Dr. Joel Rosen:
Hello everyone, and I’m really excited to introduce our next guest, Georgie Ding Cough, he probably doesn’t need an introduction to you. But for those that may not know who he is, his academic training is in Computer Science and Mathematics. However, due to his strange circumstances of events, his first job out of college was in the biochemical outfit called National Biomedical Research Foundation located on his campus, and at his job, he was one of three to four IT specialists that was tasked with developing the projects you need Prot and PIR under the guidance of 40 to 50 top medical professionals and renowned biochemistries biochemist from places such as the NCBI, NIH and all others. In order to better implement the project and also establish rapport with the stakeholders.
He decided to embark on a self study project in the field of bioinformatics and physiology and under the strong encouragement of his supervisors hailing from the institutions mentioned above, and under their guidance, he read several medical school level intro books on biochemistry, physiology endocrinology, while also auditing a number of biochemical class biochemistry classes taught by those stakeholders.
Thus, over the period of three years and entirely through self study, he managed to acquire sufficient control over the Health Science lingo, so that he could better understand the medical aspects of the IT project and was also reading scientific publications on PubMed by himself. This interest in health topics continued after he left his job, while researching aspirin and its effects on the brain circa 2011 11.
That’s when he stumbled on Ray Pete’s website and articles and his ideas on bio-energy as opposed to genetics. And it’s controlled by dietary and environmental factors, such as causal health factor disease, and even aging immediately appealed to Georgie, and since 2011, he’s been doing research in that field. That’s what we’re really excited to be talking about today, Georgie. Thank you so much for joining us here on this podcast today.
Honored to be here. Thanks for inviting me.
Dr. Joel Rosen:
Yeah, so we were having a background and conversation about what we should talk about today. We’re talking about bio and energy and an energetic perspective. What I’d like to start with Georgie sort of giving your definition of what it means to be metabolically flexible, and then we can kind of go into how we produce energy and what goes wrong and how that impacts chronic health.
So the metabolic flexibility, I guess, to me, the best example is a young healthy child. Basically, they will oxidize whichever one of the two major macronutrients you give them at the time either fats or, or glucose. And of course, we can also oxidize protein, but it gets converted to glucose, ultimately, by oxidizing your fats or glucose. So I think everybody who’s been around should or has children has noticed that children, you know, processed food very quickly, they get hungry very quickly, they can also get tired very quickly, but they also recover much faster.
And let’s say if you don’t provide them with glucose for a period of time, they will get a little cranky here because they’re kind of switching over to the observation of fat. But but you know, the energy is still there. And then when you feed them, they usually try, they usually get sleepy, and then they fall asleep, they recover and they wake up, they’re ready to go again. That’s the kind of process that we’re seeing start to degrade as age advances.
And, and with doors, I think the late 30s, maybe even the mid 30s. We’re starting to see various degrees of insulin resistance in the in the general population, if they’re not even if they’re not formally diabetic, or have a health problem. Yeah. In other words, they’re seeing Used to be both the accumulation of extra fat especially around the middle section, and also a tendency towards inability to properly oxidize the glucose.
And a lot of a lot of people interpret that as Oh, I just need to cut down on my glucose intake. But a child can handle this glucose intake without any problems. So something is happening metabolically or, you know, maybe even genetically, as you said earlier, that is that is shifting us towards insulin resistance as we age.
And there’s been a, you know, great debate going on for at least for at least 100 years. What exactly is causing that? And there was a gentleman called John Randall, who published the study on the so-called infamous Randall cycle. He said: ‘At the very base there’s a very fundamental level of biology, there’s competition between fatty acids-free fatty acids and glucose for oxidation because they’re competing for cofactors.
They’re competing for the cellular machinery that is in the cell that basically converts all fuel that we’re eating into carbon dioxide, and water. Ultimately, those are the final products and of course, ATP. So if you’re, if the cell is getting a supply, because that’s the only thing the cell can do is whatever is being supplied when there’s fuel. If you supply glucose, the cell will oxidize primarily glucose. If you supply fat to the cell, or oxidized, primarily fat, if you supply both, then it really depends on two things: what’s the relative amount of each.
And I guess that threshold, that ratio, the ideal ratio, is different, not ideal, but the ratio, which will become metabolically inflexible is different for everybody. But if you supply, let’s say, a ratio of three to one fatty acids to glucose, the cells will mostly oxidize the fat. And if the glucose amounts are beyond what the cell can currently oxidize, given that it’s oxidizing, mostly fatty acids, there’s something that needs to happen to the glucose and the two pathways are, one is because the glucose builds up. And when it comes out of the the pathway called glycolysis, we have a buildup of pyruvate. Now, because the process of oxidation creates these.
the metabolic process creates these reduced equivalents, known as NADH NADPH FADH (two), and they need to be out there to carry in the electrons, the energy from food, it needs to be met with oxygen in order to release it. And that’s the whole process of conversion, when there’s a buildup of these reduced equivalents because the metabolic chain is occupied. By oxidizing the two fatty acids, whatever reduced the coolants, glucose producers have to go somewhere.
And the two pathways the cell has is one to synthesize fast with them. But in order for that to happen, they first need to go through the Krebs cycle. But the Krebs cycle is part of the mitochondria. And when we see people that are basically stuck in oxidizing too much fat, the byproducts of glucose metabolism from glycolysis cannot get into the mitochondria, they start to build up in the form of pyruvate. Also, the reduced equivalents. The cell says, Okay, I need my oxidized cofactors, such as NAD plus, because if I if NAD plus levels drop below critical level relative to NADH, which is the reduced equivalent, then the cells simply die. So for emergency oxygen, the cell uses pyruvate in order to oxidize NADH back into NAD and also FADH back into FAD. And in the process, it produces lactate. We’re seeing this process in order continuous spectrum. In other words, the levels of lactate are probably rising. Progressively, if you look at people that are progressively older.
We also see that in people that are progressively sicker. So which means that whenever there is a some kind of a problem in the organism, the glucose, the oxidation of glucose is inhibited. And when a person is relatively healthy, they don’t have an official diagnosis. This usually gets diagnosed as metabolic inflexibility. So they give oxidized fat perfectly fine, but if you give them glucose, they don’t seem to oxidize it. They seem to waste it, quote, unquote, into lactate, and maybe even the synthesis of fat.
And the question is, well, what’s causing that? And this gentleman Randall said, well, there is under behind the scenes, there isn’t an oversupply of fatty acids. And until that thing is not reined in, you will never be able to oxidize glucose properly again, it also manifests disease and resistance, right? So in young children, when you feed them glucose after a long bout of fasting, glucose lowers the levels of free fatty acids because glucose and glucose release the rising insulin, insulin is anti lipolytic.
So eating sweet things for young children. Listen, the rise of insulin, which lowers lipolysis, means there is less supply of fatty acids to the cell. Now the cells can oxidize glucose. That’s what happens in children. That’s what should happen to Healthy People. For older people, that does not seem to work as well. We call this insulin resistance. So even if a person, let’s say, been eating a fatty acid meal for let’s say, 10 hours, and then after that they switched to a sugary meal or like milk or carbohydrates.
They don’t get the same lowering of like bonuses that a young person does. So lowballs have been Isn’t lipolysis in these people with metabolic flexibility or diseases that tend to be chronically elevated. Consequently, according to gentleman Randall, they will not be able to properly oxidize the glucose. In other words, they will not be able to switch completely over to oxidizing glucose the way young children are. And if you start looking through parameters, 1000 studies on PubMed, and now showing the same process, this metabolic flexibility, but in a much more extreme form, we’re seeing it in diabetes type two, we’re seeing in cancer, we’re seeing the cardiovascular disease, various neurodegenerative diseases, see, all of them seem to be at the very base, metabolic.
And the reason I say that is because some of these studies also tried to force the sale into metabolic possibility, usually by administering pharmacological agents that either inhibit lipolysis, or block the fatty acid oxidation directly in the beta oxidation level, there’s a drug called Ito Muxer, currently used for heart disease. There’s also another called Meldonium, which inhibits the transport of fatty acids from mitochondria. All of these have the end effect of limiting the supply of fats to the cell. And when you do that, even in very severe diseases, what is an animal human model? The cell seems to revert back to restore its metabolic flexibility. So there’s there’s some, I think, I would say decent evidence.
The gentleman Rando was Mr. Randol was right. So there’s nothing structurally defective about this, even though it can happen, depending on how long the metabolic disturbance goes for. But, you know, if for most cases, if you give the cell a break by limiting the oversupply because it’s really oversupply. It’s not the fatty acids that have grown the series that were over supplying them and in the cell, it has to oxidize them. And then while this is happening, they cannot oxidize glucose. So when so, Mr. Rando says, if you have metabolic flexibility, it means you’re over supplying fat to the cell to set the cells over oxidizing fatty acids. As long as that’s the case, you will be metabolically flexible enough to mostly oxidize fats. If you want to restore metabolic flexibility, you have to limit the supply of fat or limit their oxidation. Several studies have already been done with this, demonstrating that, in cases where they looked at both animal studies and humans, this seems to be the case that may require high doses of these fatty acid oxidation inhibitors or beta blockers.
But it seems to work at least at least for the cases that have been so far. So biology theory says, if there’s metabolic flexibility, it’s due to oversupply of fat that oversupply of fat could be due to a number of different factors. Whether you’ve already over accumulated fat, in other words, you’re obese, in which case your baseline levels will be higher, because you just simply carry more fat, or you under stress, because when under stress, especially chronic stress, cortisol and adrenaline will be higher than baseline higher them optimal. And one of the biggest, one of the main roles of adrenaline is to increase lipolysis. So you will be over supplying fat. And that’s, that’s really energetic.
There’s nothing wrong with that mechanism, because it was meant for us to be able to handle acute stress. The problem is when it becomes chronic stress, because when you when you do when you do this for a long time, then over time you end up in this metabolic inflexibility, but Mr. Rando is saying, Don’t worry, nothing’s damaged yet, all you have to do is kind of like shock the system a little bit and switch it over, you know, help it switch over into the other direction towards oxidizing glucose. Now, of course, if you stop administering these, if you don’t change the underlying conditions, in other words, if the person remains obese, or if the person is under chronic stress, etc, when you administer and these agents that inhibit that inhibit the oxidation or supply of fats, it’s just a patchwork, it’s not going to fix the underlying problem.
So the underlying problem is that chronic stress, chronic inflammation, which may come from many factors, but the polyunsaturated fats are very are a great source of inflammation, or the person who has accumulated more than optimal amount of fat, and then until that is lost, then they will be in a state of oversupply and fats to their sales for oxidation. So that’s, that’s pretty much it in a nutshell. So these things are reversible, at least in the initial stages. They’re metabolic in origin, but their ultimate cause can be a number of different things usually having to do with chronic stress, poor diets, or just, you know, already established chronic conditions that basically keep them it keeps the HPA access activated, as you mentioned.
Dr. Joel Rosen:
right? No, thank you so much for that explanation. So that’s all things created equal, not considering the quality of the sugar, the quality of the fat, um, but just from a from a, I guess, a genesis of how we got here, because now we’re, I could see as a listener might be thinking okay, perhaps because we vilified sugars, and we’ve gotten into getting into ketosis fast and fast doing these intermittent fasting and increasing our fat intake.
But I would argue that it started before that when we vilified fat, and we started so maybe it kind of got us to how we got here from from having this whole Randle cycle, which is saying we’re preferentially we’re not preferentially too much demand to have to do beta oxidation. And then when you combine that with getting carbohydrates or unhealthy sugars, that creates a load on the system where metabolic flexibility breaks down, and insulin resistance ensues, or it’s anyways, kind of gets us to how maybe the evolution of how this came from when we started off with, with having low fat diets and going from there. I think
it started in the early 20th century. If you look at some of the older publications and how people ate back in the day, they didn’t worry that much about macronutrients or how much fat or sugar they were taking, they were eating, you know, according to taste. If you look at some of the older commercials from the 1940s, and 50s, these housewives were geared to housewives and saying, You need to feed your children at least five or six meals a day. We did milkshakes, ice cream, drinking several bottles of Coke a day, old, and people were not obese back in the day, at least per capita, which is the reason that we’re seeing today. Something happened I will say in the 1950s, where I think that’s when the cholesterol hypothesis first started forming. Were basically the the outset, Big Pharma really started that.
But for whatever reason, medical professionals shifted towards limited lipid-like molecules and started with cholesterol, saying that, yes, cholesterol and high cholesterol are associated with cardiovascular disease. And that is true, but associated, does not mean causative. And there have been several cases that have demonstrated that it’s only oxidized cholesterol, but it’s problematic. But oxidized cholesterol only happens when you have a normal amount of reactive oxygen species that generate other ones. Cholesterol by itself is absolutely crucial for the cell. It’s part of the bilayer.
The bilayer lipid membrane is a precursor to all steroids, right. So it’s clearly something that the body definitely needs. But I think a lot of cholesterol gurus think that if you eat too much fat, you will get fat. And then I would say around the 1960s, there was also another push to switch the saturated fats with bullet to replace the saturated fats with polyunsaturated or monounsaturated, because there was another study that demonstrated that saturated fats are associated with cardiovascular disease, even that I think that has now at least the latter part has been debunked.
The cholesterol thing is still there. But recently, the FDA – not many people know – has changed its four-decade-long stance on cholesterol and said, You will no longer need to worry about dietary cholesterol. It’s not the dietary cholesterol that is basically causative of cardiovascular disease, something else is happening with the cholesterol that you already have. And if you don’t have it, you can synthesize it yourself. So we need to worry about that something is going on in sick people that are prone to cardiovascular disease, they have more cholesterol synthesized and also more close to oxidized.
And it’s the oxidized cholesterol, especially seven keto cholesterol, that’s, that’s causing these lesions in their in their arteries. So a generous shift from eating fat-rich, but saturated fat, of animal origin. in our diet, especially and also decent amount of carbs. If you look at the macro origins of the early 20th century, they were about equal percentage wise to calories, about 30 to 33% of each. And then as the century progressed, I will say around the 1950s, there was there started being a push towards lowering the amount of fat lowering the amount of cholesterol, and then it was in the diet.
There was also a push towards eating more polyunsaturated fats, because some studies there showed, and I think that’s the mechanism is true, but I don’t think it’s beneficial as that bullet saturated fats tend to lower cholesterol. So so this, the campaign that that that unfolded over several decades, made the switch from a roughly equal percentage of macronutrients, calorie wise and union fat, has mostly saturated animal origins to basically lowering the total amount of fat in the diet. And switching over towards polyunsaturated fats is monitored already, but usually partially because, especially of corn oil, because there was cheap and widely produced oil at the time.
And to this day, it is because it’s a crop that is subsidized by the government. Soybean oil is another one. So soybean oil and corn oil are the oils that were heavily advertised in the 50s and 60s and 70s. There were even commercials called Mazola. Your family Mazola is a Cornell product sold by Gallup because you know that she and I think that continued and there was another crazy thing in the early 80s saying that we need to completely eliminate fat.
And it was this craziness about eating almost zero fat diets, I would say in the 80s and early 90s. And then we saw the opposite switch towards the Atkins diet, which I will say it was in the 90s. And now it’s kind of like I guess there’s this confusion because everybody has been trying to write that nothing seems to act to effectively cure the disease. So everybody’s up, you know, up there up in their arms and saying, okay, so what do I do?
What should I eat? Everything seems to cause disease, everything except eating natural food of mostly animal eating natural food in roughly equal proportions calorie wise, in terms of the macronutrients and the fat mostly saturated from animal or So that’s the thing that worked. If you look at the curve of cardiovascular disease, it was puny in the early 20th century compared to what it is now.
Now, it’s not entirely dietary, there’s, I think I will say, these days, we’re also in there a lot more environmental stress, which ultimately translates to biochemical stress, which means we’re exposed way too much, to way too much blue light, I’m sitting in an office right now, this light above me is heavy, the blue spectrum, Multiple studies have demonstrated the blue light is toxic to the mitochondria.
At night it suppresses the production of melatonin, so it interferes with our sleep. That’s when there’s a causal link now between exposure to blue light and even minor amounts in type two diabetes, cardiovascular disease and cancer. So if you’re sleeping at night, they’re saying, if you have like a watch or another device that’s near you, and it’s got produce, or just a tiny little beam of blue light, that you can see what your eye, that’s already bad enough.
But we’re exposed on a daily basis to much more of that, because we’re sitting in offices with these fluorescent lights that are mostly blue spectrum, unlike the sunlight, which is heavier in the red and the orange spectrum, which is stimulated to the to the mitochondria. I think we got to a point where things were mostly working. And people were going to the doctor rarely to fix a problem that was mostly a traumatic or infectious origin, not so much chronic disease, to now where we’re basically mostly chronically ill, most of us, and we’re in this precarious position.
So there’s this famous analogy, he used to be used to look like a you curve, you’re at the bottom, it’s very stable, you may swing a little bit to each side, but then when it’s just a little bit of push, you’re gonna go back into the middle, which is a stable thing. And that’s the natural position. Now, health seems to be switched to the inverted yield curve, we’re sitting at the very top of a very precarious position, or even a slight nudge in each direction, it’s going to send you into the precipice.
I agree, I think that’s what we are in this situation. I didn’t one of the reasons is that what multifactorial, but one of the reasons is poor diet, chronic stress, and surrounded by spending too much time indoors, and surrounded by devices and, you know, things that are that are stressing us out chronically. And when we’re chronically stressed out, we will be shifting the rental cycle towards leisure, mostly fat.
Dr. Joel Rosen:
Yeah, no, that’s a great explanation, I would only add on to not so much that the sky is falling, but we have EMFs pesticides, iron rich foods, lack of minerals in our soils, which just compounds the high fructose corn syrup, which now is no longer just what you said. But it’s all these other things that we have to contend with.
So maybe that’s a good segue into bringing back the importance of having a clean burning fuel and not vilifying sugar as much as it has been and maybe partitioning out why sugar versus high fructose corn syrup is potentially the preferred fuel to get you to be more metabolically flexible, which is paradoxical to what people are hearing and learning and doing. So maybe kind of enlighten us on that, Georgie.
So the first example that I bring to when I start arguing with people about how bad glucose is for us, I say, when you go to the hospital, and you’re in a pretty precarious situation, one of the first things they’re going to do is hook you up to an IV glucose drip. How can this I mean, even if you’re diabetic, how can sugar be that bad for us if that’s the actual standard procedure in the ER?
The second thing I want to bring up is that so again, it’s not a shoe, what the problem is the fact that we’re not metabolizing in property. But the way to correct the problem is not limited glucose, because the cell doesn’t need glucose, especially our brain. To this day, I don’t think it’s been completely resolved. How can the blood brain even survive long term strictly on ketones? I know I can do it in a couple of months. I know it’s been done. The ketogenic diet is used to treat and bring under control, treating resistant epilepsy. But from what I understand from doctors who are working in those words, even they’re saying,
This is not something that can be done in a lifetime over life. We love these people around the world. We’re giving them a ketogenic diet for three months, they’re always being monitored, they can get dehydrated, they can get like into nutrient deficiencies. So being under a heavy monitor is not something to do on the outside by yourself, in risky, risky way. So often, we get them stable, and they start responding to drugs, anti seizure drugs, then we stop that diet and they go back to their normal diet, which has sufficient amount of carbs. And when asked, well, what sufficient amount? Surprisingly, they gave me the answer.
They used to be given in the early 20th century, they’re saying about 30 to 35% of their daily daily calorie calorie intake. So I think the reason we’re demonizing sugar is because we’re seeing high blood glucose into the, into the blood in front of the diabetics, and many other people, especially people under stress, but several studies already demonstrated that the high blood glucose in the blood levels of diabetics is not of dietary origin, it is mostly due to gluconeogenesis which means that even if you in fact more than 90% of the of the glucose present in the blood of type two diabetics is of non dietary origin.
So what this means is something and something in the body of these diabetics that’s caused them to auto over produce glucose. And the question is, what is that thing? Recent studies demonstrated that this is the hormone cortisol. Cortisol is involved in both training muscle mass and various other tissues because they’re composed of amino acids and then shoveling them over to the liver where the process of gluconeogenesis Dmns This amino acid converts them into glucose. So the type so the body that diabetics is what is causing the high blood glucose. The question is why? Well, several studies have suggested that there’s a perceived actual lack of glucose inside the cell. Because if the cell is stuck in the render cycle, oxidizing mostly fat, it still wants glucose, it uses glucose for a number of different intracellular pathways repair and maintenance, the PARP pathway is heavily dependent on the availability of glucose. But if glucose is not available, or is being wasted into lactate, as I said, Because of over over oxidation of fatty acids, the body perceives that as a relative deficiency of glucose, it says, Give me more.
So the worst thing you can do in such a situation is limit the dietary glucose even more. Now, supplying more doesn’t necessarily mean you’re going to fix the problem, because you still have to address the fact that it is over oxidation of fatty acids. And there’s some very interesting studies demonstrated that it can completely reverse the insulin resistance and high blood glucose of established morbidly obese type two diabetics by administering very high doses of aspirin, 90 milligrams per kilogram daily. It’s like, I don’t know, seven to nine grams daily, like for most people, an absolutely massive dose.
But these people, despite remaining morbidly obese biochemically, were no longer diabetic. And the explanation, the mechanism, proposed mechanism of action that the study authors gave was that it was with humans, number one drastic decline in the inflammatory profile of these people, so that whenever there’s inflammation, cortisol will rise, right? We expect that.
And the second thing is that aspirin is acting similarly to the drug mildronate, also known as meldonium, which is an inhibitor of the transport of long chain fatty acids into the mitochondria. So it has the indirect effect of lowering the oxidation of fatty acids into the mitochondria. And that was all that was required. These people were already established diabetics, morbidly obese, hypertensive cardiovascular disease, but as long as they were taking aspirin, aspirin didn’t fix the problem, I’m sorry, aspirin, fix the symptom. So they were so diabetes is a symptom.
So they were no longer diabetic. But when they stopped, the aspirin went back to their normal diet, of course, morbidly obese lipolysis is very high, they will immediately go back to their, you know, hyper glycaemia state. This shows us that we can change all of this, at least at the symptom level,, by simply helping the cell become more metabolically flexible. Now, what’s the way to cure it? Well, these people are already morbidly obese, for as long as they carry this extra fat, they will all their baseline lipolysis will always be higher, so they will naturally be shifting their cell in the render cycle towards the oxidation of fat for as long as that’s the case, they will not be cured.
And incorporation of that several studies demonstrated that you can cure for good type two diabetes if you somehow cause drastic weight loss in those people, bariatric surgery, uncoupling agents, etc, etc, which increase thermogenesis. In fact, these were established drugs for weight loss back in the early 20th century, but they’re dangerous because they can kill it through hyperthermia. So FDA banned a lot of them, they nitro phenol is the most famous well, so if these are hyper, hyper obese, type two diabetics lose the excess weight, their diabetes disappears, which to me is a direct proof irrefutable. Diabetes is a factor in a disease. It’s not a sugar driven disease.
In fact, it’s just a fad that’s causing it and sugar is just a symptom that you have diabetes, right, you’re not oxidizing the sugar, you’re converting it into lactate. Recently, some studies demonstrated that another class of people which have diabetes, but it’s a secondary disease them people with Cushing’s syndrome, and Cushing syndrome is caused by excess cortisol. Anyone who would exceed cortisol with officially diagnosed Cushing’s Syndrome has some degree of insulin resistance, and a good portion of them are type two diabetes type two diabetics.
But that’s not demonstrated if you administer a potent glucocorticoid antagonist, and that was blocking the effects of cortisol, these people’s type two diabetes and insulin resistance rapidly disappears. Not only do they lose the extra weight that they have, but they also get to keep it. That’s really the hard part of any diet. Yeah, many people can lose weight, but can they really keep it and you know, without going on a very extreme without staying on a very extreme diet.
This study demonstrated that in without any change in the diet, people would only establish this resistance in diabetes due to high cortisol, where they were completely cured by this drug, which implies that the same process cortisol is involved in non Cushing driven non Cushing based type two diabetes, which also corroborates the recent findings that the high blood glucose in those people is mostly of gluconeogenic origin, which means that it’s probably driven by excess cortisol. So people with type two diabetes are either or, and not, this is not mutually exclusive. Either they’re obese or chronically stressed are both. And if they’re eating mostly polyunsaturated fats, they’re also chronic inflammation as well, because these fats are the precursors to the inflammatory prostaglandins and leukotrienes and Chromeboxes. So I’ll say three major pathways here chronic stress, and they feed off of each other chronic stress, obesity and chronic inflammation.
Dr. Joel Rosen:
Yeah, no, that’s great. So, so part of the solution as well would be to, as you mentioned, have that macronutrient ratio of 3333 33. But if you’re chronically inflamed, potentially driving up your carbs, and mostly driving down the fats, and especially the Kufa. So maybe for people that don’t understand what’s poof has explained to them what that is.
So it just refers to the number of double bonds on the fatty acids, the saturated fats have none. Their very stable oxidation means they cannot, they’re not subject to radical attacks, which happens to be this double bond. And then which is proven by you know, if you have like fully saturated fats such as coconut oil, well, it’s actually 98% saturated, but close to fully saturated, you can leave it out in the open even under intense sunlight, and you can stay in the open for two, three years, it will not go rancid because it does not break down very, very, very, very stable.
Then you have the mono unsaturated fats, which have one double bond. And they are things like oleic acid, which is mostly present olive oil, but there are other things as well. And with olive oil, if you really want to refine olive oil, if you do the same experiment, you leave it out in the open, you’re probably going to get it to last for about six months, without any antioxidants being present any kind of preservatives. Now there’s also the polyunsaturated fats, which have three or more double bonds.
And those include things like line oleic acid line, linic acid, they’re, they’re, they’re metabolites, arachidonic acid. And they also they had the DHA and EPA, which are mostly they’ll call omega trees. They’re mostly a fish origin, marine origin, and the line of Lake and line linic. In our economy, they’re known as omega six. They’re mostly of plant origin. So these fats are highly unstable. Please leave them out in the open without any preservatives. Within a day or two, you’re going to start smelling or acidity.
And this is why most of the oil sold on the market inclusive kind of a preservative in these oils. And usually it is vitamin E. And the reason is, vitamin E is present in most plants to protect the plants themselves from from these oils that are being produced. Now the question is why would plants produce polyunsaturated fats? It turns out and actually this kind of shows you how good these fats are, the plant produces a defense mechanism. Polyunsaturated fats are toxic to most life forms. And the only species that has adapted to eat them well and traveled them are the ruminant animals.
Ruminant animals cannot try cameras stomach, like a GI tract, and special bacteria that live in that in that GI tract that saturates these polyunsaturated fats back into saturated ones. So if you’re eating so that’s why the meat of ruminant animals such as sheep, goats, cows, it contains mostly saturated fats and the milk that they produce contains most of saturated fats. So they’re the only animals that can take a high, very high amount of polyunsaturated fats and thrive on them. All the other animals that are being given these fats, the not only do they accumulate them in their tissues, but these fatty acids are also precursors to these inflammatory mediators that we mentioned earlier.
The prostaglandins leukotrienes, the Chromeboxes, and are also subjected to spontaneous peroxidation. This means that these fatty acids get attacked by molecular oxygen in the cell. They form highly toxic aldehydes and various other oxidation products. Many of those other kinds are already proven to have no human carcinogens. But more importantly, recent studies demonstrated the plaque the atherosclerotic plaque that forms at the arterial wall 80% Of the eight zero, if not more, consists of a very specific oxidation byproduct of lighter lake level lake acid. It’s an aldehyde.
And basically, it’s a form even more saturated than line lake as it is. So the bottom line is, saturated fats seem to be very stable. In court, we oxidation machines. So the fatty acids, the saturated fatty acids are very resistant to spontaneous combustion. In other words, they can only get oxidized if they go to the machinery that is in the cell that we have designed for their proper oxidation. The monounsaturated fats are slightly less beneficial, but at least I’d say they’re neutral.
They don’t combust this as easily as the woofers at the end of militaries, and then we have the polyunsaturated fats, both Omega three and Omega six, which we can oxidize to the enzymatic pathway, but a good portion of them don’t even make it to the pathway. They’re so unstable that they get attacked by molecular oxygen in the cell and start forming these toxic aldehydes.
And there’s a chain reaction actually, which never stops unless there’s a chain breaker and a chain breakers are known as so called antioxidants, vitamins The vitamin C, there are several synthetic ones already producing BHT, I think is one that’s used in many in many foods. The bottom line is they break the chain reaction of, of a polyunsaturated fat getting oxidized, producing aldehydes.
These articles are getting reacted again with a reactive oxygen species producing other aldehydes attacking a new ball of saturated fat and the whole process starts again. So the whole process, the whole presence of polyunsaturated fats in the body seems to basically be dangerous for us. Because if the polyunsaturated fats are not processed, they can they can spontaneously not combust, but they’re oxidized, right? And while the byproducts are toxic, universal, it’s not, it’s not even a question here.
And then even if they get oxidized, some of the enzymatic reactions that it was some of the some of the pathways through which the bond saturated fats can go into such as the cyclooxygenase and lipoxygenase pathways produce highly inflammatory molecules, which are now known to be involved in fibrotic conditions, liver failure, kidney failure, insulin resistance to, I forgot to mention the many of the fatty acids and their byproducts, but specifically, the polyunsaturated was actually capable of binding to the insulin receptor and blocking it.
So if you’re, if you have an excessive presence of excessive amounts of these fatty acids in your tissues, meaning insulin is not going to, you’re not going to be able to do its job. So the normal reaction, which is when you ingest carbs, easily rises, and suppresses lipolysis increases uptake of the glucose into the cell and oxidizing glucose properly. If you have something blocking the insulin receptor, that process will not work.
You can be insulin resistant. In fact, there’s a great video I can send you later of a guy who is perfectly healthy lean, he does, he checks his blood, blood, blood glucose regularly, I think it’s in the 80s. And then he chugs a glass of olive oil, or like corn oil, I think it was corn oil. Within 30 minutes. His blood glucose is already registered into the hundreds, which is pre diabetic. I think he managed to get it to the diabetic level, which is I think, above 125. I think it’s the cutoff currently. And then as he slowly metabolized the fat, his blood glucose slowly dropped there basically return to normal.
So to me this is a great example of insulin resistance and what ultimately diabetes is driven by these fats, it’s just sitting there already diabetic people, instead of checking one glass, these people have some have an endogenous continuous supply of these fats. And for as long as that’s the case, their blood glucose will stay elevated above normal.
Dr. Joel Rosen:
Right? No, that’s excellent information. So obviously, eliminating polyunsaturated fats is the key, having as much of a stress-free life as you can possibly do.
Dr. Joel Rosen:
Alright, I hope you’re getting a lot of value out of today’s podcast with Georgie and how we’re talking about the Randall cycle. And how we talk about a broken metabolic flexibility, challenging someone who is not able to burn carbs and not able to burn fat because of too much stress in their life too much cortisol release, which Geordi has talked about in terms of that is responsible for gluconeogenesis, which means you’re putting more glucose on the assembly line to have to be processed, combined with either the excess body weight from the adipose tissue and fat, or even too much fat in the diet or too much Koufos. And what I want to suggest is supporting cortisol can be very, very helpful.
We have two major project products that we recommend. We have a salary comm AM and we also have a salary comm PM. What happens is cortisol is known to up to create more glucose demand gluconeogenic And when your body 11 Beta HSD is up right up regulating the production of cortisol because of stress that’s putting too much load on your system.
So we formulated both of these products celery, new am and celery new PM, which is used to modulate that extra production of cortisol from the 11 Beta HSD enzyme, the main ingredient being Pinocchio or Magnolia bark, and we are selling this you’ll get a special discount for listening to this podcast and be able to purchase the cell renew am and pm m can be used at night it’s just has a lower concentration of the honokiol bark and is less calming or less fatiguing when you take it at night when it’s a stronger dose. So now back to our interview.
Dr. Joel Rosen:
I guess my question will just as an aside, choline is a really important nutrient for so many things. And when you have someone who’s a vegan, and they’re not eating animal foods, and potentially when I look at genomics, they’re weak on PMT and certain other new enzymes. I guess I got into a little bit of a a tussle with a patient of mine because one of the suggestions that I was having them recommend was a lecithin non GMO from like a safflower or sunflower. I guess the question on the air is, is that considered a seed oil that’s going to create an inflammatory reaction in their body? Are they getting more benefit out of the choline that they’re taking from that supplement?
I think it’s better to take call in. If you find phosphatidylcholine in a saturated form. There’s this thing called Bobby to phosphatidylcholine. So it’s a palmitic acid BOUND bound to call it there’s also steroidal phosphatidylcholine is the stearic acid bound to go in. So these things are very hard to find in isolated form, but you can get them from organ meats. One of the highest concentrations of these saturated phosphatidylcholine is, is actually present in hearts of ruminant animals.
Dr. Joel Rosen:
So begins do though, if they’re vegan,
then I don’t know I think there are a look, they have to take some kind of a choline supplement.
Dr. Joel Rosen:
Think that the safflower or the sunflower is worth the polyunsaturated exposure, because
it depends on the amount. So let’s say if you’re eating like a couple 100 milligrams daily, which I think should be sufficient to cover the choline requirements, then I think it’s safe. There are supplements on the market that use safflower oil as a solvent for various fat soluble vitamins. I know people will be indicative for years, they’ve measured their inflammatory profile, nothing has changed for the worse.
So I think it depends. It’s like a dose that makes the poison here if you’re doing a gram or more. So which sub portion of that is choline? So it’s not all polyunsaturated fats, but I’ll say a gram or two grams or more days, probably a problem. Bodybuilders that take multi-gram doses of choline daily. If they’re doing the safflower oil based one I did, there will be a problem, but a gram or under a gram is probably fine.
Dr. Joel Rosen:
Right? I know. I appreciate that. I have when I was researching for today’s and I gotta make sure I asked you this because I do think that the ends have to justify the means if you’re not getting it, but at the same time you have to be aware that you don’t want to have it’s the dosage for sure.
So getting into into glucose testing, I know that’s a pretty big Vogue and in vogue these days. They also have continuous glucose monitors. There’s also blood glucose ketone machines. I guess the first question I wanted to ask you was before with those kids that are metabolically flexible, and they can burn beta oxidation effectively and then go into glycolysis. and burning glucose effectively. When you have someone who’s metabolically flexible and you take their ketone levels with a blood meter, are they going to be necessarily in ketosis? Or does it mean that they won’t be? I guess that’s the question.
Well, I think it also is already extreme like you must have been like in a complete lack of glucose availability for several days. So when you get into those metabolic wards to get all the ketogenic diet, they put you under completely glucose free diet, right. And then they measure your ketone body levels, but they don’t rise until they are three or four, to the point where you’re actually officially in ketosis. Now, if you buy the urine glucose, ketone body monitoring strips, you will register some level of ketones if you limit glucose, but I don’t think it’d be full blown ketosis because initially gluconeogenesis will kick in and won’t be supplying some level of glucose. Right?
Dr. Joel Rosen:
Sorry, rephrase the question, mildly ketogenic so like maybe point five millimoles on a blood meter, would that be something that you would expect to see someone who’s not necessarily trying to eat in a ketogenic way, but they’re metabolically healthy? The Randall cycle isn’t competing for each other. They’re not getting polyunsaturated oils? Would you expect to see a mildly Kadett ketogenic marker to see if they are actually the metal is ketones in a mildly ketogenic number? Evidence of being metabolically flexible?
Yes, yes. And also, in addition to that, if what happens if they ingest let’s say, a sweet drink, would the ketone levels dropped? If they dropped to me, that’s the biggest sign that they are that they are metabolically flexible, but they are metabolic. Yeah, if they’re, if they don’t drop that, that’s a problem,
Dr. Joel Rosen:
right? And then and then I’ve heard on another podcast, which I think a lot of longevity experts don’t understand. Because they haven’t there’s no science to back. This is uh, oh, you can’t have any spikes. And maybe you can talk about that, Georgie, in terms of when you are metabolically flexible when you’re limiting your macros to an equivalent ratio, especially if you don’t have a metabolic disease and your metal a polyunsaturated fats are not being ingested. And you’re not eating high fructose corn syrup. What would a profile look? I mean, it’s obviously unique to every individual that maybe you could dispel the fact that it doesn’t have to have a spike or it can have a spike and what we see with with that,
as far as spiking, Alicia in terms of blood, blood glucose and insulin, I think is a marker of actual healthy pancreatic function. If you ingest, let’s say, a drink of pure glucose, which is the most insulin magenic I think that’s the test day give to a to pregnant women for gestational diabetes, they make the oral glucose test for 75 grams of pure glucose. And then they measure both their blood glucose and their insulin levels. I think the insert a cannula. They have taken several measurements over a couple hours and have to stay there while this is going on are busy.
And I don’t think what they want to see is basically a parallel and proportional rise of both. You want to see both blood glucose levels rise together with insulin. And then you want both of these to decline steadily over the next couple hours. When one or the other is out of whack, that’s usually not a good sign, right? If you have a high rise, high spike of a very, very high spike in glucose, but not of insulin, then they start worrying about insulin resistance. So potentially even type one diabetes, if you have something else basically releasing too much insulin, but that’s high glucose also, you’re expected to make more insulin, so we’re more worried if you don’t produce enough insulin, relative to the glucose to the glucose low. And of course, that’s their first word. The second word is how fast the glucose declines after that. I would I would prefer to see spike in both.
Also, a rapid decline afterwards,, a volt, a less ideal situation would be basically rising bolts, but then prolonged, long time takes for the glucose insulin to drop. Right? Yeah. And then the worst I think, to me, the worst situation is basically there’s a spike in glucose and not enough insulin produced. Several studies came out just to show that if the if this response of insulin to glucose is sufficiently blunted, in other words, if you’re real and you’re not type one diabetic, then there is usually some kind of a tumor in the pancreas or in the surrounding area.
And I think most often, they say it’s people that that are about to be diagnosed with something called mense type one or two, multiple endocrine neuros. It’s an it’s a tumor of the of the enteric nervous system. So if you want to be you want to be able to respond to glucose with the production of insulin, that’s the first step second, you want the cells to be able to see that signal right to be insulin sensitive, uptake all the glucose a quickly metabolize it, which leads to a drop in blood glucose. So I’m not afraid of the spikes I’m afraid of if only one spike or the other is right, and then also how long it takes for a blood glucose repair.
Dr. Joel Rosen:
So with that being said, then are you in favor of the of a new vote for people to get these glucose monitors to monitor their metabolic health?
I think it can help but it can also lead to a bit of orthorexia. Like people checking their blood glucose like every hour or so, like their continuous if there is some kind of a batch I didn’t know they have it for diabetics where you basically attach this device, and he’s got these micro needles, right, and it can check your blood glucose levels continuously. I think that there’s, you know, it can be useful. But to me, the glycated hemoglobin is usually good enough unless you’re already sick.
So if you’re in generally good health, your glycated hemoglobin is a good indication. Now interestingly enough, a lot of people think that glycated hemoglobin is mostly driven by the average blood glucose level concentrations over the last six, three or six months right. Turns out that it’s fats that contribute more than glucose, especially polyunsaturated fats. Several studies have demonstrated that if you give people with high HBA one see if you give them our antioxidants such as alpha tocopherol, which prevents the formation of advanced glycation end products and also prevents the the limits per oxidation of polyunsaturated fats.
Glycated hemoglobin declines despite no change in glucose intake. So once again, it shows you that even when we’re dealing with blood glucose the underlying cause has a lot more to do with fat and it’s per oxidation and inflammation that causes than the actual supply of glucose. Oh, another study showed that giving people with high HPA will see aspirin also leads to the decline of their biomarker.
So in aspirin, anti inflammatory classic, you know, this is a classic mechanism, but it’s also an anti-fat acid oxidation agent as well. Not as potent as meldonium or for boxers but still enough to cause, you know, a 10 to 50% Drop in HPA one sees, which doctors love to see. So yeah, so I think HPLC is good enough as a start if you don’t have an already established problem. If you do that I don’t do continuous glucose monitor which is truly continuous instead of you having to prick your finger like every couple hours. I think the former one is better if you have to break your fingers too often that can create a stress reaction. And in fact, it can raise your blood glucose levels above what we open because scary even though it’s simply a reaction to the stress because cortisol rises and whenever cortisol rises, blood glucose rises.
Dr. Joel Rosen:
right? Yeah, I can see how cuz I with some of the patients that I work with, we supply them with a blood glucose ketone machine, and I want to see some of their reactions and if they’re mildly ketogenic, but it can create a dual comp, you know, competition between the making sure that they’re getting fats and then trying to control their carbs and then they’re in that metabolic purgatory range where they can’t get into into either, I guess, I guess the question or the shift now would be okay, so so far, you just mentioned Alpha tocopherol. Is it suggested or above and beyond just a mix of Vitamin E and tocopherols? what’s your what’s your feedback on that?
I think all four of them all of the four isomers are fine. The problem recent studies have shown that alpha tocopherol has the highest affinity for the tocopherol transfer protein, which is the one that’s carrying it around the body in distributing to tissues. So even if you take mixed tocopherols, most of what will be absorbed and stored will be the alpha tocopherol isomer.
The other three seem to be excreted much more rapidly. But they do have the same and the opposite is potential. So a good mix of tocopherols without the presence of much polyunsaturated fats, because most of them were mostly of these, most of the coffers are extracted from soybean oil, or sunflower oil, safflower oil. So as long as it’s mostly pure tocopherols, then I wouldn’t worry too much about the like the actual composition of the of the mixture, you can try getting pure Alpha tocopherol.
But more often than not, isolated isomers are synthetic origin. And very often they have contamination with heavy metals and other things that are less than desirable. So you know, if you can find a good mix of natural oranges without too much polyunsaturated fats in it, I will go for that.
Dr. Joel Rosen:
Right, great. And then you mentioned aspirin and I know you’ve talked with Dr. Mercola, about the difference between acetyl and assilex. Sick and willow bark, maybe you can give us some insight on that.
So aspirin is simply to hurt, I’m sorry for acid till two jewels it doxy salicylic acid in the body that quickly metabolizes into an acid acetyl group and pure salicylic acid. Most pro anabolic anti lipolytics. uncoupling effects of aspirin are due to solic acid, it’s just the acid teal group, which I think has an anti fever effect and a platelet anti platelet aggregation effect.
And for a lot of people that are simply taking aspirin as a blood thinner, I think they may want to go with aspirin. But as long as it’s most of the other Brahma anabolic effects, inhibiting the oxidation of fat etc, etc. Please listen to Cassatt, the major metabolites of aspirin should do just as fine. So willow bark is great, it’s perhaps the the oldest drug in existence, I think there are references in the the Egyptians using it up to 3000 years before BCE. So it’s a great thing, just to make sure that, you know, it’s a decent product, you know, just like anything else, if it’s an herbal extract, it has tendency to contain, you know, some kind of toxic residue solvent in it. And then, you know, that could be a problem. But as far as salicylic acid, I don’t have a problem with using salicylic acid compared to aspirin, unless you look specifically for the blood thinning effect.
Dr. Joel Rosen:
Right, so the with the willow bark, is there a percentage that they extract that you’re looking for a total dosage amount that’s suggested.
I think between 10 and 20% is, is probably the max you should be looking for? Because anything above that, in order for them to get the AX extract standardized for such a high concentration of salicylic acid, they have to use more and more complex processes and potentially more toxic solvents. And first of all, it will be more expensive. If not, then I think there are signs that there’s something nefarious about this specific product. But 10 to 20% is probably fine, because for the metabolic effects of salicylic acid, you just need a couple 100 milligrams daily.
So if let’s say there’s like a, if it’s been sold in pills, there are 500 milligrams each, it will take you to those pills. I mean, if it’s 2010 to 20%, then it’s probably okay, that probably should be enough. These are the studies that have been done with salicylic acid aspirin with very, very high doses in the grams range in the early 20th century, more recently for diabetes.
These are, you know, extreme doses, which I wouldn’t administer, I wouldn’t do self medication with that and if a doctor approves it, and adequately is willing to monitor your drop in time prothrombin time in other words, how likely you are to bleed to death, then it may be worth doing it but there probably safer ways to achieve that to achieve these effects. Caffeine is a great coupler so if you want to raise your metabolism, you can do that, right. Progesterone is great and coupler salt is a very thermogenic protein that is highly thermogenic.
So there are lots of safer dietary ways to achieve what has been done with aspirin salicylic acid and if you want to take this assessment salicylic acid a couple 100 milligrams daily are probably fine. You can control bleeding risks with things like Vitamin K, which is also available over the counter.
Dr. Joel Rosen:
Right and when you say uncoupling GA you Talking about the the Randle cycle that is preferentially doing beta oxidation is that what you mean by uncoupling non coupling
meaning that it’s basically a coupling, it uncouples the production of ATP from the flow of electrons. So in other words, you generate a lot more heat per unit of substrata oxidized instead of ATP. So things like die nitro phenol, which is a uncoupling agent, basically, you produce less ATP but a lot more heat, so and so which means you can eat a tremendous amount of food but you’re going to either dissipate most of it is heat.
And the risk of course with that is that there is no break in that process. You can uncouple yourself to the point of raising the temperature to on physiologically potentially lethal levels. So aspirin isn’t a coupler but not to the level we can kill you just like die nitro phenol Chem is still can kill you, if you take there is the resource lead poisoning. People have attempted suicide with it. But we’re talking about 10 to 15 to 20 grams in a single dose. And, you know, unless somebody’s really trying to kill themselves, I don’t think it’s likely for people to end up in the situation.
So a milder couple likes aspirin, especially when combined with another moderate uncouple like caffeine. In fact, there is a study showing that caffeine can achieve the exact same amount of a couple is that nitro phenol, but you have to take again, high doses, but a combination of milder doses like 100 to 200 milligrams aspirin, 100 200 milligrams caffeine, it looks great. It raises your basal metabolic rate by about 10 to 15%. The good news is that this elevation stays for at least 10 to 12 hours. So you can do it once or twice a day. It should be fun.
Dr. Joel Rosen:
Right? And that’s a whole other rabbit hole I would love to interview you with because in terms of the cytochrome c oxidase and bioavailable copper and more exhaust coming out of the electron complex. And I guess just this in this uncoupling method, it’s creating more heat which is driving your metabolic activity which is ultimately burning nutrients or in a non exhaust producing ways that Is that accurate?
That’s accurate. In fact, children which are fat known as fast oxidizers, are very metabolically flexible and produce a lot more heat than we do. In fact, they’re, they’re moderately uncoupled compared to us, the adults in this process, she declines with age. One of the explanations that about energetic theory gives us what it is adaptive or pathological that remains to be seen.
But one of the reasons for our declining temperature and declining uncoupling levels is the decline of citizens of T three, the active thyroid hormone, what we produce less or why we convert less, it’s a separate story. But it’s indisputable that our core body temperature drops with aging. And you know that you know, the higher the temperature in general, the higher the basal metabolic rate, the more calories you can burn without getting yourself into exercise or you know,
Dr. Joel Rosen:
it’s funny, it brings back sort of memories. When I was an exerciser. In my early 20s. There was a triple stack. I don’t think you can get it anymore, but it was the white willow bark. It was the caffeine and it was the ephedra
yep, yep. Yeah, they benefit her. But you can still get the I think they replaced the federal now with something called yo Hemby, which is like an extract of African plan. But you can still get aspirin, caffeine and you him but I don’t think it works as well as the as the as the federal component. Maybe that’s why they banned it. They’ve killed it’s good as a weight loss drug.
Dr. Joel Rosen:
Yeah. So So one of the questions that I had, which, which is maybe a bit of a rabbit hole, but the other supplement or the nutrient you talked about was niacin amide. And I do have a patient that I work with that when I showed you the DNA, she has some major challenges in synthesis and utilization of NAD. But maybe talk about the utility of niacin amide. But also the bell shaped curve of it inhibits its own production that can leave you in sort of a limbo area. So let’s let’s talk about that.
So now I see them I probably his most important role is a precursor to NAD plus, which is the oxidized cofactor which is necessary for pretty much all of the reactions to step the steps of the Krebs cycle and the electron transport chain. So without sufficient amounts of NAD the cell dies, which is why the cell takes extreme precaution into not letting NAD levels drop.
One of the ways and one of the emergency mechanisms you mentioned earlier is that if you have a deficiency of NAD plus, which usually means an excess of NADH which is the reduced equivalent, the cell will do everything it can to oxidize NADH back into NAD plus and the emergency oxygen because it cannot get you to directly use oxygen. Emergency oxygen is another oxidizing agent that can accept electrons in the case of NADH and NAD plus that’s pyruvate, which is a byproduct of the which is the output of the glycolysis cycle. But the problem with that is you know when you’re using parameters and oxygen, you’re creating lactate.
So anyways, NAD plus is the chosen one an extremely important molecule NAD plus is for the cell and it’s been shown This will be now that the rates of NAD plus and the total nicotine adenine dinucleotide pool, which means NADH NADP NADPH. Total nuclear nicotinamide adenine nucleotide pool declines with aging and is also low in various chronic diseases, especially diabetes, cardiovascular disease and cancer. And they’re so the question naturalized okay.
So, if we assume that this decline is pathological, what can we do to raise it back right to increase the total pool, and specifically the oxidized portions of the pool? Well, one way is to take a precursor and niacin amide as well as niacin and, and also something called nicotinamide ribose. And another one called nicotinamide mononucleotide. All of these are precursors to NAD plus, however, they have to undergo several steps in order to get converted to NAD plus. And the the crucial the rate limiting step of the process the enzyme is known as nampt.
The nampt enzyme has very quirky requirements if you give it too much. And by too much, how much is too much is unique to each person, just as you demonstrated with that genetic analysis of that specific person, then this this, the activity of this enzyme gets inhibited. So you’re going to get a buildup of niacin amide, which is not always good because the body has to process it somehow. And one of the ways to reach the body processes is that it modulates it converted to something called six methyl nicotinamide. So this means that higher doses of niacin amide, or methyl six, there are metal detectors. Now for some people, there is access manipulation.
So you can argue that for them I’ve seen in my explanation will be good. But for others, there are deficiencies, there are deficient metal areas, so you have to be very careful with them. So in other words, you have to find your sweet spot. If your goal is to raise NAD plus, you have to find the sweet spot for nice cinema and you better not exceed it. Because then you’re going to be human in nampt. It takes a team couple hours for this block to be removed. So you’re going to have a real problem for a couple hours, probably feeling quite crappy if you take too much. And for most people, I think based on experiments and what I’ve written all the literature on animal studies, the sweet spot for raising NAD plus without interfering with anything else seems to be between 50 and 100 milligrams of niacin amide per dose.
For some people, that’s enough for an entire day in other emit they may need to take this dosage several times daily. But you know, I think it’s better to err on the side of safety. I would say 50 milligrams three times daily is probably safer, safer for most people, safer. In terms of inhibiting nampt If you take 500 milligrams or more, you will definitely be in nampt inhibition territory.
So it’s a problem. Is there anything else that can be done to help without these risks? And I think the answer is yes, just as the body can directly oxidize NADH and all of the other reduce the coolants back into the oxidized equivalents. You can use other oxidizing agents to achieve the same process without taking niacin. Now, if your total pool at the end of the nicotine adenine dinucleotide is low, then you won’t need a precursor because the only way to raise the pool is to take a precursor, but if you have enough of the pool, it’s simply shifted towards toeless reduction.
In other words, not enough of the oxidized equivalents. What you can do is take an oxidizing agent methylene blue is one oxidizing agent, and various other keweenaw such as vitamin K and Imodium, which is found in Kiss Cara, the tetracycline antibiotic. And there’s several other like even hydrogen peroxide will be able to basically oxidize some of those reduced nicotinamide adenine dinucleotide, throw this back into the oxidized version. So perhaps ideally, it will be a combination of low dose niacin, amide.
And an oxidizing agent. I did a study where I read a rat study somewhere a couple of years ago that showed that the combination of low dose niacin amide and the human equivalent of about 10 milligrams of methylene, blue increased the NAD plus levels by I think seven to 800%. But each one of them taken on its own was only increased by about 150. Such a highly synergistic effect. I think that’s the best way to go low doses of things that deck the pathway from different angles is better than higher doses of each one of them specifically.
Dr. Joel Rosen:
Right. So maybe that thank you very, very helpful. So with this particular individual as well, that there’s a fine line with, you know, too much too little but then adding more complexity to the issues. It’s a very generic genetic week for their methylation. So would your suggestion be to be able to add an oxidizing agent like, or in the sense of more methyl support while they’re doing that like TMG choline.
Yeah, gives you refine and also like if they have a problem with methylation, then I would probably skip the nice cinema for now. Just try the oxidizing agent on its own. If that improves the situation. Yes, you’re not going to get the cemetery 2% increase in NAD plus, but maybe you don’t need to maybe all you need to do is basically, if their total pool is sufficient, then all you need to do is shift it back to oxidation. Because, you know, again, you gotta be, we have to be careful with giving a person in that state to have a dose of nice cinnamon. And we don’t know how much of a choline or GMG would be enough to offset the manipulation depleting the effects of nice cinnamon? Or is it one to one, you know, is a two to one. I don’t know of any studies that have done that. I mean, we can make some calculations, but I will run a play, it’s a first try to think that is not likely to hurt, which is the oxidizing agent on its own. And only if that doesn’t work to try to play with nicely termite and choline and other methyl donors.
Dr. Joel Rosen:
That’s interesting. Thank you so much. I mean, I’m getting maybe part two will be because I would love to talk to you about actual testing in terms of what your feeling is on omega aquat testing and looking at local trainings, prostaglandins, cortisol to DHEA I’m really interested to talk to you about that or cortisol to testosterone. The way that people get in contact with you is the website haid ru t.me. Is that correct?
Yeah. hadal.me here, notice my alias on the which I post online.
Dr. Joel Rosen:
Okay, perfect. All right. Well, listen, I enjoy your your knowledge, I can tap into so much more. I always like to ask my guests because this is a longevity pathway. Podcast. What do you know now that you wish you would have maybe known earlier in your in your journey, Georgie that would have been helpful for understanding or prolonging your own longevity had you had a head start with that?
A couple of things. Number one, chronic stress, do not underestimate it, it kills. And it can get you in a situation which I myself experienced where even the best doctors in the world and they kill you. They’re good doctors, they don’t mean any harm. They cannot do much for you simply because you’re already a wreck. Don’t get yourself into cert to be a wreck. Even if you’re making tons of money.
There is some things that even with our advanced knowledge, these days, it will be very difficult to reverse. Thankfully, I didn’t get to that point. I know people who did get into that point. And they regretted not listening to their body earlier. So chronic stress, especially if you feel like, oh, you’re always, you know, in a fight or flight reaction, you can’t sleep properly, you’re agitated, irritated at everything. That that is a good example. I mean, maybe psychiatrists will tell you the press. But before even that sets in, I will say it’s a sign that you’re under chronic stress if you’re lashing out at the world constantly.
Number two diet. I wish I had known about the polyunsaturated fats earlier, there have been some I’ve known I’ve heard little bits and pieces since I was a very little child. I remember when I was growing up in I’m originally from Bulgaria was to a communist country, there was this great debate on the radio, because they were saying, well, the western science shows that, you know, we need to eat more seed oils and all these animal oils, they’re, they’re artery clogging. So they were fighting about whether that’s true or not, that was one of the first things but at the time, I didn’t know anything about that. So you know, you just do whatever you think. So avoidance of polyunsaturated fats, and avoidance of many toxins that are present in foods that seem benign by name, and things like silicon dioxide, titanium dioxide, talk caridina. It’s even approved in organic foods, but actually, in several countries, it’s banned as a non colon carcinogen.
So things that seem very benign and even if they’re organic origin can really wreck your health. They’re very nefarious because they’re on the label, but they’re very tiny amounts, and no doctor will suspect them. I mean, it’ll take decades before the publications that are available now make their, you know, kind of seep into the into clinical practice. So definitely pay attention to the labor in what you’re eating, you are what you eat, as the saying goes, right.
So that’s number two. Number three is knowing about aspirin earlier, and how important it is to help. So it’s not just an inflammatory molecule, there is a reason why the Egyptians used it widely. What is 5000 years ago, and in fact, they will always place a little bit of willow bark into the tombs of their mummified Pharaohs to help them stay healthy on the other side.
So not we’re now finding out that aspirin has a number of different properties that are there that go way beyond inflammation. It happens to be the main stress resistance agent the plants produce at anything that attacks the plant, what it’s like when it’s a pathogen or an herbivore, or even somebody kicked the plant and injured it. Immediately the pathways are activated to synthesize salicylic acid, which makes the plant very, very resistant to subsequent damage and helps to heal the same process to be activated by aspirin in mammals. So, you know, unless you have a medical reason not to use aspirin, I would consider it especially now that there’s evidence that aspirin is a great longevity booster.
Our study of yeast and several other animal studies on yeast had the most dramatic effect demonstrating that the human equivalent of about a gram of aspirin daily increased the maximum lifespan, not average maximum lifespan by 400 20% Caffeine increases also demonstrated the need to increase lifespan, pro metabolic things in general, and avoiding stress seems to be the best way. And of course, being mindful of your diet seems to be the best way of increasing longevity and lowering stress and making life more enjoyable because I think it’s not only making not just putting more years into life, but also putting more life into the years, and avoiding stress and being mindful of what you eat and being surrounded by healthy like minded people. I think it goes, it goes a long way towards achieving that.
Dr. Joel Rosen:
It does I mean, it can get real complicated really quickly, but the solution is always common sense just back to nature, food, the medicine and, but it’s a lot harder to achieve, because of the adulteration and what we’ve done to our environment to to be able to do the easy stuff. But listen, you have a wealth of information, I appreciate your knowledge.
And I definitely want to be able to tap into it another time and get into biomarkers and you know, hand strength and FET you know, different different things that you can look at that are not just the traditional medical biomarkers, or the analytes. But now these things that show that studies correlate higher with longevity that are more functional base than then you know, treating through taking this pill or that pill and getting this number lower or higher. Such awesome information. Anything else you wanted to add there Jorgen?
No thanks a lot for inviting me. I’m really honored to be here.
Dr. Joel Rosen:
Thank you so much. Hi, thank you so much for watching our age reversing blueprint podcast. If you’ve made it this far, we sincerely thank you for your attention and your interest in reversing your age. If you’re looking to get more information on today’s topic or other podcasts that we’ve had, be sure to check out the show notes and be sure to check out Dr. Joel rosen.com. Have an awesome day.
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