#162 - Sarah Hallberg, D.O., M.S.: Challenging the status quo of treating metabolic disease, and a personal journey through a grim cancer diagnosis

Hey everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in depth content. If you want to take your knowledge of this space to the next level, at the end of this episode, I'll explain what those benefits are. Or if you want to learn more now, head over to peterattiamd.com subscribe Now without further delay, here's today's episode.

My guest this week is Sarah Hallberg. Sarah is a physician who has spent the better part of two decades focusing on treating patients for first with obesity and ultimately really finding her niche in type 2 diabetes. About 10 years ago, she became a huge believer through her clinical experience in the efficacy of carbohydrate restriction in the treatment of type 2 diabetes, and that led to her becoming involved in a company called Virta Health, which I'm an investor in as well. So I want to disclose that in this podcast we talk really about two completely separate things, each of which is important in its own right. In the first part of this podcast, we discuss the research role of dietary fat and carbohydrate on the plasma makeup of fatty acid and triglyceride. In other words, does the type of fat you eat play a role in the type of fats that are found in your bloodstream? Because we have a pretty good understanding of what type of fats in your bloodstream are good and bad, how much is that impacted by what you eat? And I think for many people who are new to this area, this will be quite shocking. And suffice it to say, it's not so simple as you are what you eat, and there is enormous implication here. But I think one of the most important takeaways is that one of these fatty acids in particular which we get into, it's a monounsaturated fat with 16 carbons, turns out to be a very interesting early predictor of metabolic disease. We then pivot off this admittedly somewhat nerdy discussion into perhaps one of the most emotionally riveting discussions I've ever had on the podcast, which is discussing Sarah's personal journey through the diagnosis of lung cancer. She was diagnosed with lung cancer at the end of June 2017. As I discuss in the podcast, it was just a few days after I had seen her appearing to be completely healthy. And to say that the last four years have been anything other than difficult would be an understatement. And I don't really want to say more about the second part of the podcast because I won't be doing it justice. I think ultimately it's something that, frankly, everyone would benefit from listening to. And it was an admittedly difficult discussion, but one that I feel very privileged to have had with Sarah. So without further delay, please enjoy my conversation with Dr. Sarah Halbert. Welcome to the show. I'm super excited to be speaking with you today. This has the potential, of course, to be a 10 hour podcast, which it won't be, but I think that speaks to the depth of insight that you've got into so many topics that I actually want to talk about.

Thank you. It's great to be here.

Well, in thinking long and hard about how to navigate all the threads I want to pull on, I figured we would just start with the nerdiest of all topics, which is something that I know you're so passionate about and yet I don't think gets nearly enough attention. And that is basically the role of dietary intake of both carbohydrate and fats and the relationship that has on the distribution of fatty acids within the body. So let me just start by asking, why is that even of interest to you?

Well, it's significant interest because it really hits at one of the things people criticize a low carb, high fat diet about is, oh my goodness, you'll get more fat in your muscles, in your liver, and it's going to lead to increased insulin resistance and there by default, going to lead to increased cardiovascular disease. And we know that a therapeutic carbohydrate restricted diet brings down so many cardiovascular risk biomarkers that we're all used to hearing about, okay, it decreases triglycerides, okay. It actually can reverse type 2 diabetes in most cases and certainly significantly improve glycemic control in all but fatty acids. That's not something that's talked about all that often. And what is talked about all that often is this idea of you are what you eat, right? We hear that still every day. Remember, you are what you eat. And this example of what happens when you consume saturated fat in the matrix of a diet that includes carbohydrate restriction is so against that long worn out idea of you are what you eat. And so fatty acids play a critical role. Study after study will show us in cardiovascular risk and in future Diabetes risk as well. But again, it's not discussed because fatty acids are confusing, let's face it. Okay? And most people would rather just fall back on this idea, you are what you eat, which just really flies counter to what the evidence in the peer reviewed, published literature says.

So maybe taking even a greater step back from that, Sarah, what is it that attracted you personally as a physician towards the management of type 2 diabetes? Because, I mean, that's how you and I got to know each other was through a company that you're a big part of called Virta Health, which I'm sure at some point today we will talk about. But what attracted you to this patient population? And how is it that you stumbled upon the idea that there was perhaps another way to treat patients with type 2 diabetes that was not kind of the standard treatment which was chasing glycemic control with insulin or insulin increasing drugs?

Well, I tell you, it's by accident. If you had told me 20 years ago that I'd be playing this role in the healthcare system, I probably wouldn't have believed you. So it goes back again to the fact that for a very long time, I mean, I've been in the world of obesity care for well over 25 years now. And just the first half of that was telling people that the way to fix everything was to eat a low calorie, low fat diet. I grew up as a product of the 80s, like so many people, where that was the dogma, There was no other way. And of course, entering into college and grad school where I got both my bachelor's and master's in exercise physiology, I mean, that's what we were taught. Moving on to med school, you know, reaffirmed once again. So when I went into practice as a primary career physician, I'm board certified in internal medicine, it was more the same. But again, it was so frustrating to me all along the way really to be continually giving this advice and then have people show up being worse. I'm not making them healthier, I'm making them or I'm watching them become more unhealthy. And that was depressing. And it was really quickly became just to the point where it was like, I can't continue on with primary care for the rest of my life because I felt like a legal drug dealer. I got really lucky here. Okay. I like to say a lot of my pivots are pivoted on anger. Right? Pivots in my career. And I was really angry at what was happening on the primary care level. And as Luck would have it, at Indiana University Health, they knew about my background, knew about my past work in obesity care, and asked me to start a program, obesity program. And I jumped at the opportunity. And I was lucky to be able to take some time off over the next year, spend time figuring out what was this going to look like, how are we going to tackle the untackleable, if you will, problem, you know, that is obesity. And I started sticking my nose in the literature, which is something that every physician wants to do, but not every physician is afforded the time. Let's face it, we are just boom, boom, boom, C patients. There's just such a busy lifestyle in everything right now. But I was given a chance to step back some, so I had time to prepare for this. And in that, I discovered carbohydrate restriction as a means to weight loss. Initially listened to some lectures by Dr. Steve Phinney and Jeff Folick, and I was like, whoa, that makes total physiologic sense. And so, boy, did I dig deeper into this. I read everything I could get my hands on and really came to the conclusion, which required a lot of cognitive dissonance. Overcoming that what I had been saying for well over a decade to so many people was really not founded on good science, and that the field of carbohydrate restriction, while still relatively in its infancy at the time, showed much more promise. And so we opened the clinic as a carbohydrate restricted clinic. But the fact of the matter is, although people were losing weight, what we were seeing that was so much more meaningful was that people's diabetes was, like, going away. They were having normal blood sugar. We were pulling them off of insulin at rates that I could never have believed had I not been the physician who was taking care of these patients. I mean, it was astronomical. Hundreds of units of insulin.

First of all, there's two questions I guess I want to ask you. One, were these patients primarily patients with type 2 diabetes, or was it primarily obesity, of which a subset had diabetes? And secondly, how much resistance did you have in your own institution when you showed up and said, hey, I know you guys brought me in to do this thing, I'm gonna do it, but, oh, by the way, my secret sauce is gonna be this, at the time, very unconventional approach.

As you probably can imagine, when patients come into an obesity clinic, most all of them, if not all of them, have some form of metabolic disease, the biggest being type 2 diabetes. So we were seeing type 2 diabetes all of the time, consistently daily, and you're Right. I had to take precautions because Again, this was 10 years ago. And not as much about carbohydrate restriction was known at that time, certainly among general practicing physicians in any discipline really. And so I knew that I had a head off the potential resistance that was going to come. There was just no question of it. So I actually went about and spent an entire summer meeting with all the departments in our local med center and giving them a 15 minute slide presentation of when your patient comes back to says that Dr. Hallberg told them to eat a lot of fat and not a lot of carbohydrates, that I wasn't crazy, that this was actually based on evidence. And here it was. And you know, Peter, you'd be surprised. I didn't get any pushback. I actually pushed it even to the next level. I was part at that time of the ambulatory quality committee at our institution. And I actually brought up a amendment that all patients with metabolic disease should at least be provided the option of trying this if they wanted. And it passed unanimously. I mean, people got it once they had time to pause, take a look at the physiology behind this and realize, okay, yeah, that makes a lot of sense. So in changed my life, right? And again, I like to always say my career is built of inflection points of anger. And as we were seeing these huge changes of diabetes and patients just resolving their diabetes, I became really angry because I was like, where is this? Where is this in the guidelines? How come I've never heard of this before? I mean, this is. I mean, I hate to be like overdramatic, but it truly is quite miraculous. For a disease that everyone thought was chronic and progressive, to see people recover from it is quite astounding. And so I decided that I needed to get into research. So actually, to start off with, I called Purdue University's nutrition program and asked one of the researchers there if they wanted to help me on just an early unfunded pilot study to prove my point, looking at metabolic improvements and looking at financial improvements too, because obviously if people weren't taking all this medicine, they weren't costing themselves and of course the health care system as a whole as much money. So I talked about that study, presented it at the National Lipid association quite a long time ago, talked about it actually in my TED talk, and then was speaking at the Obesity Medicine association quite a long time ago, and actually met Dr. Steve Phinney, and that really changed the course of my life as well.

So all this time you're sort of putting into practice What Steve and Jeff had been writing about for a long time. And obviously Steve is someone I've been dying to have on the podcast. And we were actually supposed to do it at one point in time and then scheduling got in the way. But I didn't realize that you had already sort of gone down this path and yet hadn't actually met him. Because I took the opposite approach, which was when I started kind of implementing some of these treatments. I'm just a bull in a china shop. I just reached out to Steve right away. I might have been one of the first people to get a copy of the book that he and Jeff wrote in 2011. I think I got a preprint of that book, which I still have, by the way, the art and science book which I have. It might have more highlights and post its in it than any book I own. Because I think like you, I was kind of going through the. This can't be. There's something so counterintuitive to this that I need to read this over and over and over again to make sure I get it. So it's funny that that's the case. Now tell me, where did you know were you at this time going to ADA meetings, the American Diabetes association meetings, and when you would discuss what you were seeing in your practice with your peers who were also on the front lines taking a more traditional approach? How is your experience being. How was that met?

Well, it's interesting if I was speaking with someone who took care of obesity patients for obesity, they were totally, I get it, I'm doing the same thing to some varying degree. But when you moved out of that space to other subspecialists, the first thing was, oh yeah, their diabetes will go away, but you're gonna kill them with heart disease, right? Or, oh, you know, we all know it works. I'll never forget one of the leaders in the endocrine movement said, look, we all know it works. This is not a secret, but nobody can stay with it. And I was like, you know, I don't know, here in my practice I have thousands of patients that would beg to differ with that. And so, you know, those are the feedback that I got. And one of the things was I knew that there had to be even more research done. I mean, you know, we had wonderful pioneers in Steve and Jeff and Eric from Duke Westman, but we needed even more. They needed to be larger trials, they needed to really specifically focus on patients with type 2 diabetes. Because I was convinced almost from the get go that that is the target population here because that's where we see the biggest improvements. So this chance meeting with Steve at Obesity Medicine association conference led to a dinner and led to funding of the large clinical trial that we're actually wrapping up in the next couple of months. Right now, we're at the tail end of our five year data collection of the longest and largest trial looking at nutritional ketosis as a means of reversing type 2 diabetes and pre diabetes, which I'll just kind of stick in really quick here. Today actually happens to be the day that the prediabetes paper was published. So I'm really proud to say this is the eighth paper already that's come out of this large trial started by a chance encounter at a conference. We haven't published the prediabetes results until today. So this was a paper that looks at the first two years of prediabetes utilizing remote continuous support to help patients adhere to a diet aimed at nutritional ketosis.

And Sarah, these are patients defined as pre diabetic by hemoglobin A1C.

Correct.

And that's being defined as 5.7 to 6.4. Is that the range?

That's correct, yes.

Okay, tell people what that means. I think most people are aware of what a hemoglobin A1C is, but what does that translate to in an average glucose? Approximately.

Yeah. So we really start to get, for example, fasting. That's the one most people are familiar with. And once you get a fasting glucose over 110, you know, that's the worrisome pre diabetes range. And I do have to say here, though, that doesn't mean normal glucoses are okay for everyone. And I think you've had many people on here talking about the perils of insulin resistance and how it starts to cause significant problems in people who still have normal blood sugars. And I just think that's such an important point and can't be overstated. Again. But in this study, we're looking at people who had insulin resistance long enough that their pancreas and the beta cells could not keep up with the insulin that was needed to keep blood sugar normal and their blood sugar started to rise, not yet to the level where a diagnosis of type 2 diabetes could be made. But. But once again, where we see the impact of insulin resistance affecting the body's ability to keep blood sugar normal due to pancreas being overworked for far too long.

And if we believe that, I mean, I don't know what the latest numbers are, but I'm guessing It's still about 10% of the US population has type 2 diabetes. Is that approximately correct or is it appropriate? Are we more than 10% now?

Approximately. With also the caveat of much more concerning levels in different minority populations, which of course hopefully we'll get a chance to talk about later, is just a huge goal with improving health equity in this country.

So if it's 10% in all comers, do you have a sense of what it is in Hispanic and African American populations?

Yeah, it gets even higher. It's well into the teens in those and Pacific Islanders as well. So these are populations that we need to be paying attention, of course, to everyone who has type 2 diabetes, but we also need to be paying attention to who's at greater risk.

So what percentage of the population do we believe is formally in the pre diabetic camp? Which again, I think what you said a moment ago is very important for people to understand. If we go back to the podcast, which Jerry Shulman, which is one of my favorite discussions ever on the topic of insulin resistance, I mean, Jerry really laid out elegantly the long time course of this disease. And even if you have normal fasting glucose and fasting insulin, but that early sign of elevated postprandial insulin is really that early sign of insulin resistance that will then lead to postprandial glucose elevations. And even that can still exist in the presence of normal fasting glucose. So to your point, by the time someone registers as a pre diabetic, quote unquote, I mean, this has been a process that's been going on for five to 10 years. What is our belief about how many or what percentage of Americans, just to make it American centric for a moment, what percentage of Americans are in that bucket?

Well, I tell you, recent studies will show us that over 50% of Americans, adult Americans, have diabetes or pre diabetes. And a study released a couple of years ago, and I mean this, this should shock everyone to its core. Based on NHANES data, that 88% of Americans are not in optimal metabolic health. I mean, let me say that again, 88% of adult Americans are not in optimal metabolic health. And that is by looking at NHANES data and taking a look at the criteria for metabolic syndrome. And so the 12% are those who didn't meet any of the criteria for metabolic syndrome. I mean, that's frightening.

Yeah, so I was gonna ask you if that's exactly what it meant. So just let's state for the listener what metabolic syndrome is. We've certainly discussed it on this Podcast. But it would be great to remind people. What are those 12% doing? They have none of the following five. Right. They have normal blood pressure. They do not have elevated blood pressure.

And they're not on medication, and they're.

Not taking medication to lower blood pressure. And normal is now being much more stringently defined. But I believe the latest CDC definition of normal is less than 130 over 80. In our practice, we advocate less than 120. 80. They have normal fasting glucose, and that's defined as less than 100. They have normal triglycerides, which are being defined as less than 150. We argue in our practice that's very high and anything over 100 is elevated. They have normal HDL cholesterol, which for men is defined as greater than 40 milligrams per deciliter, for women, greater than 50 milligrams per deciliter. And they do not have truncal obesity. And I forget. I think for men, that's defined as 40 inches of waist circumference and women 36. I don't know if that's still the latest.

Well, yeah, and I will also point out one really important thing here when it comes to waist circumference, too, and the definition of metabolic syndrome. And it a little bit goes back to what I was saying before about the consideration of minorities and different ethnic populations, which is we have to take that into account even when we're defining metabolic syndrome, because for Southeast Asians, they are defined as having metabolic syndrome at a much lower waist circumference. And for African Americans, we need to really consider as well, because they tend. Even in the face of having insulin resistance, they tend to have normal triglycerides and hdl. And so, again, we can't be treating everybody the same, but we often do.

Yeah, I'm glad you pointed that out. I still remember it was about 10 years ago when I learned that lesson, which was taking care of an African American patient who had about the most uncontrolled diabetes I'd ever seen. Hemoglobin A1C of 14%. This is a person who. Who's basically going to have their limbs amputated in the next hour. Triglycerides of 89, just. Yeah, just totally normal. You look at their lipid panel, you wouldn't think anything is wrong.

Right. And so that's the thing is they can get missed. And so knowing this and educating people on things like this, again, goes back to our working on health equities. And it's so important and so often not something people take into account. And just going back to pre diabetes, the most frustrating thing. I shouldn't say that it's one of the most frustrating things. There are many things about our health care system I could enter into the most frustrating. But one of them is patients coming in to see me whose lab showed prediabetes. And I said, oh, you have pre diabetes? Oh, no, no, no. My physician said I was fine. The fact that we don't appreciate that by the time you get to pre diabetes, there's some really serious things going on here. Their vision is being impacted, their nerves are being impacted. You know, these are things we can't just say, oh, they haven't gotten bad enough to bother with because they're not at the criteria for type 2 diabetes yet. I mean, we have to pay attention. And so if that's one thing, if there's any physicians listening, which I know that there are, don't ignore any elevation in blood sugar. That means there's been a problem for a long time already.

And patients should be also hyper vigilant about this. I mean, I've seen patients in that pre diabetic camp, and this is using an example of a male patient, when their insulin sensitivity is restored and their blood glucose comes down by an average of 10 milligrams per deciliter, they'll say, wow, I have better erections all of a sudden. And that speaks to even the microvascular damage that's being done long before you get to diabetes. I actually was exchanging emails with a really good ophthalmologist recently and kind of trying to ask, how far are we away from being able to use, use retinal imaging as a screening tool for early, early, early microvascular disease? Because I think the hemoglobin A1C is just far too crude a metric for this. And I actually have seen some interesting literature, and I'm sure you've seen even more of it that suggests that this is, you know, if you look at the microvasculature in the eye, it might be one of the earliest warning signs of when things go awry. And so in an ideal world, I would love to love it if we had tech that basically allowed for quick and easy evaluation of that. So that to your point, it doesn't really matter if your trigs are up or down and your waist is big or not. Let's look at the actual place where the damage is taking place and make the assessment on an individualized basis as opposed to using these sort of population based Metrics which move in the right direction, but for any one individual can be quite misleading.

Yeah, and then I love the eye discussion because, you know, one of the other I think, really important questions is, once we do get to damage, can we make it better? Can we make it better without. And skip some of the horrors of having diabetic eye disease for millions of patients? I mean, that is a really burning question for me and one that I think we need to really explore.

Yeah, indeed. So with that background, let's kind of dive into some of this nerdy, nerdy fatty acid stuff. And I got to tell you, I find this stuff really interesting in part because I think it's complicated enough to make sense of just the eating side of this stuff. In other words, I think people that have listened to this podcast, we've done a number of shows that have dealt with fatty acids. People probably understand that there are saturated fats, monounsaturated fats, and polyunsaturated fats. The saturated fats have no double bonds, so that means every carbon is fully saturated with hydrogen. The monounsaturateds have one and only one unsaturation. So one double bond, and then the polys have at least two of these double bonds. But it's the manner in which these things can be made from each other that becomes quite interesting, isn't it? It's really the way that you can ingest one form and it can be turned into another. So I'm wondering if the easiest place to begin this discussion is to introduce what the fate of a very common fat in our body is, which is the C16 saturated fat. So can you talk a little bit about how abundant that is and what our body's options are for it, what it's called? Let's start with the nomenclature. What does pure C16 look like?

That's palmyolytic acid. So it's really interesting what happens. And do you mind if I jump on and share screen here so we can talk a little bit more about it?

Yeah, that would make it easier for everybody, I'm sure.

I want to start by talking about saturated fatty acids in general. And what we know is that going back here to the basics and looking at the liver, when we have incorporation of saturated fatty acids into our triglycerides, that is correlated with insulin resistance and adiposity, likely reflecting accelerated hepatic de novo lipogenesis, or also it can be what is actually returned to the liver. So, really, two, we certainly know that hepatic de novo lipogenesis is A big part of the problem when it comes to elevated triglycerides. But we can also make these with some what is delivered exactly back to the liver. And so when we see saturated fatty acids as a makeup of triglycerides or maybe even phospholipids there, we say, oh my goodness, that's a marker of increased saturated fatty acid consumption. Right. These people are eating a high saturated fat diet. And that seems to make sense. And this is the problem with a lot of things in science in general, and nutrition science is no different, is that just because it seems to make sense doesn't mean it's the way things actually work.

Sarah, can I explain a technical point on this slide that you and I will take for granted? But I want to make sure that a listener understands. So when a patient goes and gets their blood drawn, let's just say they get a standard lipid panel, it will spit out the following. Total cholesterol equals 200 mg per deciliter. LDL cholesterol equals 140 mg per deciliter. Triglycerides equal 150 mg per deciliter. HDL cholesterol is 35 mg per deciliter. And VLDL cholesterol, if I remembered the numbers I just spit out, would be 25 milligrams per deciliter. In other words, the VLDL cholesterol, HDL cholesterol, and LDL cholesterol sum to the total. And then the triglycerides are independent. What I want to make sure people understand is those are all found within the lipoproteins. So VLDL cholesterol is the amount of cholesterol ester contained within the very low density lipoprotein. LDL cholesterol is the total content of cholesterol ester found within the the low density lipoprotein, et cetera, for the hdl. Here's the part that's really interesting. We always check these things fasting, because when it comes to measuring the triglyceride, we want to eliminate what's in the chylomicron. We want to eliminate the immediately absorbed triglyceride from the gut. And by doing that, we basically capture what you have on this photo. When we measure a triglyceride, for all intents and purposes, we are basically measuring the 90% of triglycerides that are captured within the VLDL. So let me restate that. Cause that was a bit rambling. When you go to the doctor and get your blood tested. And it says your triglycerides are 150mg per deciliter. That's basically saying, look, 90% of that 150mg per deciliter is within your VLDL cholesterol. Some of that is in intermediate density lipoprotein, but that's v virtually non existent. There's a trace of that in the LDL cholesterol and even a smaller trace in the hdl, but the lion's share is in the VLDL cholesterol. And as you're going to explain to us, this process of de novo lipogenesis, the conduit from fat being made in the liver and exported, that conduit is the VLDL particle. That's going to become very important in this discussion.

Absolutely, yeah. And that's really important. Thank you for the precursor explanation because it is real, this is technical stuff and that is really important for people to understand. Then the next question really becomes, okay, so if we have a high saturated fatty acid content within the vldl, okay, again it's being in the triglycerides, the phospholipid membrane, wherever we find it, where did the saturated fatty acids come from? Is it directly from consumption? And I just want to first point out, before we get into maybe more of the technical stuff, some of the clinical trials that can help us understand this a little bit better. And so this is one of my favorites by Dr. Brittany Volk, that was published a while ago. And it's really great because this was a feeding study. So, you know, they kept track of what the patients were eating. It wasn't a free for all. Are they eating what they were telling them to eat or not? They provided all of their food. And this was patients with metabolic syndrome. They went through six feeding phases. And so they did a run in with a very low carbohydrate diet for everyone, less than 50 grams of carbohydrates a day. And every three weeks they increased the carbohydrates in the diet all the way up to a 346 grams, which was C6 feeding phase. The other thing to note here is the saturated fat content. So when we were at the low carbohydrate end here in C1, they were consuming 84 grams of saturated fatty acids a day. Okay, so that blows away any guideline on saturated fat, I mean, so far above what anyone would consider at goal. And then we get down to the C6 and we're much less 32 grams. Again, what happens to the fatty acids as people are run through these six phases?

And Sarah, just to be clear, this is basically an isocaloric feeding study, which means as you're ratcheting up the content of carbohydrate, you're commensurately reducing at a caloric level the amount of saturated fat. Right. I believe this study did not change the number of calories they were consuming.

Correct. They did not. And so what happened over these six phases? So here we have saturated fatty acid levels marked. Okay? So here's the baseline at that run in. And we see when we have the very high saturated fat level, very low carbohydrate. Here we go. And what's really interesting is what happens as we march along here down to C6. And if you remember, this is much lower saturated fatty acid content of the diet, much higher carbohydrate intake. What we see is that it's actually the saturated fatty acid content is actually higher with the lower saturated fat intake. And we're going to come back and talk about the science behind that. But I think it's really important for people to see this clinically. And then maybe when we get into a little bit more of the nitty gritty, it can make more sense.

I mean, it's actually statistically insignificant in terms of C16. Right. Which is the dominant saturated fatty acid. So palmitic acid. It trended towards an increase as saturated fat. Dietary saturated fat went down and carbohydrate went up, but it didn't reach significance. And the only one that actually did Significantly increase was C14.

Right, yeah, actually C16.1 as well. And that one is we're going to spend hopefully a little bit of time on.

Yeah, yeah, yeah. No, but as a saturated fat. It was really fat.

Oh, as a saturated fat, yes.

Yeah, yeah.

But the point of this is we didn't have these really high levels of serum saturated fatty acids when we were consuming. When these participants were consuming this very high saturated fat diet, essentially. And this is important, it stays the same. If anything, there's a trend to higher serum saturated fat in the low fat arm. Okay. But certainly we do do not see a rise in the high intake of saturated fat. That's super important. And again, it goes against what I was saying earlier on. You are what you eat. Well, okay, if that's true, then when I consume a very high level of saturated fatty acids, why am I not seeing that again in the blood, in the serum? Why are we not seeing that?

And what's nice in this study is you've exhaustively looked at where the fatty acids are. So obviously the most efficient place we store fatty acids is in the triglyceride, but you also store it within the cholesterol ester and it's obviously in the phospholipid as well. But regardless of where you look, you see no association between dietary saturated fat and fatty acid composition with respect to saturated fat.

That's right. That's right. And I want to really quick draw attention here to one more that we are going to be talking more about. And that's 16, one, that's palmitoleic acid. And we're gonna talk more about why that's important. But as we can see here, when we follow that across, it significantly rises when we have less saturated fat and more carbohydrates. And you can see that is statistically significantly different in every place that we're looking. So moving on one other trial that shows that this. And then we'll bring up the table that I had erroneously brought up for the first study. But when we take here a low saturated fat diet. Low fat, low saturated fat diet. And we compare it to a low carbohydrate, high saturated fat diet over 12 weeks. This is from Jeff Volek's group from 2008. And what I like here is you can see very readily with these pie charts exactly what the content of the two diets were. So again, we really have it flipped. High carbohydrate, low carbohydrate, low fat here on the left to a very high intake of fat on the right. And again below it, the two different levels of saturated fat that we're comparing 12 grams to three times as high in the low carb diet at 36.

These are both really low calorie studies. Was this an ad lib feeding study or were these deliberately calorie restricted? How was this study done?

Yeah, these were both that wanted the calorie intake of the two studies to be the same. So as you can see, they're about 1500 calories apiece.

And were they deliberately calorie restricted?

Yes. So what we can see here is that what we have when we take a look at these two arms is taking a look on the right to the change in serum saturated fatty acids, we can see in the carb restricted diet, significant decrease versus the low fat diet. So again, in the much higher saturated fatty acid arm, we see a significant decrease down, whereas we do see a drop in the low saturated fatty acid intake group, but not nearly as Much as we see with the carbohydrate restricted group, once again, arguing against you are what you eat. And I want to now get in a little bit more to this, what I think is actually even more important, which is the change in the palmyleic acid.

Yeah. So palmitic acid is 16 0, palmyleeic acid is 16 1. They look almost the same, except that palmitoleic, the 16 1, has that double bond at the N7 position. And you're gonna explain in a moment which enzyme does that and why that matters. Right?

Right. Absolutely. You know, what is it about this? It's not a saturated fatty acid, so why do we care so much what happens to 16 1? But it's pretty evident here what happens first of all, and then we'll talk about why. What happens is that with 16:1 in the high saturated fatty acid group, it drops significantly, where in the low fat group, again, low saturated fatty acid group, it actually goes up. And this is a statistically significant difference. Okay. Much more significant, even as we look than the change in the serum fatty acids. So now I'm going to pull up a graph of these results to look at it a little better, and then I want to get into the actual science of it. This is the very low carbohydrate arm on the left, and it is the low fat arm on the right. And so what we see here when we look at total saturated fatty acids is that it has dropped 5% between the low carbohydrate group and the low fat group, total saturated fatty acids. What about the 16 one? And what we see here with the 16 one in, much more significant statistically, is that we see between a low carbohydrate diet and a low fat diet that we have a more significant decrease in the 161 with the low carbohydrate, higher fat diet.

So there's a couple things going on here for people that are going to be overwhelmed by this table. And I apologize if you're just listening to this without watching it on video. I'll do my best to explain what's going on here. So the first thing to notice here is both of these groups of patients started out with quite elevated triglycerides. So in the first group in the group that was randomized to the very low carbohydrate diet, their average triglyceride at the start of this study was 211 milligrams per deciliter. That's sky high. At the end of 12 weeks, it was down to about 100 milligrams per deciliter, it fell by about 50%. Conversely, the group that started out in the low fat arm, also very high triglycerides to start, 187mg per deciliter. By the end of 12 weeks, they saw about a 20% reduction to about 150mg per deciliter. Now this is where these tables get a little bit confusing because the table is showing both the relative and absolute reduction of the relative or constitutive fatty acid. In this case, 160 and 16 1, n 7, the two we're talking about. What does that mean in English? It means that when you look at the total amount of saturated fat reduction on a relative basis, both groups saw a slight reduction, but it was statistically more significant in one group than the other. The low carb group was a 12% reduction versus 5% in the low fat group. And on an absolute basis that difference was even greater because the low carb group had such a significant reduction in total triglyceride as well. And that's the dominant source of where you're gonna see these fatty acids. And of course, the reverse is true when it comes to 16:1. So let's now ask the question, Sarah, what is it about palmitoleic acid that you think is such an important biomarker? Because we wouldn't be having this discussion if you didn't think we should be paying attention to this.

I think it's a really important biomarker. And if you would allow me, let me point out one other thing here regarding the triglycerides, because clearly the low carbohydrate arm decreased more in the triglycerides. The low fat arm decreased too, which may come as a surprise to your listeners because we do associate low fat with an increase in triglycerides. But I do want to remind everyone that this was a calorie restricted. This was around 1500 calories. So that drop in the low fat diet arm, although maybe not what we were expecting, affected, does make sense with the reduction in calories overall. Now let's go back and talk more about your question. Okay, I think palmyleic acid, or again, that's that 16:1 is really not appreciated as the health predictor that it really is. Okay, so let's go through. I'm going to just jump ahead a little bit here. So palmydoleic, or we like to call it poa, is a product of something called sterol coa desaturase and stearyl coa desaturase is going to determine what is going to happen with some of the fatty acids in our system. Specifically, what's going to to happen to poa. Now, what we know ahead is that sterol coa desaturase is actually an independent marker of triglyceridemia and abdominal adiposity. So in other words, an independent marker of all those things that go along with insulin resistance. So if we have high levels of sterol coa desaturase activity right there, we got to start thinking things may be concerning even if someone has a normal blood sugar. Right. Because right now I think one of the important things, based on the earlier part of our conversation where we see so many times these things are missed, people can still have normal blood sugars. It's going to be really important, you know, number one, that we make everyone aware that a normal blood sugar doesn't mean, mean that you are healthy. But number two, what are some easy ways and some easy markers maybe that we can check to know that we're headed for trouble even before we have blood sugar go up? So plasma triglycerides, and let's take a look at again, POA in those plasma triglycerides in the way of looking at it in quartiles. So again, low versus high. And what we can see is the poa, the byproduct of sterol coa desaturase, is much higher. The higher. The triglycerides are very important. So if your triglycerides are really high, again, what's happening very likely is that your POA is elevated as well, brought about by increased activity of sterol coa desaturase.

And this shouldn't be surprising, right. Because if you look at the very unfriendly diagrams of fatty acid metabolism, one of the first steps we see in the conversion or elongation of fatty acids is the conversion of C16.0 palmitic acid into C16.1 palmyleic acid, N7 through an enzyme that has two names, I guess, depending on the name, nomenclature. Right. So Delta 9 desaturase desaturate, the number 9 carbon from the delta end, also known as sterol coa desaturase, which I think is the more popular name, is SCD1. Right?

Right.

And if you go down that pathway, what you're basically doing is bundling and packaging fat to leave the liver, right?

Yes. And here is one of the. That is an interesting point because the question is if we're trying to change the serum saturated fats into something else, I mean, the body is obviously doing that one would have to wonder, is that a protection mechanism? Why do we want to do that?

To me, that's a great question, Sarah. It seems counterintuitive if I'm going to be obvious because we would think that a saturated fat is much safer. It's inert, there's no chance a reactive oxygen species can be formed out of it. Why is it our body, even if we wanted to export fat from the liver, which we could argue all the reasons that's not a great idea, why would we go to the trouble of this conversion?

All right, well, let's go through it really quick and then get to answering that question because I think it's really important and really sheds light on why we need to be paying more attention to the all important POA and of course, the precursors and enzymes that act in its creation. So let's go through, if you will, this cartoon that I know looks really busy initially, but let me just kind of run through it starting here in the intestine. And remember, you know, we'll start off by saying our focus in healthcare and in nutrition recommendations for so long has been low fat, low fat, more carbohydrates, higher carbohydrates. Well, let's take a look in the intestine at those carbohydrates changing the focus for a minute. So they come in rapidly absorbed carbohydrates or even our slowly absorbed carbohydrates are starches. Okay. And what happens when they come in as glucose that feeds in again through glut 2 into the pancreas, pushing out more insulin. Insulin then feeds into the liver. And what we get here is going through a big, big part of this is SREBP 1. Okay. And I don't know if we need to get that technical, but will lead here to that enzyme we were talking about, the SCD1 or Stearyl COA desaturase increasing. Very important. And it comes about through other means as well. Fructose coming in through GLUT5 or glucose coming directly into the liver through GLUT2. They're all feeding into this by slightly different mechanisms to increase this SCD1. Now we're going to look more at the process in a different way. So we have increased hepatic, first of all, saturated fat. Okay, here's our 16,0 the saturated fat increase hepatic levels of this. What gets turned on as from the past cartoon. We get that SCD1 activity increasing. That leads to this increase in POA coming down here. What's the end gain here, increased VLDL, same thing over here. Looking at it different, we see again SCD1. If it's blocked, we won't see that. We'll see a decrease in vldl. And this again has to do. If this SCD enzyme is blocked, we're going to have an increase in the saturate, a decrease in our poa. But again, what we have when we're consuming the high carbohydrates, even if they're the again more refined carbohydrates or the less rapidly absorbed carbohydrates, this is the path path that we wind up going on. 160 saturated fat is elevated and it turns on this cascade leading to increase in vldl.

Yeah, again, I think for folks that are watching this, it's going to make a bit more sense. And if you're not, I just want to make sure we're bringing you along for the ride. So in the liver when you are taking C16 or C18, but let's just keep the discussion simple and start with a saturated C16, the first committed step is going through SCD1 as an enzyme and it adds that double bond. It makes a few more steps along the way, but ultimately it is increasing a process of lipogenesis, it is making more lipid, it is increasing the amount of lipid within the cholesterol ester and the triglyceride, it is being exported from the liver. So in response to your question, Sarah, is this protective? I guess the answer looks like the body is saying, well, gosh, I would rather get this fat out of the liver than keep it in the liver. And we know that it's not fully successful in doing that because of course, although it hasn't come up yet on this discussion, everything we've talked about today runs hand in hand with non alcoholic fatty liver disease, which is truly an epidemic at the moment. But I suspect that the body is still doing its best, even in the case of non alcoholic fatty liver disease, to try to export this fat as much as possible. The triglyceride is a very efficient place to store it. I've always believed obesity is a protective mechanism. I think that obesity is not the cause of metabolic illness, but the result of it. Which is not to say that the inflammatory environment that comes with it doesn't pour more gasoline on that fire. But it is my belief that everything we're talking about here is the body's aim to protect itself from an abundance of nutrition. And so that's how I read this is the body is doing. And specifically the liver, which is arguably the most important organ in this situation. The liver is really trying to protect us. And it's saying, I'm making so much extra fat right now because you, as my individual, are so far above your carbohydrate consumption tolerance, your tolerance for carbohydrate consumption. And this is the most efficient thing I can do, which is turn that into fat, send it out via the vldl, get that into the adipose site, and yeah, you're gonna be a little bit fatter, and it's gonna come with some downstream problems. But in the short term, it's protecting me, the liver. Would you agree with my teleologic view of that?

I 100% would agree with it. And again, I think that we are going to have more and more details on this coming out very soon in many research projects that are currently ongoing. But what it really comes down to is we want to know what an individual's carbohydrate tolerance is. Okay? I mean, that's key to personalization, right? Does everybody need to be very low carbohydrate, low carbohydrate? I mean, where does we can say population level? What happens in large clinical trials, but what's happening with the individual? Because, let's face it, Peter, and you know, you and I as practicing clinicians know this, when you're sitting with one patient in front of you, you can go over group data from a clinical trial, and that's important part of the decision making. But the only thing that really matters is what's going to happen with the patient right in front of you. We really want to know what the individualized reaction is going to be. We know that this happens with a carbohydrate consumption above a certain threshold, but what that certain threshold is in the individual, we don't know. And based on these pathways, you know, what is the marker we want to be looking at? Actually, it's probably poa, surprisingly not a fatty acid. But what this tells us is that when someone has consumed carbohydrates above their individual tolerance, that POA level is going to be a great biomarker. It's going to go up as, again, a particular protective mechanism in the liver. Our livers are really, I mean, we talk about livers all the time, so related to insulin resistance. It's just always amazing just how sophisticated and how our livers, although we think of them as producing things that aren't necessarily good for us, and that may be true, they're also really working for us as well. And so, again, I want to also go back on one other thing that you said. And the other thing that you said is, so this comes before the adiposity. And I think that that is such an important point and one I like to preach every opportunity I can get it. But this is starting to happen before people gain a lot of weight. Okay. This is a disease process in and of itself that causes obesity. So we have to really take that into account when we're in the office with someone who's struggling with obesity. And I know, Peter, you take this really to heart, approaching and treating these patients without bias, as I do. But it's so important for other providers to be looking themselves in the mirror and asking themselves, what are the biases I hold against patients who come to me struggling with their weight? And what do I really know about the science? And what it really, one must conclude is that this is not their fault. These are things that happened beforehand and they're suffering the consequences of it. And the problem is the consequence is on full view for everyone to see it's not something that they can hide. And that makes them so vulnerable to bias in health care. And again, one of the other things I come back to is part of our whole battle in health equity.

So, Sarah, I want to keep digging into this idea because it's so interesting to me of having a leading indicator for this early, early, early warning sign. We talked about it at the outset of this discussion, which is in some ways the tragedy of using hemoglobin A1c as the marker of when somebody gets on the race radar. I mean, you said it yourself, patients will show up and nobody's ringing the bell until their hemoglobin A1C is above 6.5. But that literally is happening 10, 15, maybe 20 years after there were early, early molecular warning signs. And if measuring palmidolic acid is one of them, that's exactly the kind of stuff that I find interesting, because in our practice, we use CGM a lot. So continuous glucose monitoring, non diabetics are wearing CGM like it's no tomorrow in our practice because of that exact reason. We're basically holding them to a very high standard of average glucose and high excursions and all these sorts of things. I want to go back to something that you alluded to, which is the association between palmitoleic acid and triglyceride is so tight that would we miss, for example, African American patients? Do we know if they are failing to synthesize C16 1 in the way a white patient is, wouldn't we love.

To know that there's not been a good trial looking at that? I mean, one of the problems that we have in research in general is that we tend to focus on white people and actually worse middle or upper middle class white people. So there are a lot of questions with this in specific populations. There have been a couple of studies recently coming out looking specifically at what we're talking about, POA and its marker for future problems and predictor of future diabetes and other issues. One was a study recently published called the Panic study, looking at levels in childhood and seeing how they translate to health consequences decades down the road. And then there was another study, I believe it was from the Netherlands, where they looked at POA levels at 50 to correlate them with C reactive protein levels at age 70. Right. And what we see is what we would expect based on our discussion here, which is the POA was a predictor of protein problems down the road in people who were healthy when their POA was elevated or healthy. So we thought what we really want to know ahead of time, and I know this is very meaningful to you and your practice is I want the person who's healthy so I can get to tell them how to stay healthy. We talk a lot about trying to work on people who are already, so to speak, behind the eight ball and we want to work them out and we want to regress their disease, clearly an important goal. But we also really, if we're going to make a difference again with the individual and population wide, we need to know who's headed for trouble again.

I hope there's an ongoing effort here because I think this is the future of medicine, right? I mean, I think the future of medicine has to be coming up with tools that allow us to take broad, sweeping population based insights and very quickly target individuals. And if we have biomarkers like this that can say, look, the moment this is triggered above a certain level, it doesn't really matter what your glucose is and your insulin might still be normal. This is time to intervene. And then of course, the second part of that equation is what's the right intervention? And how do we pair people to the right intervention? Again, you and I have a very similar set of experiences, which is patients with hyperinsulinemia and elevated glucose generally respond well to carbohydrate restriction. My practice also focuses so much on the role of glucose disposal and non insulin dependent glucose disposal through exercise. And I know that that's probably not a surprise to many people, is Sort of correcting the sleep, exercise, nutrition trifecta, and then adding to that the role of cortisol in all of this. So I think this is a very hard problem to solve. That's the bad news. But I think the good news is if you get this one right, you get a leg up on every chronic disease, so your risk of heart disease, cancer, Alzheimer's disease, all go down. And so it's worth this enormous effort to continue pushing on these questions.

On that note too, and when we talk about individualization and risk prediction before we're seeing our classic biomarker issues come up, has to do, I'll circle it back to carbohydrate restriction, because we know very low levels of carbohydrate restriction can reverse the disease process, bring about normal glycemia in patients and be able to get them off of medications. But we could put a risk predictor like POA into wider use. Okay, which would give a person their individual carbohydrate threshold. What if it didn't need to be as low? What if we caught them earlier in the disease process and we're like, hey buddy, you go over 175, that's where trouble comes in. Rather than you need to stay very low indefinitely. Because we've caught you on the spectrum of the disease so late, and this is what we really need to do to control this, to keep your glucose normal without the use of these many medications, especially insulin.

I want to ask you another question on this, Sarah, and again, I don't know if it applies to patients that you've treated with diabetes or those in the pre diabetes category, but have you treated patients for long enough on ketogenic or very low carbohydrate diets who showed up in a state of metabolic disarray, ran through a lengthy period of this, so maybe spent years on a carbohydrate restricted protocol and everything gets better, so the weight goes along for the ride, but obviously, and more importantly, their metabolic markers improve and they gradually reintroduce some amount of carbohydrate back in the diet, and all of a sudden they're fine, Almost as though you reset them during a long enough period. How often do you see that and what do you think is the best explanation for that?

See it all the time. And the best explanation for it is what is their insulin reserve? So the majority of people can go ahead starting out, even at longstanding diabetes, reverse their disease, get normal glycemia, get off of all their medications, and then slowly reintroduce carbohydrates as long as they have functioning beta cells, okay? The problem is the longer you've had diabetes clearly is a risk factor for this. And we can. We see evidence of that in the bariatric surgery literature as well. I mean, there's been so many studies looking at beta cells, and the fascinating thing is who is getting back some of their beta cell function. In other words, maybe their beta cells were only dormant and were able to wake them up again versus which are gone and not coming back. I mean, the fact that people were on the incredibly high dose of insulin, okay, starting on a very low carbohydrate diet, and then they got better right away, a lot of the change is swift, but they couldn't get off insulin. And it was just years went by, right? And they're just staying on this much lower level of insulin, and then all of a sudden they come off of it. I mean, logic would tell us that some sort of beta cell function has returned. It took a long time. Reset the system, help them heal. You know, I mean, we don't completely understand this. There's so many great scientists looking at this right now, but we still don't have a certain answer. Because the answer on the personalized level is how many of mine are dormant? How many of mine are dead, right? What's it going to take for me to wake these up if it's impossible? I'd like to know that because that sets expectations ahead of time, right? You can get a lot better, but there's always going to be a little insulin in your life. It doesn't mean if they are someone who doesn't have any insulin production capacity, that they can't get a lot healthier, but they may not ever be able to get off of insulin. And so that's where it gets down once again into that nitty gritty personalization aspect. And wouldn't that be nice to know? But I think that the answer to the larger question is why is this happening? That some people can start to eat carbohydrates? Not anywhere near to where they were, but. But they're able to put some back into their diets versus people who can't. Is beta cell function something in there.

That you said is very important that I don't think historically has been communicated well enough to patients, which is that insulin, while an amazing and important hormone, is not benign. And there's a big difference between taking 100 units of insulin a day to achieve normal glycemia and taking 20 units of insulin a day to achieve normal glycogen glycemia. And you'll take the latter over the former, all day, every day, non negotiable. And some patients will say, well, gosh, I'm still on insulin. This hasn't worked. And not realizing, no, you've had a five fold reduction in your insulin requirement. That's an enormous improvement in your health outcome. And let's put the economics aside. The economics are enormous, but ignore that for a moment. Just in terms of health outcomes, the negative effects of hyperinsulinemia, I just want.

To say with that, you know, if we really think about the way we manage diabetes rather than work to actually reverse the disease process and get people off of medication, I mean, management constantly leads to more and more and more insulin, which we know. I mean, on the outward, the, the appearance of it is that people gain more weight when they go on more insulin. But, you know, if we really get down to that, the nuts and bolts, when we take someone with type 2 diabetes whose glucose is out of control to the point where we need to put them on insulin, the mandatory discussion that needs to occur is, I'm going to give this medication, this insulin that you're going to inject to you, and I'm going to do that because your blood sugars are so high that they could acutely kill you, put you into the hospital, put you at risk of all these complications. But I just want you to know you're more likely to die on insulin. That's what we need to tell people. That's the truth. And, you know, that would have changed the approach a lot of patients want to take. And it would certainly, if providers were forced to look at it that way, when they're staring each individual person in the face, maybe they would treat it differently as well.

Yeah, I agree. So I want to talk about something that has been such a big part of your life in the last few years. And people who don't know you may be almost surprised at where we're going in this discussion now, but this discussion could basically continue down the path if we could talk more about diabetes. We could end this discussion here and people would say, wow, that's a really insightful, thoughtful person. But there's a whole other side to your experience with healthcare, Sarah, that started, gosh, almost four years ago. I'll tell the beginning of the story just from my end. So you and I obviously met each other through Virta, your early part of the creation of this company, which is basically scaling up a way to remotely treat patients with type 2 diabetes. This is a company that Steve Phinney is also a co founder of along with Jeff Volek. I believe I have a minimal involvement in that company. I'm a small investor and it one point was an advisor, but it was during one of these advisory meetings that you and I happened to be sitting next to each other. Now, we'd met many times before that, but I do remember this very well. It was, I think June of 2017, it was up in San Francisco, a large U shaped table in the room, and it was a two day ordeal and you were sitting to my left. And that gave us more time than most times to be chatting about this, that and the other thing. And you looked in perfect health as always. And at the end of the second day, I said goodbye and see you next time and blah, blah, blah, blah, blah. And then about a month later, I heard from a mutual friend that you had been diagnosed with lung cancer. And I just about fell off my chair. So can you tell people what happened that summer? The summer of 2017?

Yeah. So I'll just start by saying I've been someone who's taken care of, care of themselves to the max all my life. Eaten well, I've kept my weight at a normal weight. Even nine months pregnant, I would have still been considered normal weight, exercise like crazy. Competed in, you know, half marathons, triathlons, Olympic distance. I did everything right. Never smoked, never drank to excess. And it was June 30th, so. So right after that, it was June 30th of 2017, I was having a normal day. I went to exercise, I had a big IRB meeting in the morning, went home due to my wonderfully full house of three kids, and took a business call in the basement because that's always my escape place where it can be a little less noisy. And all of a sudden I couldn't talk and I couldn't figure out what was going on. I knew something wasn't right, but I couldn't speak. And all I know is that I hung up the phone at some point because I was embarrassed. I remember thinking, he's going to think I'm drunk. The next thing I remember was being in the car with my husband and him saying, I don't think we could take you to urgent care. I have just very flat flashes of this day. And the next memory is in the trauma bay at the hospital, the hospital that I work at where I had seen patients many, many times. And I'll have to tell you, the other thing is the Last time I had been in that particular trauma bay was when I brought my then 4 year old daughter in, or my husband did. I met them via an ambulance after a traumatic brain injury. So it was like a very bad place for me, although my daughter completely recovered. And I remember screaming at my husband that they're wrong, they're wrong. And I wanted to see the computer because what had happened when they first came in is they thought it was a stroke. And so my poor husband was all of a sudden tasked with, you know, are you going to give her clot busting medication or not? Because we think she's having a stroke. But lo and behold, the imaging showed a really large tumor in my brain. Then they imaged the rest of me, and it turns out I had multiple tumors in my chest. And so they presumed correctly at that point that this was lung cancer. But I also needed emergency brain surgery. I remember most of this by people telling me about it. So anyway, the next day I had emergent brain surgery. And then being a physician and lung cancer. You know, I was like, that can't possibly be. You know, I have never smoked. You know, how do I have lung cancer? I am the healthiest person I know. I remember being in the hospital because of course, you know, you're on drugs and everything else and shock and everything. And I kept saying, look at my nails. These are the healthiest nails you've ever seen. How can this be a person who's sick? Because somehow that was like just one example of how that's impossible. Talk about the stages of grief and denial, right? And being a physician and knowing what lung cancer meant. The next thing that came out of my mouth is I want to move to Oregon. Because I was like, I know what this means for me and I know what this means for my family. And I don't want to play any part in this. I don't want them suffering.

Can you tell folks what you mean by that? Not everybody might understand the implication of what you're saying.

I wanted to go to Oregon because they had physician assisted suicide. Because I, you know, I knew, I have treated so many patients with lung cancer. I knew the horrible end. I knew what this meant, the suffering.

Especially when it's spread.

Yeah. And it had spread everywhere. I mean, I had stage four lung cancer. You know, the day before, I had been fine, 100% fine. That morning I had exercised vigorously, and suddenly I'm in the hospital recovering from a brain surgery, being told that I have a rapidly fatal disease. And, you know, all you can think of in that moment of panic is your family. Right? And so, you know, my only thought was, I don't want them to watch me go. I want them to remember mom. And so, I mean, there began my so far almost four year journey of a new me. You know, cancer changes you. So I'm not that person. One of the many things is sometimes at this point in time, you know, I mourn that person because I really, I liked her.

I mean, one of the things that I think is very shocking for people to understand is that probably between 12 to 14% of people who get lung cancer are not smokers. And they all tend to get a certain type of lung cancer. Lung cancer is broadly divided histologically by small cell and large cell or non small cell. I'm sorry. And within the non small cell, there's large cell adenocarcinoma, squamous cell. And most of the people like you, who are not smokers get this type of adenocarcinoma, non small cell. And it is really shocking to think that given the prevalence of lung cancer and the lethality of lung cancer, Lung cancer kills more people than any other cancer. And I believe that's true for male and female still.

Yes. I mean, by far, yeah.

To think that such a high percentage, 12 to 14% could be non smokers, tells us the severity of this. I also think it's worth reiterating something you've said, which is sort of the miracle of the fact that we're sitting here having this discussion four years later. The median survival, meaning if you took 100 people with stage four, which means a type of cancer that has spread from its original site of origin, and in your case, it went to your brain, which is a particularly devastating place for this cancer to grow. The median survival of people with stage four lung cancer is probably 12 months or less, correct?

Well, it depends on what kind of lung cancer that you have, and sometimes even eight months or less. Those were the stats that I knew when I was first diagnosed. And one of the things that I'll say is non smoking lung cancer is growing at scary rates. It's being diagnosed and it hits people in their prime. It's growing rapidly, especially in young women. So it's hitting a lot of moms. Much more common in women than it is in men, although it does happen in men. Happens in Caucasian and Asian women predominantly. And the interesting thing is most of the people that it impacts are thin and in shape or athletes. So it goes against everything.

Do we have any insight into why?

No. And it's one of the things that's not being investigated as much when you look at, okay, what studies have been out there. Oh, we get the typical. It's radon. It's being next to a smoker. I never was. My father was a smoker. He quit smoking the day I was born and never went back. I was not raised around smoke. So the fact of who it's impacting and the fact that the demographics of the people that it's impacting are the healthy people, unlike what we associate with our epidemic of insulin resistance, that's not who these people are. We know that insulin resistance is responsible for a huge number of cancers and cancer rises. That's not this. It's young women and again, who have presumably done everything right. And it's just, it's something that is not getting enough press. I know the Guardian did a big story about it about a year ago, but otherwise it's not getting the attention it deserves. And these women really wind up with two different kinds of cancer. They wind up with EGFR driven cancer, that's epidermal growth factor receptor, or they wind up with something called ALK positive cancer. I have the EGFR, specifically something called EGFR EXON19 mutation. The thing I didn't know at diagnosis because again, I had been focused on obesity and metabolic disease and diabetes for so long. I hadn't been seeing as many people with active cancer as I did when I was in primary care. And so I was quite frankly behind on some of the newer treatments and newer diagnoses, if you will. And we're talking the genomics of cancer. But for EGFR cancer, there was something called a targeted therapy. This class of medications is called tyrosine kinase inhibitors. And people can go on them and they can get better. Okay. They can even in many cases have all of the cancer go away. Doesn't mean they're cured though, because it always comes back. And so after initially, again, going through all these, I mean, I'll tell you the denial grief stage, I want to.

Actually ask you exactly about that, Sarah. I want to go back to what is it like when you were recovering in the hospital from the brain surgery, because I assume they had not taken out the primary tumors in your lungs. They were just alleviating the most life threatening symptom you had at the moment, which was a mass inside a part of your body that can't accommodate a mass, which is why you had a seizure. So they take that out. You're recovering from a surgery that by itself is difficult to recover from. But then coupled with the knowledge of, here's this disease, and my lungs are full of this. What do you remember of those days?

Overwhelming grief to the point of not being able to think. You know, of course, I come and approach everything in life as a mother, and I'm not saying as a mother only like fathers would do the same thing. But you approach every problem in life through what it means for your children.

How old were your children at the time, Sarah?

They were 712 and 14. And they needed me. They still need me. And so the grief is overwhelming about. What I quickly realized is, I'm gonna break my children's heart, and there's not a thing I can do about it. And to have that realization, because it comes quick and have to sit with.

That.

Is a grief I can't. I can't even explain. And so initially, I just was. I couldn't handle the grief. I had to be denial. In denial. I came home from the hospital. I had just been discharged from icu, and I walked seven miles the day I got home. And my feeling was, see, I can't be sick. I just got out of the brain surgery. I'm still on medication. I walked seven miles today. I'm healthy. I don't know what you people are talking about.

What did your kids know at this time? Had your husband already spoken with them?

Well, sadly enough, and I actually didn't find this out until quite a bit later, they are the ones who found me in the basement. So, you know, talk about not telling the children. That was never an option for us. So they knew I was having surgery, that there was a tumor in my brain, and that this was cancer. This is not good. And that's a lot for a kid to unpack, right? Especially a kid, you know, again, it's hard for any kid to unpack. But, you know, one of the things I remember when my kids were going through each of their own, every kid goes through it. The phase of, what if something happens to you, mommy? What if something happens to you, Daddy? Right. All kids go through that. And the one thing we used to kind of laugh together, my husband and I, about that, say, oh, honey, your mommy and daddy are the healthiest people. We are so healthy. You don't need to worry about that. And I remember that, you know, it's one of the. One of the first things that you think of when you're put in this situation is, oh, my God, you know, they have to unpack this in that context. And it's hard to be a teen. It's hard to be a seven year old, but to be one whose mother suddenly had a, you know, diagnosis of advanced cancer. And we, it was hard decision on what to do but you know, in talking and how do we handle the kids. But the one thing we decided together, I mean my husband and I, is that we were never going to lie to them. We were always going to tell them the truth. Because I thought that the worst thing for a kid is to constantly be wondering if something, if there's going to be a huge shoe that drops. And so we told them, we tried to open up the lines of communication. They mostly didn't want to talk about it, but we told them that we were making that promise to them. And we have never, never gone back on that problem and promise and never will. I mean that's one that it's really important to me. We may delay telling them something for a little bit until we really know the facts, but as soon as we really know the facts, they're going to hear about it. And over time, in grief, you learn to accept many things. My husband and I, our dream had been to retire to a farm and make gourmet butter. Like that's what we were gonna do. That was gonna be the second career, right? And you learn to make peace with that's not the case anymore. You know, we always used to joke that the way we wanted to die was 95 years old on the way home from a skiing trip in a fiery car accident where our kids would not have to deal with the bodies. But we wanted to make sure it was on the way home.

The cremation, the two for one, a twofer.

It was going to be on the way home because we were going to be having fun up until that point. So that's acceptance. You know, you're not going to retire, you're not going to have all these things, things. But you can't accept that you're not going to be a mom. Impossible.

Now, at some point, I'm guessing kind of the problem solver in you started saying like, hey, I'm going to learn as much as can be known about this. And we're going to talk about this in the context of the asymmetry that exists. I just had a discussion about this with. We have a weekly meeting in our practice with all the providers and we just had this weird situation recently where basically a patient of ours who has another physician was kind of caught in the middle of a recommendation that turned out not to be the Right. Recommendation. And we were able to get them a referral to somebody else who basically got them out of a very unnecessary surgery. And we were just sort of thinking, man, we're so glad that that patient was able to dodge that bullet. They were going to have a surgery that they totally didn't need. That's a very big surgery with lots of risks. And we realized the asymmetry of knowledge in medicine is so overwhelming that it's not even just about money or education outside of medicine. Like a smart person still has a hard time digesting medical literature. And like I said, we're going to talk about this, but you very quickly must have figured out, hey, I have this EGFR19 deletion. So we no longer talk about this as you have lung cancer or you have adeno, or you have non small cell. We're really going to refer to it by its mutation. And everything will come down to how do we treat. How long was that process for you to say, I'm going to. I don't know if this is the right word, but I'm going to partition my grief and my problem solving brains and I'll do both of them, but I'll move back and forth.

It happened pretty quick, which is okay, this is terminal. Right. You have to come to grasp with that. But terminal when? And what can I do to control the when?

But when you say that, Sarah, did you really come to that realization so soon? Because technically life is terminal. I mean there's nobody listening to this podcast, watching this video who isn't going to die. So that's all terminal. But when you say that, do you mean that immediately and without question or reservation, you, you felt that you would not live a normal life expectancy. There was no Hail Mary out there that was going to take you to being the 95 year old skier?

Yeah, I mean, I think just reading and understanding, although the advances that this was going to be terminal really soon in my life. And I was only 46 at the time and my first thing was just please, please let me make it to 50. I'm 49.

You're going to be 50 soon.

Yeah, I'm going to be 50 in the not too distant future. So you know, that was like my first one was just like, okay, let's. But right from the beginning I'll tell you the when was 11 years. Okay. And that has not left. I don't need to be 95. I can accept all those things that I'm going to miss out on by not growing, growing old I just need 11 years, which to everyone was unrealistic. But why 11 years? Because my youngest would be graduated. So immediately my goal was, I can't settle for less than 11 years. I have to make it to 11 years. And so in became that, like my war cry. 11 years. 11 years. I have to make it 11 years. And that started me on a path of, oh, my gosh, so much. So the first thing I thought in reading all the. I mean, read everything is I got to get this primary tumor out. You know, I'm considered inoperable. But we know that having this primary tumor here increases my risk for mutations. Okay, remember I said that the tyrosine kinase inhibitors or the TKIs, they work amazingly well, but only so long, you know, somewhere between eight and say, you know, on average eight. And with the more advanced ones at the long end is like 24 to 30 months. Okay, so that's not enough time. That doesn't get me to 11. So I was like, okay, you know, this is increasing the risk for mutation, which is how these develop resistance to the tyrosine kinase inhibitors.

And remind me, Sarah, you. Cause I remember you emailing me probably by August and starting to explain some of the details. Your biggest tumor was like 5 centimeters. That's a monster tumor. How many tumors did you have? It was 6 centimeters. Or you had six tumors?

It was 6 centimeters, which is amazing in the sense that I never had pain from it. I never had a cough.

Probably because you were so healthy.

I think so. Because talk about being caught out of the blue. You know, there just wasn't this premonition of something is awry, and I'm just not addressing it.

So the standard of care was just that we typically don't operate on patients with metastatic tumors. The only reason they operated on your brain was it was an acute. Cute way to save your life. I think it's hard for patients listening to this to understand that. But that's the playbook in oncology, right? When a patient shows up with metastatic cancer, they're considered not surgical candidates. And this was the exception and not the rule. You were going to be dead probably within days if they didn't operate on your brain. But all this time afterwards, you still have this burden of tumors in your lung. And now the question is, can we improve your prognosis? And maybe that doesn't mean you live to 95, but can we reduce. Can we make your cancer less resistant to therapy by taking the majority of the cancer cells out of your body.

Right. And decreasing the Tumor burden, because really quickly, the TKI got rid of every single small tumor. I had them throughout, you know, like paint splatters throughout both lungs, and they were gone in a matter of weeks.

That's staggering, isn't it?

I mean, it is. It's remarkable. But, you know, again, the primary tumor was huge. So I had. Unfortunately, the large tumor in my brain was not the only one. I had two other ones that they radiated. They didn't need to be surgically removed. They were small. They could be radiated. And then I set about trying to find someone who would take out this primary tumor.

Can I ask you about the stereotactic radiation? Sarah? That's. I mean, we glossed over that, but that's not a benign process either. Did you suffer nausea from that? How difficult was your stereotactic treatment? Did you take it all in stride?

I did great with the treatment to the brain. I didn't have any issues. You know, I did have issues at the beginning, but they were more to the tki. You know, one of the things with every specialist that I saw, they couldn't believe it. Or they told me if I saw them earlier, it wasn't going to happen. You know, at least you'll keep your hair. All my hair fell out. Like it wasn't supposed to happen. Like your hair is not supposed to fall out with tkis. All my hair fell out anyway, so the brain radiation went fine. And then I met a surgeon who was going to take out the primary tumor for the reasons that I was saying. Anything to decrease the risk of developing a mutation that keeps me from being sensitive to the TKIs. And so I went in for surgery in September, and I can remember her saying, we're going to take this tumor out. We're going to take out your right upper lobe. Unless, of course, we've seen that there's disease in the mediastinum. But there was no disease on the PET scan in the mediastinum. So she was feeling pretty positive about being able to take that out. But I knew for several weeks beforehand that that was a possibility.

And just so folks know what we're saying, on the right hand side, you've got these three lobes here, but they drain into these lymph nodes that are in this middle structure called the mediastinum. And so you had this monster tumor that was going to require the entire upper right lobe to be taken out. But if the surgeon felt that on visual inspection at least, or maybe even sampling nodes, that any of those nodes had cancer, it was her opinion that this is really futile, because now we know it's all already escaped the lung. It doesn't matter. So you went into that surgery knowing you could wake up with a huge scar in your chest, chest tubes coming out, and the cancer is still in you. Right?

And that happened. And that was. It was terrible. I kept apparently under the influence. I mean, everyone told me I was so hysterical, screaming in the recovery room, I'm a mom. You can't let this happen to me. I'm a mom. That's all I kept saying. And I, of course, don't remember any of this, but they had to actually take me away, put me in a private room. And that was all that I kept saying. So, you know, I had to come home and learn to accept that I now was bald. And I definitely fell into a deep depression. But at the same time, I refused to completely give up. I mean, like, for example, I went back to work at the clinic the same month that I had brain surgery, which sounds crazy, but this part of this whole process, and then. But after the surgery failure, that was terrible. And then I didn't really recover back into my determined place until a really very specific moment. And that was just a couple of weeks before my diagnosis. I had been selected to be an Aspen Health Innovator Fellow, which was. I mean, this is among the highest honors for your work. The Aspen Institute is a place that brings together thinkers in all kinds of disciplines. And to be chosen to represent people who are innovating in the health care space was such an honor. And in order to do that, you had to commit to four weeks of leadership sessions in the next two years, which, of course, at the time, I was like, of course, sign me up. But as that first session inched closer, it was in November. I was, so what do I do? I couldn't make up my mind. I literally didn't make up my mind for sure until I sat, I got on the airplane because I was ready to run back, because it was like, I'm going to leave my kids for almost a week. I have terminal cancer. And at that point I decided, you can live feeling sorry for yourself and of all the things that you're going to lose, or you can go out and live and your kids are going to be better for it. This is what really made me decide, your kids are going to be better if you choose to live. And so that was the moment, sitting on that plane seat crying. I've cried on a lot of planes since this diagnosis, deciding I just chose to live. This was a moment I made My choice now I got to stick with it. And that's how I've tried to live my life since then. Because I have a platform. I had a platform. I had done what I feel was a lot of good for a lot of people and it wasn't finished. And I knew that this was good for my children. And I'll tell you, one of the, the most impactful moments of my whole life happened before my diagnosis. And it was one of these times where we were at the dinner table and the lottery happened to be one of those hyper inflated lotteries. Oh my God, you can win bajillion dollars. And so my husband and I were at the dinner table joking around about it, right? I mean, we don't play the lottery, but we were joking around, maybe we should buy tickets. We could retire. We, we could retire. And here at the time was my 13 year old son at the dinner table and he got really upset about us discussing this. You can't retire, mom. You're doing so much good for the world. How could you even think of it? I've never been so. That is a defining moment of my life. And like I was like, oh my God. You know, at the time I just, I was so taken aback by that. Certainly that weighed heavily on my decision to get on that plane and to continue doing what I'm doing. And what I'm doing has morphed since my cancer diagnosis into an even greater focus on health equity because of my experience as a cancer patient and someone who is privileged because I'll tell you, you have a much greater chance of surviving cancer if you are, has privilege, you know, one of the lucky ones. And I didn't realize the stark differences until I became a patient.

I want to talk about that in some detail, Sarah, but I want to also understand how it is that we're still talking today, frankly. In other words, how have you managed to stay in an equilibrium with this disease? Right. I've always, I mean, let me share with you a couple of things that I've always struggled with when thinking about cancer. I, I'm not fond of the language that we sometimes use around cancer and that we beat cancer and that we can't give up and things like that, because it almost suggests that the patients who don't survive cancer have somehow given up. And I just don't find that in my experience, having taken care of many patients with cancer to be true. I think it doesn't make sense to me. And I think the way that you said it, described it earlier Makes the most sense, which is basically finding a way to coexist with your cancer for as long as possible. And you've exceeded all odds. I want to kind of understand that journey a little bit more. It's one thing to go through the tyrosine kinase inhibitor, have this immediate response that's remarkable. But then get this setback three months later where your primary is not only still there, but you actually realize now there's. There's mediastinal involvement, which basically means there's no question you have cancer cells elsewhere in your body. It's not like they stop when they get to the lymph nodes. So pick the story up for us in terms of what your ongoing treatment has been like. How have you stayed in this state of equilibrium, so to speak?

So I haven't. Okay. On many occasions, I haven't. So after the surgery, the next thing that happened is they found another brain tumor. There's argument as to whether it was there from the get go or whether it was something new, but either way, they decided it would be considered that the first line TKI that they had put me on had failed me. And so I got switched to. I got more radiation to the brain, and I was switched to the newest TKI happens to be called osimertinib or tagrisso. I was put on that in November, right before I went off for my first Aspen leadership conference. And I had decided that I do not accept being a sitting duck. Because what the cancer world then wants is for a patient like me to just sit and wait for the cancer to come back. Right? That's what you're doing. You know, it's coming back. There's no question about it. And, you know, it's coming back soon, and you are just waiting. And I couldn't accept that as a mother. I think I could accept it as a human, but I couldn't accept it as a mother. And so I went on a journey to find someone who could treat me in the most aggressive way possible, who shared my view that sitting around and waiting for this to come back was totally unacceptable. I traveled the country. I saw everybody. Let me tell you, first of all, of course, that shows I have means to do that right. That a lot of other people don't. And I actually, along the way, met another mother physician my age, just a bit younger, younger kids who had the same attitude towards it. I refused to accept this. We sort of became a team, so to speak, and wound up by complete serendipity, meeting a group of physicians who really Felt that the way to treat this long term was to be constantly battling it with something new. So in other words, the cancer dogma right now is you put people on something at the highest dose possible and, and you keep going until it doesn't work anymore. That's how we deal with cancer. And then we switch and it's the same thing over again. And the idea is, what if we hit it with less and then change it up all the time? Right. And this goes to the idea of beating the mutations before they can get you. So thankfully I had a physician here at home who was willing to say, okay, that is worth a shot. February 2019, because it took a long time to get to this point of searching, trying to find something. I started chemo, regular chemo. I went through the regular cycles of chemo and then when I was done with that, I immediately went to anti estrogen therapy because I had a very specific mutation besides the EGFR one. And there was a medication to treat just so happened to be a breast cancer medication, but it was the same mutation for either cancer. So immediately upon stopping the chemo, I went on the anti estrogen therapy. So I was put into early menopause with a number of regular medications. Lupron, fulvestrant. And then I was started on a medication called pablocyclib. Okay. Which again is primarily a breast cancer medication, but was targeting one of my very specific secondary mutations. I was on that for the summer. And all this time I'm still on the Tagrisso or asimertinib. That never stopped. As soon as the eight weeks of that was over with, I went back on chemo. But very different. Low dose chemo, single agent, very low dose. So the first one was cisplatin. And you know, everyone says, oh, cisplatin, you know, you're gonna do terrible on this. I mean, this is harsh and it is, but, you know, I did fine. I mean, I'm not saying I wasn't tired. I'd basically been nauseous for the last almost four years. Every single day. You know, it's just you learn to manage that. So I learned to manage it. I learned to manage, you know, being tired and the things that came along. I still traveled for work. I was still able to do everything. I just, I could tell you some really crazy stories of, of things I had to do while traveling to accommodate how I was feeling that nobody knew about at the time. But anyway, some really wacky stuff that you do, but you just, you manage, you figure it out, right? You Improvise, Lots of improvising. And then I got switched to another after eight weeks, got switched to gemcitabine.

Or Gemzar, which, again, these are so crazy. You just don't think of this because that's a drug that's typically used in pancreatic cancer, right?

Well, yeah, and it can be used in lung cancer, too.

I mean, it just depends on the mutation. I think that's the point.

Right, Right. Yeah. Believe it or not, there's no standard chemo for lung cancer. Can you believe that? There's not a standard, like, standard of care regimen. So the thing is, I wasn't doing any outlandish things here, okay? These are all treatments for lung cancer. Like you said. Gems are. Is used more for other things. But this is not an outlandish thing that's never heard of for lung cancer. I mean, same with cisplatin. I mean, none of these things are, you know, I was, oh, my goodness, we're gonna, you know, do something that's never ever been done before, you know, so to speak, things.

And at this point, which is now the fall of 2019, where if you go and get a PET scan, where do you actually have tumor in your body at this point?

So, yeah, let me back up for a second because, well, the quick answer is I had no tumor. There was no tumor anywhere. And to back up, is that the tagrisso this is pre chemo had stopped shrinking my primary tumor in March of 2018. So this was almost a year before I began chemo. And so since they wouldn't surgically operate it to get it out, I had it radiated again. I was lucky enough to have a radiation oncologist who worked with me. And like I said, I tolerated brain chemo well. The same was not the case to the lung. I had real issues. And interestingly enough, we were leaving for to hike the Inca Trail in May of that year. So I had had radiation that we were leaving to hike the Inca Trail, and I started having kind of bad chest pain, like a day or two before we hiked the ink trail. I was like, okay, I'm sure this is just reflux. I'm going to take some reflux medication. And then I was like, look, okay, if it's not. If it's more, you know, what a better place to die than surrounded by your family on the Inca Trail in all the beauties of the Andes mountains. Okay, I can accept this. Let's go. You know, I didn't even tell anyone. I was like, going forward and did that Successfully. It was great. My 8 year old toodling along, you know, she was always the fastest of any of us. We went with our friends and I mean, amazing experience. I just have to say that it's those things, especially if you can get kids in it. I'll never forget that. When we all got back and we went and checked into the JW because we were like, give me a shower, a very clean bed and a spa. My middle child, my daughter said to all of the adults, I developed my third eye during that. It was one of those experiences like you don't normally think you're going to get that out of a. You know. She was what, 14 at the time? We were all like, what? But anyway, so it was a super special time. I was still having pain and then my rest of my family flew home. I actually had to fly from Lisbon to Switzerland because I had a conference I had to go to. And at that conference things started to get really bad. I made it through, but not with again, some funny stories that of how I accommodated to it because I was having crushing pain, got home. Turns out, of course I had some rare. I had this rare complication where it actually impacted my bones. My radiation oncologist said the only treatment for this is to put you on long term opioid therapy. And I was like, oh, no thanks, I will accommodate. There was no way I was doing that. So I had to get through that. Which was a. Which that was a little bit of a saga. But anyway, I had no disease then after that, radiation, none. And so I was in this state, they call it Ned. No evidence of disease. I like to always say Ned. Right. I was Ned for a really long time. I had no evidence of disease. It was a great place to be. Right. Still on treatment, still trying to do everything to keep this from coming back. And started. Gems are. And everybody had said all these terrible things about cisplatin and gemzaar was 10 times worse. Everyone was like, you'll be a breeze. Gemzaar is a breeze compared to cisplatin.

You are really the exact opposite of everybody because. Yeah, I mean we used to tell patients Gemzaar is. It's non chemo.

Yeah, everybody tolerates Gemzar. I can still remember sitting because I was feeling too crappy to drive. My mother driving to pick me up to take me to chemo one day, sitting on my front porch and throwing up in a plant on the way to chemo.

There are nutrients in there, Sarah, that are very good for the plant. So I wouldn't feel bad about that. It's a very healthy part of the carbon cycle, I'm sure.

But I was determined to keep on. I was really close to getting switched to Taxol, which, you know, I'm like, this is going to. That'll be better. So then had to take another trip for another meeting and had lots of friends there. And I can remember them standing behind me after we had eaten. And they were pushing me up this hill in San Francisco because I literally couldn't walk. And I kept thinking to myself, I'm a hypochondriac. This is just because I'm anemic. Whatever. I was super short of breath, but I'm like, okay. I had convinced myself I was making it all up in my mind. I fly back from that trip and the very next morning head in for chemo. And they immediately said, oh my God, no chemo. Everything is a mess. My liver numbers were through the roof. My kidney numbers were high. I had pancytopenia. So bad.

How anemic were you, Sarah?

I was like six at this point. I mean, it was bad, really bad. The low sixes at this point.

Right. And just so the listener understands, the normal would be 13 or 14 of the hemoglobin in year six. So that's really low. And your platelets Were how low?

23.

Which means you basically don't have the ability to form a single clot.

Right. I was a disaster. And the funny thing is I was still up and doing okay. You know what I mean? I was tired, I was shortness of breath with activity, but I was doing okay. And they sent me home. And I was like, that doesn't seem right. Am I crazy that I shouldn't be home? So of course I call some of my other physician friends.

Aha.

Privilege.

Right.

Because I was getting sent home and they're like, oh my God, we're admitting you right now. So I actually get a backdoor admission to the hospital and a complete workup starting right then. I had to have a thoracentesis. Drained a whole bunch from my lungs. That was unknown when I got sent home.

So you had tons of fluid around your lungs?

Tons of fluid around my lungs explaining.

The shortness of breath.

Yeah. And once I was admitted, I was promptly transferred to ic. Things were going downhill. I had to be put on BiPAP. So I had multi organ failure, had respiratory failure, liver failure, kidney failure. I was a big failure. Okay. Everything was bad.

And was this believed to be the result of your body's response to the tumor or the chemo it was the.

GEMS R. So I got taken care of in the hospital. I just want to cry to think about the care I got. It was so wonderful, and I just had the best team. I would have died. Nobody can believe that. This was well over a year ago now, and I'm healthy with no persistent failures because I was near death. And I was in the ICU for a really long time. And everyone, every day, it went from, I think your kidneys will rebound to 50, 50. They're never going to be normal. I was on plasmapheresis, and it turns out I had something called atypical hemolytic uremic syndrome. And to just explain, over 70% of people are either dead or on dialysis, you know, right away. I mean, it's got an incredible mortality rate. Incredible. It's incredibly difficult to treat. And so outcomes are you're dead or you're on permanent dialysis. So I was put on a new medication after going through kidney biopsies, all these kinds of things in the hospital, sent home, did outpatient plasmapheresis for a while, and then things miraculously started getting better, right? Not miraculously. It was because of this medication I was put on. Of course, that meant an infusion every eight weeks. And the worst part to me is it meant no one would put me back on chemo.

Just. They wouldn't put you on Gemser or they wouldn't put you on anything?

Wouldn't put me on anything. And to me, that was devastating because I said, well, kidney failure is one thing, but having this cancer that we know come back is another. So that was another hard pill to swallow. And long story short, I got better. I went to pharmacogenetics, which is where they actually take a look at what your genetic profile is in response to different drugs. And it turns out I had a genetic mutation. Hey, I have lots of them. It turns out I had a genetic mutation that didn't allow the GEMS R to break down. So I was getting toxic doses of this, and I was on a very low dose. But the thing is that I couldn't get rid of it. So normally, if you see atypical hemolytic uremic syndrome with Gemzaar, it's after months and months of treatment, and I got this within four weeks. Why? Because I was getting mega doses of it because my body couldn't get rid of it due to this mutation, was the explanation. And they said, there's no reason you can't take any other chemo. This is very specific to gems are but that was that sit and wait mode. Back to sit and wait mode. It took another year, but the cancer came back in September of 2020. And here's my story from that which really made me so determined to work even harder for health equity. Here I am, a physician, able to grasp really difficult concepts, able to read and scour the literature and know what I'm looking for. Able to call at a moment, time, you know, anytime, someone to help me sort through something I didn't understand or help maybe refer me to someone, you know, I had all the resources in the world and the reoccurrence was in September, even with all my constant pushing and self advocacy. The one thing is, I had, by the time I was diagnosed with cancer, I was an expert patient advocate, expert, hardcore. One of the other advantages I had is it didn't take much to switch that and to become a self advocate, an advocate for myself. I was diagnosed in mid September with a reoccurrence. I did not get on a clinical trial until I got started December 30th. That's a four month delay. That's a four month delay for me. And in hindsight now, looking back before, I was panicked, right? And I couldn't really, I was like, something has to get done. Something has to get done. Something has to get done. I can look back in hindsight and say, how many people die during that time? How many people who don't have the advantages I had just die during that delay? How many? I shudder and I just want to cry. And what I've done is I've reached out to other cancer patients to say, has anyone else been in this situation? And I find out it happens all of the time. It seems that we have a really good system. As I experienced, when someone is diagnosed with cancer, they get a health nav, a cancer navigator, you know, they get all these things and we're boom, boom, boom, boom, boom. But when that cancer comes back, it's kind of like the system seems to give up on you. I had to advocate the heck out of getting a biopsy done, a biopsy that would be enough tissue to make me eligible for a clinical trial that would actually get me a full genomics report. I mean, that wasn't going to happen. I'm telling you. I had to get almost obnoxious about it. And the stories that I'm getting from people are the same.

Where was the recurrence?

In my right upper lobe.

So you had to get another lung biopsy to do this. And can I ask you Another thing, Sarah, what has been. You obviously have health insurance, but I assume that there's been a non trivial amount of out of pocket costs as well in the last four years.

Oh yeah. Oh yeah.

Do you have a sense of what the out of pocket cost has been for your care?

Tens of thousands of dollars.

Which obviously speaks to another challenge. I don't know if this is still true, but it certainly was true at one point that the greatest source of personal bankruptcy in the United States is healthcare. An inability to pay healthcare costs and.

A cancer diagnosis is so high up.

There, I would have to believe that cancer is the leading subset of that as well.

So now I'm like, especially when I got feedback that I'm not alone in this, it wasn't just me, you know, and again, I always keep saying in the backdrop of I am one of the privileged and I was put in this situation. And the fact of the matter is, by the time the reoccurrence was diagnosed to the time I finally got treated, I had progressed so much that I had compression in my bronchus. I couldn't get up a flight of stairs without desaturating. I mean, this all just happened. I was in horrible shape. Which of course, again, and remember, I'm starting out before my diagnosis in general, I was so healthy, which gives me an advantage in this. Which gives me a significant advantage in this. But it goes back to that question of how many people just die.

Sarah, you're very realistic about the fact that your time on this earth is less than it should be, right? A 49 year old, otherwise healthy person who's done all the, you know, done the right things for their health, should have another 40 years on this planet. And at least statistically speaking, that's not. Doesn't seem likely. It suggests to me that you're very cognizant of how you spend your time. So should take a moment to thank you for spending a couple hours with me here. But how do you now think about the time that you allocate to your family, to your work in the diabetes community, and now to this third important pillar to you, which is cancer advocacy. How are you managing that and how do you think about how to even balance that? Because I think time is the most important currency. I think everybody can appreciate that in a vague sense. Sense, it is the great equalizer. But of course most of us can't appreciate it the way you can because you have a real visceral appreciation for it that comes exactly with this type of an illness. And so Therefore, I think that your appreciation for the balancing act of what you described earlier, which is living your life to the fullest, regardless of its duration, that's your legacy. That's what your kids are going to remember about their mom being the advocate for other patients. So that in 10 years, when another Sarah Hallberg gets this diagnosis, even if she doesn't have your education or your means, she can have an extension of life the way you do. It's a bit overwhelming for me to think about how I would do that, because as I put myself in your shoes, my intuition is I'd want to retreat from everything outside of life, everything outside of my family, I would imagine. And it's hard to put yourself in another person's shoes without being there. But my intuition is, I would say I don't care about anything outside of the walls of this house. And I would take a selfish approach in some ways, I think. And you've done this very selfless thing, which is continuing to sort of prioritize everything else as well. How do you do that?

A couple of things. Number one, believe it or not, originally it was actually hard to be around my kids when I was so deep in grief, because. And that sounds crazy, right? That sounds counterintuitive, but they reminded me of everything I was going to lose, right? They were what I didn't want to lose. And so it was challenging. And I knew I had to overcome that. That was a big motivator for me to not be thinking about that and thinking in that way. And I'm happy to say I clearly have overcome that. But my kids come first. You know, I'll drop anything and everything if they need me now. But I also think again, and I go back to sort of what I alluded to before. They need to see me not getting knocked out by the stressors and bad things in life. You know, I mean, bad things happen to good people. Like I said, there's been a pivot in every part of my career based on anger, and I certainly am angry about this. But what do you do with it? That's what's going to be the important question in life. You can take anger, you can take all these things and you can get lost and buried in it, or you can try to turn it into something else. And I have to say I haven't become as big a cancer advocate yet, and I'm working on it. But the reason for that is. And this was a question I had to ask myself a long time ago, which is, shouldn't you be a Cancer advocate now, but I have a platform for diabetes, and, damn it, that's important, too. All these people suffering from this is important. So I can't just say I'm going to switch away from a platform that I have to one where I don't yet. It doesn't mean I'm ignoring it, but it's like it makes me want to work more again for health equity because it spans both. Right? It has to do with both diabetes and cancer, and that is so important.

So.

So, yeah, how I spend my time is really critical. And I want to say, it's not like I'm. I don't want to paint the picture that, oh, my gosh, I'm the superwoman. I have a terminal cancer, and yay, life is great. No, when people ask how I'm doing, okay, If I say okay, you know I'm doing okay. There's never good or never great. Okay? And that's just where I live right now. I'm definitely not sitting around and feeling sorry for myself. Okay. Definitely not enjoying things in life. But great is hard to think about. You know, great is hard to think about now. And some people say, well, so cancer really helped me get a new perspective on life and what I care about. And I'm happy to say I don't know that I got that. Okay. I mean, having cancer sucks, and I'm still mad about it. And, you know, sometimes I have to sit and have a pity party every once in a while, because the fact of the matter is, I loved my life pre cancer, and I think I was living every minute of it. I think I cherished my children. I cherished vacations. I mean, you know, that I cherished travel and showing. Showing my children travel. That's a bit of a wonderful thing. And it's also like a dagger, too. It's not like I've gotten some new life and new perspective that's so different from my old. Damn it. I liked my old life, and I liked the old me. And it's still a little hard to get used to who this person is now. She's still motivated. She still exercises, although not doing the things I used to. She loves her children with as much passion as one could have, but I'm fundamentally different. It's tough.

Sarah, you've said a lot of things that obviously resonate and I think will resonate with a lot of people. So I want to thank you from the bottom of my heart and certainly wish you the best.

Thanks. I appreciate it.

It's been great knowing you. Through this journey as well. You are, as many of your colleagues have undoubtedly told you, and we've certainly discussed it behind your back. You are an inspiration. And nobody wants to hear that because nobody wants to be the inspiration. You just want to be the normal person. But you are an inspiration.

I just want to be a normal person. Yeah.

Well, thank you for setting aside time.

Yeah. And I mean, I thank you so much for having me on. I mean, believe it or not, this is the first time I've told my story in any way, shape or form. So I have been kind of preparing for this and I'm glad I did it. So thank you for giving me an opportunity to do that. And thank you.

Thank you for trusting us. Thank you for trusting me and the listeners.

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