto kind. I, briefly mentioned in, in answering one of the questions. It’s a keto based ensure like product.

It’s a plant-based product that’s trying to get into and give some other opportunities for the kind in the in the insurer bite like, Area. And then MBX 200 is a muscle building product. It’s a polyphenol based actually product that’s that is just about to come out of this space on some of our research.

Tom Bunn: Fantastic. Thank you. Again the, keto discussion is a perfect segue to Dr. Ellen Gross, who’s working on exogenous ketones for neurological disorders. Dr. Gross, can you tell us what you’re working on and would love to dive into the, second indication of Alzheimer’s disease. As it relates to, to, to nutrition as well.

Dr. Elena Gross: Yes. Great. Wonderful. Hello everyone. Great to be on such a, good panel. I agree with a lot of what has been said. Basically I’ve been a chronic migraine patient for several years. Been a ER for about 15 years, and so I swapped into neuroscience to figure out more about this debilitating disease and also have a PhD in clinical research by now and towards the end of my degree funded keto Swiss to potentially.

Bring what I stumbled upon to other patients like me. So what I realized is that migraines are at least as much a metabolic issue as they are a neurological disease. They’re extremely under-researched, but it seems like that that basically energy deficit in the brain or metabolic dysfunction. In brain mitochondria as well as increased oxidative distress.

Basically the common denominator, there’s lots of research being done. More and more research being done in this area. Let’s put it this way. And for example, you can find up to 20% less a t p in IOUs brain between attacks. Even that’s shown with neuro imaging studies and and more research suggesting that energy metabolism and especially an energy deficit in the myness brain, could be the core issue.

For example, AOUS brain is very hyperexcitable. One of the reasons. Why it might be expanding more energy than the common counterpart or a healthy counterpart. A bit similar to epilepsy and the way we eat today, and we’ve already talked about this at length now. A energy hungry brain is just not supported very well anymore.

So as you go back 10,000 years there was lots of periods of starvation or carbohydrate scarcity, where our livers would produce this alternative energy substrate for the brain called keto bodies. And ketones bodies, as Keith has already alluded to or touched upon, are just not just an alternative energy substrate, but they can also be a much more efficacious.

Because they use you require less oxygen for them to produce the same amount of a t p. They, when they’re burnt, they’re actually producing more reactive oxygen species compared to glucose. Molecule. Molecule. This will then enhance mitochondrial functioning. There’s enhanced mitochondrial, biogenesis and other things going on.

Reduced inflammation, reduced excitability in the brain when you are in ketosis and all of these things seem to be migraine protective. But when I got into this area more, I realized that these things are not only migraine protective, they probably play a role in all neurological diseases. And there’s a shared role in even all chronic diseases.

Potentially most of these diseases come with elevated oxidative stress and reduce mitochondrial functioning as one of their pathophysiology, path pathophysiological mechanisms. Sorry. Now we’re, In a patient, or we’re looking at patients like me who’ve now had been overusing painkillers for about 20 years.

And they’re already sick because of, I think the biggest culprit always is a highly processed diet. And this could also be in addition to highly available carbs. I think we all agree that highly processed. Not in the sense of fermentation, but in the sense of frying foods or that’s, one of the reasons I think why in the ketogenic community, those vegetable oils are condemned.

They’re not condemned per se, but only when they’re heated and used for frying. So again, you have this oxidative stress component that is damaging mitochondria, but also I have been living low. Low fat for most of my teenage years because I wanted to do it. Migrants tend to be perfectionist sometimes, and I’ve done everything wrong basically from the advice that I’ve been giving.

So, now the bridge to Keto Swiss is basically, I think that if you grow up on a Whole Foods, Somewhat low carb diet depending on your genetics, right? I don’t think that everybody needs to be ketogenic or low carbs. I think depending on your genes, a whole foods higher carb diet can be good for some, but if you are having a disease and that could be Alzheimer’s, that could be migraine, then chances are that you are a metabolism.

Your mitochondria already deranged and your liver function might not be optimal. As we’ve heard also with Robert Lusk, that liver function can be compromised. So we need to get the liver back in order and during that times, I think it’s essential that we support the brain with an energy substrate while we’re getting metabolism back on track.

And so we’ve seen a migraine patients that. Keto body levels might not be high enough to fully support brain function as well as with Alzheimer’s. We have in in migraine, we have something called glucagon deficiency or resistance. So that’s basically the opposite to insulin resistance, which makes a migraine are potentially prone to difficulties with fasting which is basically somewhat opposite to diabetes.

So what Keto Swiss is doing now, my mission with Keto Swiss is to bring ketones bodies back into the modern world. In potentially metabolically deranged patients with compromised liver function as a tool, we use the human identical molecule. We synthesize it in such a way that it sticks around in the blood for longer.

We add other mitochondrial protective substances on top of that. For example, trace minerals vitamins and so on. Active version of MI to get mitochondria functioning again. And giving the patient the nutrients that they need in order to be able to metabolize those keto bodies, because as we heard, they need to be metabolized in mitochondria.

And we are looking at that as a preventative for migraine and in the future, also Alzheimer’s to be added on top of a hopefully. Very wholesome, hopefully also low carb diet, but just to get levels of keto bodies high enough to supply the brain in a significant percentage. And we will enter the market with a nutraceutical first, but we’re also looking at a, at another version of formulation that can be used in the clinic.

And that will go through extensive clinical trials if we get the necessary funding for that as a second program, more an RX or pharma program.

Tom Bunn: Yes. Thank you, Dr. Gross. Next we have Susan Bratton from Saver Health. Susan, can you walk us through what you’re doing in the context of, nutrition and cancer?

Susan Bratton: Sure. So Saver Health is a digital health company that provides personalized nutrition nutritional, As interventions to prevent and manage the symptoms of cancer and cancer treatment. So we’re starting in oncology using nutrition as an effective lever to improve response to treatment, reduce symptom burden and then moving into other therapeutic areas like cardiovascular disease, renal, autoimmune and.

Providing these interventions for cancer, for symptom management moving into cardiovascular where we’re now looking at nutrition as a lever to not only improve outcomes, but ultimately reverse disease and gathering the data on patients. And this is very simplistic. I know I have to go fast to analyze the data and understand based on cohorts of like patients.

Very simplistically what works and doesn’t work for different types of, patients comorbidity profiles. And then ultimately move from nutrition as a symptom management intervention to precision Nutrition, that is a standard of care that’s pr that’s prescribed when someone’s diagnosed with a specific type of cancer, cardiovascular disease.

So this is all kind of active disease focused today whereby we can incorporate data-driven interventions. For active disease. The longer game here, of course, is what Dr. Lustig referred to, which is this root cause. Right now we’re gonna be treating people who are undergoing treatment for X, Y, Z type of disease or cardiovascular conditions, cancer.

But ultimately the way we use nutrition as a lever is through prevention. We’re a long way from that. I think Dr. Ma Farian talked about how we’re in the early days of nutrition science. But ultimately as we build this this science, I think we’re going to understand not only how we can use nutrition as a lever inactive disease, but back to that prevention.

And it’s going to involve things like the gut microbiome. We see this in oncology, that patients with a more healthy gut microbiome are more responsive to immunotherapy. We need to understand that more, and I think that applies to all of these other therapeutic areas as well. So it’s both an active disease and a prevention.

And that’s a very long game, but we’re taking a data-driven approach to providing responsive nutritional strategies and interventions as, the first point, and then ultimately moving through data analysis to precision nutrition.

Tom Bunn: Fantastic. Thanks so much for walking us through that. We are right at the top of the hour.

Understand if folks have to. To leave for other meetings, but would love to open it up for a, broader q and a session. I know we have a couple questions that have come in. An anonymous attendee says there is increasing awareness about processed food and its impact on health, but do you think access and affordability to unprocessed food.

Is also a problem. I’d rather have way I’d rather have way to get milk from milkman, but that option is not available. Even the vegetables we eat are not fresh. Who knows how long it’s been in supply chain. Do you think access to healthy food creates a main problem in eating healthy? The problem is exaggerated when someone is in lower socioeconomic position.

Any thoughts from, the pi?

Dr. Elena Gross: I have a few thoughts. I, do agree that this is potentially an issue for sure, but I also agree that we’re wasting quite a lot of food and that some parts of an animal, for example, Can be acquired or purchased quite cheaply. So I think we need to stop wasting the fanny cuts of meats.

We need to eat the whole animal again, nose to toe. And that can feed quite a lot of people actually, if they are eating meats. And vegetarian options that might be a little bit diff different. Maybe also source foods more locally so we don’t have to ship them around the world and we don’t have.

Keep them in warehouses, which cost energy, money, and time. And also flying things around the world isn’t cheap. So if we looked at local vegetables again grazing foods animals and cows, and eating the whole animal, I think it can potentially be done and then go to your local butcher and and maybe also get some, I dunno, some bones for a bone broth that can be very nourishing or maybe less attractive cuts of meat that have fat in them that make you more full than just eating the, muscle meat.

So these would be my suggestions for eating whole Foods on a budget. Or go to the goods and collect there’s so many herbs that you can eat. Actually, almost anything out there can be eaten. You just need to learn plants again. So then you can go to the next meadow and make a wild, herb salad with, I don’t know some, eggs and, a meat in them or that’s delicious and that’s completely free almost.

Tom Bunn: I wanna thank all of you for joining us today. Really, very much appreciated. Great comments, great discussion. For all those in attendance, I believe this will be emailed out to you and possibly, on YouTube as well. And I would like to highlight a conversation we’re having via Coronia conversations on Wednesday, March 24th between Dr.

Dmo Farian, who you just heard from, and Carter Williams, the c e o of I select Fund. So we’ll be talking about more advances food is medicine and accompanying research and so we hope you can join us then. And with that, thank you all again very much and we’ll see you first or second Wednesday of April for our next deep dive webinar series.