 Welcome to Ancestral Health Today, evolutionary insights into modern health. Welcome to Ancestral Health Today. I'm Todd Becker. Today's podcast is part of our second look series where we replay selected talks from past Ancestral Health symposium conferences that we think will interest you. For today's second look, I'm combining two AHS talks by Dr. Ron Rosedale. His 2012 talk at Harvard on Diabetes, and his 2019 talk in San Diego on Cancer. Through the Rosedale Center, the Colorado Center for Metabolic Medicine, and the Carolina Center of Metabolic Medicine, and also through his international work, Dr. Rosedale has helped thousands of patients reverse their diabetes, heart disease, and other chronic conditions without reliance on drugs or surgery. He was an early pioneer of the low-carb movement, and one of the first to focus on the metabolic value of increasing dietary fat rather than dietary protein. Based on a deeper understanding of the roles of insulin, leptin, and mTOR in human metabolism, he crafted his Rosedale diet, not just for weight loss, but for preventing or treating heart disease, diabetes, hypertension, and other metabolic disorders that are on the increase in the industrialized world. These two talks that you'll hear today may seem to be about entirely different diseases, but if you watch and listen carefully, you'll appreciate how Dr. Rosedale applies a unified framework to understand metabolic diseases on a fundamental level as revealing an underlying problem in communication between different parts of an organism, problems stemming from aberrations hormone signaling, growth factors, and nutrient sensors. Modern medicine often goes down the wrong road in misconceiving diseases in terms of a lack or excess of some particular chemical, gene activity, or mitochondrial dysfunction. So for example, diabetes is thought of as a disease of too much glucose, cardiovascular disease, too much cholesterol, osteoporosis, too little calcium, and similarly cancer has been thought of as a disease stemming from too much glucose, or activation, or damage to certain genes, or to mitochondria too. Dr. Rosedale's reframing of diabetes and cancer leads to a few practical approaches to treating these diseases. So in the first talk on diabetes, he focuses on hormone signaling, in particular the need to keep insulin and leptin signaling in check by avoiding not just too much processed carbohydrate, but too much protein in the diet. In the second talk on cancer, he focuses on restraining the potential of cells to grow unchecked by controlling insulin, leptin, and mTOR signaling pathways. These are the hormones and pathways that communicate to ourselves the message to grow, which is good when we're young, but can cause problems like cancer, particularly as you get older. As Paul Newman said in the movie Coolhand Luke, what we've got here is a failure to communicate. I hope you enjoy both of Ron Rosedale's talks and perhaps gain a new way of looking at disease, and also get inspired to check out some of his practical advice that he gives in his book, The Rosedale Diet, and on some of his other online talks and lectures. Enjoy. Just by way of a very brief introduction, in the low carb circles, I'm kind of the last man, last original man standing. There were several people espousing a low carb diet 20 years ago. I'm one of them. Most were correlating it with a high protein diet, and I'm glad to see that I've convinced people that's not the case, or that shouldn't be the case. I was also the first person to connect leptin to diet and health. And then mTOR. I've fought against cholesterol being a villain for 20 years, and it might be new to you now, but you'll soon be hearing about not taking calcium because taking calcium is quite detrimental to health and increases mortality and does not increase strong bones. And I've talked about that on National Public Radio for 20 years. And there's a reason, not because I'm a genius, but because 20 years ago I recognized that it was much more important to look at the commonalities among life and treat those commonalities if they were going wrong. I looked at the pathway that we took to life to know what is vital to life, and if something was out of whack, then that needed to be looked at. So let's go on a little bit of a journey for just a short while. I don't have very long. And so in what, 15 minutes or so, we're going to tell you everything you need to know about nutrition, the formation of life, and medicine. About four billion years ago, life formed in the oceans, the prevailing view could have come from another planet where the same scenario might have taken place. Fatty acids coalesced like bubbles, and they formed around amino acids. And we had primitive cells that ultimately were able to divide into two and learn how to reproduce. And at that point then it was a numbers game. Cholesterol at this point was vital right from the start because it helped in the rigidity of cell membranes. Otherwise it would break apart too rapidly. That tells you one thing that cholesterol cannot be the villain it's being made out to be since it is common to every cell on earth. You get rid of cholesterol, you get rid of life. That told me way back that we should not be taking statin cholesterol lowering drugs. They cannot be good for you and will increase mortality and that has shown now over and over and over again. They failed to tell you that. It became a numbers game. Those organisms that could reproduce the fastest were those most likely to survive. And at that point glucose was the dominant fuel. It's a very simple molecule and you can burn it without oxygen. There was no oxygen in the atmosphere at that point. Fat could not be used as a fuel, fatty acids. Good thing didn't have to eat its own membrane which delineated it from the world and made kind of kept its separateness. But you cannot burn fat without oxygen, but it's very easy to burn glucose with that oxygen. That's really important that fact. So we know that glucose was used as a fuel for billions of years before fat could be used. There had to be nutrient sensors that formed that told cells when to start reproducing when fuel was available meaning glucose. So when glucose was dominant and there was a lot of glucose cells said let's go let's make hay while it's getting good and they would reproduce as fast as possible. Those are our ancestors. We still have that genetic heritage in us. And when that those signals come forth when glucose is very available and nutrient sensors such as insulin start telling the cells to start reproducing as fast as they can we end up calling it cancer. Cancer is a default condition. It has to constantly be kept in check dependent on nutrient availability. Cells formed colonies because in unity there is strength. There's a physical limit to how big cells can form until to get bigger there were colonies of cells. That required then extracellular communication. There had to be communication among the parts to tell the parts what to do for the common good. Forming colonies was really smart for two reasons because by this point there were plants single cell plants that were putting out oxygen. Oxygen was not the life-giving chemical that it's made out to be right now. It was likely the very first weapon of mass destruction. It was theorized that it destroyed at least 90 percent of life on earth. It oxidized and the the poor ancient life had no means of anti-oxidation. Oxygen burns and it virtually burned up almost all life. So cells would huddle together and those that could be more resistant to oxygen were on the outside and those that were more sensitive were on the inside and we got sort of a division of labor. Anti-oxidant systems were built up and especially mitochondria which was a type of bacteria learned how to use oxygen to burn food rather than burn itself. Symbiosis took place where a mother kind of ate a mitochondria and learned that they could cooperate together and use that mitochondria to generate energy from food while at the same time protect itself from the damage of oxygen and it in turn would supply the mitochondria with food substrates to use. That division of labor was really important because another division of labor came forth. There had to be a means of documenting what was good and what worked and what wasn't. So genetic apparatus came along very early in the ball game. At first it was probably some sort of informational protein molecule then it's probably acknowledged that it was RNA later morphed into DNA. So we had then a division between the important informational molecules that tell how to make and maintain life called the germ cells or the germ line and the soma, the body that took care of the germ cells. We still have that division of labor. It is the most important division of labor that there is. Why? Because that is why we age. That is why we die. Early on when you were just single cell bacteria dividing and dividing and dividing a numbers game there really was no death. They just kept dividing. There's no corpse. Maybe occasionally from accident if you stepped on it but not through disease as such. However with the advent of the division of labor between the genome and the soma the soma's purpose now was to protect that genome. It's the temporary caretaker. It's supposed to handle that baton and run with it to the next soma. Protect it. Be its shield and take the environmental hits and then pass it on tired and spent to the next soma to do the same thing in a perpetual relay race and then get off the track and die. This is what nature wants and this is nature's purpose and it is very important to understand that that the soma that you think of yourself as yourself the body is there to protect the genome and all nature cares about is that we can protect that genome enough to get it to the next generation and allow the progeny to stand on its own two feet and then nature does not care about us and it allows us to die because we've fulfilled our purpose and have no more purpose. So when you hear let's just do what's natural doing what's natural is making a baby making sure that it can walk and eat and then dying. Post reproductive lifespan is irrelevant to nature with that exception. So what we're trying to do at least if you're my age and post reproductively and you are trying to live as long and as healthy a life as possible that is not natural. We are trying to do what is not natural and the only way that we can accomplish that the only way we can really make headway into the chronic diseases of aging is to learn how nature has endowed us with tricks so as to at least get to reproductive age and it has. We know now that there is a common genetic pathway that virtually all life has and especially all animal life and it can be turned on or it can be turned off and it's regulated by nutrient sensing hormones that correlate nutrient availability with reproduction. In the ancient ocean I told you that was one very important fact and that was that glucose was a dominant fuel and these rules were set up when glucose was a dominant fuel and not fat. Fat came later. Fat didn't come until mitochondria became incorporated in other cells because mitochondria are the only organisms organs that can burn fat because it can use oxygen. So you have insulin that is the major nutrient sensor of glucose. You've got million target of rapamycin which is a metabolic pathway that is a nutrient sensor for protein and you've got leptin which is the nutrient sensor for fat. The two main building blocks of life early on that were required to build any life nutrients were glucose as a fuel and proteins and so the nutrients that regulate all nutrient sensors that then regulate a genetic pathway of longevity are insulin and mTOR the nutrients being glucose and protein. Leptin came later and is probably the most important one in humans but it and I get arguments with people all the time on various blogs that tell me oh leptin is just regulated by how much fat you have that's false. It's regulated by every meal. You can double your leptin levels in 12 hours if you eat a high carbohydrate meal and it is those spikes in leptin and spikes in insulin that cause insulin and leptin resistance so that then you have a miscommunication. So just like communication was required for life to form when you had multi-celled colonies, miscommunication is the cause of all disease. There is no exception to that. It is the communication you have to deal with when you're trying to treat somebody. Diabetes is not a disease of blood sugar. It's a disease of miscommunication of insulin and leptin. Sugar is just listening to the orders. Medicine just treats glucose, lowers glucose to hell with insulin and almost always insulin goes up and people die faster. That was seen in the Accord study if you want to look that up and they were puzzled. How could that be? They took more medicine and they had better glucose control and yet they had a much higher mortality rate that was because they were raising insulin. Same thing with leptin. We are not our genes. We are the music that our genes play, genetic expression. Meals regulate genetic expression more than anything. Who does? The meal, the breakfast I ate this morning will change at least 8,000 genes. I've got maybe 13,000. The difference between a man and a woman is about 200 genes. You can take a piano of 84 keys or so and how many different songs can you play? Almost infinite variety. You can take your same genes and you can play the music of diabetes or you can play the music of a long life and healthy life. It will be determined by what you eat because what you eat regulates nutrient sensors, insulin, mTOR and leptin that regulate a longevity pathway. When they were all kept low, which fools your body into believing that you are experiencing a famine, it up-regulates repair mechanisms, DNA repair, intracellular antioxidant systems, autophagy, which is kind of a cellular garbage collection, heat shock proteins, all sorts of things that will allow you to stay healthy and outlive the famine so that you can reproduce at a future more opportune time and we can keep those things going post-reproduction if we keep insulin, mTOR and leptin down. The only way to do that is to keep glucose down and to keep protein down. Fat is a free fuel. It's not really involved in regulating the nutrient sensors. That's interesting. In other words, you can make your body believe that you are experiencing a famine and get all the benefits of fasting, get all the benefits of caloric restriction, but you don't have to do it. Just eat a lot of fat and you get the same benefits and I wrote a paper on that. It's published and it is the way to go. Any questions? I think I have about what, two minutes? Use the bikes on either side. What is the opposition on fiber and sort of access fiber versus moderate amount? Sure. Fiber. Fiber is either soluble or insoluble. Soluble is a fiber that can only be digested by bacteria into short and medium chain fatty acids. So it's fine. It's good. It fills you up, makes you believe that you've eaten something and you actually are going to end up eating fat. Insoluble fiber is just like eating nothing. It just goes in and out of you. It's essentially a non-factor. You might say it helps scrub out the intestines a little bit, so it might have a little bit of benefit, but for the most part, it's no more than that. Another question. Dr. Cressa mentioned yesterday in the debate that you had that the brain, the evolution of the brain was from carbohydrates. He's totally wrong on that. A lot of things that you hear are just, I don't know where they get these things. It could not have been that way, impossible, because we know that our brain consumes a lot of energy. A newborn consumes almost 70% of the energy requirements of that body. The only way that the brain even currently can operate properly but especially could evolve into a larger brain was to start eating a more nutrient-dense food because you can only utilize fuel that has energy over and above what you're going to expend to get it. You have to expend a lot of energy to hunt and gather vegetables. You don't have a lot left over. They've shown that our mouth became smaller and our intestines shortened because our intestines are also an expensive tissue, uses a lot of energy. We had to use less energy in our intestines so that we could put more energy into our brain. The only way to do that is that if we evolved into eating a higher fat diet, this is called the expensive tissue hypothesis. It's widely accepted in paleoanthropology and many other papers now have come out in support of that. That was wrong. The safe starts debate, if I had more time, really boils down to we know that glucose is maintained up until death. You can starve yourself and your glucose will maintain. There is no such thing as a glucose deficiency. That's wrong. All you can say is they might say is that it's more advantageous to eat glucose than to have your body make it. That's what they might say. That's all they could correctly argue. But that's wrong because you will never know exactly when and where and how you will need that glucose. Your body will make it when it needs it and where it needs it and let your body do its thing. It's also when you eat it, you have adverse effects that take place such as it will raise your insulin, it will raise your leptin, you will shut off your maintenance and repair mechanisms, that pathway we just talked about. You want to keep them low and by eating the glucose, you can't keep them low. So there's an adverse effect from eating it as opposed to the gluconeogenesis. Furthermore, with gluconeogenesis, the substrates matter. In other words, if you are making the glucose from amino acids, that is not good. That's why I've always recommended a lower protein diet because I don't want you to burn protein for fuel. All food can be used either to supply the parts that you need or to burn for fuel. You want protein to supply the parts. You don't want it to burn for fuel. To burn protein for fuel, you have to deaminate it, take off the nitrogen, make urea and ammonia, which is a poison that your kidneys then have to get rid of. So we do not want to use protein as a substrate to make glucose, but we don't have to. On a high fat diet, you use the fat to make glucose, the glycerol you can make glucose. The ketones, your body preferentially burns ketones. Studies show that ketones are a much healthier fuel for nerves and your brain and almost every other tissue, including your heart, which will pump harder on ketones than it will on glucose. So between the ketones, between the glucose manufactured from the glycerol, between recycled lactate and pyruvate, you can supply all of your glucose needs. You know, they keep saying, well, glucose is necessary for glycoproteins, blah, blah, nobody's arguing that. We know that glucose is necessary, okay, but it's not necessary to eat it. In fact, it's very disadvantageous to eat it. Your body can make what it wants, when it wants, and it can make it through a easier mechanism, a more efficient mechanism that is a healthier mechanism, i.e., through ketones. Okay, thank you. And now for the second talk by Ron Rosedale, delivered at the Ancestral Health Symposium in San Diego in 2019. The title is, Was Otto Warburg Wrong? Well, for those who don't know the somewhat esoteric reference, Otto Warburg was a Nobel Prize-winning German physiologist of the early 20th century, who noticed that cancer cells are adept at burning glucose and who thought the cancer could be starved by denying it glucose. This view has been recently revived in light of failures of genetic and free radical theories of cancer, but as you'll hear, Dr. Rosedale pokes holes in all these theories and provides support for his own view that cancer is a problem of communication and hormonal and cellular signaling, signaling that allows cancer cells to grow unimpeded. And he suggests how diet can restrain those cancers. Listen and enjoy. Now, right now there's two schools of cancer that are kind of duking it out. There's a traditional cancer is a genetic disease where you get a bunch of mutations and it turns a normal cell into a cancer cells that starts proliferating everywhere. And the other is the so-called metabolic theory of Otto Warburg that is now being picked up by other people like Tom Seyfried, who say that cancer is a metabolic disease due to an addiction to glucose and that addiction to glucose is because of mitochondrial damage. If they can't use the mitochondria, it's stuck using glycolysis. And what I'm going to be showing is that they're both wrong and they both not only are wrong but they both cannot be right. And for that, I want to start out by unteaching you. So here it says the most useful piece of learning for the uses of life is to unlearn what is untrue. Our ability to open the future will depend not on how well we learn but on how well we are able to unlearn. And that will also determine how many more people die unnecessarily from faulty cancer treatment and faulty cancer research. We spent half a century on the war on cancer and have made almost no progress as far as cancer being a genetic disease and trying to figure out which genes cause cancer that got us nowhere. And I'm afraid that the current theory on mitochondrial damage causing cancer will follow the same road and I want to prevent that. So is cancer a genetic disease caused by the accumulation of several oncogenic mutations? And here we show that patients in leukemia could be divided into 11 classes and each of those classes had unique genetic profiles. In other words, almost every case of cancer has a unique genetic array of mutations. There aren't specific mutations for each cancer and that's really important. So if it were a genetic disease we'd be out of luck because every disease then would be a different genetic disease. Here's another study in Cedars Sinai which is right here or close to it. Now investigators dramatically illustrates the complexity of cancer by identifying more than 2,000 genetic mutations in tissue samples of esophageal tumors. The findings reveal that even different areas of individual tumors have various genetic patterns. And I should mention that in non-cancerous esophagus they find almost the same thing. Is cancer a metabolic disease? I'm going to spend a lot more time on this one. A disease, especially a chronic disease of aging like cancer, cannot be genetic or metabolic. To me that's a silly argument. If you look at the origin of life, the genetics of life and the metabolism of life came together. In other words, the genes do nothing. They have to be read and we know about genetic expression. So the genes make proteins, that's all they do. The proteins regulate metabolic pathways which turn around to then control genetic expression. You can't have one or the other. They're always intertwined just like life. Out of Warburg and the Warburg effect. He basically says that cancer relies on glucose and aerobic glycolysis due to mitochondrial failure to grow itself. It was noted initially I found by other than Warburg, in other words Warburg effect probably wasn't even discovered by Warburg, but Warburg was very well known. He came from a very prominent German family in the turn of the century around 1900. His father was a physicist and good friends with Albert Einstein so he had a ready voice. He noticed that the cancer produces and tumors produce lots of lactate meaning they're using glycolysis. Glycolysis is a fermentation process that produces lactate and he went on from there to notice that even if there were a lot of oxygen, there was a lot of oxygen available, cancer would still prefer to use glycolysis and he and his current proponents assumed that cancer had to use glycolysis to make the copious fuel necessary to make all sorts of baby cancer cells. Even when there was plenty of oxygen available, they did not use their mitochondria. Why would that be? Why would cells not utilize mitochondria if they were healthy? Since they can produce in a given amount of time supposedly at least 16 times more ATP than glycolysis and our typical healthy cells if oxygen is available will always utilize their mitochondria. So he said that cancer had to be due to mitochondrial damage and not just mitochondrial damage but irreversible mitochondrial damage and he was adamant about that for many many decades he espoused that and then in 1950s when they found their first so-called oncogene his theory kind of fell into disrepute or at least was kind of covered up and is now being resurrected as they're finding that the genetic theory of cancer is probably not right either. So there's four elements to Warburg's theory of cancer. Cancer cells have irreversibly damaged mitochondria that because of the irreversibly damaged mitochondria cancer cells must ramp up glycolysis that this this effect is unique to cancer and differentiates cancer from normal cells and that this causes cancer. We're going to look at all four of those. So number one, do cancer cells really have significantly and irreversibly damaged mitochondria? Well it's well known that glutamine is a well-known fuel for cancer. Cancer gobbles up glutamine and glutamine is metabolized in mitochondria so that makes the scratcher head a little bit of mitochondrial damage. How can I use so much glutamine? Not just glutamine but lactate. We mentioned that glycolysis is a fermentation process that produces lactate but then the cancer then eats the lactate and here they say the researchers see that lactate is like candy for cancer cells and cancer cells are addicted to this supply of candy and indeed they are and also I might mention that cancer uses lactate for other things too. It uses lactate to penetrate tissues and implantant tissues. The lactate is actually a really good thing for cancer so it wants lactate. Taken together our results demonstrate a link between lactate metabolism and the mitochondria of fermenting mammalian cells. In other words, lactate is utilized in mitochondria. They can't be too damaged. Ketone body utilization drives tumor growth and metastases. Nutrition-deprived, hepatocellular carcinoma cells employ ketone bodies for energy supply and cancer progression under nutrient deprivation stress just like us. You don't have a lot of nutrient, just burns ketones but the thing is ketones are also burned in mitochondria. In other words, mitochondria are apparently used for lots of things here and not just ketones and not just lactate and not just glutamine but fatty acids. Many cancers use fatty acids especially those cancers that have a ready supply of fatty acids such as the omentum, the fat in the belly surrounding the pancreas for instance. Pancreatic cancer we know also utilizes fatty acid oxidation. Breast cancer uses fatty acid oxidation and of course fatty acid oxidation is done in exclusively mitochondria. In particular, the proliferative clonal expansion of cancer stem cells appear to require mitochondrial metabolism related to the reuse of ketones and lactate. In other words, cancer stem cells, we know now that cancer isn't just a single type of cell. It's a society. It's a colony of cells and just like we have stem cells, cancer has stem cells too and it's the stem cells really that perpetuate the cancer and in particular they're the ones that are instrumental in metastases and proliferation and so our effort to research cancer in petri dishes almost exclusively misses the cancer stem cells. Cancer stem cells are a tiny, tiny fraction. You know, a fraction of a percent of all the cells. So when they take a biopsy and put it in a petri dish, the chances of them even getting a single cancer stem cell is somewhat remote and yet it's the cancer stem cells that are really instrumental in determining whether that patient is going to die or live and it's really the cancer stem cells that we have to focus on and cancer stem cells have different metabolism than other cells. In particular, they use a lot of mitochondria. Mitochondroloxfos and here they're saying they like to use ketones, lactate and fatty acids and anything that they can get and ketones and lactate increase cancer cell stemness, driving recurrence, metastases and poor clinical outcome in breast cancer. Lactate and ketone promotes the cancer stem cell phenotype resulting in significant decreases in patient survival consistent with the idea that cancer cells use their mitochondria to generate energy. The metastatic phenotype is directly associated with an increase in mitochondrial metabolism in cancer cells. An increase in oxidative mitochondrial metabolism in cancer cells is associated with tumor recurrence, metastases and poor clinical outcome. Here oncogeneablation resistant pancreatic cancer cells depend on mitochondrial function, a lot to burn fatty acids. The oncogeneablation resistant pancreatic cancer cells by the way is the most virulent kind that kills almost everybody. The entire premise of Warburg and its current proponents such as Tom Seyfried was based on the assumption that an uptick in glycolysis means reduced mitochondrial activity. Why would cells not use mitochondria if they were healthy? The entire theory is based on the assumption that cancer is having to use glycolysis but it can't use mitochondria. We'll see why it uses mitochondria anyway. But does an uptick in glycolysis even mean reduced mitochondrial activity? Here it shows no. The assumption is wrong. There's another alternative and that is this is what is typically thought that you turn up glycolysis and mitochondrial oxfoss is turned down. There's like a switch one or the other. But here they're finding there isn't a switch one or the other, it's both. Cancer is proliferative. It wants all the energy it can get, not just the energy, but the components that glycolysis makes during the pentose phosphate pathway is a component manufacturing pathway from glycolysis. It doesn't even use glycolysis for most of the ATP. It doesn't use it for fuel. It uses it to make components. It's like ribose to make genes and NADPH to make fatty acids and glutathione to prevent oxidative damage. There's two kinds of metabolism. It's not just how you're burning fuel. Thank you. Thank you. But also even more important for cancer or any proliferating cell is how rapidly you can accumulate the parts you need to make new babies. Here, limiting glycolytic ATP production fails to prevent tumor genesis, suggesting that the major role of glycolysis is not even to supply fuel, ATP. Many studies have demonstrated that the great majority of tumor cells have the capacity to produce energy through glucose oxidation in mitochondria. Moreover, mitochondrial metabolism is necessary for cancer cell proliferation and tumor genesis, like we've seen. Thus, despite their high rate of glycolysis, most cancer cells generate the majority of their ATP through mitochondrial function. The observations that cancer cells simultaneously oxidize and ferment glucose has engendered confusion over the role of mitochondrial respiration in the Warburg effect, particularly as Warburg misinterpreted his own early observations and promoted the erroneous idea that damaged respiration is the synquanon that causes increased glucose fermentation and cancer. How many people have heard of Herbert Crabtree? Nobody. Herbert Crabtree was kind of an obscure English gentleman. People that know him are wine manufacturers. All wine manufacturers know about the Crabtree effect. And he lived virtually identical time as Ida Warburg. But Ida Warburg was, as I say, much better known because of his family. And he was German. And this was the heyday of German science. Everybody listened to the German scientists. And rightfully so. They were really smart. They did a lot of really great things. And here's little Herbert Crabtree noticing some things. And in 1929, so Herbert, Ida Warburg started publishing his papers on mitochondrial damage causing cancer in 1926. 1929, Herbert Grace Crabtree states that Warburg postulates a disturbance of respiration, meaning mitochondria, as beating the fundamental cause of the development of aerobic glycolysis. Aerobic glycolysis, again, is when glycolysis is used even when oxygen is present, when typically cells would kind of switch over to more mitochondrial oxfoss. In many of the tumors, the respiration is very high, exceeding that of any tissue, normal or malignant so far examined. This respiration is ineffective in checking the aerobic glycolysis. In other words, they're both being used. He was right on. And nobody was listening. His cancer, the second part of Warburg's theory is that cancer is forced to use glycolysis. Well, we've already cast doubt on that, but we'll continue. Glycolysis has great advantages, not just to make ATP, but first of all, it's anaerobic. And you can burn glucose without needing oxygen. So for those cancers that don't have enough oxygen, of course, it uses glycolysis. But the pentose phosphate pathway is needed to make components that we've talked about. So it's a little detour. It's an anabolic pathway off of the catabolic pathway that manufactures ATP from glucose. You can also make ribose and other components that are really necessary for making any cell, really. But here's a real kicker that even for fuel, you can make ATP far faster using glycolysis than mitochondrial oxfoss. And cancer is dividing rapidly. And if there's enough glucose available, it'll far prefer to continue to use glycolysis, whether oxygen is present or not, because it can make sometimes up to 30 times faster ATP than mitochondria. So in a given amount of time, given the resources, you can actually make more ATP using glycolysis than you can mitochondrial oxfoss. That's a little known. Also, I mentioned that cancer actually wants to use the lactic acid that it makes in fermenting glucose. Also, it's been shown now pretty interestingly that cancer purposely tries to steal glucose from white blood cells. It's competing with white blood cells. White blood cells are rapidly proliferating, too. And we will show that they prefer glycolysis also. In other words, glycolysis, you'll see, is not just unique or aerobic glycolysis is not unique to cancer cells. It's found ubiquitously in all rapidly dividing cells. They all prefer aerobic glycolysis. And so we have white blood cells that are trying to kill the cancer and the cancer doesn't want to get killed. One way that cancer can outpace the white blood cells and avoid being killed by them is to steal the glucose from them. So the more rapidly it can take glucose, the better off it will be. I mentioned this much faster. At least half the carbon atoms required for nucleotide synthesis are derived from the pentose phosphate pathway intermediate ribose 5-phosphate. Ribose is made in the pentose phosphate pathway, the detour of a glycolysis. You can't make new genes, which means you can't make new cells without ribose, which means you have to use glycolysis. What this is telling us is that cancer doesn't have to use glycolysis because of mitochondrial damage or anything. Cancer, like all rapidly dividing cells, wants to use it. It's purposely going out of its way to use glycolysis. It doesn't care if oxygen is present or not, but when it's rapidly dividing, initially, it's going to use glycolysis. And so the whole premise is that cancer is using glycolysis because of mitochondrial damage. It just gets thrown out the window when you find out that cancer is not forced to use glycolysis but is actually desirous of it. Is the Warburg effect unique to cancer? Does it differentiate cancer from normal cells, which is the third part of Warburg's theory? The answer to that is absolutely not. It's in all rapidly dividing cells. It's in rapidly dividing white blood cells when they're called upon, the T killer cells, the NK cells, all the cells that rapidly divide to try and fight an infection or cancer has an almost identical metabolism to cancer. Also, when we're a fetus and you start out, sperm hits the egg and they start rapidly dividing. Same metabolism and they use aerobic glycolysis. The Warburg effect is no Achilles heel. It's common to all rapidly dividing cells, including immune cells. Now mitochondrial damage, what Warburg noted, was correlated with cancer. I cannot tell you how many times correlation is confused with cause and medicine. You see that with cholesterol. You see it with calcium. It's all over the place. And in other sciences, you just don't make that mistake. But in medicine, it's made all the time, and this is just another example of it. Yes, mitochondrial damage may be correlated with cancer, but does that mean that mitochondrial damage caused the cancer or possibly did the cancer actually cause the mitochondrial damage? And we'll find it's actually the second. We have found that mitochondrial dysfunction in cancer cells correlates with abnormally increased mitochondrial replication. Okay, you have rapidly dividing cancer cells. That means you have to have rapidly dividing mitochondria. Rapidly dividing mitochondria has less quality control. You're going to have more damage to mitochondria. And indeed, also, that mitochondria are destroyed by lysosomal degradation, leading to the production of highly energetic nutrients to support cancer cell growth. It's finally promotes the onset of Warburg glycolysis and cancer associated fibroblasts because of the mitochondrial dysfunction. Translation. The cancer eats mitochondria from their neighbors. They're nice and nutritious. So when they're multiplying rapidly and they want to use glycolysis, there's no need for the mitochondria. They'll eat them. Obviously, producing fewer in number and some damage to the mitochondria because they're being used as fuel. The cancer is actually causing whatever associated mitochondrial damage there might be. Also, they're talking about the cancer associated fibroblasts, by the way, are non-cancerous cells. We find that cancer is a society and it's made up of cancer cells and non-cancer cells. And the non-cancer cells are basically captured and coerced into doing metabolic functions that the cancer wants. And cancer will eat the mitochondria of the fibroblasts, forcing them into glycolysis so that then cancer can use the components of that glycolysis like ribos for themselves. Slavery, basically. Now, Tom Seyfried is probably the leading proponent of this so-called metabolic theory of cancer and mitochondrial damage. And he's written papers currently. And he uses the results of hybrid experiments that Warburg didn't have the use of at that time. So, I want to look at some of the hybrid experiments. So, this is a paper in 2015 from Tom Seyfried. And he states that in contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease according to the original theory of Otto Warburg. The findings are reviewed from a nuclear cytoplasm transfer experiment that relates to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease. We're going to see that that's also a correlation. Tumors reappeared in some clones after extended cultivation of the cells in vitro. The effects of the unnatural cell culture environment on mitochondrial respiration could account in part for the reversion to tumorigenicity. So, what these hybrid experiments do, they take a cancerous nuclei and fuse it with a non-cancerous cell and they find that the cell does not become cancerous. Well, they're thinking, well, if cancer is due to genetic mutations, if you take a cancerous nuclei with all the genes and stick it in a non-cancerous cell, it should become cancerous. But he's saying it doesn't for a while. They carried out these experiments for like three, four months or three, four weeks. But he did notice that after a while, the cells did become cancerous. And he's blaming that on the unnatural cell culture environment on mitochondrial respiration, which could account in part to the reversion to turning into a tumor. In other words, the effect only lasted for a while and he's blaming the rest on some weird thing on culture. The other part is if you take a non-cancerous nuclei and put it into a cancerous cell or fuse it with a cancerous cell, the cell will stay cancerous. What he's saying is that cancerous resides in the cytoplasm and not the nuclei. And he's saying this is really good evidence or he calls it almost proof of the mitochondrial cause of cancer. Well, there's another thing wrong with that. Number one, there's a lot of other things in the cytoplasm other than mitochondria, such as ribosomes that make all the enzymes that carry on chemical reactions. So you set up the genes, make ribosomes that are in the cytoplasm that make proteins in their factories. They keep churning out the proteins. The cytoplasm continues to do its job. And you have all the chemical reactions that are continuing to take place because the ribosomes are still there. The factories that make all the enzymes that dictate all the chemical reactions that are taking place, they didn't know about this paper apparently. Preservation of normal behavior by enucleated cells in culture. In other words, if you take the nucleus out of a cell, it just goes about its merry way as if nothing has happened for at least three to four weeks. It takes that long before the genes can actually manufacture new ribosomes that can manufacture new enzymes that can then dictate different chemical reactions and make the cell do something different. In the meantime, the cell is just going on its merry way with the stuff that's already been made previously. This is why it took four weeks that, you know, Tom Safry noticed that, oh, yeah, tumors reappeared in some clones after extended cultivation, like four weeks, the effects of the unnatural cell culture environment. No, it's not the effects of the unnatural cell culture. It's the fact that cells are not able to make new proteins. So the cyber experiments you can throw away, they mean zero. Suppressing mitochondrial function, conversely, inhibits cancer rather than encouraging it. Oh, I've only been going for 25 minutes. I got 15. So 12 minutes. Do I hear 13? 14. Okay. Because I don't need it all. We know now that one of the really good ways to suppress cancer and to treat cancer is actually to inhibit mitochondrial function. Metformin, we know, inhibits mitochondrial function. Now it's being used quite extensively to treat cancer and really extend life. It's being used as a life extension drug. One of the major reasons that extends life is by suppressing mitochondrial function and inhibiting cancer. Antibiotics. I mean, mitochondria used to be like bacteria that got gobbled up. And antibiotics will kill, not kill, but inhibit the function of mitochondria. All of these things they find inhibit cancer stem cells, and that inhibits cancer and metastases. And metastases is what kills everyone. And so it kind of flies in the face of this mitochondrial theory. In other words, injuring mitochondria, inhibiting mitochondria, hurts cancer, not causes it. The mitochondria damage theory is just another genetic mutation theory. They hear they're saying, well, you know, we don't believe in genetic mutation, but that's what they're talking about when they talk about the mitochondrial theory. They're saying it becomes mutated and irrelevant. It doesn't work. It's an offshoot of the mitochondrial free radical theory of aging. My background is in the biology of aging, and I can tell you right now that the mitochondrial free radical theory of aging is passe. It's like archaic. Nobody really believes in it anymore. Here, findings suggest that the age-dependent mitochondrial dysfunction is not sufficient to limit lifespan. Mitochondroreactive oxygen species are not always deleterious, in fact, can stimulate pro-longivity pathways. They find that like we take too many antioxidants, you actually can increase your risk of cancer. And you actually shorten your lifespan. That we need oxidation. The oxidation elicits what's called a mitochondrial damage response. That, you know, it's like exercising. You damage your muscle, you get stronger. You know, you damage the mitochondria, they actually get stronger. You get healthier. And here what they did is they, in mice, the proofreading function of the DNA polymerase was mutated. And these mutator mice are born with a mitochondrial mutation burden 30 times higher than that of wild-type mice, yet they lack overt phenotypes and have a normal lifespan. In other words, causing mutations 30 times more rapidly doesn't hurt anything. That's not where the problem lies. It calls in the question whether naturally occurring slow mutation of age-related mitochondrial DNA mutations has a leading role in causing aging rather than representing only one of the types of damage accumulation that accompany aging. That's true. So Warburg interpreted tumor lactate secretion as an indication that mitochondrial oxfoss was damaged. However, numerous studies, including Warburg's original work, failed to demonstrate defective respiration as a general feature of malignant cells. Instead, mitochondrial respiration and other mitochondrial activities are required for tumor growth. In fact, help tumor growth, especially cancer stem cells. Furthermore, in non-cancer cells, the Warburg effect is a reversible phenomenon tethered to proliferation, indicating that it reflects proliferation associated changes of metabolism rather than a unique feature of malignancy. It's kind of a summary of this. So if cancer is not a disease of glucose and mitochondria, just like, cancer is not a disease of glucose and mitochondria, just like diabetes is not a disease of glucose. Coronary disease is not a disease of cholesterol. Osteoporosis is not a disease of calcium. Why not? Because life isn't in the parts. That's not where life is. Life is in the interaction of the parts. It's in the communication of the parts. All disease, like life, is due to communication or miscommunication. That's where you have to look. You have to look what's being miscommunicated between the parts. It's not a defective part. If it's defective mitochondria, then why are they accumulating? Why aren't we getting rid of them? Where's the communication that allows mitophagy, so-called the gobbling up of defective mitochondria? Everything's going to be in some sort of defective communication that otherwise would preserve life and health. Here's what's missing. This is metabolism. This is communication. Somewhere in here, there will always be a problem. It's not going to be in the mitochondria. It's not going to be glucose. It's not going to be calcium. It's not going to be fat in arteries. It's not where you look for disease if you want to really get to the root of it. So if cancer is not a disease of fuel or mitochondrial dysfunction, then what? Well, it looks like I don't have any time they're saying. Okay. About five minutes? Ten minutes. Seven minutes. Okay, seven minutes. Okay. Cells don't mutate into cancer. They start out that way. That's one clue. We come from an ancestral history of unicellular organisms whose main directive was to out-replicate their neighbors. All of that predilection is in all of ourselves. It has to constantly be suppressed. You don't have to mutate cells into cancer. All you have to do is prevent them from not being cancer. And that's what happens. Cancer is obviously a disease of growth. So it would make sense to look at what controls growth. And sure enough, Hans Krebs, you've all heard of the Krebs cycle, very famous German who was actually a protege of Otto Warburg. And he wrote a biography about a Warburg. But he stated, and rightfully so, and he also won the Nobel Prize for his citric acid cycle, the Krebs cycle, also another German, Warburg neglected the fundamental biochemical aspect of the cancer problem is the mechanisms which are responsible for the controlled growth of normal cells and which are lost or disturbed in the cancer cell. No doubt the difference in energy metabolism discovered by Warburg are important. But however important they are at the level of the biochemical organization of the cell, not deep enough to touch at the heart of the cancer problem, the uncontrolled growth. Warburg's primary cause of cancer may be a symptom of the primary cause, but is not the primary cause itself. Exactly right. This was actually taken out of another book, tripping over the truth by Travis Christoperson, who used it as an example of how people wouldn't look at the truth when they saw it on water out of Warburg. It was actually, he was advocating for Otto Warburg and using this as an example of why people were ignoring the truth. But in fact, this is the truth. Now we're talking about this, you know, back, what is this now, 20 years ago? I was talking about what insulin does. Insulin is a growth factor and it causes, it affects cancer right there. Insulin increases cellular proliferation. What does that do to cancer? It increases it. And then in teleclinic with Joe Merkola in 2005, two of the major factors that will determine whether a person has cancer are the amount of sugar and insulin. Sugar is just listening to orders. It's listening to orders from insulin and leptin. You get insulin and leptin right, your sugar is going to be right. However, the converse is not necessarily true. You can bring down sugar with drugs, but you're not really improving that person's health if it's causing insulin and leptin to increase, which is what almost all the drugs do. All you're going to do is increase your risk of cancer. And then I see stuff like this that drives me crazy. This was just published August 3rd, 2019. In a new study, researchers have demonstrated for the first time a causal link between high insulin levels and pancreatic cancer. They still are not linking growth factors to cancer. And insulin, by the way, you've heard of IGF, insulin-like growth factor produced from growth hormone. We'll talk about growth factors, growth hormone and IGF. Obviously, that ought to be linked to cancer, and it absolutely is. Dwarfism. This is a group of people in Ecuador that have a syndrome called Leron syndrome. It's a defect in the growth hormone receptor. So they have low growth hormone, and cancer is almost unknown. And this doctor, Guervera Guire, noticed this. And they're talking about why Leron syndrome is almost completely avoided. Cancer and diabetes, it could be because cells must invest energy in either trying to grow and reproduce or in repair and preserving themselves. Ponies live longer than horses, small dogs live longer than large dogs. It's a fascinating field in aging. We notice a lot. And a good friend of mine who won the Methuselah Prize in aging research, biggest prize in aging research, did so by mutating a mouse so that growth hormone was suppressed. And these mice lived over four years, normally two years. It's the longest living mouse. Maybe you actually got them to live longer than that. So there's a huge theory in aging that growth plays a huge role in the aging process itself and cancer. Ungrowth hormone increases longevity. If you restrict growth hormone, you limit and inhibit cancer, including prostate, breast, brain, and lung cancer. IGF is associated with cancer, very much so. In fact, almost all cancers have some sort of IGF signaling increase. Leptin, not a lot of time to talk about Leptin, but Leptin is at least as important as insulin, and it is a growth hormone also. And it works through proteins. Dietary protein increases IGF, increases Leptin, and most of all increases target of rapamycin. Target of rapamycin is not a hormone. It's a kind of a switchboard where all the other growth pathways and nutrients kind of feed into it, and it then makes the decision in all cells whether that cell should replicate or whether it should upregulate maintenance and repair. We want repair. We don't want cells to replicate out of control. They're finding now that the vast majority of cancer cells have upregulated target of rapamycin. And so they're using drugs to lower the target of rapamycin, like rapamycin. That's why I'd call it target of rapamycin. Rapamycin is a natural product actually found in the 70s. Only recently found what it does, and it lowers the target of rapamycin, and it greatly decreases cancers. Kind of a new drug for cancer. I mentioned that. It is one of the most common molecular alterations in human cancer is an upregulation in the TOR pathway. Emerging studies indicate that the TOR modulates mitochondrial function. So any of the mitochondrial damage that you see, a lot of it is due to TOR being too high. So that when TOR is too high, you don't gobble up defective mitochondria. Lower TOR, you increase autophagy and mitophagy, you basically eat all your junk. TOR is responsible for ketosis. A lot of stuff is going on in ketosis. You have to lower TOR to produce ketones. Here is a study that was interesting that showed that longevity and health were optimized when protein was replaced with carbohydrate. In other words, when you between protein and carbohydrate, you will increase longevity by lowering protein as opposed to carbohydrate. That doesn't mean carbohydrate is good for you. It's not. But protein is what actually controls almost all of these growth factors, including IGF and M-TOR. One minute. We see that a long lived diet is a low protein diet, and we have found there's a mechanism how that may be working. TOR, a recent study appeared in Nature showing that feeding rapamycin to mice inhibited TOR and extended their lifespan. Here they're using it now for breast cancer. You can read more about TOR in a talk I gave in 2006, protein, the good, the bad, and ugly. It's all over the internet. The best drug to reduce TOR signaling to slow aging and the chronic diseases of aging associated with it is already available, avoid high protein. Avoiding high protein is probably the most important thing you can do to both treat and prevent cancer. Lower TOR, increase autophagy and mitophagy, eat and recycle your own damaged proteins. The protein content of breast milk, how much protein should you eat? Well, the protein content of breast milk is about one gram per kilo per day. Nobody will ever have more rapidly dividing cells than when you are an infant. Nobody should need more than one gram of per kilo per day. In fact, most of us certainly as adults shouldn't need more than 0.75 kilograms or if you're 75, 0.75 grams per kilo per day. If you have cancer, I'd go down to even six grams per kilo per day. Your health and lifespan will mostly be determined by the proportion of fat versus sugar you burn over a lifetime and that will be determined by the communication of insulin, IGF left and especially TOR. Cancer is not glucose driven, it is not driven by mitochondrial dysfunction, it is driven by growth signals, particularly TOR and that is most controlled by the protein that you eat. You've got to be careful of your protein. Done. Thanks. Thanks for joining us on this episode of Ancestral Health Today. We hope you enjoyed our discussion on how evolutionary insights can inform modern health practices. 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