(Use the link here to convert blood glucose levels from mg/dL to mmol/L.)
Dr. Eric Westman: My guest today is Dr. Christy Kesslering. She’s a radiation oncologist and a member of the Society of Metabolic Health Practitioners, of which I’m a board member as well. You’ve also held many leadership roles through the years. You’ve been named a top doctor multiple times by Castle Connolly and Chicago Magazine. But you now spend all your time helping patients – real-world patients – with cancer and without cancer. Thank you so much for joining me today.
Dr. Christy Kesslering: I’ve been working in the cancer field for a long, long time – over a quarter of a century. I have been incorporating metabolic health into my own practice for a number of years now because we have seen so much in obesity-related cancers, and it became an area of great interest to me. I have slowly left my conventional practice to really work on metabolic health full-time because there’s such a need, and patients don’t typically get the support when they’re in the conventional medical world. There’s so much conflicting information. We’ll go over a little bit of why the diet world is so confusing when it comes to cancer. We’re going to talk a lot about how low-carb ketogenic diets play into this.
Cancer as a lifestyle disease
First, we hear all the time that cancer is a lifestyle disease – that the genetics of cancer are such a small percentage of our actual cancer diagnoses, that about 90 to 95 percent likely are attributed to lifestyle factors. The top five being some that we already know very well: smoking, alcohol use, sedentary behavior, being overweight or obese, and then, of course, just poor dietary choices. If we’re drinking a bunch of soda pop and processed foods, it’s obviously not optimal for keeping cancers away. But there are also other things that are lifestyle-related – we have environmental toxins, things that are coming in through our soils, our waters, and circadian rhythm. Are we going to sleep at a regular time? Are we getting up at a regular time? Are we in front of screens 24/7 right up until bedtime and maybe into the wee hours of the morning, etc.? And just getting outdoors and being in the sunshine – we rarely do that anymore because we have such an indoor life. So just a few things to think about. What I want to touch on mostly is the metabolism, diet, and obesity piece.
Cancers associated with obesity
What we know is that more and more cancers continue to be associated with obesity. We can’t say 100 percent that obesity causes these diseases, but there are patterns that we see. Obviously, our most common cancers –breast cancer, prostate cancer, and colorectal cancer – are in there, but we’re even starting to see some links into cancers that maybe we wouldn’t expect as much, like even lung cancer. It’s an interesting conglomeration of cancers from all different walks, so to speak, not just our normally associated hormonally-driven cancers.
What about obesity might “cause” cancer?
When we think about obesity [View image] and I think a lot of you guys are probably very aware of this insulin connection, IGF-1, or insulin-like growth factor, but obesity can drive elevations in these hormones: insulin, IGF-1, the leptin-to-adiponectin ratio, so maybe leptin resistance, low adiponectin, again other hormones that are associated with obesity. And then other inflammatory cytokines and what’s called VEGF (vascular endothelial growth factor). But if those are high, they drive obesity. If obesity is high, they drive those numbers. They’re interconnected – they go both ways. What we know is that this picture, these hormones, then can drive growth factor signaling, vascular changes, the microenvironment changes, and systemic inflammation. All of those things can cause increased cancer risk and cancer progression as well.
Carbohydrate intake and the risk of developing cancer
If people eat carbohydrates, eat sugar, what happens? This was a study [View image] that looked at carbohydrate intake but also at the glycemic index and glycemic load. Glycemic index is how quickly does it raise your sugar after you eat it, and then glycemic load is how much of that food you are eating. So, a bite versus a whole big box of cookies. What this study showed was that there was an increased risk in the development of post-menopausal breast cancers. In the first panel, we’re just looking at ER-negative breast cancers and in the second panel, we are looking at ER-negative cancers. You can see that the light blue bars are all set at a hazard ratio of one, and then that was for the lowest intake group. The darker blue bars show how much increase in risk was there compared to that highest carbohydrate group. So, highest carb versus lowest carb, highest glycemic index versus lowest, highest glycemic load versus lowest. You can see that, in fact, there are multiple or all of those steps that increase risk. But this is not enough risk to actually say that that causes the disease. When we look at observational studies, this is where we get into confusion. If there’s an increased risk, this might get reported in the literature as “High carbohydrates cause ER-negative breast cancer,” but that’s not what this is showing. It says there is an increased risk, but that hazard ratio doesn’t reach two or more. It’s only 1.6, 1.2, 1.4. They’re not high enough to say that that’s the actual driver of the disease, but it does say that there is some association there.
This one [View image] is showing early-onset colorectal cancer, so that, by definition, is a colorectal cancer that develops in someone younger than age 50. This was a study done in women looking at sugar-sweetened beverages – things like colas and juices and other sugary beverages. What they found is that if the women averaged fewer than one sugar-sweetened beverage per week, that’s somebody who really doesn’t drink sugary drinks, versus somebody who drinks two or more every day, there was a dramatic difference – a two-and-a-half times increased risk – of developing that colorectal cancer. And interestingly, they also found that for every additional serving per day in high school, going way back, if during their high school years they admitted to drinking multiple or even just one a day, but every additional serving per day increased that risk by an additional 32 percent. You can see that that really is now starting to say, “Hey, maybe this is really driving the cancer that if we actually drink sugar, that is bad for colon health.”
Blood glucose levels
Most of us are pretty aware that when we eat sugars, high-carbohydrate foods, we may eventually develop higher levels of blood sugar. That’s pre-diabetes and diabetes. Our sugar levels at fasting might be higher. And what this shows [View image] is a lot of different cancers – colorectal cancer, esophageal, liver, pancreatic. As your fasting glucose goes from less than 90 mg/dL, there are slightly higher risks if we’re in the 90 to 100 and much higher risk as we are to 109, much higher as we get into that 110 to 125 mg/dL. Those risks continue to go up. This was an observational study. These hazard ratios do not hit two.
Let’s look at the next one [View image] If we just pull out fasting glucose and risk of developing pancreatic cancer, pancreatic cancer. This is actually looking at over 25 million patients, looking in their National Health System database and looking at fasting glucose and rates of cancer incidents in the pancreas. But remember, pancreatic cancer is not very common compared to breast, colorectal, prostate, etc. But what you can see is that this was only a five percent incidence rate per year at low levels of sugar, but at high, so 126, that’s three times as many. So that is pretty dramatic, three times. And then if they were actually on medication for their sugars, that actually got up to almost four, four and a half times as many. So now we’re starting to see, oh, this may really be real. And from a pancreas standpoint, if we think about it, if our sugars are high, our pancreas is overworking 24/7, right? It is dumping insulin all the time. So that is a very interesting link: pancreatic cancer, glucose, and insulin.
Glucose/carb intake vs blood glucose vs insulin/insulin resistance
We can look at glucose and carb intake or blood glucose, but I think all of us in this community realize it’s really even before that. It is insulin, it’s insulin resistance, and that is really where I think the light starts to shine. We know that based on glucose responses to macronutrients, the different macronutrients we eat, we may have different blood sugar spikes, time to elevation, and length of elevation. Our foods are not individual macronutrients. Everything is a combination of carbohydrate and protein or protein and fat or all three, depending on what we’re eating.
What is very interesting and, and as we all know, that we all have different glycemic responses to the same food in non-diabetics, glycemic responses to the same foods. This was a study [View image] that looked at non-diabetics, so we weren’t anticipating differences. They all had relatively in theory nice low fasting glucoses. But if you actually look here, there’s probably a pretty good spread. Having 120-ish (mg/dL) fasting glucose is probably a little high for a non-diabetic, but you can see that the higher that fasting glucose maybe, the higher the response to this meal. And this, I believe, is a relatively high-carbohydrate, I think it was a sandwich or something. I can’t remember exactly. But you can see how there is a difference in people’s response, how quickly that glucose comes up and how quickly it goes down. We kind of see this general play out that when somebody is diabetic, a small carbohydrate load can cause dramatic elevations in glucose that may stay up for many, many hours.
When we’re in the pre-diabetic or even maybe before that, where our insulin levels are starting to go up a little bit more but by fasting, they’re still back to normal, and our glucoses still look normal, we do still have a more dramatic rise to glucose. If I put a continuous glucose monitor on somebody, I might see where that glucose is actually bumping after really a relatively small amount of carbohydrates. I will tell you just for an example, I had a patient wearing a CGM and, well, I can’t remember if I had her wearing a CGM or if she was doing her blood glucose with a finger stick. What she found is that she ate one piece of “keto bread,” and her sugar went to 177 mg/dL. So, don’t believe labels. Trust your own body and know that different foods and different combinations are going to affect everybody differently. That’s why I come from the camp of we should really be testing in certain situations. A lot of times we just want to keep it simple. If we’re doing this just for general health, changing our way of eating and making sure that we’re losing weight and feeling great, that’s awesome. But sometimes I will have people thinking they’re doing everything right, but their insulin isn’t really coming down. So, I always like to get testing before and after making changes and see where things are going. When people are stuck, it gives me a lot more information to know where all these markers are so that we’re using that test and don’t guess the method.
Insulin responses to glucose – Kraft Curves
These are the Kraft curves [View image]. Some of you may be familiar with Dr. Kraft, and he was much more interested in that insulin response, not in the glucose response. He gave a dose of carbohydrate or glucose and then what he found was that there were a wide variety of insulin responses. The top line, that gray line, is likely an undiagnosed diabetic because these were supposed to be normal fasting sugar patients. But that patient had a significantly elevated insulin. That insulin could have been keeping his sugar looking normal; it just needed more and more and more to do that. So, really, that high insulin is an undiagnosed diabetic. The next two, the dark gray and the dark blue, are overproductions of insulin. When insulin gets overproduced, then it’s constantly on, and it’s constantly pushing sugar down, which often then makes us hungry again at that two or three-hour point. Then we need to eat again because our sugar is going to drop too low because our insulin is still high. The only way to really fix that is by changing the foods that we are eating so that we are not getting that dramatic insulin response.
Fasting insulin and risk of prostate cancer
Now, let’s think about that more from a cancer perspective. When we start looking at insulin and cancer risk, fasting insulin and risk of prostate cancer. This is a study [View image] that looked at prostate cancer. This was looking at a fasting insulin, if you had one less than 6.4 compared to an insulin of 8.8. So I didn’t put some intervening groups, but just to show you the lowest to the highest, you can see that in this group of patients, there was a two-and-a-half to three times the risk of developing prostate cancer just because your insulin was two points higher. I will tell you that the average American probably is 9, 10. So, all of our average Americans are already in this highest risk group. So then, interestingly, this group then also looked at waist-to-height ratio. You can think about waist circumference being belly fat, visceral fat, right? So, the apple shape. If somebody also had a high waist-to-height ratio and a high insulin, they were over eight times as likely to develop prostate cancer than if they had a lower insulin and a lower waist-to-height ratio. That’s pretty dramatic. That is saying that insulin is very likely driving that disease process. We know that insulin also tends to drive that waist-to-height ratio.
Fasting insulin and risk of developing postmenopausal breast cancer
When we look at breast cancer, fasting insulin and risk of developing postmenopausal breast cancer, this was a study [View image] again, just observational looking at postmenopausal breast cancer. They found again that a very low fasting insulin, so this one they used 3.6 if you were greater than 9.5, you had a two-and-a-half-fold increased risk of developing breast cancer. It was graded, meaning the more insulin, the more likely you were to get cancer.
Insulin-resistance and insulin, not obesity, as risk for breast cancer
Why do I want to pull it back away from obesity? This was a nice study that looked at weight [View image here]. Either you were overweight/obese, or you had normal weight. But then they took it a step farther, and the right panels of each of those are the insulin. You can see that with low insulin versus high insulin, overweight people were twice as likely to get breast cancer, and normal weight people were twice as likely to get breast cancer. So, it wasn’t about weight; it was about insulin. HOMA-IR, which is an insulin-resistant score, uses a combination of glucose and insulin to test that insulin signaling sensitivity. Both of those were elevated in both groups similarly, but they did not hit that doubling of hazard ratio. So those were both around 1.7, 1.8.
Then there’s another hormone that I mentioned – IGF-1, or insulin-like growth factor-1. So again, it’s a sister hormone to insulin; it has been associated with the growth of cancers. We hear a lot about mTOR as a growth pathway, but IGF-1 can turn on that mTOR growth pathway. We hear a lot about it and that we should try to lower IGF-1 just like we should try to lower insulin. This is a nice study [View here] that showed that with increasing risk or increasing levels of IGF-1 it dramatically increased prostate cancer in men. So, four to four and a half times more likely to develop prostate cancer with high IGF-1 versus if you were in the lowest risk group. Interestingly, when they looked at men older than age 60, it actually almost doubled that risk. There was an almost eight-fold increase in risk in men who were over the age of 60 in the highest IGF-1 group.
Prostate cancer risk by IGF-1 and PSA
When we look and pull in the PSA [View image here], because that’s kind of what the conventional world looks at, interestingly, if you had a high PSA and a low IGF-1, you were actually less likely to develop prostate cancer than if you had a high IGF-1 and a low PSA. But you can see on the right, those are all PSAs over four and how they really are much higher than those who have low PSA. That combination of having an elevated PSA with an elevated IGF-1 is much more powerful of a risk predictor. So in theory, if somebody had a rising PSA, maybe we should be checking IGF-1. You know, it makes sense; we don’t have that data yet.
Breast cancer patients with high insulin levels by disease status
And what has also been shown is if you are diagnosed with cancer, if you have elevated insulin, you tend to have elevated risk of disease or a worse disease status [View image from video here]. In the first group is tumor size. If you have high insulin, you are more likely to have a bigger tumor; you are more likely to be diagnosed with node-positive disease. If we’re just looking at the stage, you can see how the stage that goes along with a bigger tumor size, more nodes involved, etc. As insulin goes up, so does the risk for a higher stage disease.
Can diet impact the risk of developing cancer?
I hope I just told you the story that high levels of insulin and IGF-1 do appear to be direct causes of obesity-linked cancers because they have very high or at least meet a hazards ratio of two. But we’ve seen even fours, eights-pluses, so we know that there seems to be this direct cause. Again, these are observational. It makes sense that if insulin and IGF-1 appear to be driving this cancer link regardless of weight because we saw that with the BMI study or the overweight to normal weight, if we all follow diets that will help lower insulin and IGF-1, then we should lower the risk of developing a cancer.
But why is there so much conflicting advice then about diet and cancer? And we should be following a low-fat diet, a Mediterranean diet, a plant-based diet, and a ketogenic diet. But why? Well, as I believe everybody would realize is that any diet is first and foremost going to get rid of the processed foods. We’re going to get rid of pizzas and ice cream and cakes and donuts. Those are the fat + carb combinations that are very insulinogenic. When we combine fat and carbs, we really drive insulin and IGF-1. Step one is getting rid of that. But let’s look at some comparisons.
Metabolic changes with ketogenic vs low fat diet
Looking at a very low-carb ketogenic diet versus a low-fat diet [View image from video here], you can see that all of those or both of those diets do help lower insulin, help lower leptin, which I mentioned upfront, lowers HOMA-IR, lowers even the triglycerides and the triglyceride HDL ratio, which is a surrogate for insulin resistance. It lowers abdominal fat, which is an insulin-resistant type of fat. But you can see that the blue bars (ketogenic diet) always seems to do it much, much better and in more patients. When we start to pull outpatients with varying levels of metabolism, Dr. Volek has been so wonderful in this arena and gives us so much information. But when he looked at metabolically, you know, patients with metabolic syndrome, he found that it was really only the low-carbohydrate diet that reversed the metabolic syndrome. It is very interesting to see that and to know that a lot of cancer patients are in that. Even though they may not meet the full criteria for metabolic syndrome, they obviously have some degree of metabolic dysfunction because of this glucose and Insulin signaling piece.
Metabolic changes with ketogenic vs Mediterranean diet
When we look at the Mediterranean diet [View image from video here], which is the American Cancer Society diet, compared to a ketogenic diet, this was actually done in cancer patients. We see again some lowering of glucose and insulin and IGF-1 in both diets. But you can see how the ketogenic diet does that much, much better. And when they actually surveyed the patients, the patients who were following the ketogenic diet felt like their cravings were much better controlled in comparison to those on the other diet.
What about other diets?
We always hear, “Oh, but you shouldn’t do a ketogenic diet because meat causes cancer and fats cause cancer and dairy causes cancer.” I want you to all think about my initial comments about epidemiologic data and hazards ratio because pretty much most of these things that we get scared off on are usually observational data that don’t control for all of the known factors. As we have learned from the ketogenic space, most meat-eaters eat a high carbohydrate diet, and that may be why meat is associated with cancer. But I always say, come on. If you go to McDonald’s and you look at a value meal, you’re going to tell me that the one thing in there that is driving disease is the meat, which is probably the only real food in that whole thing? We have to look at everything with a grain of salt. Any of the data or the studies that have really dug in to meet inflammation growth factors in the setting of a ketogenic diet does not turn those things on. We have seen even in the carnivore space that we can reverse insulin resistance and diabetes putting people on 100 percent high-fat meat diets.
The fats really that are the problem are these processed fats – these seed oils, old-fashioned Criscos and Western oils and all of those things. There’s a lot of data on linoleic acid omega-6 fats driving cancer in randomized trials putting them on saturated fats versus polyunsaturated fats, and usually those polyunsaturated fats actually drove cancer. So there is some laboratory data in that. Then there’s also some observational data that those eating kind of fried foods and things like that. But we would say people who are eating fried foods really are not looking at their diet in any way, shape or form.
Milk in and of itself is a high-carb, high-fat food that can drive insulin and IGF-1. But if we’re doing dairy fats like butter and ghee and maybe some cheeses, is that really leading to cancers? I would say no. That again is my bias, and I do think there are some people where dairy is inflammatory or where certain things, you know, we all come from different genetic makeups, different heritages where our natural foods may all be just a little bit different. But we, if we are testing, if we know where our insulin started and then we’re making changes, and then we see where our insulin ends up, we know if we’re doing things in the proper manner for us. And so again, I usually recommend doing some lab work and knowing where we are and what is moving in the right direction because sometimes we feel great, but maybe things aren’t exactly how we think they are. I can sometimes see things a little bit earlier when uh when I’m looking under the hood so to speak.
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