Dr. Eric Westman: Hi, everyone. My guest today is Dr. Christy Kesslering. She is a radiation oncologist and a member of the Society of Metabolic Health Practitioners, of which I am a board member as well. Christy practices in the Chicagoland area as a “seeing patients” oncologist, which I love.
You’ve been on the leading edge of cancer and metabolic disease, incorporating metabolic ideas into your practice for many years now, which caught our eye as metabolic practitioners. You have also held many leadership roles through the years and you’ve been named the Top Doctor multiple times by Castle Connolly and Chicago Magazine. Now, you spend all of your time helping patients, real-world patients, and many with cancer. Thank you so much for joining me today.
Dr. Christy Kesslering: Thank you so much for having me. I’ll just go back a little bit into my background. I started as a radiation oncologist but realized, as I think we all realized, that obesity and metabolism really do play a role. I think that the whole metabolism piece is becoming a little bit more well-known. We always knew the obesity part but I think that that is really exciting. I finally decided to leave my radiation oncology practice to focus one hundred percent on the metabolic health aspects. Non-cancer patients are often a patient’s husband or daughter or mother that wants to prevent cancer. I work with everybody to optimize their own personal health.
Dr. Eric Westman: It’s really fun to see that spillover into the whole family and relatives. It’s like a grassroots movement.
Getting into this lifestyle thing, as a practicing physician – I first trained in the 80s and 90s – we do training all the time. Smoking is pretty written in stone as a cancer issue. Occasionally, lifestyle is considered and the diet comes into it a little bit, but I’m not so sure obesity is as solid as you say. I see a lot of doctors in my area gloss over the whole obesity thing and they’re focusing on these, what seems to us, rather minor nuances in the blood, for example. What is this connection with lifestyle and what can people do about it?
Dr. Christy Kesslering: That’s a great question. What we know is that it seems like every year they add another one or two or three cancers to our list of cancers that are associated with obesity. We started with breast cancer and endometrial cancer but now it’s colon, prostate, and even lung cancer. There are a lot of different cancers that are associated with obesity. I keep saying the word “associated” because it may or may not be the direct cause. When we look at lifestyle factors, yes, we know smoking and maybe alcohol [are associated with] head, neck, and bladder cancers. We know certain infections and things that we might get – there are a few viruses out there like HPV and such – that can be associated with or lead to cancers. What I, and we, know is that poor diets, and eating a lot of processed food and sugars, just like with any other chronic disease, sets you up for problems.
What’s so interesting as we learn more and more about “What is obesity?”, “What drives obesity?” – is that it’s really the underlying metabolism. How many times do I have a patient who’s thin come to me and say, “I do all those things, I don’t eat sugar and I work out and I don’t smoke and I don’t drink, but why do I have cancer?” When we look under the hood and we actually look at metabolism, you’d be surprised. Well, I know that you wouldn’t be surprised – but so many people actually have higher fasting insulins. Their glucose still looks normal and their hemoglobin A1C still looks normal, but there’s a lot of data in cancer that as we slowly tick up our fasting insulin, as we slowly tick up even our fasting glucose, we are at higher risk for developing a multitude of cancers.
I always say that even though obesity is associated with cancer, it’s likely the underlying drivers of obesity that are actually the cause. Sometimes people can be obese but still, their fasting numbers look okay because subcutaneous fat is somewhat protective when we are consuming too many carbohydrates for our own personal tolerance; our body is like “All right, let’s just stick that away for later,” waiting for that famine to come along and then we can let go of that fat. But, in today’s world, the famine never comes and eventually, those fat cells get overfilled and we become insulin resistant. We can find that so much earlier than waiting for the glucose to become elevated. That’s what I’m really trying to get out there in the world, especially in the cancer prevention world. Let’s look under the hood and let’s see where you are on the spectrum and what can we do now to optimize your metabolic health and hopefully prevent that cancer.
Dr. Eric Westman: We’ve come through an era, it seems to me, where the science and researchers and doctors focus on genetics. They say, “Oh, it’s a family thing.” I think that gives you the impression that there’s nothing you can do about it. Can you comment on what we’ve learned about genetics? I’ve always been taught that it’s a combination of genetics and lifestyle. Have genetics been a distraction for the medical field, do you think?
Dr. Christy Kesslering: Absolutely. I thought about it as I grew up in the era of genetics. It’s this two-hit hypothesis that one gene gets damaged because of diet, lifestyle, etc., and it’s only when that second gene gets damaged that we create a cancer. People who have actual genetic mutations (like BRCA1 or 2 [breast cancer gene 1 or 2]) are born already with one gene mutated and so it’s very much sooner in their lifetime that they get that second mutation which drives a cancer. Now we’re starting to hear the words, like epigenetics, where just because you’re born with a set of genes, that doesn’t mean that those genes are expressed. Why is it that some people with BRCA1 and 2 never get cancer and yet others do? It’s really about diet and lifestyle changing your epigenetics, which means turning a gene on or turning a gene off.
We have tumor suppressor genes that help keep cancer away and we have oncogenes that drive that cancer in process. When we choose to not live the best lifestyle, maybe we’re smoking and we’re drinking, and we’re eating sugary, processed foods, or maybe we’re exposed to environmental toxins, all of those things can create damage and stress signals which can change the expression of our genes. Back to why thin people get cancers, they may also be in similar environments but just not be putting on the fat. It’s really about epigenetics.
I think it is so exciting that we’re starting to think about that. Interestingly, even in cancers, when they’re diagnosed now, they’ll take a sample of the tissue from the cancer and run what’s called a “genomic profile” where they’re looking to see which genes are turned on and which genes are turned off in the actual cancer specimen.
Dr. Eric Westman: I find myself sometimes being a translator between fields and not even between eras because I thought this was called “genetic expression.” Epigenetics is really genetic expression and it’s always been there but we have to make it sound like it’s something new! Let’s get back to the theme of metabolism. Metabolism is so important in diabetes, weight gain, and weight loss. People, I think, have that cemented in their minds. The idea, however, that metabolism affects cancer preventively or even therapeutically gets even more interesting in our world because a ketogenic diet, specifically, can actually be helpful. Can you please give us an update on that?
Dr. Christy Kesslering: There’s a growing body of literature that actually goes back many, many years on using metabolic therapy, ketogenic diets, and various forms of fasting-mimicking. That’s what a ketogenic diet is, it’s the original fasting-mimicking diet introduced for a seizure disorder. What is so incredible is that even though there are some small studies or animal studies, they all seem to show the exact same thing – if we include some kind of ketogenic-style eating and/or fasting around chemotherapies, radiation therapies, targeted therapies, you name it, it seems to augment that cancer therapy. It really seems to say, as I always say, that one plus one equals four. They both have some power in and of themselves, but the combination seems to be far more powerful than either one individually.
Dr. Eric Westman: Let’s go back to the idea that a keto diet is like fasting. I find, again, it’s a translation of words. When anyone doesn’t eat for two days, they go into a fasting state or a keto state, or a fat-burning state – this all really represents the same thing. When you say “fasting”, a lot of my patients out there are thinking that’s something totally different and that it might be not eating anything at all. I remember the early Dr. Cahill and Dr. Owen called a keto diet “fed fasting”, which means you get the benefits of fasting while you’re still eating protein.
You mentioned the term “fasting-mimicking”, which is a buzzword now in cancer treatment, isn’t it?
Dr. Christy Kesslering: Yeah, it is. Part of it was one of the researchers in the space created a product and a calorie restriction-type fasting protocol which he coined the “fasting-mimicking” diet. When you say fasting-mimicking, most people think straight to that particular thing. I always say, “No, it’s about getting your body into a fasting-mimicking state.” That can be done in a lot of different ways. It can be done by fasting, it can be done by severe calorie restriction, and it can be done by a ketogenic diet. There’s a little nuance between how to actually construct that. The beauty of a ketogenic diet is that you can mimic many of the benefits of fasting. We can talk a little bit more about how that works in the setting of chemotherapy, for example, but the beauty is that you still can eat your essential amino acids, your essential fatty acids, and all of your vitamins and minerals that are really necessary for the health of your normal cells and your normal immune system. You obviously can’t fast forever, which then becomes a big stress on your body and it almost does you a disservice with those long extended fasts.
Dr. Eric Westman: I go along with that theme of you can get everything you need, or just about everything, from real food. You don’t need to add in products and especially not to get into a fasting state. It just means not eating! But we want you to also eat while you’re getting the benefits of fat burning. I’m using the term “fat burning” or “fat burner ketosis” being a healthy thing that everyone gets into after you don’t eat for two days. I mean, how can that be harmful? Would you make a computer go into a toxic state when it’s running low on energy? No, you put it in safe mode. I see fasting or fat burning or all of this as a healthy thing. It’s all got to do with the metabolism.
What changes in the metabolism, and how might this be helpful in treating cancer or helping with chemotherapy? What do we know about the changes that occur now?
Dr. Christy Kesslering: There’s really interesting data, it’s called the “differential response.” For instance, normal cells are normally going along their merry way, dividing, etc. (cancer cells are doing that too) and when we go into a fasting fat-burning state, our normal cells slow down their division or their replication. They start to say, “Let’s clean house, let’s get rid of damaged cells. Let’s recycle, let’s rebuild.” So we’re in a little bit of a slow-down mode. With our cancer cells, that doesn’t happen. Our cancer cells typically are “sugar hogs” and are not able to utilize the fuel byproducts of burning fat. They are slowly getting weaker because they’re getting less fuel.
When we add a therapy like chemotherapy, it is going after those more rapidly dividing cells. Our normal cells now have slowed down, they are not rapidly dividing, but our cancer cells continue in that rapidly dividing but “getting sick” state because we’re starving them. Chemotherapy is, in theory, giving a bigger bang to those cancer cells which are already weakened a little bit, but they are actually giving less toxicity to our normal cells because they have slowed down their growth. That has actually been shown in a number of studies where either using pure water fasting around chemotherapy or fasting-mimicking diets around chemotherapy causes you to decrease the toxicity of chemotherapy. That means fewer hospitalizations, less need for dose reductions, fewer of those commonly associated toxicities like fatigue and maybe GI distress, and other things, that there’s less toxicity when we combine those two therapies.
Dr. Eric Westman: What is the state of the science? I know there are anecdotes in my clinic, but are there some published studies?
Dr. Christy Kesslering: Those two studies that I just quoted are published in the literature. The water fasting was in gynecologic malignancies and the fasting-mimicking diet or the calorie-restricted diet around chemotherapy was part of a large breast cancer trial as well as an all-cancer trial. There are a number of publications that keep coming out.
We start to look more at the true benefits of chemotherapy, there is some human data and a lot of animal data. There was a recent chemotherapy study – stage four colon cancer with chemotherapy, following a standard diet versus a ketogenic diet. I believe they added some MCT oil as well, as part of that ketogenic diet, and they showed significantly greater response rates [in the latter]. In the ketogenic arm there were 50 complete responders whereas in the standard diet, there were no complete responders. Both groups did have partial responders but there were dramatically more complete responders in the ketogenic diet arm. It seems like it’s a win-win.
Dr. Eric Westman: If I can summarize, it’s that “safe mode” idea. The fasting, normal cells slow down but the cancer cells are still going really fast, they don’t slow down. Then there’s the whole other sidebar of sugar being a major fuel. With chemotherapy, I remember many side effects – hair loss and gastrointestinal diarrhea – are caused because those cells turn over really fast. The chemotherapy side effects are because they’re hitting cells that turn over – of course, the cells will regenerate. The theme of the keto diet is giving the nutrition that normal cells need and slowing things down so that the ammunition (chemotherapy) that we’re using will actually still be effective against the cancer cells, which are still very fast. Is that a good way to summarize it?
Dr. Christy Kesslering: Yeah. I will also say that I’m not telling anybody they won’t lose their hair with chemotherapy if they do a ketogenic diet. Certainly, there are some drugs that affect hair and others that don’t. There are new techniques to help preserve hair because I know that’s a big one, especially for women, but the GI is definitely different.
Interestingly, a lot of times to prevent toxicity, patients will be given steroids around chemotherapy. What do steroids do to us? They increase our blood sugar and our insulin. In one of the trials they actually held the steroid during that fasting-mimicking diet and still had the same or better quality of life measures.
Dr. Eric Westman: Again, getting into the metabolic changes that are occurring. That’s just fantastic.
Switching gears just a little bit, how is a keto diet for cancer patients or in preventing cancer different from a keto diet that you might see on the internet or for weight loss or diabetes control? Are they the same thing?
Dr. Christy Kesslering: I think of them a little bit the same and a little bit different. I think you are very aware that you should eat real food, don’t eat a bunch of keto products, and don’t make all your fat bombs and your fatty coffees. We’re just gonna eat real food, we’re gonna restrict carbohydrates, we’re gonna eat optimal protein, but we have to get our fuel from fat. We don’t want to eat a low-fat, low-carb diet. That can be very painful for most because you just don’t get the fuel that you need and you certainly will burn your own fat. Again, not all cancer patients have excess fat, so we want to optimize the diet for the individual patient.
Interestingly, there was a study done many years ago that just took 10 patients who were done with the standard of care and they were just in palliative mode. Those 10 varying cancer patients were put on a ketogenic diet and all the patients, on average, lost weight. They restricted calories, but it was only the patients who reduced their insulin, which was correlated with the elevation in ketones, that actually had stabilization or regression in disease. When we’re looking at a cancer patient we are really trying to drive down insulin. Insulin is a growth factor; insulin turns on our mTOR (mechanistic target of rapamycin) pathway, which is a growth and regeneration pathway.
Some people can lose weight and feel better but they’re not actually reducing the actual driver of that cancer. I always want to test and track and look at these things – what are your ketone levels? I don’t know that we know what the exact right answer is, but what we know is that rising ketone levels are indirectly associated with insulin, so if ketones go up, insulin comes down. If ketones go up, IGF-1 (which is insulin-like growth factor) goes down. We know that both of those growth factors decrease with increasing ketones. Again, we don’t know the right answer. Everybody really has different genetics as to how they produce ketones. Their weight may drive their ketone production, etc. I always follow that up with insulin – let’s put you on a ketogenic diet, let’s look at your fasting glucose and ketone levels, let’s look to see what happens to you throughout the course of your day, but then let’s follow that up with another insulin, another IGF-1 [test]. Are they coming down? If they’re not, what do we need to do to troubleshoot?
Just to tell a couple of quick anecdotes, a woman with progressive stage four metastatic breast cancer with skin nodules and progressive disease in her breast switched to a low-carb diet. She didn’t even go all the way to a ketogenic diet because she was just learning about this, and said, “I cut out sugar, I cut out those high-carb foods and my tumor for the first time started shrinking!” Just the idea that little changes can make a relatively dramatic bump in our health is just mind-blowing. I think people just don’t realize how much diet can really play into their health.
Dr. Eric Wesmtan: There are a couple of elements in there. One is the benefit of cutting carbs, whether you’re in ketosis or not. Then there’s a benefit of being in ketosis, and the extent to which you need both is just being studied now. Even then, checking a ketone level doesn’t mean much about the flux – how much is going in the blood or how much is going out of the blood. These are crude markers but they hang together and then the lower the insulin, the better it seems.
A lot of my patients will come to me and say, ”Keto, that’s a weight loss diet. I don’t want to lose weight.” I even tried it in one of my classes and said, “This isn’t a weight loss diet; it’s a metabolic diet, and weight loss is a side effect,” and one of my patients got up and said, “Well, I’m leaving, I want to lose weight!” I got misconstrued. It’s not a weight-loss diet; It’s a fat-burning diet.
Dr. Christy Kesslering: Ketogenic diets are weight-balancing diets. If you are underweight, it can actually help you gain weight and if you are overweight it will help you lose weight. There were actually a couple of trials done in our patients that typically really struggle with weight maintenance. They’re too skinny or depleted to begin with – our head and neck cancer patients, especially, because it’s very hard for them to eat and swallow and so they become malnourished. Many stage four GI cancer [patients, too], because the gut is wrecked, whether that’s esophageal or stomach or colon. There were some trials done in those patients where they were put on ketogenic diets and they actually increased their lean mass, their muscle, and bone density. We know that there’s data also on muscle wasting (sarcopenia) and cachexia. Those are terms for wasting muscle. Cachexia is also wasting fat, but interestingly, ketogenic diets seem to stop or at least slow down that wasting process. We hear sometimes that ketones are “muscle-sparing.”
I had a young woman recently who we were optimizing, so she had been doing a ketogenic diet for her cancer. We changed it. We really focused on getting adequate animal proteins and healthy fats. Interestingly, over the course of about four months, she put on 17 pounds of lean mass. That’s pretty impressive when somebody is underweight and needs that.
Dr. Eric Westman: That was worked out by Dr. Jeff Volek and the weight loss world many years ago. He showed that you could gain muscle mass while you were losing fat mass. The outside view is that while you’re losing weight, actually you’re changing your body composition. It was thought not possible, but now, Jeff Volek, who’s at Ohio State, is moving on to cancer treatments and investigations. I heard him on a STEM-Talk recently, talking about the latest science and the studies that they’re doing at Ohio State and that’s fantastic. While we’re talking about metabolism and changes in a keto diet, for cancer patients specifically, what kind of blood or lab or body tests do you recommend at the clinical and research level? My patients ask me what they should be measuring.
Dr. Christy Kesslering: I think that we don’t know all of the right answers yet but I always do a pretty broad metabolic panel and I look at the numbers very differently. We often will get our lab reports from our doctors and they say everything looks great. I look at that same lab report and I think, “Oh my gosh, we’re on fire. We need to take a step back and we need to make some big changes.”
In addition, I do order a number of labs that are not typically ordered. We always get the CBC (complete blood count) and the CMP, which are the complete metabolic profile, which interestingly enough doesn’t really show metabolism very well. They never check insulin. I look at insulin and I look at IGF-1. I use some of the calculators for insulin resistance – HOMA-IR is an integration or a calculation between sugar or glucose and insulin and helps predict the degree of insulin resistance. I use standard labs like a cholesterol panel and look at the triglyceride-to-HDL ratio. Elevated triglycerides – really even over 70 or 100 mg/dL (0.79 or 1.13 mmol/L) – start to say there’s a problem maybe with insulin resistance. So many of my cancer patients have low HDL and low vitamin D. There are a lot of associations there. I look at a few other inflammatory markers: some people have probably heard of these, hsCRP or sed rate (erythrocyte sedimentation rate, or ESR). Those are general inflammation markers but are often elevated in a cancering process.
Lactate dehydrogenase or LDH is really interesting when you look at the Warburg Hypothesis or the Warburg Effect and how our metabolism funnels through our mitochondria. When mitochondria are damaged, which is very common in cancer, then LDH (lactate dehydrogenase) has to be upregulated because those cancer cells are using the glucose-to-lactic acid pathway to generate fuel. They have to do it over and over and over and over again and LDH is the last enzyme in that process. When that goes up, it’s telling us that there’s a lot of damaged mitochondria in your cellular health and we need to help repair that. What has been shown to improve mitochondrial health is fasting-mimicking diets, fasting, and fat burning, which push those cells back to health. Using a lot of those really gives me an overview of where the patient is starting so that we can then go and say, “You’re eating this way, how are your markers? Are these things getting better?” It’s very rewarding.
Dr. Eric Westman: The LDH will actually be elevated in a regular blood test that we do?
Dr. Christy Kesslering: Correct. I’m looking at it from a functional medicine perspective – what’s the sweet spot? Even with insulin, there is also “too low.” We need glucose, we need insulin. We need all of these pieces, but we really want the “Goldilocks” – we don’t want it too cold, we don’t want it too hot; we want that sweet spot. I’m working with patients to try to optimize LDH, which can be too low in people with reactive hypoglycemia, meaning elevated insulin.
Dr. Eric Westman: You’re really talking like an obesity medicine doctor! We’re thinking of insulin or IGF-1, the insulin growth factor. Glucose, insulin, diabetes, and obesity pathways are the same ones involved with cancer.
Dr. Christy Kesslering: Yes. That’s why diabetics are at much higher risk of developing cancer – because really, it’s the same underlying metabolic problems. It comes back to why I think obesity is a driver, but it’s really what caused that obesity.
Dr. Eric Westman: What’s the latest thinking about the Warburg Effect? My view is that 100 years ago, Otto Warburg described some cancers as glucose centric – i.e., that they like to have sugar. That got amplified into, “Sugar causes cancer! If you just stop sugar, you’ll fix cancer!” It’s more complicated than that, isn’t it?
Dr. Christy Kesslering: Yes, a hundred percent. But I do think that, yes, some cancers have a very strong Warburg Effect. It’s not so much that sugar feeds cancer, but that when sugar spikes, insulin spikes. Insulin binds to the insulin receptors, which pull that sugar into the cells. We know that numerous cancers have significantly upregulated the number of insulin and IGF-1 receptors they have on their cell surface.
Dr. Eric Westman: Upregulated just means there are more of them.
Dr. Christy Kesslering: Yeah. There was a study back in the early 90s where they stained breast cancer cells for insulin receptors and found that the average breast cancer cell had six times as many insulin receptors, but up to 24 times as many insulin receptors. We can see a similar thing for prostate cancer, for instance, which is more common to have elevations in IGF-1 receptors.
Very interestingly, if we really dig, they have higher levels of fructose receptors. Again, sugar and different forms of sugar. From a fructose perspective, we already know that high fructose corn syrup is bad; I say juicing is bad as it’s giving you more fructose. If you are “metabolically broken” (i.e., diabetic, pre-diabetic, or even just hyperinsulinemic), you’re going to slowly increase the amount of fructose that you produce inside your body from glucose. There’s a special pathway called the polyol pathway that converts glucose into fructose. The more problems you have with your metabolism, the more of that conversion you actually make, so you don’t even have to eat any fructose but you’re going to be making more from your glucose if you’re broken.
There are so many different pieces to the puzzle. The beauty of a ketogenic diet where you’re eating real food is that you’re removing all of the pieces that can drive [those metabolic processes]. The simplistic view is always to take away glucose, take away this, take away that, but you can’t address it all. I think the beauty of a ketogenic diet is you tend to address it all but it’s not as complicated as we want to make it. From the conventional world and even the alternative world, with all the supplements, we keep trying to block pathways and address this one thing in cancer. The reason why I think ketogenic diets augment each of those things is really that it’s addressing all pieces at the same time.
Dr. Eric Westman: I think the general consensus view, now in 2023, is that sugar and ultra-processed foods in excess drive so many things. This is a common theme for cancer too, it seems.
Dr. Christy Kesslering: It really is. There’s so much overlap in all of our chronic diseases. Sadly, in medical school, we all sub-specialized [to become] the brain health specialists, the cancer specialists, and the obesity specialists, when really, it’s the same disease.
Dr. Eric Westman: Switching gears: I hear a lot of doctors saying that exercise fixes everything – it’s actually not necessary for weight loss so it’s more complicated, but there’s a lot of science saying that exercise is important for cancer treatments or prevention. What’s the latest science on this?
Dr. Christy Kesslering: There’s a lovely breadth of data looking at muscle and fat mass, lean mass versus even belly fat, etc. They’ve actually done some imaging studies, like CT scans and MRI scans, to characterize the amount of lean mass or what does the muscle look like? Is it this nice solid piece of meat or is it marbled with fat? Is it shriveled and marbled? How does that fat look in characteristics? What they have found is, the more robust your musculature, the better the outcome in the cancer patient, even if that patient was obese; if they had really good musculature, they did better.
The worst combination is a lot of fat mass and very little muscle mass. That’s what we have come to term “sarcopenic obesity.” Sarcopenia means muscle wasting, but the patient is still fat. Unfortunately, when you just look at the outside of a patient, you’re really only seeing potentially the fat mass. You’re not looking at the muscle density itself. Why might that be an issue? Our muscles store glycogen, and glycogen is made up of sugar. When we eat a higher carbohydrate meal that is broken down into individual glucose molecules, then we’re going to store that glucose in our muscle glycogen. If we don’t have very much muscle, we have less storage for that glucose. In addition, when we are moving and doing exercise, we’re using up that glycogen and creating more space for the next load of glucose, which can then just flow in, less insulin. You don’t need insulin in that setting; the muscle becomes a sink for glucose. If we can build lean mass – and we just talked about how a ketogenic diet can build lean mass – we now have more glucose-operating tissue, which improves insulin sensitivity and decreases that insulin being up all the time.
When we use other exercise techniques, maybe it’s high-intensity exercise (there is randomized data looking at steady-state cardio versus high-intensity interval training – you’re working really hard, getting into that lactic acid burn, and then you’re recovering and you’re up and you’re down and you’re up and you’re down), that actually has a dramatic insulin lowering effect on a patient’s health. We can do chronic steady-state cardio, and I think that that’s exactly why the whole “move more” doesn’t work in weight loss, because it’s really not changing insulin. Weight loss is insulin reduction to allow that fat to flow out of your cells instead of constantly pushing into your cells. Insulin is a storage hormone.
Dr. Eric Westman: We’ve talked a lot about associations versus causations. As a clinical trialist, I like to focus on clinical trials going forward in time, especially if you randomize or have an experiment going on to really isolate one factor. Do we know the relative potency or the strength of exercise? I know it can be hard to figure out because if you’re just looking at associations and now trying to figure this out prospectively, sometimes we’re fooled into thinking something more important or less important than we thought.
Dr. Christy Kesslering: Unfortunately, in a cancer world, that’s really hard to know. With cancer patients, you’d have to follow them for so long. Our cancer trial follow-ups are between 5-20 years because we’re waiting for that potential recurrence to happen; those recurrences don’t happen in six months or a year, typically.
What we do know from a quality-of-life perspective, exercise decreases fatigue associated with cancers. There’s a nice study out on prostate cancer patients using a ketogenic diet and just walking, actually. Those were patients, you’re very well familiar with that group, that had androgen deprivation therapy. They were on hormonal therapy for their prostate cancer, which typically decreases bone mineral density, yet we improved bone mineral density in those folks or they maintained better than the group that wasn’t using those techniques. I think that from cancer outcomes, we may never know, but I think that we know so much about insulin and we know so much about those drivers that I can say, “If you lower your insulin, we know that there is a significant improvement in outcomes in patients with lower insulins compared to patients with higher insulin.” I think we just have to continue to build upon what we know. I don’t know if we can ever get to that [definitive answers] unless we used, unfortunately, patients with those stage four or more aggressive cancers where we would expect earlier recurrences. But they may be almost too debilitated to do some of those things.
Dr. Eric Westman: We learned in the COVID-19 area that if you had diabetes, obesity, hypertension, and all these chronic medical problems, you had worse outcomes with this disease. I have to think common sense is that if you’re going to have to go through a chemotherapy regimen and radiation or if there’s a cancer propensity predilection in your family, then you’re going to want to be in the best shape you can be now, preventatively, just in case you’re going to have to go through that. Even if this approach doesn’t totally prevent it and you didn’t reduce the cause, I think you want to be in the best shape you can be just because you may undergo a difficult treatment.
Dr. Christy Kesslering: Absolutely. I do have some patients who do take a step back instead of jumping right into chemotherapy. They do take a month to optimize their diet and their exercise and things to prepare for this upcoming big surgery or big chemotherapy. They want to optimize that potential outcome and how they’re going to feel while they’re going through it.
Dr. Eric Westman: So, sometimes there isn’t an urgency to get the traditional treatments? I guess that would be dependent on the person.
Dr. Christy Kesslering: A hundred percent.
Dr. Eric Westman: Just so that people know, we’re not saying that a keto diet can cure cancer. That’s not been shown yet, but certainly, it can be helpful in all these other ways.
Switching gears: there are a lot of myths about keto diets. What are some of the myths about cancer?
Dr. Christy Kesslering: Just as with all chronic diseases like diabetes and obesity, we constantly hear this plant-based diet mantra. That’s the biggest one – that all cancer patients should eat a plant-based diet or a Mediterranean diet. We have to remember that the majority of that data came from observational, healthy user bias studies, meaning they look at a population and they say, “These people are more likely to get cancer and these people are less likely to get cancer,” but they fail to control for all of the other nuances. People who tend to eat more meat also tend to be obese and diabetic and smokers and sedentary and eat processed foods and high-sugar diets. What we really need to do is look a little bit more at the mechanisms as well as any true randomized trial.
I will say that I hear a lot in the prostate cancer space, “I have to eat a low-fat plant-based diet because that’s what the Dean Ornish trial showed.” Just to be clear, Dean Ornish looked at less than 30 patients, half of them following standard of care, and the other half underwent intensive dietary and lifestyle management. Yes, they ate a low-fat, mostly plant-based diet but what do we do when we eat a low-fat diet? We cut out donuts and pizza and french fries – a lot of those high-carb, high-fat foods that are big insulin drivers are removed. In addition, they did support groups and meditation and exercise; they did a lot of other things that might also help lower insulin. This was in early-stage observation patients, so they weren’t even actively undergoing any kind of cancer therapy. There was a slight reduction in PSA (prostate-specific antigen) in the group that was doing the aggressive interventions and there was a slight increase in PSA, but they were plus or minus, if I remember correctly, like 0.3. So, they went from, for example, 6.2 down to 6.0 and 6.2 up to 6.5. Really, in my world, that’s the same number. It’s still 6’s. That gets used a lot for, “We need to eat this way,” but what we know in prostate cancer is insulin, IGF-1 – IGF-1 is one of the bigger ones – and I will tell you that I’ve had people following plant-based, high fruit and vegetable diets and they’re driving their IGF-1’s up. It’s really about looking under the hood.
Dr. Eric Westman: I credit Dr. Ornish with bringing lifestyle to the table as a treatment in an era when all doctors, including me, were thinking of drugs and all. It was really important. However, you can think of it like Ford and the Model T; credit the discovery of the automobile but there are so many other automobiles now, you wouldn’t get any mileage saying, “Those Teslas don’t work; you have to drive a Ford because Ford was the first one.” It’s the idea that if it’s the only one it must be the only one… well, if it’s the only one you studied, it doesn’t mean it’s the only one [that works]. The disservice that that world has done to the lifestyle approach is that they’ve made it seem like theirs is the only way.
Dr. Christy Kesslering: I try not to get people to follow plant-based diets because I’ve just seen over and over that it doesn’t do the job, but if you wanted to flavor your ketogenic diet differently, you want to do it more Mediterranean, you want to do it slightly more plant-based, let’s work on that and let’s move your numbers, the ones that matter – like insulin and IGF-1 – into the optimal range.
Another thing why some folks are almost nervous about a ketogenic diet is meat, the protein which stimulates mTOR, which stimulates that growth pathway… “Meat is bad.” Again, meat in the setting of a high-carb diet can stimulate that but there’s some beautiful research. To really get into some of these interventions you’ve got to go back decades when diet was actually looked at as therapeutic. Really looking at taking in protein in the setting of a low-carbohydrate diet, there is far, far less insulin stimulation than in a high-carbohydrate diet. If you do it with protein and fasting – they fasted people and then gave them protein and they really didn’t have that drive. If we’re following a ketogenic diet, a fasting-mimicking diet, and we’re including that protein we should have far, far less insulin driving. I will tell you I can put people on almost carnivore-ish diets and see their insulin and IGF-1 come down.
Dr. Eric Westman: We’ve come to the point where we can monitor whatever dietary pattern someone chooses to do. I would greatly recommend that you check your own labs and be with someone who’s in tune to this rather than a practitioner who’s just giving a recommendation, a mantra of a plant-based diet. You want to make sure the insulins come down and then the inflammatory domain markers. That individualization of metabolism is really neat. It seemed to me that, like an antibiotic in a bacteria, one day we played out the tumor in a thousand treatments and then you will find the exact chemo that would work for a tumor. Has that progressed?
Dr. Christy Kesslering: Absolutely. Back to the genomics, the epigenetics – which genes are actually turned on, which genes are turned off – and can we maybe do some targeting specifically for that? We’re also then back to just plugging one of the holes. What I see as a ketogenic diet is we are changing the epigenetics; we are helping the body turn off those oncogenes and turn back on their tumor suppressor genes. I would say cancer is like your “check engine light” going on: you have something wrong under the hood even though you think you were healthy or you think that this isn’t in your genetics, this isn’t supposed to happen to me. This is your body saying there is something amiss. Let’s take a step back, let’s look under the hood, and let’s figure out what your body was trying to tell you. This is a cell that was you, in whatever organ it started in, that slowly got out of sync. What can we do to help revert that cell back into itself? Not just kill it or cut it out. That’s like taking your two-year-old that’s throwing a tantrum and saying, “Kick it to the curb.” No, let’s get down on hands and knees and ask it what it’s trying to tell us and then help support and yes, maybe take care of the cells that we can’t revert back, but let’s take those cells better still producing and let’s roll things back. I really think a ketogenic diet addresses every single one of those hallmarks of cancer at the same time.
Dr. Eric Westman: These myths can be measured in your own body and your patient’s own.
Dr. Christy Kesslering: Yeah, let’s look at these inflammation markers, angiogenic markers, insulin markers, and immune function markers. Just to bring about one common thing that I hear stated quite a bit is regarding a BRAF mutation. There was a lot of excitement. There’s a specific mutation called a BRAF mutation and there was a lot of caution being thrown out as we’re starting to really embrace ketogenic diets. The question is, “Is it good for everybody? Is there a particular cancer that maybe shouldn’t be doing it?” There was some talk about this BRAF mutation that grew with ketones. I always have to explain, “Let’s look at the trials that have shown ketones grow cancer.” This happened to be a cell study; cell studies are not even animal models and they are definitely not human models. The medium – meaning the food that was given to the cells – was a high-insulin gel. That is an important nuance.
Just to give an anecdote – I know they’re not science but they generate science – a woman with stage four, aggressive colon cancer, BRAF mutation (she didn’t know what a BRAF mutation was, she just got a diagnosis of cancer), the next day or week she started on a ketogenic diet, on her own, figured it out, said, “I’m just gonna do this until I start my chemo,” and they were still doing work up and staging and testing on her tumor. Her CEA, which is a tumor marker – normally we want it very low, in the single digits, maybe low teens – was almost 2,000. Yet, just by employing a ketogenic diet while she waited before starting chemotherapy, she halved it. Fifty percent reduction. That’s pretty powerful to then have people scared that because they have a BRAF mutation they shouldn’t be doing a ketogenic diet. I’m always trying to educate on the nuances.
Anytime I see, “A ketogenic diet is bad for something,” I have to go and look to see how was that constructed. Was it truly a ketogenic state? Were they looking at insulin and IGF-1? Were they tracking anything? As we know, we can tell a patient to follow a ketogenic diet, but are they? Are they doing it in an optimal state for them? Maybe they’re feeling better because they got rid of the biggest junk food out there but maybe they aren’t really making those metabolic changes that I would like to see from a cancer perspective. It really is the beauty of using testing and tracking and not guessing.
Dr. Eric Westman: What would you say is a summary of our talk?
Dr. Christy Kesslering: I think the summary is that cancer can be a disease in anybody. You don’t have to be obese and you don’t have to have a family history. It truly is about diet and lifestyle and how those things impact your personal environment, your labs, on everything under the hood. Conventional doctors don’t typically look at the things you really should know. I would love to have everybody have a list of the things that they should know. You can hear some other experts in different fields saying, “Do you know what your insulin is?”, “Do you know what your CRP is?”, “Do you know what some of these markers are?” I wish that everybody knew what their markers were because then you might find things earlier rather than when the whole thing breaks down.
Test and understand what different things you’re doing are doing to you. Sometimes we can tell that we feel better but sometimes we’re missing a piece. For instance, if somebody was doing even a vegetarian or vegan diet, sometimes they’re cutting out the worst foods, so initially they feel better but the numbers aren’t gonna maintain. I just feel like there’s so much knowledge out there that just doesn’t come into the conventional world. If you really dig into the science, there’s quite a bit. It is slowly coming into the conventional world, which is great, but certainly not at the pace that many of us would like to see it. What harm is there in eating real food and becoming a fat burner?
Dr. Eric Westman: Thank you so much. What a great discussion with theory and practical advice. I really appreciate your time.
Dr. Christy Kesslering: Thank you so much, it’s been great.
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