Published on Mar 22, 2021

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, Chief Medical Officer at WebMD, and you're watching Cancer in Context. We've been talking a lot about different therapies that are used for cancer, but I also want to talk about the role of sugar. How does sugar impact the development of cancer-- the treatment of cancer?

So to find out the answers, I went to the world's leading expert. Joining me is Dr. Lewis Cantley. His Professor of Cancer Biology and Medicine at Weill Cornell Medicine. Dr. Cantley, thanks for joining.

LEWIS CANTLEY: It's a pleasure to be here and talk about sugar.

JOHN WHYTE: Now, I have to tell you, I read that you have not eaten sugar in decades. Is that true?

LEWIS CANTLEY: Well, what I do, is I avoid foods that have sugar added to them. So avoiding all types of sugar, of course, is difficult because there's natural sugar ingredients in a lot of foods-- fruits, for example. I eat fruits.

JOHN WHYTE: And why are you doing this?

LEWIS CANTLEY: Well, there are a number of reasons. Historically, I started doing it because I noticed, back 50 years ago, that a lot of my friends and colleagues from high school were gaining a lot of weight. There was a huge change. I grew up in rural West Virginia, and back in the '50s when I was there, I didn't know anyone who was really overweight by today's standards, much less obese.

And then through the '60s and '70s, suddenly there was a gradual change that was quite noticeable by the mid '70s already, that almost everyone was overweight. And now a major fraction of people in West Virginia were obese. Now I noticed that they were drinking a lot of sugary drinks, and ironically, a lot of diet drinks as well. They were addicted to sweet things. They had to have sweet things all day long.

So there was clearly this connection of addiction to sweet things that was driving consumption of food. So that's-- I just decided I wouldn't eat or drink anything that had sugar added, to avoid that addiction, and got stuck with stuck with that.

JOHN WHYTE: So we know there's a relationship between obesity and certain types of cancer. And in actuality, those are some of the cancers that are increasing in incidence. And there's different theories as to why obesity is causing this increase, particularly in terms of inflammation, but you suggest that it's sugar that's the cause. Is that right?

LEWIS CANTLEY: Yes. And there are two mechanisms that we can get into some detail on. The cancer that correlates best with obesity is endometrial cancer. And if you look at the mutation of events that cause endometrial cancer, they are events in a pathway that my laboratory discovered back in the late 1980s, early 1990s. And what those mutations do are allow insulin to activate PI3K much more efficiently.

And what PI3K does, is it drives growth. It drives sugar intake, glucose intake-- normal glucose intake from the bloodstream. And we know insulin drives glucose into muscle-- this is how you maintain your normal glucose level in the body-- and it suppresses glucose production in the liver. And so that's how you maintain your normal glucose level-- insulin is critical.

But we also know that insulin is required for the growth of almost all tissues.

JOHN WHYTE: It's a growth hormone, correct? In terms of--

LEWIS CANTLEY: Right. It is a form of growth hormone. It is a growth factor, if you will. We know this because type 1 diabetics who-- children who can't, whose bodies cannot make insulin, the first phenotype you notice is they fail to thrive. They're very small. They don't grow at a normal rate. And this is a consequence of not having enough insulin to drive the growth of their tissues.

As adults, insulin is primarily used to keep glucose constant. But during development, it helps tissues to grow. So if you're hyperactivate PI3-kinase through insulin stimulation in tissues, you can drive the growth of cancers. And cancers will take up glucose better, even, than your muscle. And we use this in the clinic to visualize where the tumor is.

JOHN WHYTE: Is it insulin causing the increase in cancer, and not directly sugar?

LEWIS CANTLEY: Well, so the blood sugar-- we talk about high blood sugar, that means it's a factor of two higher, two to three-fold higher than normal. So that's not a huge difference. The difference in glucose going into tumors is not because there's more glucose in the blood, although that contributes a little bit, it's because something's telling the tumor to take the glucose up.

JOHN WHYTE: And this is that switch pathway that we were talking about?

LEWIS CANTLEY: That's right. And it's insulin, generally, that does it. Now, there are other growth factors besides insulin-- epidermal growth factor, for example-- that can also tell tumors to take up glucose. But insulin is better at doing that than any other growth factor.

JOHN WHYTE: But let's talk about patients with type 2 diabetes who are insulin resistant so they're pumping out a lot of insulin, especially early on. What are we seeing about the development of cancer at that stage?

LEWIS CANTLEY: So that is-- the real dangerous stage is the stage of insulin resistance, as you indicated. Now, once one progresses from just insulin resistance to type 2 diabetes, that says that your islet cells in the pancreas cannot make enough insulin to keep up, and that's when people typically diagnose. But in fact, even before being diagnosed with type 2 diabetes, many people are insulin resistant. They don't know they're insulin resistant because it's not easy to pick up if they have insulin resistance.

JOHN WHYTE: And what do you say to people that are watching, and that are thinking-- and we've seen this around where people will say, sugar feeds cancer cells? So it's an accurate assessment?

LEWIS CANTLEY: It's true that most tumor cells primarily use glucose to grow, but they can also use other amino acids and fats to grow. But typically, they use glucose more so than these other nutrients.

JOHN WHYTE: But we can't make that correlation that people that eat a lot of sugary foods are more likely to develop cancer. We haven't made that straight correlation, is that correct?

LEWIS CANTLEY: Well, we know-- no, endometrial cancer, absolutely clear.

JOHN WHYTE: Endometrial, which is--

LEWIS CANTLEY: Endometrial cancer, it's very clear. But there is a trend-- and I would say more than a trend-- in breast cancer, and in fact, in many, many cancers. And we'll get to colorectal cancer in a minute. That's a special case. But yes, there are many cancers that share this correlation. Prostate cancer, for example, is-- in advanced prostate cancer, the best prediction that you're going to have a short lifespan is that you gain weight after anti-androgen therapy. And that correlates extremely closely with elevation of insulin, insulin resistance, and the insulin now driving the growth of the prostate cancer.

JOHN WHYTE: But some people suggest that the consumption of sugar is more important when we're talking about some of the chemotherapeutic agents and the impact in terms of receptors there. Particularly in lymphomas and leukemias, it's more relevant there. Is that accurate?

LEWIS CANTLEY: Well, I would say that the evidence for lymphomas and leukemias is not as good as in solid tumors. And again, it's about insulin. It's not about the level of glucose in the bloodstream, it's the fact that your pancreas has to spit out maybe 10 or 20 times as much insulin as normal in order to bring the glucose level back to normal. And that 10 or 20-fold increase in insulin is more important than a two-fold increase in glucose in driving the glucose into the tumor.

And if the tumor has mutations in this pathway that my lab discovered, it's going to respond to insulin much more dramatically than any other tissue in the body. So that sugar that you eat, or that elevated glucose in your bloodstream-- even if it's not elevated, even at the normal level of glucose, if you're insulin is high and you have these mutations, that glucose is going to preferentially go into the tumor rather than into your muscle.

JOHN WHYTE: It's really the issue of insulin, then--

LEWIS CANTLEY: It's insulin--

JOHN WHYTE: --insulin related to sugar, which there are other aspects. But in terms of then how we should manage this, you've talked about the ketogenic diet. And I want you to define what that is, because that's different than what some people are thinking in terms of the percent carbs. And some people say it should be 5% carbs, whereas most people consume 65% of their diet is carbs. What's the role of the ketogenic diet, then, in terms of either cancer prevention or in terms of cancer treatment?

LEWIS CANTLEY: Yeah. So ketogenic diet, I like to call it an insulin sparing diet.

JOHN WHYTE: An insulin sparing diet. OK.

LEWIS CANTLEY: So you know, it's that diet-- the diet was originally designed-- actually, the diet really comes from a way of treating patients with epileptic seizures. So children who have epileptic seizure syndromes, it was noticed that if they had a birthday party and drank a lot of sugary drinks, and lots of ice cream and cake, that they were very likely to having an epileptic seizure that evening.

We now know that what causes epileptic seizures are mutations in PI3-kinase, the same gene that my lab discovered, and they happened in neuronal cells during development. So there is a cluster of neuronal cells in the brain that have that mutation in PI3-kinase. It's the very same mutation we see in endometrial cancer, colorectal cancer, breast cancer it also can happen.

It's not a cancer at that stage because it's in a non-dividing cell, a neuronal cell. It allows that neuronal cell to respond to insulin. So if you drink sugary drinks, insulin levels goes up. That will fire those neurons and that will cause an epileptic seizure. Now this was not known to explain why the sugary drinks, and cake, and ice cream was driving the epileptic seizures because we only understood about five years ago that those neuronal clusters had PI3-kinase mutations, but in retrospect it now all makes sense. Those mutations were allowing those cells to fire because of elevated insulin.

So that's how the diet came about. It was called the ketogenic diet because the assumption was that it was the elevated ketones that's protecting you. But in fact, I think the explanation is it's the decrease in insulin that actually is protecting, not the elevation of ketones.

JOHN WHYTE: Now Dr. Cantley, I want to follow up on this insulin sparing diet premise. If that's the case, then why aren't more advocacy groups recommending this type of diet for other patients at high risk for cancer or for those that actually are undergoing cancer treatment? No advocacy group recommends a certain type of diet, let alone an insulin sparing diet. Is that accurate?

LEWIS CANTLEY: Yeah. I think it's pretty accurate, although we're starting to see changes as the message is beginning to get out. I mean, one concern that physicians have is that patients die with or if not of cachexia. So if you--

JOHN WHYTE: Wasting.

LEWIS CANTLEY: --wasting-- muscle wasting. And so a lot of the oncologists who are managing patients with cancer, with advanced stages of cancer, are really worried that the patient is going to lose so much weight that their heart muscle-- they lose heart muscle. And if you lose heart muscle, you're at very high risk of dying of a cardiac event.

So that's why most physicians are telling their patients, keep your weight up. And the truth is that eating sugar doesn't really protect you from cachexia. You obviously have to eat something to stay-- to keep your weight up. But you can keep your weight up without-- it's harder, I should say-- it's harder to gain weight without eating sugar, but there are ways to maintain your weight without a very sugary drink. It could be a slow release carbohydrate is fine. It doesn't raise insulin levels.

A sugary drink will raise insulin instantly, while eating, for example, whole grain rice will take a long time, even though the composition is similar. It will take longer to digest it, and as a consequence, the insulin levels won't go up as high. So there are ways to keep a pretty balanced diet-- it doesn't have to be ketogenic-- that will keep your insulin levels from rising. So my focus is in preventing insulin levels from going up, not from making ketones.

JOHN WHYTE: Do you consider sugar a carcinogen?

LEWIS CANTLEY: Well, I wouldn't call it a carcinogen, but I'll give you an ex-- it's insulin.

JOHN WHYTE: What would you call it?

LEWIS CANTLEY: Let's think about, why are we addicted to sugar? Sugar is historically-- in the evolution of humans, and in fact most animals-- the ability to eat and to be addicted to sugars is critical. And that was because we went through-- most of humans have gone through seasonal availability of food. And before it was possible to can foods and store them in various ways, whenever food ran out, you starved to death.

And the only way you could stay alive through long periods of time with essentially no food available is to have some fat on your body. And by consuming fruits that are high in the mixture of glucose and fructose, it stimulates the appetite to eat food in general, and it's easier to put on weight if you make the food sweet. So naturally, we are addicted to fruits. And since they are only available at the end of the growing season, you put on weight exactly when you need it. And that's why we evolved to be addicted to sugar. It allows us to gain weight.

But the expectation is that you put on 50 pounds and then you go through a period of about three or four months in which there's nothing to eat, and all that 50 pounds goes away. So humans have gone through this starvation, gluttony stage throughout the history of the evolution of humans. And the difference is that today, we never have that starvation period. So we can put on the weight, but it's harder to take it off because there's food always available.

JOHN WHYTE: But also in fairness in the role of sugar, there's also the role of the endocannabinoid system, the role of dopamine, in terms of the pleasure seeking hormones. There's also-- you mentioned sugar, but in terms of central adiposity, there's also the role of leptin and ghrelin, those hormones that either tell us we're hungry or tell us we're full. And sometimes they get messed up.

And there's the role of cortisol as well, that's involved in this. And some people will say sleep, and melatonin, and orexin, and other hormones have as much role in the development of obesity as sugar. So that's a long statement, but what it comes to though, is how do we know it's sugar that's causing these issues in terms of increased cancer incidence?

LEWIS CANTLEY: I'd say because historically, if you just go back and look, as I said, a group in rural West Virginia. 1950s, I didn't see anybody overweight. Almost everybody grew their own food and canned their own foods, et cetera, et cetera. There wasn't a whole lot of-- certainly, no sugary drinks available at all, unless you squeezed your own orange juice. And even that was rare hundreds years ago.

So it's an extremely modern event that there's rapid release carbohydrate in the forms of sugary drinks, in particular suddenly rampantly available and cheap. Sugar was one of the most expensive things to get. My grandparents-- my grandmother, I remember going to the store with her. She would save up her money to buy a five-pound bag of sugar that would have to last the entire year. And when she made a cake, it would be hard to tell it from a biscuit. It was not that sweet.

And so I can tell you, sugar just was not consumed in the '50s and earlier, certainly in rural West Virginia the way it's consumed today--

JOHN WHYTE: But these are associations--

LEWIS CANTLEY: --a huge increase in consumption and a huge increase in obesity.

JOHN WHYTE: But that's associated, Dr. Cantley, not necessarily causation.

LEWIS CANTLEY: OK. So we can get to causation. We know the molecular mechanism by which this occurs because the responses to having fructose plus glucose ends up, as I say, raising insulin, but also allowing the fructose to go directly to the liver and be stored as fat. So even though glucose and fructose have the exact same calories per gram, in our body they behave in different ways. The fructose is the one that makes it taste sweet. Pure glucose is not that sweet.

JOHN WHYTE: So if we're taking this concept up particularly in sugar and insulin, and it's the amount of insulin, why don't we see a greater incidence in cancer in persons who are obese, overweight, pre-diabetic? Because they're pumping out a lot of insulin as their islet cells in their pancreas start to fail.

LEWIS CANTLEY: Well, in order to get a cancer, you still have to have a mutation. So, and that's pure luck whether you get a mutation in the endometrium, or in the breast, or in the prostate. And so if you don't get a mutation, yes, you can be very obese, no mutation ever occurs, doesn't happen in PI3-kinase scheme, or that pathway, then yeah, you can get obese and nothing will happen.

A lot of people smoke cigarettes their entire life and never get a cancer. So there's no guarantee that being obese and drinking a lot of sugar is going to cause cancer, but if you happen to be unlucky enough to get a mutation, it's definitely going to accelerate the growth of that cancer and make it a much greater risk. So it's outcomes as much as incidence where we see the influence of sugar.

JOHN WHYTE: Why aren't more people talking about this?

LEWIS CANTLEY: Well, I think they are. But keep in mind, I'm a biochemist. So a lot of people just study food consumption with regard to observations. You just do correlation. You tell people to eat this, or don't eat that, and then you ask them, are you adhering to what you said? And you follow them for five or six years, 1,000 people, and then you trust that they did exactly what you told them to do and then you write down the results are.

That's not the way that I do research. I'm actually a biochemist, and I ask, what actually happens to the carbon atoms of glucose and fructose when they go into your body? Where do they get absorbed? Where do they go? What did it get converted into? Which ones raise insulin levels? We know that insulin will drive-- the PI3-kinase, the enzyme that I discovered, its role, it mediates everything that insulin does. It evolved for the purpose of driving growth by responding to insulin, and it's the most frequently mutated gene in cancer.

So this is all biochemistry that explains this is the way it works. And once you understand how it works, it makes perfect sense why what we're eating can exacerbate the problem of driving the growth of the cancer.

JOHN WHYTE: Well, we're going to have to continue this conversation about the role of various elements of our diet in the development of cancer. I really find it fascinating, and I want to thank you for taking the time today to come on and answer our questions.

LEWIS CANTLEY: OK. Very good. Nice to talk to you.