The Dr. Hyman Show - How Fructose Drives Obesity, Type 2 Diabetes, And Chronic Disease

Episode Date: August 29, 2022

This episode is brought to you by Rupa Health, InsideTracker, and Pendulum.   The majority of foods on our market shelves contain insane amounts of added sugar. One of the most problematic of these s...ugars is fructose, which raises our levels of uric acid, a central player in the metabolic mayhem affecting so many of us. This doesn’t mean all foods containing fructose are bad. Like all parts of health and nutrition, there are nuances we need to consider to create optimal health.   In today’s episode, I talk with Drs. David Perlmutter, Casey Means, and Richard Johnson about how fructose and uric acid impact our physiology, why measuring uric acid levels is so important, and how fructose impacts our energy.    Dr. David Perlmutter is a board-certified neurologist and five-time New York Times bestselling author. He serves on the board of directors and is a Fellow of the American College of Nutrition. He is the author of Grain Brain among others, and his new book, Drop Acid, was just released. Dr. Perlmutter received his MD from the University of Miami School of Medicine, where he was awarded the Leonard G. Rowntree Research Award.   Dr. Casey Means is a Stanford-trained physician, Chief Medical Officer, and cofounder of metabolic health company Levels, an associate editor of the International Journal of Disease Reversal and Prevention, and a guest lecturer at Stanford University. Her mission is to maximize human potential and reverse the epidemic of preventable chronic disease by empowering individuals with tools that can facilitate a deep understanding of our bodies and inform personalized and sustainable dietary and lifestyle choices.   Dr. Richard Johnson is a professor of medicine at the University of Colorado in Denver and has been a practicing physician and clinical scientist for over 25 years. He is internationally recognized for his seminal work on the role of sugar, and its component fructose, in obesity and diabetes. His work has also suggested a fundamental role for uric acid (which is generated during fructose metabolism) in metabolic syndrome. He previously authored The Sugar Fix with Timothy Gower in 2008, and The Fat Switch in 2012. His new book, Nature Wants Us to Be Fat, was just released.   This episode is brought to you by Rupa Health, InsideTracker, and Pendulum.   Rupa Health is a place where Functional Medicine practitioners can access more than 2,000 specialty lab tests. You can check out a free, live demo with a Q&A or create an account at RupaHealth.com.   Right now InsideTracker is offering my community 20% off at insidetracker.com/drhyman.   To receive 20% off your first purchase of Pendulum’s Akkermansia probiotic supplement, go to Pendulumlife.com and use code MARK20.   Full-length episodes of these interviews can be found here: Dr. David Perlmutter Dr. Casey Means Dr. Richard Johnson

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Starting point is 00:00:00 Coming up on this episode of The Doctor's Pharmacy. Uric acid elevation in metabolic syndrome is no longer an innocent bystander, but playing a central role. It doesn't just happen to be elevated, it is the cause. Hey everyone, it's Dr. Mark. Now, I know there are a lot of functional medicine practitioners out there like I am, and we're all trying to get the best data we can to help our patients optimize their health. And that means we're often looking at things like hormones, organic acids, nutrient levels, inflammatory factors, gut bacteria, and more to help us find
Starting point is 00:00:34 the most effective path to health and healing. But it usually means having to order multiple tests from multiple different labs, which makes the whole process of ordering, tracking, and compiling lab results really difficult and time-consuming. And that is where Rupa Health can help. Rupa Health is a place for functional medicine practitioners to access more than 2,000 specialty tests from over 20 labs like Dutch, Vibrant America, Genova, Great Plains, and more. They make the process of ordering labs simple and fast, allowing you to cut down on the paperwork and giving you more time to spend with your patients. This is a much-needed option in the functional medicine space. It means better service for you and your patients. You can check out a free live demo with a Q&A or create an
Starting point is 00:01:14 account at rupahealth.com. That's R-U-P-A-H-E-A-L-T-H.com. You're unique, which means your health and wellness plans should be unique too. But it can be tough to optimize your health and nutrition programs because it's often difficult to get the data you need. And even if you do get your numbers, you actually have to understand them and then be able to make meaningful action based on them. This is where InsideTrackers comes in. InsideTracker is a wellness tracker that uses science and technology to deliver ultra personalized healthcare guidance.
Starting point is 00:01:44 They can analyze your blood, your DNA, your lifestyle habits, and then give you actionable recommendations to help you meet your health and wellness goals. They'll tell you what you need to do and why, and you can track your progress and adjust your plan based on real-time feedback from your own body. Since 2009, their science team at Harvard Tufts and MIT have been bringing personalized nutrition and wellness to the world with their powerful evidence-based digital platform. InsideTracker is simple, customizable, and most importantly, it's based on you and your body. If you're curious about getting your own health program dialed in to meet your unique needs, I highly recommend checking out InsideTracker. Right now, they're offering my community 20% off at InsideTracker.com
Starting point is 00:02:21 forward slash Dr. Hyman. That's I-N-S-I-D-E-T-R-A-C-K-E-R.com slash D-R-H-Y-M-A-N. And you'll see the discount code in your cart. Hi, this is Lauren Feehan, one of the producers of the Doctors Pharmacy Podcast. We live in a food environment that can make it hard to maintain a healthy metabolism, and 88% of people are metabolically unhealthy. But reducing our sugar intake, especially fructose, is a huge step we can take towards metabolic health. The problem with fructose metabolism is that it generates uric acid in the body, which is a key contributor to metabolic syndrome.
Starting point is 00:02:56 In today's episode, we feature three conversations from the doctor's pharmacy on how limiting our fructose intake and minimizing uric acid levels can prevent and reduce inflammation and chronic disease. Dr. Hyman speaks with Dr. David Perlmutter on how fructose and uric acid affect our physiology, with Dr. Casey Means on the importance of measuring uric acid, and with Dr. Richard Johnson on fructose impact on our energy. Let's jump in. Fructose is a bad player, right? We see correlations between fructose consumption and the very things that we're talking about, but we've never really understood, well, how in the heck does that happen? What's the link? And what Dr. Johnson was doing 20 years ago is he
Starting point is 00:03:40 was creating hypertension, elevated blood pressure in laboratory animals by feeding them fructose. They would develop high blood pressure. And he noted that as a matter of fact, that their uric in doing a blood panel, looking at all kinds of things, that their uric acid levels would go up when he gave them fructose. Well, you would expect that because unlike glucose, fructose is metabolized directly into uric acid. That's where it comes from, from fructose. There are two other sources we'll talk about. So he noted that. He said, well, isn't that interesting? Uric acid levels increased. Then he did something really fascinating. He gave them a lot of fructose, but he blocked the uric acid production by giving them
Starting point is 00:04:26 a gout pill called allopurinol. Lo and behold, here they're eating all this fructose and they're not getting high blood pressure because uric acid was not elevated. Fascinating. That is huge. Fascinating. And he determined then by repeating the study in men, the same thing happened. Give them a lot of fructose, within a couple weeks, blood pressure goes up, weight goes up, insulin resistance increases, blood sugar goes up. But if you give them allopurinol, and where you and I are going with this today is not to say everyone should take this drug. We'll talk about what you can do.
Starting point is 00:05:02 But lo and behold, the same thing happened in humans. So that was groundbreaking. And at that point, you know, he began his research. But it's interesting to note that in 1894, Dr. Alexander Haig, a different Alexander Haig, wrote a book entitled Uric Acid, a Factor in the Ca the causation of disease and looked at things like dementia and hypertension and depression and certainly rheumatism or joint problems and really discussed it way back then but it remained buried you know until just about 20 years ago now researchers around the world are are looking at this and describing what to do. So, you know, yes, it's a marker. You were correct in saying, you know, you notice that it's elevated.
Starting point is 00:05:51 But there was an interesting report that came out of Turkey and Japan in 2016 that looked at uric acid elevation in metabolic syndrome as no longer being in the title, innocent bystander, but playing a central role. That it's actually mechanistically involved in causing these problems. It doesn't just happen to be elevated because people have a crappy diet or they're not exercising or sleeping well. It is the cause, a cause, an important cause. Wow. So David, people are listening probably going, well, geez, does that mean I can't have an apple or is it just high fructose corn syrup that you get in soda and processed food? Like what's the deal? It's a great question. I can't, I can tell you it's something I'm asked every day. And here's what the literature tells us. And it's really quite interesting in that if you eat an apple, if you eat five grams of fructose
Starting point is 00:06:42 or two apples, 10, 15 grams of fructose, all well and good. An apple has quercetin. It has other bioflavonoids. It has vitamin C. Fiber. Fiber, which slows fructose absorption. It has vitamin C, which aids in uric acid excretion. As opposed to drinking a 12-ounce glass, 42 grams of fructose, you know, of orange juice or apple juice or certainly a soda, those are the
Starting point is 00:07:07 potent sources of fructose that we need to stay away from, immediately tells your body something very important. That fructose signals your body that winter is coming. It's telling your body that caloric scarcity is coming. You starve you better make fat you better turn on your production of glucose to power your brain you better elevate your blood pressure because you're not going to have water to drink it's setting the stage for survival for you know and this is a fascinating story that dates back about 15 million years ago when the earth cooled. And there was some very powerful selective pressure on our primate ancestors for survival during times of food scarcity. And it turns out that around that time, there was a mutation, was actually a series of mutations
Starting point is 00:08:01 in the genes that made an enzyme called uricase. Uricase breaks down uric acid and would lead to a lower uric acid level. But this mutation disrupted how uricase worked. So those who inherited this mutation had higher levels of uric acid. They made more fat, they survived. So we as humans and other great apes still have that mutation in uricase. So we have four to five times higher levels of uric acid than other non-primate mammals. These days, what we're experiencing is called an evolutionary environmental mismatch. So we're stuck with these outdated physiology that allowed our paleolithic ancestors to survive, our hunter-gatherer forebears to survive when there wasn't any food. If they could stumble on some berries, a little bit of
Starting point is 00:08:57 fructose, make a little bit more fat, didn't take a lot. Not that it made them fat, but just enough fat to hold them over until they could find food, you know, whether it was on the ground dead or they dug it up or whatever. Well, David, I know you spent a lot of time on your boat up in Alaska, but, you know, the grizzly bears up there, they eat salmon in the early part of the summer and they don't really gain much weight. Then they go up in the mountains and they eat all the berries and they gain like 500 pounds from eating berries. That's right. And what you're saying is really important because we have a lot of mechanisms that are
Starting point is 00:09:24 adapted to starvation. People don't realize this, that we have hundreds of genes and mechanisms in our body that are really good at dealing with scarcity, but almost none that are dealing with abundance because we've never had to deal with this before. We never lived in a food carnival before. We never lived in a food Lollapalooza where there's everything all the time in abundance and the worst possible crap you can imagine. So our bodies don't know how to cope with it. And so this mechanism, which is actually designed to help us stay alive, is actually killing us now. That's right. And again, we call it an evolutionary environmental mismatch. I wrote my first article on this in the Miami Herald in 1971 when I was 16.
Starting point is 00:09:59 Oh, wow. You're ahead of the game, huh, David? I was, you know, I said, what, you said, what about us, the people of today who are sort of saddled with this outdated machinery? That was how I ended the article. Because evolution isn't going to save us. We're not going to be able to evolve quickly enough the mechanisms to deal with exactly what, Mark, you've been writing about for years. And this horrendous assault upon our physiology by the very foods that are now global. You know, we used to talk about the American diet, the standard American diet, the Western diet. It's global now. Face it. And, you know, we talked about in Brainwash how that
Starting point is 00:10:37 threatens connections in the brain that make us less empathetic. But, you know, that's for another conversation you and I have already had with Austin. Well, that's a good podcast. You should all listen to that podcast because just to summarize it quickly, if I get this wrong, tell me. But essentially, our modern diet, which is super inflammatory, disconnects our frontal lobe, which is the adult in the room, from the limbic brain, which is the reptile, lizard, fight or flight, reproduction, feeding behavior, which is very triggerable. And so all of a sudden, the grownup in the room is not managing the intense emotions of this limbic part of our brain. And so we act
Starting point is 00:11:11 in ways that are destructive or violent or aggressive. And we see that in our society now as being a massively divided society, whether it's your paleo or you're vegan or Republican or Democrat or Jewish or Palestinian or Muslim or Christian. It just goes on and on. And your argument is that part of that divisiveness could be related to what we're eating. That's right. And, you know, what a match made in heaven that you and I are talking today. Because we've been doing that thing for so long. And, you know, for me, it's more about, well, what are the implications of that as it relates to behavior and the brain?
Starting point is 00:11:45 And now we know that, you know, this uric acid, because of its elevation, threatens some really important physiology. As an example, it compromises the action of a chemical called nitric oxide. We need nitric oxide to do two very important things. It allows our blood vessels to relax. So we have good blood flow to our kidneys, our heart, and certainly to our brains. And in addition, nitric oxide and that effect of nitric oxide in blood vessels is what helps insulin do its job. Insulin requires nitric oxide to get out of the artery and also into the muscle cell to let
Starting point is 00:12:27 it change glucose into glycogen to help keep our blood sugars under control. That is threatened by uric acid. And, you know, one of the really interesting mechanism, I think that you hinted about on when you were talking about the bears eating all the berries to get ready to hibernate, is that that's a uric acid mediated event in them. They shift over between two very important pathways of metabolism. One is called AMP kinase and the other is called AMP deaminase. When we are stimulating AMP deaminase, we are favoring fat production. We are favoring locking up our fat. We are favoring the metabolic issues that we want to avoid. AMP kinase, on the other hand, which is not something that uric acid favors, is when we burn our fat, it keeps our blood sugars in check. Your insulin sensitivity goes up. And basically,
Starting point is 00:13:25 that's what we do. We want to stimulate AMP kinase. It's why we exercise. It's why diabetics take metformin. It's to stimulate this AMP kinase. That's exactly what's not happening when bears are getting ready to hibernate. Once they're hibernating and they're burning their fat, then AMP kinase is activated. And it looks like uric acid is involved in that switch one way or the other. Where does the AMP come from? Very interesting. The AMP comes from the metabolism of fructose.
Starting point is 00:13:58 When fructose is metabolized, it's an energy consuming event, unlike glucose. ATP is converted into AMP. Then where does the AMP go? We just talked about that. So it's totally a different kettle of fish, you know, how fructose is metabolized. Fructose is the sugar of energy storage, and glucose is the currency of energy utilization, and as different as night and day. You know, the real concern is that the metabolism of fructose into uric acid feeds back to cause more metabolism of fructose. It's a feed-forward cycle. So uric acid stimulates the production of an enzyme called fructokinase, which is the first enzyme to break down a fructose.
Starting point is 00:14:47 So it just, it's self-perpetuating. And what does that fructose do? It inhibits leptin sensitivity. So we eat more. Leptin is the hunger suppressing hormone. Right. And that's inhibited by our consumption of fructose. And this was a great mechanism to get ready for winter,
Starting point is 00:15:05 you know, so we would eat more. That's why the bears are doing what they're doing. They're preparing to hibernate. And if any of your viewers are getting ready to hibernate, then have at it, you know, this, then that's for you eat a lot of fructose. But I think it's, uh, you know, to get back to your original question that, you know, you and I talked about or learned about uric acid in the context of gout. If you had high uric acid, you might get gout, you might get kidney stones. But now we have a term that's called, it's pathetic, it's called asymptomatic hyperuricemia, which means you have elevated uric acid, but hey, you don't have gout. Therefore, it's not important. And asymptomatic hyperuricemia, it's clearly associated with hypertension, with obesity, with chronic kidney disease, and non-alcoholic fatty liver disease.
Starting point is 00:15:58 One interesting study out of Japan looked at individuals with so-called asymptomatic hyperuricemia and found that they had significant increased risk for becoming overweight, for developing problems with their lipids, and even hypertension, you know, important components of the metabolic syndrome. And, you know, you started off with our discussion saying that 88% of American adults have at least one component of the metabolic syndrome. It means only 12% of American adults is metabolically healthy. And these are the big issues of our day. You know, you can talk about viruses all you want.
Starting point is 00:16:36 Sure, that's important. But that's not what's killing most people on our planet. What's killing most people right now are the chronic degenerative conditions. Coronary artery disease, Alzheimer's, cancer, diabetes. These are metabolic issues. What's killing most people right now are the chronic degenerative conditions, coronary artery disease, Alzheimer's, cancer, diabetes. These are metabolic issues. It's almost 50 million deaths a year. Yeah, and related to the food.
Starting point is 00:16:52 50 million, million deaths a year. Within them, that's right. David, I just want to sort of loop back a little bit because I want people to understand what this fructose thing is. So basically, we're getting it from high fructose corn syrup, which you said is 55% fructose, but it's actually in some studies I've seen up to 75% fructose. And also it's important to understand that in traditional sugar, fructose and glucose are bound together with a chemical bond. So they take some metabolism and they're not as quickly absorbed. Fructose in high fructose corn syrup is free fructose and the other thing
Starting point is 00:17:25 you didn't quite mention i'd love to hear your opinion about this is work from bruce aim is where fructose requires energy to be absorbed as opposed to sugar which has a transport channel doesn't require the use of energy and when you use that energy for fructose and you're having mostly fructose as your sugar it's causing de depletion of ATP in your gut, which then causes the tight junctions, which are the things that prevent you from having a leaky gut to keep your cells stuck together like Legos. It causes those to separate and then you get leaky gut, which then even exacerbates the problem of obesity and insulin resistance and diabetes through another mechanism, which is endotoxemia from the metabolic byproducts of bacteria and weird things in the
Starting point is 00:18:05 gut. So it may be that fructose is causing problems with many, many reasons, partly, obviously, this metabolic effects, but also the gut effects, which exacerbate the metabolic effects. That's right. And again, this is all amplified by then the metabolism, which is an energy-dependent event, ATP to AMP, then to uric acid. And that uric acid then enhances in the gut more pro-inflammatory bacteria, also dramatically increases the gut permeability, therefore increases inflammation. And how interesting it is that one disease that is associated with elevated uric acid, which is gout, has actually been demonstrated to be significantly improved
Starting point is 00:18:50 in people undergoing what's called a fecal microbial transplant, where healthy fecal material is taken from an individual and then put into the colon of a person with gout. Remarkable reduction in the number of gout attacks without any significant dietary change. So, you know, we're back to talking about the gut, you know, a place where you and I default to over the years, and rightfully so. But so uric acid itself is having such a dramatic effect on the gut. You bet,ances inflammation. So if we recognize that inflammation is certainly a centerpiece of the damage done by uric acid, then all of the downstream issues related to inflammation might well be anticipated to be increased in people with high uric acid levels.
Starting point is 00:19:42 And in fact, that's what we see in a 2018 study, looking at 42,000, I think I mentioned earlier, 42,000 men and 49,000 women, and followed these individuals over an eight-year period of time. What did they find? They found that all-cause mortality was dramatically increased in those individuals with high levels of uric acid. Yeah. Those who had high uric acid had a significant increased risk of cardiovascular-related mortality of close to 40%, and about a 35% increased risk of stroke-related mortality. This is a big study.
Starting point is 00:20:22 I mean, we're talking about 100,000 people followed over eight years, having a 35 to 40% increased risk of death from either a heart attack or stroke. And here's something else that the study found, I think was really interesting. And that is for every point elevation of uric acid above seven milligrams per deciliter. For every point, there is an eight to 13% increased risk of all-cause mortality. So this is mortality. When we look at the cardiovascular, we look at the stroke, this is mortality related to issues that have inflammation as their cornerstone. So it's very important that we consider this, that we consider that uric acid is not just happens to be elevated, that it's playing a mechanistic causal role, and that we should do what we can to check our uric acid levels. You can use a home monitor,
Starting point is 00:21:18 I'm going to send you one. Or, you know, people get their annual blood work, uric acid is almost always on the annual blood work. What is it? And for your viewers, the place where it needs to be is at or below 5.5, the units are milligrams per deciliter here in America. Typically, the lab will call it out at seven or higher, because that's the level that it starts to become an issue as it relates to gout and kidney stones. But as it relates to the metabolic issues that we're talking about, the increased blood sugar, the hypertension, the risk for all the things that we're talking about, we want it at 5.5 or lower. And again, you can go online, go to Amazon, buy a uric acid monitor and check your level. I recently checked mine again and it's 4.6. So I'm feeling good
Starting point is 00:22:05 about that. That's good. So basically, this uric acid phenomena is really not well understood by most physicians. It's really driven by diet, but normally our processed diet, high fructose corn syrup. And it drives all these secondary effects of cardiovascular disease, death, Alzheimer's, cancer, diabetes. And it's something that you can actually easily measure. Your doctor can check it for you when you go to the office. It should be less than five and a half, as you said. What should we do in terms of our diet to reduce uric acid? And what are the worst things that cause uric acid? And what actually helps reduce uric acid? Sure. Let's talk about the causes or the sources of uric acid.
Starting point is 00:22:47 Where's it coming from? And did we mention fructose? Yes, you did. Fructose is the gorilla in the room, right? So fructose, again, was our signal that scarcity was coming, that winter is coming, eat the berries. Fructose is telling your body make fat, raise blood sugar, raise blood pressure because you might not have water to drink. So fructose is, by and large, the biggest player. Fruit juice, sodas, added to sauces, added to just about
Starting point is 00:23:16 anything that's in a package these days. Salad dressing. You bet. And we love it because it's sweet. Tomato sauce. And again, fruit is okay. An apple a day keeps the doctor away. Not apples and cherries and high fructose fruits all day long, but have some fruit by all means. The next thing to consider that's certainly less important are something called purines. Purines, all fruits, vegetables, and meats, really anything we eat has in it some DNA and RNA. When our bodies break that down, then purines are formed and purines are directly metabolized into uric acid. And interestingly, uric acid favors that and enhances the production of
Starting point is 00:24:03 purines in our bodies. Again, a feed forward cycle, it's trying to keep us alive during times of food scarcity. So again, we want to avoid those foods that are really rich in purines. I mentioned them already, the organ meats, the shellfish, the smaller fish that we were favoring over time, the anchovies and the sardines. Sure, you can have the anchovies in your Caesar salad, but you don't want to make big meals having six ounces or more of any of those. Oh, I love anchovies. Yeah, me too. White anchovies, one of my favorites.
Starting point is 00:24:32 And the last thing to consider, I think it needs a little bit of – we need to double-click on this a bit, and that is alcohol. Because alcohol shares the exact same metabolic pathway as fructose. As Robert Lustig has called it, fructose is alcohol without the exact same metabolic pathway as fructose. As Robert Lustig has called it, fructose is alcohol without the buzz. So it similarly consumes ATP down to AMP. But in this case, it really matters what kind of alcohol a person is drinking. Wine consumption in men has about zero effect on uric acid. Wine consumption in women actually is associated with lower uric acid. Hard liquor will raise uric acid, but the worst offender is beer. Why?
Starting point is 00:25:14 Because beer not only contains alcohol, but it contains purines that we just talked about from the yeast, the brewer's yeast that is used to make beer. So now we understand the biochemistry that underlies the beer belly. It's coming from this elevation of uric acid, packing the fat away, getting ready for winter. So if you're going to choose a beverage, coffee, a good choice, actually associated with lower uric acid. So those are the big things that we should avoid. I will make one other comment as it relates to high purine foods. Many people will pull up a list of high purine foods and see many vegetables, things like broccoli, the cruciferous vegetables in general, like kale. Many vegetables
Starting point is 00:25:57 have higher levels of purines. Their consumption, though, is associated with lower uric acid. Why? Because again, fiber, bioflavonoids, vitamin C, which increases uric acid excretion. So eat all the vegetables like that that you want. You'll never hear, I don't never say never, but it's going to be hard for me to imagine there'll be a time when I tell people not to eat broccoli or broccoli sprouts. That's going to be a tough one for me. Hey, everyone. It's Dr. Mark. Now, a few years ago, I went through the worst health crisis of my life. And as a key part of my recovery, I had to revitalize my gut, which meant encouraging the growth of a specific good bacteria called Ackermansia mucinifolia. Yep, that's a mouthful, but it's essentially the bacteria that keeps the mucus layer in your gut and protects from leaky
Starting point is 00:26:52 gut. Now, back when I went through my healing journey, I kind of had to be creative and then use lots of different ingredients to support the right kind of growth in my gut of Ackermansia. But now it's easier than ever to up your Ackermansia thanks to Pendulum Therapeutics. They've done something nobody else could do because of the first and only company to offer products that directly contain acromantia mucinophilia. Now, acromantia is the bacterial strain known for strengthening and regulating the gut lining and is also one of the most important determinants of maintaining your long-term health, your weight, your metabolism, and so many other factors.
Starting point is 00:27:26 Increasing the acromancy in my gut has such a big payoff for my health and I've become a real super fan. If you want to try it for yourself, Pendulum is offering my listeners 20% off their first month of acromancy subscription with the code HYMAN. Just head over to PendulumLife.com to check it out. That's P-E-N-D-U-L-U-M Life.com with the code Hyman for 20% off. Now let's get back to this week's episode of The Doctor's Pharmacy. Fructose alone will not spike blood sugar or insulin, but we know from the mechanisms of how insulin resistance develops that it directly contributes to insulin resistance through a really interesting pathway. Fructose is broken down into a byproduct called uric acid, which goes into the mitochondria, you know, the seed of our metabolism in the cell,
Starting point is 00:28:17 and generates oxidative stress, you know, this damaging free radical activity that actually causes the mitochondria to become dysfunctional and process glucose less effectively and shunt glucose to fat storage. So then you start getting fatty liver disease because of fructose and that fatty liver disease causes liver insulin resistance, which then makes you less able to stabilize and regulate your blood sugar. So fructose has this really interesting side pathway that ultimately leads to more instability in glucose, but will not show up on a CGM if eaten in isolation. Now, of course- It's a really important thing. I just want to stop there because you said something super important. If you, for example, eat a sugary soda with, you know, with high fructose corn syrup, you know, you'll get a mixture of glucose and sucrose.
Starting point is 00:29:11 But if you have like pure fructose, which is like agave, for example, that's just pure fructose. And that actually turns out to be pretty bad for you. If you're eating fructose in the matrix of a fruit, it's probably not as bad, right? It actually can be okay to have it in a complex of a meal. We'll talk about food pairing in a minute. But the idea that you can be eating certain foods, fructose, which a lot of, like, for example, processed food is mostly fructose. Like they use high fructose corn syrup, but it could be 75% fructose.
Starting point is 00:29:39 And that isn't going to spike your blood sugar like you said, but it's going to create a cascade of events that actually makes you more likely to get diabetic by increasing the uric acid in the liver, the insulin resistance. And the uric acid story is a very fascinating one. And David Perlmutter just wrote a book about it called Drop Acid, which isn't what you think it's about. It's about the uric acid in the blood that's causing so many of these issues. And fructose is a huge culprit. So I just wanted to pause there. It's about the uric acid in the blood that's causing so many of these issues. And fructose is a huge culprit. So I just wanted to pause there. It's so important.
Starting point is 00:30:07 So going off of like what else should we be thinking about, I would love to see a uric acid continuous monitor. Because then all of a sudden, if we could measure both those things, then we start to see a more holistic view of how food is affecting us. Because ultimately, our mission at Levels is to help people know how food affects their bodies so we can reverse the metabolic disease epidemic. But right now, there's still some blind spots. So like you mentioned, David Perlmutter is coming out with a book called Drop Acid about how fructose is affecting our health. We also in February are getting another book by Rick Johnson from
Starting point is 00:30:38 University of Colorado that's called Nature Wants Us to Be Fat, which is also all about uric acid. And so I think we're going to be starting to talk a lot more about that come February, which is awesome because fructose is absolutely killing us. There's just absolutely, you know, really no two butts about that. And like you said, it's not the fructose that comes in fruit, which is in a complex of fiber, in a whole food, slower to digest, and smaller quantities. It's the refined liquid versions that go into our processed foods and that we find in juice that we should really avoid. Because what happens is the liver knows how to process fructose, and it knows how to just produce small amounts of uric acid that our body knows how to handle. It's when we overwhelm
Starting point is 00:31:26 those pathways in a short period of time that we get the uric acid skyrocketing and create that oxidative stress. So it's really a lot about pacing. And they've even done research showing that if you drink a Coca-Cola slower, like over the course of an hour or two hours versus in five minutes, it actually has less of a damaging effect on liver because you have to think we're just made up of a ton of cells that are trying their hardest to process this stuff, right? And so if you can process and clear, process and clear, it's better than if you just jam it down your throat and overwhelm the enzymatic, all these enzymes in the body that are trying so hard to get through it. And then you end up creating excess of these damaging byproducts that ultimately
Starting point is 00:32:08 lead to organ dysfunction. So fructose is a big one. The second big one I would mention is the pro-oxa of stress inducing foods that come from more like refined fat. So it's like the seed oils that we talked about. Again, the name of the game is in many ways oxy of stress, which is this process that damages our mitochondria. So you want to avoid those refined seed oils that are in everything that's packaged. And you really be vigilant about looking at labels and trying to opt for things that only have oils like avocado oil, olive oil, coconut oil, ghee, butter that are less prone to oxidation. So are you saying this based on your data from levels around the refined seed oils or just in a general way?
Starting point is 00:32:56 Not saying that based on our data set. None of these actually, these ones for this question, not talking about our data set. The thing is about the data set is that what we're seeing is the real time response to different foods. But the next layer of this onion, when we have lots and lots of people using this type of technology over long periods of time is we think we'll start to see the longer term, the lagging effects of how these other products like fructose and refined seed oils and excess alcohol over the longer term lead to glucose instability. A lot of that we just don't have much knowledge about because we haven't been looking at pre-disease very much in our
Starting point is 00:33:40 medical system. We don't really study healthy people and how they go from healthy to pre-disease to disease because that's not the way that our healthcare system works. We wait until disease and symptoms emerges and then we react. And that's a problem. So I think we're going to see a shift here in starting to understand. But this is more based on what we just know from the mechanisms, the fructose and the seed oils. Take us through how fructose actually causes a problem. You eat fructose and how does it get all the way down?
Starting point is 00:34:11 Take us on the scientific pathways. So it turns out that, you know, almost all, basically anytime you eat calories, the calories are then, go in and they're used to help produce energy. And you produce energy. Energy is called ATP. And a lot of it is produced by these energy factories called mitochondria. So when you eat food, you're trying to make energy. And that energy is used to help us do whatever we want. There's really two, maybe three types of energy really
Starting point is 00:34:45 there's the immediate energy that we make which is called atp and that's what we're using to you know what i'm using to talk to you is on my brain is using atp etc if there's excess energy it can be stored as fat and stored fat is a stored form of energy. And then, you know, the burning of the production of energy can also generate heat and heat is kind of a wasted or dissipated energy. But anyway, basically when you eat food, you're trying to make energy. So, so when we eat a fructose, instead of making all the ATP we normally would make, we actually dampen the production of ATP and produce more stored fat. So the mitochondria, which are normally making the ATP, are suppressed. There's a suppression of the mitochondria. And so they make less ATP. And so
Starting point is 00:35:47 more of the calories that we're eating go into fat. And this is associated with a fall in ATP in the cell. So I call it a fall in energy. It's true. It's not a true fall in total energy because more stored energy is being formed. More fat is being made as there's less ATP being made. And so it's kind of shunting the calories to fat and reducing the amount of ATP. Now, when that happens, you have a lower ATP in the cell. And so your body reacts to that by saying, hey, I don't have enough energy i'm going to eat more i'm thirsty i'm going to drink more i'm going to forage for food you know this is uh it triggers these biologic responses that what makes you end up eating more and so forth and
Starting point is 00:36:39 eventually exercising less right and exercising less yes yes. So the way you're saying is that being overweight and storing the fat makes you eat more and exercise less. Yes, I guess that is the logic. Exactly what David said, yeah. So anyway, so the way it works is that when fructose is metabolized, there is this production of uric acid. Ah, now we're getting into it. Yes. And so uric acid is a breakdown product of energy. And what happens is, you know, we always use a little bit of energy to make energy.
Starting point is 00:37:24 So, you know, you have to use some energy to absorb the food you eat. You have to use some energy to break down the food we eat. Fructose is like all foods this way, but the enzyme that breaks down fructose, it breaks it down so rapidly and it uses a little energy in the process that there's a drop in the ATP in the cell to about, you know, goes down 30%. And that's not true for other foods. So this is unique about fructose. Alcohol does it too, by the way, but fructose is really the only food that really does it. And when that happens and the energy drops, it triggers a reaction. And that reaction, of all things, tends to remove.
Starting point is 00:38:10 You know, ATP gets converted to, you know, AMP, and then AMP goes back to ATP. But there's a reaction that sweeps away the AMP and makes uric acid from it. And now you can't rejuvenate your your atp very well it's hard to make it because you've removed you know it broke down and then you can't repair it so well because you've removed it to make uric acid okay that's a lot okay hold on hold on that's a lot i just want to unpack that because people are listening i'm trying to follow you and this is my thing so just let me unpack it a little bit because so we basically saying is you absorb fructose you eat fructose by the way when you eat fructose it uses extra energy to be absorbed so that causes an energy deficit then you store fat which actually
Starting point is 00:38:54 uh causes you to actually want to eat more but exercise less but then it when you're when you depleted the energy in the cell you actually cell, you create AMP, which is basically the byproduct of actually – Yeah, well, let me take you through this again. So what happens is when you eat fructose, you burn ATP faster than normal. And so that ATP level drops, and then there's the generation of uric acid from that. When the energy drops, that triggers a reaction to make uric acid. Got it. And then the uric acid goes into where the energy factories are, what we call the mitochondria,
Starting point is 00:39:41 and causes oxidative stress to those mitochondria. And that's the key. And that suppresses the mitochondria from making more ATP. So there's an initial consumption and then there's decreased production. So it's a double whammy. It's a double whammy. So it lowers the ATP, but then doesn't let you bring it back up very quickly. And so everything's kind of suppressed. Now you have a low ATP. And when that oxidative stress occurs to the mitochondria, it blocks the mitochondria from working, but opens the pathways to make fat. And it also blocks the burning of fat.
Starting point is 00:40:24 So there's this shunting of calories into fat and now the fat can't get burned so it starts to accumulate yeah but your your energy is still low so you've been eating all this food but your energy's still low so you keep eating and you keep eating until it repairs but what's happened is you've lost your control, your normal month that you would eat. No, now you're going to eat more and you're going to be accumulating fat. So it's this brilliant system by reducing the ATP. It reduces, it keeps that ATP level low and no other nutrient does that. It's just fructose. It drops the energy level and it makes you feel hungry, makes you thirsty, make you want to eat more. But instead of the food making the ATP levels go back up, the energy is going into the fat.
Starting point is 00:41:17 So the energy balance is maintained. Energy balance is maintained, but the energy is going into stored energy which is fat not and you know it's so the energy balance people you know the law of thermodynamics is true and and and but what's happening is your energy levels are low and you're still hungry so you're going to keep eating and so this is the trick but the key here is that is it you know thermodynamics who can argue with that it's physics and i'm not about to over turn the laws of physics and the mind of god okay but there that what people don't realize about the first law of thermodynamics which is basically all energy is
Starting point is 00:41:56 conserved right right it's it means all energy is conserved in a closed system so in a vacuum a thousand calories of broccoli a thousand calories calories of soda are exactly the same. They basically release the same amount of energy, which a calorie is the amount of energy required to raise one liter of water, one degree Celsius. That's it, right? And so you literally would create the same rise in temperature of the water with a thousand calories of broccoli or soda. But when you eat them, there's's all this other stuff's happening like you're talking about leaky gut and metabolic toxemia and exactly how it affects your liver and how it affects fat storage and atp so it's not a closed system so yeah the energy balance doesn't quite work in a closed in a in a metabolic yeah so if you give a thousand calories of sugar and a thousand calories of broccoli and you clamp me so that I
Starting point is 00:42:47 don't eat anymore because I if I eat the sugar I'm going to stay hungry okay I would eat more but you clamp me so that I don't eat anymore the the fat the calories from sugar are are going to activate uh cause oxidative stress to my mitochondria. And I'm going to start making fat from glucose and so forth that I have in my blood already. It's going to start working to make fat from what I have. So even though both groups got a thousand calories, I'm going to start getting fatty liver and I'm going to become insulin resistant and I'm going to get a leaky gut, all that thing from the sugar, even though they're the exact same number of calories. But if I measure my weight, it's going to reflect the fact that each group got a thousand calories. The only difference
Starting point is 00:43:39 is that the sugar also drops my energy metabolism. So it's going to make me gain a little bit more weight than the other one. But is that true? Is that true? Because they had a little study where he did this with rats, then he did it with humans. It was a feeding study where they took insulin-resistant patients and they kind of created a basic equalization in the patients. And then they had basically had
Starting point is 00:44:06 them do a crossover trial where they where they ate a high fat low carb diet or a high carb low fat diet and and the ones when they were eating the high fat low carb diet they burned 400 more calories a day even eating the same amount of calories like they're eating the same amount of calories so the energy balance thing i just wonder how does that yeah yeah on the low carb diet they're gonna burn more calories and on a high carb diet they're gonna burn less calories so um so if you even if they're getting the same number of calories, okay. So the energy balance equation says that my weight is going to reflect how much I eat and how much I burn. And if we have everyone eat the same amount, but one's a low carb, high fat, the low carb is going to cause more calories to be burned. So the burning,
Starting point is 00:45:07 it doesn't relate to how much comes in. It relates to what you're eating, right? Yeah. So, so when you have a high carb diet, you want to eat more and you want to burn less. And if you eat a low carb diet, you're going to want to eat less and burn more. A low-carb diet is great. You and I both know this. And so a low-carb diet is going to create more satiety. You're going to feel more full easily. But let's say, for argument's sake, let's say, okay, I mean, obviously we should be eating high fructose corn syrup we should be in junk food processed food and most people are aware of that but let's talk about carbs kind of in the context of this fructose conversation because
Starting point is 00:45:53 you know it wasn't that david was feeding these people a high fructose corn syrup diet they were eating like a high starch diet which was beans beans, grains, healthier starches. And yet, you know, when you look at the, you know, the data with vegans and meat eaters, it's super confusing. And I think people are trying to sort through what makes sense and is a vegan diet a healthy diet or not? And how does this relate to this conversation about fructose and insulin resistance? Well, there is a big story here, which we haven't really talked about. And that is, you know, originally when I was studying this, I was focused on sugar and high fructose corn syrup
Starting point is 00:46:35 because they contained fructose. But people pointed out to me that things like bread and starch can also cause obesity. And so how can I account for that? If it's, if the story is about fructose and if you, you know, look in the wild, there are a lot of animals that will get fat that are not eating fruit or fructose, you know, they're, you know, how does the whale get fat? Not just eating berries, right? The whale.
Starting point is 00:47:07 They're not eating too many berries, I don't think. So the question was, you know, what is that? And we realized that the body can also make fructose. It isn't just about the fructose that you eat, but it's also that the body has one way it can make fructose and it makes fructose from glucose. And so what we did is we did a study where we gave glucose in the drinking water to mice. And lo and behold, they became fat and insulin resistant and diabetic, all the, all these things. And they weren't eating fructose.
Starting point is 00:47:47 They were eating starch or glucose, pure glucose, glucose. And so we said, you know, how can this be? Is it maybe it's the glucose insulin pathway? And so what we did is we we looked in their bodies and we found that when they're eating a lot of glucose, that they were making fructose in their bodies. And so what we did is we gave the glucose to animals that could not metabolize fructose. So these mice are eating glucose, they're making insulin, but they're not able to metabolize fructose. And they were, guess what? They still gained weight, but not as much.
Starting point is 00:48:32 It was much less. And they still got a little bit of fat, but not as much as the control animals, even though the control animals were eating the same amount. And, but what was striking was the fructose resistant or the animals that could not metabolize fructose, they were completely protected from insulin resistance. They were completely protected from fatty liver. Even if they had a lot of glucose. Yeah. And they were not eating fructose. They were making fructose from the glucose. And so what we now know is that high glycemic carbs cause obesity two ways. One way is because when the glucose goes up in the blood after you eat these things like bread, rice, potatoes,
Starting point is 00:49:23 it makes your glucose go up in the blood, And that triggers the production of fructose as well as the secretion of insulin. And the insulin is driving a little bit of the obesity. This is what Dave Ludwig's work has shown. Yeah. But, but, but a lot of the obesity is driven by the production of fructose and fructose is actually what's responsible for activating the switch so it's what makes the fatty liver and the insulin resistance and all this stuff and then then we said oh my god there's another way to get fat uh from fructose and that's to make fructose wow so basically you're screwed because if you're eating you know bread whatever you think oh it's got no fructose but actually it's starch is basically a lot of glucose
Starting point is 00:50:09 molecules stuck together. That in itself can generate through this pathway, more fructose in the body, which then causes more fatty liver, more weight gain and vicious cycle of pre-diabetes and diabetes. So now the high fructose corn syrup and the table sugar is a double whammy because the, they contain fructose, but they also contain glucose. And as you mentioned earlier, you know, drink, if you eat fructose, it's a little hard to absorb it. And, but if you mix it with glucose, you can absorb the fructose really easily. And the fructose also increases the glucose absorption. So you're getting a double whammy when you're drinking a soft drink, you're getting the fructose in the soft drink, and then the glucose is coming in and it's stimulating insulin,
Starting point is 00:50:54 which isn't so good, but it's also being converted to fructose. And then the fructose causes insulin resistance. And then that makes the insulin levels high all the time. And that helps block the fat from burning too. So now, now you've got this big story where, and then you realize why low carb diets are so beneficial, why you can go on a low carb, high fat diet and not gain weight because the low carb is blocking both the starches and the fruit dose, which are really key for activating the switch. I hope you enjoyed today's episode. One of the best ways you can support this podcast is by leaving us a rating and review below. Until next time, thanks for tuning in.
Starting point is 00:51:41 Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It's important that you have someone in your corner
Starting point is 00:52:09 who's trained, who's a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.

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