Podcast

Casey Means, Levels Health, on maximizing human potential

Episode introduction

Dr. Casey Means is Chief Medical Officer and Co-Founder of Levels Health, a metabolic health company that empowers individuals to radically optimize their health and wellbeing by providing real-time continuous glucose biofeedback. Coupled with real-time insights to inform personalized diet and lifestyle choices, Levels has a not-so-modest goal: to change the world of metabolic health for the better. Levels recently raised $12M of seed funding from Andreessen Horowitz and angel investors including Marc Randolph (co-founder and first CEO of Netflix), Dick Costolo (former CEO of Twitter), Michael Arrington (founder of TechCrunch), and Matt Dellavedova (NBA player on Cleveland Cavaliers). In this conversation on The Pulse podcast by Wharton Digital Health, Dr. Means shares the founding journey of Levels, the science of metabolic health, the impact of glucose on performance, and the future of health personalization.

The Pulse by Wharton Digital Health

Show Notes

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Key Takeaways

1:30 – Lifestyle choices lead to a visit to the doctor

As a surgeon, Dr. Means found that many patients had chronic inflammation linked to lifestyle choices like diet, sleep, stress, and exercise. When out of balance, these factors cause metabolic dysfunction and disease.

“The reality is that so much of what generates chronic inflammation in the body is what we expose ourselves to every day through our daily choices. Things like the food we eat, the refined sugar and carbohydrates that we’re exposed to, lack of sleep, chronic low grade stress, toxins in our food, water, air, lack of movement and exercise. These things are all translated in our body into molecular information that tells our body to be in threat mode, to be inflamed. And all of these factors feed into creating a dysfunctional metabolic system in the body, which then really leads to that chronic inflammation. So I became really fixated on understanding how we could improve metabolic health and inflammation at scale through ideally proactive approaches that would keep patients healthy. Keep them from actually developing these conditions in the first place, and ultimately helping to keep them out of the operating room.”

8:29 – Share your ideas to see them become reality

The greatest idea in the world will only become action when it is shared with others. To build your business, talk about your ideas with your networks and find connections who believe in the same future as you.

“The way I met my co-founders is I actually put a bunch of these thoughts into a slide deck for sort of a proposal for a company that I wanted to start. And it was going to be based on using lab data as a behavior change tool. And I passed this around to my close network and my family, and actually turns out that because of that people end up making a lot of connections for me. They knew what I was about and what I believed in, what my North Star was and what I wanted to do and connections started being made. So actually I met my co-founders from my brother who really believed in what I was doing, and he’s very connected in sort of the Silicon Valley network and was overhearing some people talk about something similar at a networking event and said, ‘hey, you guys got to meet my sister.’ I ended up having a call with one of my co-founders Josh and we sort of just really hit it off. I’m thinking about the future of medicine and biowearables for behavior change. And I ended up flying down to California and spending the weekend with him and a couple of the other early team members and it was a match made in heaven.”

12:52 – The little laboratory on your arm

Continuous glucose monitors (CGMs) are like a Fitbit for your diet, constantly taking measurements of glucose levels in the body through a chemical process and then sending that data directly to your smartphone.

“So for people who’ve never seen these before, you can imagine this is the size of two stacked quarters, and it’s stuck with an adhesive to the back of your arm. Sticking out of that sensor is a four millimeter probe. That’s like a hair-like filament that actually goes under the skin. So that’s inserted just really painlessly with an applicator and that filament stays just under the skin. So it’s not actually in the blood. It’s measuring glucose from the fluid that is around, it’s called interstitial fluid. So blood sugar is in the blood, but it seeps out of the bloodstream and can live also in this interstitial fluid and that seeping out into the interstitial fluid takes about 15 minutes. So your interstitial fluid glucose is usually going to be about 15 minutes behind your blood glucose levels, sometimes quicker than that, but that’s on average. Then there’s actually a chemical reaction that is happening on the sensor where basically the glucose concentration, there’s an enzyme called glucose oxidase, is stuck to the sensor filament converts the glucose into a by-product that gives off hydrogen peroxide and then that can be measured through an electrical signal that then registers your glucose levels and then that’s transmitted to the smartphone as the data.”

14:50 – Blood sugar is affected by more than cookies and carbs

Eating sugar obviously impacts sugar levels in the body. However exercise, sleep, and stress also impact metabolic fitness, the process of turning sugar into energy. High-sugar diet, little sleep, and high stress all result in unstable blood glucose levels, whereas exercise regulates energy production.

“We all think about food with relation to blood sugar, but there’s actually I would say four main pillars that go into our blood sugar response. And that is food, exercise, sleep, and stress. And so food I like to say is necessary for good metabolic health, but it’s not actually sufficient. You need to have these other things dialed in to really have holistic metabolic health. So stress is a really fascinating one. When we’re stressed, our body releases the hormone cortisol and other catecholamine hormones. And traditionally, when we’ve been under stress in ancient times, there’s always the example of we were being chased by a lion. But typically stress meant to our bodies that we had to do something physical, and so our body wanted to get glucose for our muscles. So cortisol actually tells the liver, which stores a little bit of glucose, to dump glucose into the bloodstream to feed the muscles during times of stress. And so this is sort of a historically adaptive response. But in recent history where our stressors are rarely physical, they’re usually psychological – we actually don’t need this. It’s become maladaptive. Sleep is very similar. When we lose a night of sleep or have poor sleep quality, it also increases our cortisol level, but it does many other things. It also makes us more insulin resistant. Insulin is the hormone that’s required to get glucose to be taken up into cells out of the bloodstream and when we don’t get good sleep, our cells become more resistant to that insulin and so you can imagine if that isn’t able to act on the cells, you’re not gonna be able to get the glucose into the cells. And so the glucose is going to look higher in the blood.”

18:23 – Stabilise glucose to prevent getting rusty

Maintaining stable glucose levels will provide consistent energy to the body. When repeatedly suffering from sharp spikes and drops caused by food or stress, eventually inflammation builds up in the cells causing them to function less effectively.

“So for the most part you can think of what you want is essentially a flat and stable, fairly stable glucose line. Obviously when you eat there are going to be carbohydrates that are broken down into glucose, and you might see a small rise. But you really want to keep it quite flat and stable. Unfortunately, that is pretty much the opposite of what’s happening in our modern Western world. When you walk into the grocery store, almost everything you’re seeing is processed junk that’s filled with sugar. Even ketchup has sugar in it. These days it’s everywhere. And so instead of seeing gentle, rolling glucose during the day, you’re going to see people having huge spikes and then huge crashes. And because we’ve also been told for years, ‘Oh, you should snack multiple times a day or have six small meals a day in order to keep your metabolism going.’ Well, what that’s going to do is just keep you on this glucose roller coaster up and down all day, where you’re basically spiking the glucose. That’s going to create an insulin release, which is going to drop your glucose. And you’re just up and down, up and down, up and down. So just keeping things really stable is just going to keep a much more stable environment in the body. When we have these high glucose spikes, there’s multiple physiologic problems that can happen.”

20:40 – Feel the burn with stable insulin

If you want to lose weight, keeping blood sugar and insulin stable is a must. Insulin is the hormone that removes glucose from the blood, so when blood sugar rises, insulin rises to counteract it. When this is happening too often, insulin production becomes unstable, telling the body it has glucose for fuel so it doesn’t need to burn fat.

“We also want to keep our insulin as low and stable as possible because when insulin is elevated over time, that leads to what’s called insulin resistance. If your body’s constantly exposed to this hormone, it actually gets numb to it and it sort of stops hearing that signal and you have to produce more and more insulin to get the same amount of glucose out of the blood, into the cells. And over time, what that can do is just really make your body dysfunctional in terms of how you’re able to process glucose and makes it harder to take that glucose up into the cells for energy. So high insulin is a big problem and for people who are interested in weight loss. Insulin actually blocks our ability to burn fat. So when insulin’s around, it’s telling the body there’s lots of glucose around, we’ve got plenty of glucose for energy, we don’t need fat for energy. So it’s actually a direct block on fat burning. So people who are interested in losing weight, really getting that insulin down and stable as a way to unlock those fat burning pathways. So my perspective is that keeping insulin down is going to be fundamental towards successful and sustained weight loss.”

22:20 – Make better decisions with instant feedback

The current tools for understanding how your food choices affect your body all suffer from a long delay between measurement and feedback. In contrast, CGMs mean every choice around nutrition is tracked in real time, providing a “closed loop” system of how the body is reacting and informing better decision making.

“So behavior change is a really hard nut to crack because it often means that we’re having to make choices that go against things in our life that bring us pleasure, and are culturally entrenched and part of our social life. And often it’s also really hard to know the exact benefit of our particular choices. And so I believe that when we can really close the loop between an action, a choice and a reaction, we can set the foundation for effective behavior change. And I call this creating a closed loop system. In nutrition and health we have notoriously open loop systems, meaning that we make choices every day about food and sleep and exercise, but we don’t actually see the direct payoff of those. It’s usually a lengthy amount of time before we have any real feedback. Sometimes it might be stepping on the scale the next morning. It might be that we get a cholesterol test in six months or a fasting glucose test at the doctor. But how do you take that piece of data and then say, Oh, well, this is because I ate avocado and eggs for breakfast and didn’t have Captain Crunch cereal? You can’t make that closed loop. So what we end up doing is we end up not really believing in the benefits of these tough choices we’re making, because we don’t see the result quickly. And we also can misattribute things like successes, perceived successes, to maybe the wrong thing. So fundamentally I think that the behavior change, as much as we can tighten the loop in nutrition between what we’re doing and the outcome, the better. And to me, continuous glucose monitoring is the only thing we have for nutrition right now to close that loop for things like sleep and fitness.”

24:18 – You can’t change what you can’t measure

Tracking changes in blood glucose make it possible to understand what is going on in the body in response to specific stimulus. This in turn makes you more accountable to the decisions you make on a daily basis.

“It’s hard to change a behavior when we’re not actually in touch with what’s going on inside of our body. And currently we’re living in just this hyper stimulating worl d. We’ve got our digital world. We’ve got hyper palatable foods that are focused on getting you to your fullest point, an actual term in food science. So it’s very hard to actually understand, how do I feel and what am I doing? How is it affecting my internals? So I really am focused on how can we make tools that get you in touch with what’s going on inside your body. So for instance, with Levels, let’s say someone has oatmeal for breakfast and then three hours later, they feel lethargic and they feel like they need to take their little mid morning nap and they need another cup of coffee. It would be very hard for someone to just say, ‘oh, this feeling that I’m having is because of the oatmeal.’ Like they would probably say like, oh, it’s cause I got four hours sleep or it’s having a stressful day. Or, oh it’s because this is just who I am, I’m sort of lazy. But when you can actually see the action and then show that maybe your glucose went way up, like up to 180 milligrams per deciliter, which is a really high glucose value, and then came crashing down.”

27:03 – The metabolic awareness journey

Levels recommends wearing a CGM for a month to see how your current choices are affecting your glucose readings. Experiment with different food and activity, then try to refine what you are doing to get your readings stable and create your ideal metabolic condition.

“During that month, we really encourage people to really go on this metabolic awareness journey. People can really take whatever journey they want during it but something that I highly recommend is the first week to really just eat your normal foods that you love. Eat everything that you’ve been normally eating and just make observations, see how things are scored in the app. See what is your breakfast doing to your glucose levels. And what are your snacks doing? And what is your normal bedtime seem to be doing to your blood glucose levels? So just really live your normal life the first week. The second and third week, we really love to have people experiment. So trial sorts of different things, get more sleep, maybe get less sleep, try a high intensity workout or try yoga, try eating a whole orange and a glass of orange juice and see the difference. Add protein and fat to a carbohydrate versus eating a carbohydrate alone. Eat a high carb food in the morning or eat it late at night. All of these things actually can change the way your body processes glucose. And for each person it’s going to be completely different because our metabolisms are so unique and what works for you, might not work for me. So you really have to experiment. And then based on what you learned during that experimentation, we really encourage people to optimize in the fourth week. So take what you’ve learned and try and just keep those glucose levels flat and stable and see if you can really get those levels to where you want.”

30:20 – Lay off the carb-loading for optimal performance

Carb-loading is considered necessary for athletic performance, providing glucose to build or rebuild muscle glycogen stores. However, evidence shows avoiding so-called fitness foods in favor of slow release carbs can increase fat burning.

“We have a lot of professional athletes in the program who are using glucose monitoring to help understand their fueling and their recovery. And we see people in athletic communities a lot of times really move towards changing their pre and post-workout snacks. So many things that are marketed towards athletes are just filled with sugar. So like the gels and Gatorade has high-fructose corn syrup in it and these protein powder and shakes are filled with sugar and they market this because you want to replete your glucose so you can store it as glycogen in your muscles and build muscles and whatnot. And, you know, it’ll help keep you going longer with more quote unquote ‘energy,’ but really what it’s doing, it’s causing these massive glucose spikes in people and then crashes. So just really exaggerated glucose load, just that absolutely you do not need. And people are finding that if you actually eat a much more complex carbohydrate, or even space out these high carb foods from your workout, what happens is you don’t have these huge spikes and crashes. And you get what you need, but you don’t get the collateral damage of these crazy sugar filled foods. So we’re seeing a lot of athletes kind of peel back from some of the processed athletics foods and you know, have just a much sort of gentler type of snack before or after their workout. The second thing with athletes that has been fascinating is that many seem to be moving towards more working out in a fasted state. So not actually having glucose on board when they work out, because we know that when you work out with actually low glucose, what happens is your insulin is also going to be low. And that means that you can burn fat more efficiently.”

32:19 – The future of dieting is personalized

Diets like Keto have strict rules around foods to eat and avoid. However monitoring individual responses to our food choices will grant us greater freedom to personalize a diet that works for us.

“The ketogenic community, who are people who follow a low carb diet, they have been fascinated by this product. Because normally they’re just measuring their ketones in the blood with a fingerprint, but this way they can actually see how their food is affecting their glucose. And you can pretty confidently know that if you’re keeping your glucose low, you’re going to be able to be more likely to get into fat burning and ketone generating. And so it’s another way to really stay on top of the diet. A lot of ketogenic people actually eat very strict, low carb diets, and some have found that there’s actually foods they can eat that aren’t technically ketogenic on the diet, but they don’t spike their glucose. So it works for them. And since each person responds to carbs differently, for one person on a Keto diet, they might be able to eat carrots or beans and it just doesn’t spike their glucose and so it’s okay for them. Whereas for another person, it might because the glucose response that’s problematic and kicks them out of ketogenesis. So to personalize a ketogenic diet and really usher in what I like to call Keto 2.0, a personalized Keto diet, I think it’s been really liberating for a lot of people because they’ve been able to expand this very restricted diet.”

33:53 – Empowering the 88% of people with unhealthy metabolisms

The figures are stark: in America, only 12% people are considered to have optimal metabolic health. Levels is promoting the power of self-monitoring metabolic function so that people can make their own changes before they reach the point of chronic illness.

“This was a study out of UNC last year that showed that 88% of Americans have at least one biomarker of their metabolism not being functional. Only 12% of people are optimally, metabolically, healthy. You know, this makes sense. You see crazy numbers of metabolic conditions. We’ve got 74% of the country is overweight or obese, 128 million Americans with pre-diabetes or diabetes. It’s absolutely astronomical and rampant and I think it’s the elephant in the room of modern healthcare and we’re just not talking about it. There’s so many industries that benefit off of products or services that basically don’t promote metabolic health. And so it’s really the elephant in the room and it’s contributing to really bankrupting human capital in the country. But also it’s driving our healthcare costs that are just astronomical now, you know, $3.4 trillion a year. What I am so excited about is that we are going to be approaching this from a really bottom up way. We are giving people their own data to make choices that will improve metabolic health. We’re not relying on people to wait until they go to the doctor’s office and get a fasting glucose test and that’s sort of the beginning and the end of the conversation.”


Episode Transcript

Vivien Ho: [00:00:00] Hi everyone. Welcome to our latest episode. I am Vivien, one of the co-hosts in The Pulse podcast. Our purpose is to capture the pulse of healthcare innovation spanning leaders across the healthcare ecosystem. And today we’re super excited to have Casey Means, chief medical officer and co-founder of Levels as our guest today.

Casey Means is a Stanford trained physician and chief medical officer and co-founder in Levels Health, and associate editor of the International Journal Of Disease Reversal And Prevention. Her mission is to maximize human potential and reverse the epidemic of preventable chronic disease by empowering individuals with technical tools.

Furthermore, she’s an award-winning biomedical researcher with past research positions at NIH, Stanford, NYU. Founded last August of 2019, Levels as a metabolite health company that empowers individuals to radically optimize their health and well-being by providing real time, continuous glucose biofeedback, coupled with machine learning driven insights to inform personalized diet and lifestyle.

Without further ado, welcome Casey.

Dr. Casey Means: [00:01:11] Thank you so much for having me, Vivian.

Vivien Ho: [00:01:14] Great. I love to kick off on what made you so passionate on metabolite health? It sounds like your history, even before Levels Health, has been really involved in building literature in the space and also being a thought leader in the space.

Dr. Casey Means: [00:01:27] Yeah. So the passion actually really started during my career in surgery. So formerly I was practicing head and neck surgery. So after completing medical school at Stanford, I spent about four years up in Oregon training as a head and neck surgeon. And in this field, a lot of the conditions I was treating were rooted in chronic inflammation.

These were things like sinusitis, thyroiditis, laryngitis. All these itises basically means that this is a chronic inflammatory condition, and that the immune system is revved up. And in medical practice, to treat these conditions, we frequently will throw steroids at them to quell the immune system. We’ll do nasal steroids

like Flonase, IV steroids. We’ll do oral steroids, like prednisone. We’ll even do topical steroids. It’s just lots of medications to really tamp down the immune system. But we rarely step back and ask what is causing all this inflammation in the first place. What can we do to minimize this chronic inflammation?

And that was what was so interesting to me. And this sent me on a journey to really answer that question and figure out how to bring it into my practice. And the reality is that so much of what generates chronic inflammation in the body is what we expose ourselves to, every day through our daily choices. Things like the food we eat,

the refined sugar and carbohydrates that we’re exposed to, lack of sleep chronic, low grade stress, toxins in our food, water air, lack of movement and exercise. These things are all translated in our body into molecular information that tells our body to be in threat mode, to be inflamed. And all of these factors feed into creating a dysfunctional metabolic system in the body, which then

really leads to that chronic inflammation. So I became really fixated on understanding how we could improve metabolic health and inflammation at scale, through ideally proactive approaches that would keep patients healthy. Keep them from actually developing these conditions in the first place, and ultimately helping to keep them out of the operating room. And something else that was quite interesting about the metabolic health journey is that we know that patients with metabolic diseases, things like diabetes and blood sugar dysregulation, they actually do much more poorly

when they have surgery. They have trouble with wound healing. They’re more likely to get infections. So really, all aspects of what I was doing in surgery is what ultimately led me to really focus on metabolic health.

Vivien Ho: [00:03:47] Wow. It’s crazy that you wouldn’t think to connect ENT and, you know, nose to metabolize health, but I’d love to hear more about that later when we go into the science behind it. I guess before we go into it, just because our audience member may not be familiar with Levels. I’d love to talk a little bit about what is the history of Levels? How did you co-found Levels last year and what does Levels do?

Dr. Casey Means: [00:04:08] Absolutely. So Levels helps health seeking individuals understand and improve their metabolic health. And practically speaking, what this means is it’s like a Fitbit for glucose. So this is the system involving a wearable sensor called a continuous glucose monitor that you wear on your arm, plus a software that helps you interpret that continuous data stream.

So you can imagine, you’ve got this little quarter size device stuck to your arm. It’s actually sampling. You have it on right now? Yeah. It’s sampling an internal biomarker, like an actual. It’s a bio wearable and painlessly, basically doing a little lab test every 15 minutes, 24 hours a day. And these last on your arm for two weeks. It’s sending that data to your smartphone. And then

Levels software interprets that data to help people move to a place where they can get that glucose flat and stable. When that glucose is up and down and all over the place, we see problems, symptoms emerge, and ultimately over the long-term, diseases can emerge. So when we can keep that glucose flat and stable, through personalized lifestyle and nutritional choices, we can just really up-level our lives,

we can improve our mental clarity, our memory, our endurance, our sleep, and all aspects of health. So we are here to help people understand and optimize their metabolic.

Vivien Ho: [00:05:28] Awesome. And I guess when you started Levels, how did you go? Was it like, I’m going to find a co-founder first or is it I’m going to work on this and then the co-founder came along? Like, what was the story of how you  guys met?

Dr. Casey Means: [00:05:40] Absolutely. Yeah. So I actually left my surgical career when I was really, had this revelation that I was talking about earlier that I really wanted to approach healthcare differently, much more proactively and less than sort of the reactionary way. So I actually left my surgical career to start my own private practice.

And I really was there starting the practice of my dreams. And I actually just sort of sat down over a few months ,and sketched out exactly what I would need to do with patients to understand their health as deeply as possible, and then move them on a personalized path towards health. And I just threw out the rule book and was like, we’re going to do it

however it makes sense, because ultimately the goal is to make people healthy, and fundamentally. And so really what that ends up looking like was spending tons and tons of time with patients. I needed to understand, get an extremely thorough like laboratory testing for people, but also just sit down and talk to people, understand what were the realities of their lives, and what were the barriers to making the choices every day that ultimately generate health.

And what I found over time was that spending that time with people and really understanding blockers in their lives, and then helping them create plans to overcome that and change their behavior in regards to food, exercise, sleep, stress, exposures. Those people who are able to do that and make big changes consistently, they did better.

They got better in just a couple of months. And some people would come in with 50 symptoms in their first visit, and have two after a couple of months, because they were taking control of their lives, and creating conditions in the body that ultimately generate health. So after about nearly a year of doing this practice, which was incredibly rewarding,

I stepped back again and I said, Okay, so the real linchpin to improving health is behavior change. When people actually consistently make healthy behavior choices, they get better, they thrive, they minimize their symptoms and illness. And I can do this for a handful of patients a week. It was a very, you know, high cost to patients.

But how are we going to do this at scale? We have. 128 million Americans with diabetes and pre-diabetes alone. That’s just one condition. We’ve got the vast majority of adults with at least one chronic health condition. So maybe I’m helping 20 patients a week, but how can we scale this? And that was really how this started for me. Looking at my own practice, looking at my own passion and North star.

Stepping back and saying, how do we scale this? How do we make this more efficient? How do we get this to more people? These behavior change modalities that are super high touch right now. And so I started thinking a lot about how can we use digital tools to basically do what I’m doing with patients, but in their own hands. And how can we use data to empower people, to make these daily choices on their own, without me having to kind of be on their shoulder all the time, telling them what to do. So I was thinking a lot about how to use lab and biometric data for behavior change. And I actually, the way I met my co-founders is I actually put a bunch of these thoughts into a slide deck for sort of a proposal for a company that I wanted to start.

And it was going to be based on using lab data as a behavior change tool. And I pass this around to my close network and my family. And actually turns out that because of that, people end up making a lot of connections for me. They knew what I was about and what I believed in, what my North star was and what I wanted to do.

And connections started being made. So actually I met my co-founders through my brother who really believed in what I was doing, and he’s very connected in sort of the Silicon Valley network. And he was overhearing some people talk about something similar at a networking event and said, Hey, you guys got to meet my sister.

I ended up having a call with one of my co-founders Josh, who, and we sort of were just really hit it off. I’m thinking about the future of medicine and bio wearables for behavior change. And I ended up flying down to California and spending the weekend with him and a couple of the other early team members.

And, you know, it was a match made in heaven. So really the takeaway that for me, from how this all arose for me was the importance of stepping back, looking at your own practice, really examining what the failure points are and what could be scaled. And then putting your thoughts down on paper and sharing it because that’s really the way that these connections were ultimately made, and what has ultimately become this incredible business and relationships and product.

Vivien Ho: [00:09:49] And that’s amazing. It’s inspiration for entrepreneurs where a lot of the times, it’s like, you know, how do you get started? And just got to put your ideas on this paper and share it with your close family and friends, it seemed to work out for you. I’m curious when, in your practice did you also have glucose monitoring at home at that point, or was it like you would go to visit monthly or weekly and do their tests and report how their baseline is? Or how does that work?

Dr. Casey Means: [00:10:13] Yeah. So I was doing very extensive lab testing with my patients on all aspects of metabolism and nutrition and hormones, and really getting a comprehensive picture. But I was also putting continuous glucose monitors on my patients, because I understood that for people to really personalize their own diets, and make sure that they’re moving in the right direction on metabolic health. We have to get their glucose spikes down.

We have to get them on personalized diets that aren’t going to keep their glucose elevated all the time, which is going to ultimately move you towards processes that are detrimental to the body, like insulin resistance and inflammation. So I was putting continuous glucose monitors on most, my patients.

Now, what happened though, was that I was responsible for basically interpreting all that data for them. And these are hundreds of data points a day. And so people would come in or send me spreadsheets of all their continuous glucose monitoring data. And, you know, I’m sitting looking at this and asking questions about exercise and food and this and that, and trying to basically read the tea leaves.

Like what can I tell them? And the reality is that is just a totally unscalable model. And I could do my best, but the reality is a digital tool can do this better. A digital tool can bring in other data streams like heart rate, exercise, sleep, stress data. Merge it with a glucose data stream and create really intelligent insights for people that a human brain can’t do.

So it became very clear to me that this is a powerful tool, but right now there’s no way to actually leverage this data stream in an efficient way. And I have to build that. And that’s what Levels is. We are helping people merge different data streams, and then use higher level analytics to make it very interpretable.

So someone can say, Okay, I ate this, I logged it. This is what happened to my glucose. This is how I felt. And be able to say within an hour of a meal, This was a healthy meal, or this was not a healthy meal for me. And that takes a huge cognitive load off the practitioner and the physician. So that’s really,

you know, what I was doing with patients and what, you know. Just pouring over these spreadsheets made me realize, like, we’ve got to build a tool that does this better.

Vivien Ho: [00:12:12] Yeah. I’ve been trying it out for a weekend. It’s awesome. How right after I eat like rice noodles, I can see my glucose spike. And I’m like, okay, I guess I am sensitive to this, but then I eat chicken and nothing happens or it’s pretty much stable.

So it’s really interesting to see feedback so quickly. And also, I think there’s just so much potential to even build on top of it and add a lot more insights. I was wondering, given someone who’s never really paid attention to my glucose. And I assume a lot of your initial consumers are people who are generally quite healthy right now, at least in this moment, how does glucose monitoring work?

So I know I put it in back of my arm. What is happening? Like is it measuring my blood in my skin? How does that specifically work in the scientific level?

Dr. Casey Means: [00:12:54] Absolutely. So for people who’ve never seen these before, you can imagine this is the size of two stacked quarters, and it’s stuck with an adhesive to the back of your arm.

Sticking out of that sensor is a four millimeter probe. That’s like a hair light filament that actually goes under the skin. So that’s inserted just really painlessly with an applicator, and that filament stays just under the skin. So it’s not actually in the blood. It’s measuring glucose from the fluid that is around,

it’s called interstitial fluid. So blood sugar is in the blood, but it seeps out of the bloodstream and can live also in this interstitial fluid. And that seeping out into the interstitial fluid takes about 15 minutes. So your interstitial fluid glucose is usually going to be about 15 minutes behind your blood glucose levels. Sometimes quicker than that, but that’s on average. Then there’s actually a chemical reaction that is happening on the sensor where basically the glucose concentration.

There’s an enzyme called glucose oxidase is stuck to the sensor filament. Converts the glucose into a by-product that gives off hydrogen peroxide. And then that can be measured through an electrical signal that then registers your glucose levels. And then that’s transmitted to the smartphone as the data. So it’s a little laboratory right on your arm.

Vivien Ho: [00:14:08] And is it a Bluetooth that goes to my phone or how is it picking.

Dr. Casey Means: [00:14:12] There’s three different hardware manufacturers that make continuous glucose monitors right now. And right now, some are Bluetooth and actually are sending the data stream continuously. And then others use what’s called the NFC, which is near-field communication where you actually have to hold up the smartphone as like a reader, to the sensor to transmit the information. So it’s actually done by proximity. So Bluetooth and NFC are the two main technologies right now for transmitting the data. And everyone’s really moving in the direction of Bluetooth.

Vivien Ho: [00:14:40] Got it. And I’m curious, other than food, there’s stuff like body temperature, sleep that affects or stress even with the elections and everything. How does that affect your glucose in terms of beyond food?

Dr. Casey Means: [00:14:52] Yeah, it’s pretty amazing. We all think about food with relation to blood sugar, but there’s actually, I would say four main pillars that go into our blood sugar response. And that is food, exercise, sleep and stress. And so food, I like to say is necessary for good metabolic health, but it’s not actually sufficient.

You need to have these other things dialed in to really have holistic metabolic health. So stress is a really fascinating one. When we’re stressed, our body releases the hormone cortisol and other catecholamine hormones. And traditionally, when we’ve been under stress, you know, in ancient times, there’s always the example of like, we were being chased by a lion. But typically stress meant to our bodies that we had to do something physical.

And so our body wanted to get glucose for our muscles. So cortisol actually tells the liver, which stores a little bit of glucose, to dump glucose into the bloodstream to feed the muscles during times of stress. And so this is sort of a historically adaptive response, but in recent history where our stressors are rarely physical, they’re usually psychological,

we actually don’t need this. It’s become maladaptive. And these days, we are under a lot of low grade chronic stress, you know, emails and text messages and honking. And all of these things actually registers our body as little cortisol spikes. And so you can think of how that’s affecting your liver, kind of constantly having you seep out little bits of glucose into your bloodstream and keep it elevated. So really getting stress managed, under control is absolutely critical for optimal metabolic health. Sleep is very similar. When we lose a night of sleep or have poor sleep quality, it also increases our cortisol level, but it does many other things.

It also makes us more insulin resistant. Insulin is the hormone that’s required to get glucose to be taken up into cells out of the bloodstream. And when we don’t get good sleep, our cells become more resistant to that insulin. And so you can imagine if that isn’t able to act on the cells, you’re not gonna be able to get the glucose into the cells.

And so the glucose is going to look higher in the blood. Sleep deprivation also impacts our satiety hormones, so ghrelin and leptin that make us either hungry or full. And so often people who lose sleep will actually be reaching for higher carb, higher fat foods the next day, because of that hormone balance.

So, and then the other thing that sleep deprivation does is increase our inflammation acutely and a lot of inflammatory chemicals in the blood things like TNF alpha and C-reactive protein. And these, they’re called cytokines or inflammatory mediators, they actually can rise the next morning, after a poor night of sleep. And inflammation promotes metabolic dysfunction, just as metabolic dysfunction promotes inflammation.

It’s a two-way street. So sleep is just fundamentally. You could eat perfectly and be getting really poor sleep and look like you’re pre-diabetic essentially. And then exercise is kind of a no brainer. You know, muscles are huge glucose sink in the body. And when we use our muscles, they actually can take up glucose, independent of insulin.

So we can, just from muscles moving back and forth, contracting, you can soak up glucose and get it out of the bloodstream, and you don’t even need to work your pancreas, the organ that produces insulin to do it. So it’s this insulin independent way of getting glucose out of the bloodstream. And exercise really of any type resistance, low grade aerobic or high intensity interval training.

All of these things in their research have been shown to improve our glucose levels. So aside from the food part, which we could also dive into, I can’t emphasize enough how much sleep, stress management and exercise are tied into it.

Vivien Ho: [00:18:14] Right. So is the baseline sort of metric is if your glucose is high, it is bad or is that not necessarily always true in every case?

Dr. Casey Means: [00:18:23] Yeah. So for the most part you can think of what you want is essentially a flat and stable, fairly stable glucose line. You want to. Obviously, when you eat, there are going to be carbohydrates that are broken down into glucose, and you might see a small rise, but you really want to keep it quite flat and stable.

Unfortunately, that is pretty much the opposite of what’s happening in our modern Western world. When you walk into the grocery store, almost everything you’re seeing is processed junk that’s filled with sugar. Even ketchup has sugar in it. These days it’s like everywhere. And so instead of seeing gentle, rolling glucose during the day, you’re going to see people having huge spikes and then huge crashes.

And because we’ve also been told for years like, Oh, you should snack multiple times a day or have six small meals a day in order to like, keep your metabolism going. Well, what that’s going to do is just keep you on this glucose rollercoaster up and down all day, where you’re basically spiking the glucose.

That’s going to create an insulin release, which is going to drop your glucose. And you’re just up and down, up and down, up and down. So just keeping things really stable is just going to keep a much more stable environment in the body. When we have these high glucose spikes, there’s multiple physiologic problems that can happen.

One, it can generate inflammation. And second, it can generate what’s called oxidative stress, which is reactive molecules in the body that can cause damage. And the third thing that high glucose does, it causes what’s called advanced glycation end products. And basically glycation is this process where sugar in the blood sticks to things. And it’ll stick to proteins and fat, and actually change the function of things in the body and in the cells.

And it’s kind of like the body rusting. You don’t want to glycate your body. So for quite a few reasons, we just want to keep that glucose low and stable. And we also want to keep our insulin as low and stable as possible, because when insulin is elevated over time, that leads to what’s called insulin resistance.

If your body’s constantly exposed to this hormone, it actually gets numb to it. And it sort of stops hearing that signal, and you have to produce more and more insulin to get the same amount of glucose out of the blood, into the cells. And over time, what that can do is just really make your body dysfunctional in terms of how you’re able to process glucose, and makes it harder to take that glucose up into the cells for energy.

So high insulin is a big problem. And for people who are interested in weight loss, insulin actually blocks our ability to burn fat. So when insulin’s around, it’s telling the body of there’s lots of glucose around. We’ve got plenty of glucose for energy. We don’t need fat for energy. So it’s actually a direct block on fat burning.

So people who are interested in losing weight, really getting that insulin down and stable is a way to unlock those fat burning pathways. So for so many reasons, we just really want to keep our glucose flat and stable.

Vivien Ho: [00:21:03] So overall, let’s say I’m looking to go through a weight loss plan. You would say tracking glucose monitoring is more effective than tracking calories, or do you think tracking both is important? Like, what is your perspective on that?

Dr. Casey Means: [00:21:16] Yeah. So my perspective is that keeping insulin down is going to be fundamental towards successful and sustained weight loss. Unfortunately, there has not been a lot of great research where we’ve taken basically continuous glucose monitors, put them on people who are trying to lose weight, and then looked at outcomes with this type of intervention, where we keep glucose lows.

That’s research that our company is really interested in doing, because that physiology really supports that this is an effective strategy. And some great books on this, Jason Fung, the Obesity Code, and Ben Bickman’s Why We Get Sick, both describe intense detail. And well, I should also mention Mark Hyman’s the Blood Sugar Solution. Those three books, all discuss why keeping insulin low is really fundamental to weight loss.

Vivien Ho: [00:22:03] Awesome. We’ll definitely have those books in our recommendation list. I would like to talk a little bit about once you start talking your glucose. And you wrote about this in a blog. So I’d like to highlight it, like, can you talk about the framework for effective behavior changes on a high level? I know there’s four components. I’d love to hear your perspective on how to change.

Dr. Casey Means: [00:22:22] Yeah. So behavior change is a really hard nut to crack, because it often means that we’re having to make choices that go against things in our life that bring us pleasure and are culturally entrenched and part of our social life. And often it’s also really hard to know what the exact benefit

of our particular choice is. And so I believe that when we can really close the loop between an action, a choice and a reaction, we can set the foundation for effective behavior change. And I call this creating a closed loop system. In nutrition and health, we have notoriously open loop systems, meaning that we make choices every day about, you know, food and sleep and exercise, but we don’t actually see the direct pay off of those.

It’s very, usually a lengthy amount of time before we have any real feedback. Sometimes it might be stepping on the scale the next morning. It might be that we get a cholesterol test in six months or a fasting glucose test at the doctor. But how do you take that piece of data and then say, Oh, well, this is because I ate, you know, avocado

and eggs for breakfast, and didn’t have Captain Crunch cereal. Like you can’t make that close loop. So what we ended up doing is we end up not really believing in the benefits of these tough choices we’re making, because we don’t see the result quickly. And we also can misattribute things like successes, perceived successes to maybe the wrong thing.

So fundamentally I think that the behavior change, as much as we can tighten the loop in nutrition between what we’re doing and the outcome, the better. And to me, continuous glucose monitoring is the only thing we have for nutrition right now to close that loop for things like sleep and fitness. We’ve had heart rate trackers.

We’ve had sleep trackers. We’ve had activity trackers, and we’ve even had stress trackers. But we’ve never, ever had a nutrition tracker. So that’s the key, I would say, foundation of how I feel that wearables for nutrition are going to change the face of behavior change. But I think there’s a few other aspects to it as well

aside from closed loop. I think the second is really body awareness. It’s hard to change a behavior when we’re not actually in touch with what’s going on inside of our body. And currently, we’re living in just this hyper stimulating world. We’ve got our digital world. We’ve got hyper palatable foods that are focused on getting you to your bolus point, an actual term in food science.

So it’s very hard to actually like, understand how do I feel and what am I doing? How is it affecting my internal milieu? So I really am focused on how can we make tools that get you in touch with what’s going on inside your body. So for instance, with Levels, let’s say someone has oatmeal for breakfast. And then three hours later, they feel like lethargic, and they feel like they need to take their little mid morning nap, and they need another cup of coffee.

It would be very hard for someone to just say like, Oh, this feeling that I’m having is because of the oatmeal. Like they would probably say like, Oh, it’s cause I got four asleep or it’s having a stressful day or, Oh, it’s because this is just who I am. I’m sort of, I’m lazy, you know. But when you can actually see the action, and then show that like maybe your glucose went

way up, like up to 180 milligrams per deciliter, which is a really high glucose value, and then came crashing down. And right when you crashed, you had all these subjective feelings. When you can actually see that and understand how, what you felt inside was related to an objective action, that’s just a game changer.

There’s no more misattribution. So we’re really hoping to use this product, to get people to think more about how they’re feeling throughout the day, and then link that with choices that they’ve made. And then I think a third pillar is accountability. You can’t change what you can’t measure. And when you have the data in front of you in real time, it makes it so much easier to stay on track.

And I think that part of the reason we’ve seen a lot of just huge traction in social media and people posting about their glucose levels, is because people love showing other people their wins and their successes. And they want other people to sort of hold them accountable and know. And it’s also fun to show people the surprises like, Oh, I cannot believe that this bowl of cereal shot me into hugely high glucose levels.

So I think accountability is a big piece, but those are three of the main ones that I think, really allow wearables to promote successful behavior change, closed loop, body awareness, and accountability.

Vivien Ho: [00:26:34] That’s awesome. I feel like I’ve experienced. All three of them.

Dr. Casey Means: [00:26:38] That’s great to hear.

Vivien Ho: [00:26:40] Yeah. Seeing the spikes and seeing the changes based on what I’m eating.

I share it with my friends and say like, Hey, ramen is doing pretty well for me, but you know, granola is not. So it’s pretty fun.

Dr. Casey Means: [00:26:51] That’s great to hear.

Vivien Ho: [00:26:52] Yeah. So I’d love to talk about how does it work when someone wants to sign up for Levels Health today. You obviously can speak to it. I’d love to hear you walk through the consumer journey. How do they purchase this product? What happens after the first month?

Dr. Casey Means: [00:27:04] Yeah. So the program is a one month metabolic awareness experience. So it’s a one month core offering that people go through. And our program involves three aspects of that one month. So the first is that when you sign up as a Levels customer, you’re connected with the telemedicine physician who evaluates you for this product. It’s actually a prescription only product.

It’s an FDA approved piece of hardware. And so there’s a very brief consultation online with a physician. If it’s deemed safe to have a continuous glucose monitor, a prescription is granted by the physician. And then the second piece is that we fulfill that from our partner pharmacy. So you’ll receive the continuous glucose monitors in a box with instructions about how to get access to the app.

And then the third piece is of course, the software, which is what we’ve built to help really move the needle on the behavior change component and interpret the data stream. So in the box, a customer will get two continuous glucose monitors, because each one lasts on the arm for 14 days. So that makes up the month, 28 days

of glucose sensing. And during that month, we really encourage people to really go on this metabolic awareness journey that often, people can really take whatever journey they want during it. But something that I highly recommend is the first week, to really just eat your normal foods that you love. Like eat everything that you’ve been normally eating, and just make observations. See how things are scored in the app. See what is your breakfast doing to your glucose levels. And what is your snacks doing? And what is your normal bedtime seem to be doing to your blood glucose levels? So just really live your normal life the first week. The second and third week, we really love to have people experiment. So try sorts of different things, you know, get more sleep, maybe get less sleep, try a high intensity workout or try yoga, try eating a whole orange and a glass of orange juice and see the difference. Add protein and fat to a carbohydrate versus eating a carbohydrate alone.

Eat a high carb food in the morning or eat it late at night. All of these things actually can change the way your body process glucose. And for each person it’s going to be completely different because our metabolisms are so unique, and what works for you, that might not work for me. So you really have to experiment.

And then based on what you learned during that experimentation, we really encourage people to optimize in the fourth week. So take what you’ve learned, and try and just keep those glucose levels flat and stable. And see if you can really get those levels to where you want.

Vivien Ho: [00:29:22] I guess I’m curious since you’ve been piloting with a lot of customers, like what’s the thing surprising you that you didn’t expect people to react or some feedback that you were surprised to hear?

Dr. Casey Means: [00:29:35] Yeah. So two things really jump out in my mind. The first is the concept of meals sequencing. So a lot of people have found that when they eat their carbohydrates first, they actually see a much larger glucose response than if they eat like a salad or protein or fat earlier in the meal.

And this has actually been well studied in the literature that if you eat your carbohydrates just by themselves early, you’re going to see a much more pronounced glucose response than if you sort of put something in the stomach first and slow digestion. So people have experimented with that and seen some really interesting results.

We’ve seen a lot of people be very interested in the athletic side of this as well. We have a lot of professional athletes in the program who are using glucose monitoring to help understand their fueling and their recovery. And we see people in athletic community, a lot of times really move towards changing their pre and post-workout snacks.

So many things that are marketed towards athletes are just filled with sugary crap. So like the gels and Gatorade has high-fructose corn syrup in it. And these protein powder and shakes are filled with sugar. And they market this because you want to, you know, replete your glucose so you can store it as glycogen in your muscles and build muscles and whatnot.

And, you know, it’ll help keep you going longer with more quote unquote energy. But really what it’s doing, it’s causing these massive glucose spikes in people and then crashes. So just really exaggerated glucose load, just that absolutely you do not need. And people are finding that if you actually eat like a much more complex carbohydrate, or even space out these high carb foods from your workout.

What happens is you don’t have like these huge spikes and crush. And you get what you need, but you don’t get the collateral damage of these crazy, just sugar filled foods. So we’re seeing a lot of athletes kind of peel back from some of the processed athletics foods and like, you know, have just a much sort of gentler like type of snack before after their workout.

The second thing with athletes that has been fascinating is that many are, seem to be moving towards more working out in a fasted state. So not actually having glucose on board when they work out, because we know that when you work out with actually low glucose, what happens is your insulin is also going to be low.

And that means that you can burn fat more efficiently. So athletes are often relying just on glucose for their workouts, and we only have about two hours of the stored glucose in our body. Then we have to move over to fat. But if you’re constantly keeping your insulin high, you can’t burn that fat. So the more we can actually train in a low carbohydrate, low glucose state, the more we can actually start working those fat burning pathways, and over time that can really build endurance.

So that’s been fascinating to see. And then the third I’ll mention for just an interesting sort of customer experiences is the ketogenic community who are people who follow a low carb diet. They have been fascinated by this product, because normally they’re just measuring their ketones in the blood with a finger prick, but this way they can actually see how their food is affecting their glucose.

And you can pretty confidently know that if you’re keeping your glucose low, you’re going to be able to be more likely to get into fat burning and ketone generating. And so it’s another way to really stay on top of the diet. And a lot of ketogenic people actually eat very strict, low carb diets. And some have found that there’s actually foods they can eat that aren’t technically ketogenic on the diet, but they don’t spike their glucose. So it works for them. And since each person responds to carbs differently, for one person on a keto diet, they might be able to eat carrots or beans and it just doesn’t spike their glucose. And so it’s okay for them.

Whereas for another person, it might cause the glucose response that’s problematic and kicks them out of ketogenesis. So keto little, like personalize a ketogenic diet and really usher in what I like to call like keto 2.0, a personalized keto diet. I think it’s been really liberating for a lot of people because they’ve been able to expand this very restricted diet.

Vivien Ho: [00:33:26] Right. That’s amazing. Yeah. I mean, ketogenic diets typically use a strip, right. And that’s the only thing you get. You don’t get a closed loop system. It’s hard to really track it continuously. So super exciting to see those insights. I know we’ve been covering a lot of ground today. So I guess I would just wrap up this section with just understanding what you’re most excited about for this company. This company is still very young. What is your vision for scaling this and giving more access once you actually officially launched?

Dr. Casey Means: [00:33:54] Yes. So we are laser focused. Our North star is to reverse the trend of metabolic dysfunction. This country right now, 88% of Americans have evidence of metabolic dysfunction.

This was a study out of UNC last year that showed that 88% of Americans have at least one biomarker of their metabolism not being functional. Only 12% of people are optimally, metabolically, healthy. You know, this makes sense. You see crazy numbers of metabolic conditions. We’ve got, 74% of the country is overweight or obese, 128 million Americans with pre-diabetes or diabetes.

It’s just, it’s absolutely astronomical and rampant. And I think it’s the elephant in the room of modern healthcare. And we’re just not talking about it. There’s so many industries that benefit off of products or services that basically don’t promote metabolic health. And so it’s really the elephant in the room, and it’s contributing to really bankrupting human capital in the country, but also it’s driving our healthcare costs that are just astronomical.

Now, you know, $3.4 trillion a year. What I am so excited about is that we are going to be approaching this from a really bottom up way. We are giving people their own data to make choices that will improve metabolic health. We’re not relying on people to wait until, you know, they go to the doctor’s office and get a fasting glucose test and, that’s sort of the beginning and the end of the conversation.

We’re letting people be empowered to make choices early so they can maintain their current health and prevent future illness. So that’s really our laser focus. And really our scaling strategy is to expand our market from our early adopters, which are really the athletes and the biohackers and the longevity enthusiast. And really bring that to a much wider market, and move into more of a clinical product that can really be used to reverse and prevent disease.

So right now,, we’re starting very much in the wellness market and then we’re going to expand from there. But we’re just a very mission focused company, and are excited to build a product that just makes easy for people and seamless to make good choices.

Vivien Ho: [00:35:47] Yeah. We love your mission. Super excited for you to scale and grow. It’s only been a year and you guys have made so much progress. So I’m super impressed with what you guys have built. I guess, to wrap up, I’d love to talk about maybe something fun in terms of hobbies you developed in quarantine. You know, given that we’re in our phase two with quarantine now, love to hear any interesting things you’ve been working on or doing.

Dr. Casey Means: [00:36:11] Yeah, absolutely.

Vivien Ho: [00:36:12] So Levels, building Levels.

Dr. Casey Means: [00:36:15] Beyond Levels yeah, you know, it’s something I totally drank the Kool-Aid and got a Peleton when quarantine started, and that has been a lifesaver, you know, just a stress reliever. And so I’ve really gotten into biking. And one of the funniest things about getting a Peleton, which I feel just incredibly fortunate to have is that it actually got me into outdoor biking. So I got this indoor bike, and then I was so in love with it that I dug my bike out of storage and got it tuned up. And I’ve been doing really long road rides, you know, like a hundred miles over a weekend and things like that. And so some people are like, Oh my gosh, you bought this amazing indoor bike, and now you’re mostly using your outdoor bike. But I think it’s actually, they’re very synergistic and I’m very impressed by the company for really focusing on technique and form, and challenging people because it actually gets you much more confident to do it outdoors. So it’s been this wonderful synergy.

Vivien Ho: [00:37:05] Awesome. I’ve also picked up biking, but I haven’t got a Peloton. I just bike outside with my Dixie.

Dr. Casey Means: [00:37:11] That’s awesome.

Vivien Ho: [00:37:11] I don’t go hundred miles, but I definitely, yeah, I get the feeling it’s nice to like, be able to go further, go out there, explore the world without being stuck in the city or anything. So yeah, it was a semi COVID safe thing to do, because you’re kind of on all these back roads, no people. So it’s been great. Awesome. Thank you so much for spending time with us today on the podcast, we really loved hearing more about Levels. Really appreciate you letting me try it out as well. And thank you so much for your time today.

Dr. Casey Means: [00:37:39] Thanks for having me.