The Melanie Avalon Biohacking Podcast
The Melanie Avalon Biohacking Podcast

Episode 1 · 8 months ago

#146 - Dr. Rick Johnson: Fructose & Obesity, The Survival Switch, Salt & Weight Gain, Stimulating Fat Production, Uric Acid, The Polyol Pathway, Metabolic Syndrome, And More!



2:05 - IF Biohackers: Intermittent Fasting + Real Foods + Life: Join Melanie's Facebook Group At For A Weekly Episode GIVEAWAY, And To Discuss And Learn About All Things Biohacking! All Conversations Welcome!

2:15 - Follow Melanie On Instagram To See The Latest Moments, Products, And #AllTheThings! @MelanieAvalon

3:00 - AVALONX SERRAPEPTASE: Get Melanie’s Serrapeptase Supplement: A Proteolytic Enzyme Which May Help Clear Sinuses And Brain Fog, Reduce Allergies, Support A Healthy Inflammatory State, Enhance Wound Healing, Break Down Fatty Deposits And Amyloid Plaque, Supercharge Your Fast, And More! 

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5:10 - FOOD SENSE GUIDE: Get Melanie's App At To Tackle Your Food Sensitivities! Food Sense Includes A Searchable Catalogue Of 300+ Foods, Revealing Their Gluten, FODMAP, Lectin, Histamine, Amine, Glutamate, Oxalate, Salicylate, Sulfite, And Thiol Status. Food Sense Also Includes Compound Overviews, Reactions To Look For, Lists Of Foods High And Low In Them, The Ability To Create Your Own Personal Lists, And More! 

6:00 - BEAUTYCOUNTER: Non-Toxic Beauty Products Tested For Heavy Metals, Which Support Skin Health And Look Amazing! Shop At For Something Magical! For Exclusive Offers And Discounts, And More On The Science Of Skincare, Get On Melanie's Private Beautycounter Email List At! Find Your Perfect Beautycounter Products With Melanie's Quiz:

10:50 - Beginning Of Fructose Research

14:30 - How Sugar Can Cause Weigh Gain Independently Of Caloric Intake

17:30 - Leptin Resistance

19:20 - BEAUTY AND THE BROTH: Support Your Health With Delicious USDA Organic Beauty & The Broth Bone Broth! It's Shelf Stable With No Preservatives, And No Salt Added. Choose Grass Fed, Grass Finished Beef, Or Free Range, Antibiotic And Hormone-Free Chicken, Or Their NEW Organic Vegan Mushroom Broth Concentrate Shipped Straight To Your Door! The Concentrated Packets Are 8x Stronger Than Any Cup Of Broth: Simply Reconstitute With 8 Ounces Of Hot Water. They’re Convenient To Take Anywhere On The Go, Especially Travel! Go To Melanieavalon.Com/Broth To Get 15% Off Any Order With The Code MelanieAvalon!

23:10 - Defining Glucose, Sucrose, And Fructose

26:55 - "Tasteless" Mice

28:00 - Craving Sugar 

31:20 - 5 Great Tastes

33:00 - Artificial Sweeteners

34:00 - Blocking The Fructokinase In The Liver

36:00 - How Fructose Tricks The Body

42:10 - How Fructose Uses Glucose To Create Fat

50:00 - Polyol Pathway

51:40 - Stress & Dehydration

53:50 - Salt

57:00 - NUTRISENSE: Get Your Own Personal Continuous Glucose Monitor (CGM) To See How Your Blood Sugar Responds 24/7 To Your Food, Fasting, And Exercise! The Nutrisense CGM Program Helps You Interpret The Data And Take Charge Of Your Metabolic Health! Learn More About Nutrisense In Melanie’s Interview With Founder Kara Collier At Get $40 Off A CGM At With The Code MelanieAvalon

1:00:30 - How Hibernation Mimics Metabolic Syndrome

1:04:30 - Evolutionarily, Where Did This Start?

1:07:45 - The Natural Fasting Cycle

1:08:30 - The Role Of Fructose In The Cells, AMPK, And AMPD

1:16:00 - What Happens When You Combine Starvation With The AMPK Pathway?

1:21:00 - Starvation Mode

1:24:30 - What About Whole Fruit? The Role Of Vitamin C

So we think that the craving is linked with the gut and that there's a gut brain pathway. The liver, though, is the place where the actions. The glucost goes up in the liver and in the blood, and that triggers the production of truth does. So now you have another mechanism that could drive obesity. Not just insolent, but truth does. which organ is responsible for what effects? The liver. That's the place that drives whether or not you're going to get fat or diabetic. Welcome to the Melanie Avalon biohacking podcast, where we meet the world's top experts to explore the secrets of health, mindset, onevity and so much more. Are you ready to take charge of your existence and biohack your life? This show is for you. Please keep in mind we're not dispensing medical advice and are not responsible for any outcomes, and we experience from implementing the tactics mind hearing. Are you ready? Let's do welcome back to the Melanie Avalon biohacking podcast. Oh my goodness, friends, I am so, so excited about today's episode. I Love Rick Johnson, I love his work, I love what he's doing he's also just the kindest, most intelligent, savvy human being. I am so honored to finally connect with him. I have been a fan of his work for years, honestly years, and so to have him on the show now and become friends with him is just so wonderful full and just say you know how much I really appreciate his work. We don't normally have guests on the intermitted fasting podcast and I invited him to come back on that show because that's how valuable I think his work is. We dive deep, deep, deep into so many things in today's show, the role of fructos and uric acid and health, the metabolism insulin, what really is behind waking and so much more. I think you guys will love it and, as we do dive deep, definitely check out the transcript that will be in the show notes at Melanie Avaloncom Fructos and there will be two episode giveaways for this episode. One will be in my facebook group. I have biohackers. intermented fasting plus real foods plus life. Comment something you learned or something that resonated with you on the pinned post to enter to win something that I love and then check out my instagram. Finally, Friday announcement post there and comment to enter to win something that I love. And again, friends, people to not take me up on this. You have a very good chance of winning. So definitely check that out. If you're enjoying the show, it would mean the absolute world, world, world, if you could take a brief moment and write an itunes review. It helps so much more than most people realize. It just takes a moment. It can literally just be like one sentence. Like I like the show and it really, really, really helps. So thank you so much in advance for that. Okay, super exciting updates and announcements. I know you guys are so, so excited about my upcoming magnesium supplement. I know I'm excited. I get questions from you every single day about when am I releasing it. It is coming soon, soon, soon, soon. Make sure on my email list for all of the updates. That's at avalon x dot us, a va Lon x dot US email list. Friends, my magnesium is honestly going to be the best on the market. It is called magnesium spectrum eight and that is because it has eight, yes, eight, forms of magnesium. Why is magnesium so important. It's actually involved in over three hundred enzymatic processes in the body. Basically everything that you're doing, magnesium is probably involved. And we are so deficient today in magnesium because our soils are magnesium depleted and that's historically where we would get it would work its way up the food chain. Stress also deplete magnesium and if you just look at our world now, you can probably see that we're a little bit stressed and that our magnesium levels are probably deficient. 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And if you want it at a major discount, you will get a code for that when you buy our magnesium spectrum eight at launch, if you get it before it cells out, which I anticipate that it might, so definitely be ready to buy magnesium spectrum a right at launch. And, of course, if you'd like, my Sarah Pep taste, which was my first supplement and which I hear so many incredible testimonies from you guys, including how it's clearing your sinuses, reducing your allergies, clearing your brain fog, helping with your pain and information. I love this your up days so much.

You can get it at avalon x dot us and I'll put all this information in the show notes. Another resource for you guys. Do you struggle with food sensitivities like I do? If so, you've got to get my APP foods since guide. It's a comprehensive catalog of over three hundred foods for eleven potentially problematic compounds. These include things you may be reacting to like Luten Lectins, solicillates, soul fights, THY alls, oxalates, Histamines, whether or not something as a night shade and so much more. I created it to take charge of my own foods insitivities and using it, you can learn about the compounds, create your own list to share in print and finally take charge of your foods insitivities. It is a top itunes APP. I just checked and right now it is way for it lucky number thirteen and itunes food and drinks charts. You can get it at Melanie avaloncom. Food since guide. And one more thing before we jump in. Oh my goodness, friends, I just got back from Washington DC. I went on a trip with beauty counter to advocate for safe skin care and make up. Yes, beauty counter is a company that is working so, so hard to support our safety in the cosmetic and skin care industry, because conventional skin care and makeup is full of toxins and there is essentially no regulation by the government for this. That means toxic products can be on the shelves, they can be found to be toxic and the FDA has no power to recall them. This is such a problem. Thankfully, beauty counter was founded on a mission to change this. Every single ingredient is extensively tested to be safe for your skin, so you can truly feel good about what you put on. And, on top of that, the products really work. They're amazing. Oh my goodness. I use the overnight resurfacing feel and vitamin CCRE I'm every single night of my life, as well as the countertime ultra renewal I cream. They have the entire counter timeline for aging skin, countermatch for normal skin, counterstart for sensitive skin and counter control for oil and ACMEE prone. And I love their make up. Check out my instagram. We see what it looks like. Tina fe even war all beauty counter makeup when she hosted the Golden Globes. Yes, it is high definition camera ready. You can shop with me at beauty countercom slash Melonie Avalon, and if you use that link, something really special and magical might happen after you place your first order. Also, definitely get on my clean beauty email list. That's at Melanie avaloncom clean beauty. I give away a lot of free things on that list, so definitely check it out and you can join me and my facebook group clean beauty and safe skin care with Melanie avalon. People share product re views and I do giveaway every single week in that group as well. And lastly, if you're thinking of making clean beauty and safe skin care a part of your future, like I have, I definitely recommend becoming a band of beauty member. It's sort of like the Amazon prime for clean beauty. You get ten percent back and product credit, free tipping on qualifying orders and a welcome gift that it's worth way more than the price of the yearlong membership. It is totally completely worth it and I'll put all this information in the show notes. All right, without further ado, please enjoy this wonderful conversation with Rick Johnson. Hi, friends, welcome back to the show. I am so, so incredibly excited about the conversation that I am about to have. So here is the backstory leading up to today's conversation. I historically have been very, very fascinated with energy generation and the body energy processing, even down to the granular effect of glucos versus frukedos versus Sucros. It's just been a little miniature obsession of mine, which is all I would say. It's a weird thing to be obsessed with, but if that's the case, then me and today's guests are both in on it. But in any case, back in two thousand and twenty I listen to Peter Tia's first interview with Dr Richard Johnson. He is an MD professor of medicine at the University of Colorado, and I was so excited because I finally was hearing somebody talk in the deep detail and nuance about fructose metabolism like I like I had been wanting for so long. And then what's really interesting is ever since listening to that, then I started seeing Dr Johnson's name everywhere because I realized what I've been reading all of these studies online. Sometimes they were his papers or he would be referenced in other papers because his work is just so expansive and really revolutionary in Understanding Metabolic Syndrome, again, fructos, the obs epidemic, so many things. So needless to say, that was two thousand and twenty eight. He immediately went on my list of ideal guests ring on the show. And then rick was coming out with a new book called nature wants us to be fat, the surprising science behind why we gain weight and how we can prevent and reverse it. And I think actually his publicists reached out to me and I was so, so excited because I'd been dying to interview him. Got The book, dived into it. It's incredible. It is so comprehensive. It goes into so many things. Fructos, the OBS epidemic, this thing called the survival switch, hibernation and animals and what that means, uric acid, the polio pathway, lots of keywords.

I'm sure we will dive deep into all of it, but I'm just really, really excited and I have like thirty pages of notes. So, Rick, thank you so much for being here. Melody, thank you so much. It's really a wonderful thing to be on your show. As I mentioned, you know, you've had so many experts on the show. I'm very happy to to come up aboard and to try to share with you what I have learned from my research. Yes, I am. I'm so honored for you to be here and actually we're talking about out this before, but Dr David Pearlmotter wrote the forward to your book and I'll actually be bringing him on soon for his book all about uric acid, which you talk about as well, and nature wants us to be fat. So all goes together. So many awesome topics. But to start things off, for listeners who are not familiar with your work, would you like to tell them a little bit about yourself? What led you to your obsession with Fructos? And you talked about this in the book, but just in your own words. Why are you doing what you're doing today? Well, I tell you I've been very interested in the causation of diseases. Ice Trained as a kidney specialist, so I was beginning my began my career by studying kidney diseases and I realized that kidney disease is very much linked with high blood pressure and four years it was thought that high blood pressure is a kidney problem in which the kidney has trouble excreting salt. In the process of studying the role of the kidney and high blood pressure, we realize that uric acid was playing a role in the path of genesis or in the cause of high blood pressure. And so as we studied that, we began to realize that not only was uric acid important, but we began to realize there are a lot of people with hi uric acid. If you go back fifty years or a hundred years, the prevalence of high uric acid was much lower, and so the uric acid levels have been increasing dramatically over the last century or so. And so then that question was, well, what's driving the uric acid up? And there many types of foods that do it, but one that is really good at doing it is sugar, and sugar contains fruit dose and it's actually the fruit dose component that drives the uric acid up. So we thought, well, let's see what happens if we give fruit dose to animals to raise the uric acid. Will they develop high blood pressure? And they did, and then when we lowered the uric acid we could lower the blood pressure. But then there was the twist. My Friend Taka Nakagawa, who was working with me, said, Hey, when we lowered the uric acid, we didn't just lower the blood pressure. The animals didn't gain weight as much, they didn't gain as much fat. They seem to be protected from the effects of sugar, and I said, well, that can't be. You know, how could lowering uric acid affect weight gain in animals receiving sugar? Because it didn't block their ability to eat sugar. They were still eating the sugar. And so at that point we realized that there was something besides calories the way that sugar was causing disease. And this was in two thousand and five, two thousand and four, and everybody was thinking it was all calories back then. So that turned me on to realize that that fructose was causing obesity and so far through a mechanism that somehow involved this substance, yuric acid, and that it wasn't, you know, classically involved with the calories, but with other things that that fructose was doing, and that led to hundreds of studies. Actually it's it has been hundreds of studies. It's a sad statement of how old I am. We did lots of experiments, let's say that, and we did those to try to figure out what fructose was doing, how it related to sugar and so forth, and so that's how I got in there. So I started as a Guinea dock and then switched into kind of studying obesity and diabetes pretty early on, you know, now twenty years ago. So wow, that is incredible. So with the yoric acid studies, when you reduce the York acid, was there any change in the animals how many calories they took in at all? So, no, it did not have as much effect on on calorine take it hat. It had some but not a dramatic effect, but it did. It did block weight gain and so it did reduce the food and take by some some level, but it wasn't a dramatic effect, you know. But later on we wanted to understand how sugar causes weight gain. So we began to do studies to try to separate calories from other mechanisms,...

...and so we did figure out that sugar can cause obesity and sugar can cause obesity independently of eating too much calories. It increases the fat in you and increase can cause insulin resistance and diabetes, even if you reduce your diet so that you're on a caloric restricted diet. So if you go on a actual diet where you cut back on calories and you eat a high sugar diet or high fruit dose Diet, you can still induce features of Fatty Liver Metabolic Syndrome, insulin resistance and so forth, even though you're on a diet. And interestingly, in our in our studies, most of the weight gain from sugar is by making you hungry so that you eat more than you normally do. So there is a calorie component to how sugar works. Sugar does make you hungry, so you eat more than you normally do and that certainly helps with weight gain. So if you're eating more and especially if you eat foods that are have a lot of calories, like fat, if you combine sugar with fat, animals will gain weight very rapidly. Now, if you give them fat alone, they don't really gain as weight that much because they control the most of them will control their weight. But you give them sugar, that makes them hungry so that you eat, you will eat more. And then when you give them fatty diet and it makes a difference. And that's why I low carb Diet. You know, if you're in a low carb diet, you can eat a high fat diet and you aren't going to gain weight because you don't have the hunger. And so you know the low carb diets. Great, you don't have to calory restrict because you naturally calorie restrict because you're not hungry. But when you give fruit dose, you make an animal will become hungry. Interesting it takes a few weeks. So if you if you just give sugar for one week to an animal, they control their weight, but if you give it to them for like a three weeks or four weeks, they suddenly get really hungry and we found that that was because they become resistant to Leptin. And left in is this hormone that goes up when we eat and says hey, your fall, don't eat anymore. But people who are overweight tend to be resistant to the left in and so they will continue to eat even though they have high blood levels of Leptin. In fact, the way we test for left in as we inject an animal would leapt in. And if they're resistant they'll continue to eat and if they're not resistant they'll they'll quit eating or or really reduce their food. And when you give them sugar or FRUC dose, after about a month, if you give them left in, an injection of left and, they'll keep eating like nothing has happened. But if you give the leapt into a normal animal or an animal and a high fat diet, they will reduce their intake. So there's something special about the fructose that makes you hungry and then you eat more. But even if you put the animal on a diet so it can eat more, even though it may be hungry, you can't. You don't allow it to eat the food. You know, you take away their food so they can't eat it. They will still develop Meta box syndrome. And interestingly, in our clinical trial, I mean are not clinical trial, in our experimental trial where we did this, the animals that were on a diet where we calorically restricted them, the controls loss about ten grams of way, and the ones that got sugar, even though they were on the same exact number of calories, they gained like twenty gramps. But it wasn't statistically significant, and it wasn't because it was a relatively short study. But when you take fructose, two things happen. One as you get hungry and the others you reduce your metabolism, so you you're spending less energy. So they if you give an animal fructose, they start sitting around more. They basically become couch potatoes. Melanie. Hi Friends, I'm about to tell you how you can get fifteen percent off of my favorite bone broth, which is an incredible way to open your eating one down. Also for all of you vegetation rands and Vegans, stay tuned, because there's something for you too. I've been talking about the incredible health effects of bone broth for years. Bone Broth is so nourishing for our body. It's rich in Collagen, which can really support your gut, help your skin, curb cravings, boost your energy and your immunity. But there are a lot of brands out there. A lot of them have ingredients that I don't like, and making it yourself can also be very time consuming. That's why I am thrilled about beauty and the broth. So beauty... the broth was created by Melissa Bologna. She's an incredible actress and entrepreneur. I've had her on the Melanie Avalon biohacking podcast, so I'll put a link to that in the show notes. But Melissa started beauty in the broth after she realized the profound effect that bone broth was having on her own health, specifically gut issues, and its ability to give her radiant skin perfect for the camera. She found a beauty and the broth which hits everything I could want in bone broth. It uses one hundred percent whole organic ingredients. Yes, it is certified USDA organic. It is one of the only few bone broth companies in the entire us that has a USDA certification for organic bone broth. It has no artificial flavors, no preservatives, no thalets, no sugar and, something that I love, no salt. Friends, even other bone broths that I really love always have salt at it. This doesn't. Her Bone broths are made from grass fed ranch raise beef and vegetarian fed free range chicken bones from certified humane USDA organic arms, and all certified organic vegetables are used in the broth as well. There's no antibiotics, no hormones, only the good stuff. And here's the super cool thing about beauty and the broth. It can be a little bit of a hassle to transport bone broth. It's heavy, you have to keep it frozen. Guess what? Beauty and the broth comes in shelf stable packets with no preservatives that you keep it room temperature and they are in concentrated form. That means that you add back water to reconstitute and you can make it any strength that you like. They're single serving, so you can take them with you on the go and even on the plane as yes, they are three ounces and they're delicious. Oh my goodness, friends, they will just make you light up. They're honestly one of the most amazing things I've ever tasted. And for all of you vegans and Vegetarians, beauty and the broth has a brand new vegan broth concentrate. It is US DA organic and is a slow simmered broth which is reduced into a thick gelatinous Gel. You Mix it with hot water and turn it into a delicious sipping broth. It features organic mushrooms and chick peas, Ginger, seaweed and P protein. It is so delicious. So definitely check that out. So if you've been looking to finally jump on the bone both train, do it now and do it with beauty and the broth. And Melissa has an amazing offer just for our listeners. You can go to the beauty and the brothcom or Melanie avaloncom broth and you see cupon Code Melanie Avalon to get fifteen percent off. That's the beauty and the brothcom with the Cup on Code Melanie Avalon for fifteen percent off. All of the listeners who have tried it ever since I aired my episode with Melissa have talked about how much they love it. It is so delicious. You guys will definitely love it. So definitely check that out. And, by the way, bone broth does break your fast, so this is something that you want to have in your eating window. In fact, it's an amazing way to open your eating window because when you're in that fast at state, when you take in bone broth as the first thing, all of those rich nutrients and Collagen go straight to your gut. Help heal your gut, help with leaky gut, help digestive issues. And again you can go to the beauty and the brothcom and you see keup on Code Melani Avalon for fifteen percent off. And I'll put all this information in the show notes. All right. Now back to the show. To take things back a little bit for listeners, because we're using the words sugar and fruit toast. So when you say sugar, are you referring to sucross primarily, which would be fruit toose and glucose, or you are using sugar as a synonym for fruit toes. Maybe you could tell listeners suecros versus glucose versus fruit tost what those are. Yeah, absolutely, I'll define it and then I'll be careful moving forward how I use those terms. So fruit dose is the sugar that is classically in fruit. We think of its fruit sugar and it's in fruit and it's in honey. These are things that we think of as good, right. And then fruit dose is also in table sugar and high fruit dose Corn Syrup. And so table sugar is sucross and it's what we call a die a SACURA. What it is is it's a fructose and glucose bound together. So when you are eating sugar, table sugar, half of it is frucdse and half of it is glucose. Then when you take when you eat high fructose corn syrup, you're also eating a mixture of fruc dose and Glucose, and Glucose is usually a little bit less than fructose in the high fructose Corn Syrup in terms of the ratio. So fructose is typically fifty five or sixty percent, and glucose is typically like forty five or forty percent. They do that because fructose is what gives sugar the sweeter is really responsible for the sweet taste. Glucose has a very, very mildly sweet taste, and so people like the sweetness and turns out they prefer to have something like fifty five, two hundred and forty five is like the ideal amount that people tend to like. And if it's too high then it gets...

...too sweet and people don't like it, and if it's lower, they tend to want that fifty five forty five ratio. So most soft drinks that have high fructose corn syrup have fifty five percent fructose in it. But like in Fountain Drinks, where you the people mix it slightly different, the fructose content can go up to sixty or sixty five percent of the drink. And so for people, for us, when we go to the grocery store, most of the fructose we get, most of the vast majority of fructose we they average person eats comes from added sugars. These are table sugar, sucrose, which has half fructose and high fructose Corn Syrup, and and what's terrible is that high fructose corn syrup is a liquid and it can be mixed into foods easily, and so there are many, many processed foods that have sugar in them, or when I say sugar I mean table sugar or high fructose Corn Syrup in them. And sometimes it's subtle where you can't eat when you think about you, when you eat it, you don't think they're sugar in and then someone says, Hey, you know, it tastes a little sweet in it, and then you look at the package and it is. You know, you like wheat, thence I love. When I was a kid I loved wheatnds. I don't know if you ever had those crackers, but if you taste them there's just a tiny but of sweetness to it. And so people do this and and one of the terrible things that we in experiment, and when I say terrible I don't mean terrible like terrible science, but you know something I was hoping I wouldn't see, and that was when we knocked out the sweet taste in so that a mouse could not taste sweet. In fact, we knocked out all taste. So these are called tasteless mice. They can't taste anything. They still like sugar, they still like fructose, they still like glucose, they like it eat and so they get a dopamine response in their brain even though they can't taste it. So even if you can't taste the sugar, if it's there, maybe it's encouraging you to eat it. Not only that, those tasteless mice became fat when we offered them sugar water or regular water. They're still sensitive to the effects of sugar, and so it just shows that it's not taste that's responsible for how sugar causes obesity. It isn't because it tastes good so you go back and eat more. That's not the mechanism. It's actually how it's metabolized and it's linked with this uric acid and that's how it works. So yeah, bad news. You also discussed in the book about how the cravings were also determined, about if it was metabolized in the intestines versus the liver, right with the enzyme. Yeah, so this was also kind of an exciting finding. So one of the things we know is that when you eat sugar, even if you can't taste it, you end up by craving for it. And so the another question came is, is it craving a sugar? Is that what causes you to become obese, or is it not from craving? What we did was we could create a mouse that could only metabolize fructose in the in certain organs are you know, so we could we could knock out the ability for the mouse to metabolize fructose, like in the gut or the liver, the brain, and when we did that we could we could figure out, you know, which Oregon is responsible for what effects. And what we found was that the liver, that's this the place that drives whether or not you're going to get fat or diabetic. Because when we knocked out the metabolism of fructose in the liver, we could block how sugar caught or fructose causes obesity, we could block how fructose causes diabetes. So if we could just block the metabolism of fructose in the liver, you can eat all the fructose you want, but you're not going to get fat. And interestingly, when we knocked it out of the liver, the animals still loved sugar, so they could eat all the sugar they want. But they wouldn't gain weight. So it was the liver that was responsible for the whole thing it, but they still it wasn't responsible for the craving because they animals that we knocked it out of the liver, they still love sugar. So then we knocked it out in the intestines and they reduce their sugar and take dramatically. It was like they didn't really care for sugar anymore. So we think that the craving is linked...

...with the gut and that there's a gut brain pathway involved in craving, and the liver, though, is the place where the action is. Yeah, kind of interesting. Yeah, you know, when you combine like a little bit of research like this kind of stuff and you also do studies and people and try to do things like in nature and so forth, you get a lot of insights, and so these are we were able to better understand how sugar works. So does that suggest that in general, are cravings are primarily determined by our intestines and our taste is actually just an avenue to find the things that will get rid of those cravings rather than cravings originating from our taste itself? Yes, I think taste is a secondary mechanism are. This is really kind of interesting. There's five tastes right. Two of them are bitter and sour, and those two tastes are there primarily to protect you from eating things that could hurt you. But there're three great tastes that are all taste that people love, and some people love one taste more than another. So some like sweet, some like salt and some like Umami. I love you, Mommy. I love a mommy. So the good nose is okay. So there's bad news and good news, you know. So it turns out that sugar is the number one and when I say sugar, I mean fruit dose containing sugars. That's the number one way to become overweight. And and the sweet taste is trying to drive you to pick out sweet foods that might have fruit dose in it. So the sweet taste receptor is there to help you find those foods. Now you will be come addicted to the food, even if you can't taste it. But it is true if you knock out the taste, they'll eat less, so they'll eat last, but they still prefer it to water. So like if you know, if you give them water or sugar water. They'll prefer the sugar water even if they can't taste it, but they will reduce the amount they drink, but they still get fat. Equally Amazingly, if you give them artificial sweeteners, they don't care for the artific you knock out the sweet receptor, they don't care for artificial sweeteners anymore. Artificial sweeteners is primarily driven by taste. That makes sense because with artificial sweeteners it's not actually fulfilling the guts craving, like the intestinal craving, but it's tricking the taste to make the guy think it's coming. But since it doesn't come, it makes sense that you wouldn't have that effect. And and the bad news about artificial sweeteners is they keep you kind of hooked on the likeness sweetness. So the biggest problem with the artificial sweeteners is not that they cause obesity. They make one of them may cause a little insulin resistance. But we've done many experiments with artificial sweeters. They don't cause obesity, but they do make you seek sweet foods. So in that process you can't completely get rid of your craving for sweets. And so that's all that biology is fighting you. Now your end up still wanting sweets. So it's hard to in the long term not to have some sweets here and there that you would not necessarily feel the urge for if you weren't on those sweeteners. Going back to the other piece, blocking the fruit to kindness in the liver, just the organism not experience the metabolic effects because it's literally blocking the calories? Or is it something beyond that? Because if you're blocking the preto kindness and the liver, then you're just literally not getting that fuel source right. Yeah, so, so the liver does seem to drive a lot of things, even in the periphery. The part that amazed me was that it blocked accumulation of fat in the adipose or fat tissues. So you know, I was pretty sure would block the fat accumulation in the liver because it's in the liver and we know that you if you block that fructose metabolism in the liver, you block fatty the development of fatty liver. That made sense to me. But what was interesting was that it blocked the fat accumulation in the periphery, and so there's a communication exactly. You know how this works. We haven't totally figured out. It's sort of our next series of studies is to...

...understand communication from the liver to the brain, from the liver to the fat. And there's you know, but we see all kinds of evidence, you know, that it's affecting all these peripheral mechanisms. So the liver seems to be like a sort of like conductor and it's working through the liver. It's working and in the peripheral tissues as well. So we'll have to figure out exactly how that works. Uric acid is is likely involved to some extent because it is produced heavily in the liver and then it gets in the circulation. So there's some data to suggest that that's one of the cues driving that. I don't think it's the only one. It's involved. So it's blocking the fat generated from the fructos or it's blocking fat in the meal in general going into oudipose tissue. So this is a big question, melity. It absolutely great question. So a long time ago people were thinking that it was known for a long time that if you gave fructose to people that triglycerides go up in the blood like thirty minutes later or four hours later, I'm sorry, it's four hours later, and the consumption was that those triglycerides we're coming from the fructose itself, so that when the fructose is broken down, components of you know, of the breakdown products and then get turned into fat. And there is some breakdown products of fructose that do go into fat, but, you know, it was a very small amount. It could it couldn't account for this big rise and triglyceride. So the really fantastic discovery was done by my partner, Miguel LANASPA, and he was studying how fructose works and what he found was that there was that when you eat fructose, that there's this thing called oxidate is stress that occurs. There's a burst of kind of a this kind of chemically reactive oxygen that's produced in the liver cell and that affects the Mitochondria and it's driven by the uric acid. Remember, we knew that the uric acid was involved and that oxidata stress kind of stunts the minor Chondria and what it does is it sets up for fat production from from precursors of fat that do not have to necessarily be from the fructose. So it's sort of stimulates other you know, glucose and other things present and fatty acids and so forth. It stimulates them to start making fat. So the fat doesn't actually come from the fructose, it comes from the other nutrients that are there. And so it turns out that fructose itself is sort of like glucose. It's just a sugar, that it's a type of sugar, not table sugar, but a type of sugar in the global sense, and and that, you know, it can be broken down to make energy and it can be turned into fat and glycogen. But fructose activates another process that tries to stimulate fat, not even from its own molecule but from other other things present, and it stimulates hunger, which makes you want to eat other foods. And it's not just sugar that you want to eat. It does cause craving of sugar, right, but it or sweet, but it also makes you eat more food, even if you can't really taste it. So this leapt and resistance kicks in that makes you hungry. So fructose is a different beast and and we've kind of fell into the big mechanism by which it works and it's sort of interesting because it's a nutrient, and so nutrients are provide calories and calories give us energy. And when we get energy it's either an instant form of energy, what we call ATP, which is made, you know, largely by Mitochondria and other mechanisms and it and it makes stored energy, and stored energy is like fat or glycogen. And so whenever you eat your you know, it's used to drive biologic act you know, how we live and move and act and think. That's, you know, we need calories for that. And some of the calories converted to instant energy and some of US converted to stored energy. And what fruited us does is it creates an alarm signal because it drops the instant energy by, you know, ten or twenty...

...percent. And when it end what it does is it's tells the animal that that there's some kind of alarm going on, that you don't have quite enough food, and so that's what seems to trigger food and take fat accumulation. Everything is like, Oh, I'm running low on my stores, and so it stimulates what one of my friends called an insurance plan. It's like starting fruited US stim lights an insurance plan. It isn't really it's triggered sort of by starvation, but it's not starvation, it's just a drop in the energy in the cell that makes the animal feel like it doesn't have enough things, enough fat, stored away. So when that happens it stimulates more fat storage and it does that even though you already may have fat. So it tricks you. So you actually may have all this energy available, you have of this this fat like Agen that are stored energy. But when it drops the immediate energy, it tricks you into thinking that there's not enough energy around. So you you make more fat. So it's a way to increase your fat. So all all animals, all of us, have ten you know, some body fat. We didn't have anybody fat, we'd be really in trouble. But everybody has somebody fat. And what this does is when you eat frukedos, it wants to increase your body fat, no matter where you start. So if you're at ten percent body fat, it wants to make it fifteen percent. Of you're at fifteen percent, it wants to make you twenty percent so forth. So fruit doses and insurance plan aimed at increasing your fat stores while Glucose is kind of the immediate fuel. It's there to really make immediate energy that you can use right away. So the two sugars are look very similar in composition. Once there to make immediate energy and once there to make stored energy. I have a question about that. I want to clarify one thing before that, when you were talking about how fructose does not itself create a lot of fat stores from the fructose. Rather it's how fructose affects the metabolic health of the cell and then it starts creating fat from other things. But you mentioned it creating fat from Glucose, but it since glucose is also a simple sugar. Does glucose easily become fat or is it mostly just batty acids that are becoming fat in the context of fructose? You can make fat from Glucose, for sure. Fatty acids are a major way, of course, but yes, you you can make fat from almost any kind of caloric source. So there's there's pathways to do it. So Yeah, the glucose too fat storage conversion. Is that easier to do more likely than fructose itself? Too fast stores? Not necessarily. So you know, I'm not an expert on this. You certainly can create fat by Eating Glucose and then you know, enters the creb cycle and or citric acid cycle and then you know you some of it can be diverted with the acid heal coa too, towards fat. So you know for sure you can generate fat and glucose. You know when you stimulate insulin will actually help increase fat as well, and so and glucose when you eat it. The insulin also tends to try to block the degradation of fat and the periphery. So there's definitely a carb fat pathway that is very important, and there's also a fat fat pathway and proteins maybe make fat a little bit less. But yeah, I know you definitely can make fat from both carbs and fat. And when you give fruc dose, you know you you increase fat. And it turns out that we probably should talk about one way that when you eat glucos. What another way glucose can increase fat is that it can be converted to fructose in the body. So that's a whole new story. You know, there's this big controversy going out on the scientific world about whether when you drink a soft drink. There's fruit dose in IT and there's also glucose in it, and so the question was, is one of them the dominant player in causing the obese the epidemic? And Glucose, as we mentioned, stimulates insulin and insulin and that combination in increases not only the storage of glucose, is glycogen, but the conversion of glucose to fat. And so the thought was is that a lot of people were thinking that it's the glucose that's key. It's really a problem of...

...high glycemic foods, foods that when carbs that you eat that make your blood glucose go up, that triggers the insulin response that then can drive the fat production. Certain foods, when you certain carves, will raise the glucose level in your blood substantially, and those foods are things like bread, rice, potatoes, you know, crackers, cereal chips. They tend to have a high glycemic index, which means that when you eat them there's a spill over into the blood of glucose and the and the Blood Glucose, which is normally like ninety, might go up to a hundred twenty or hundred thirty following a meal or even higher following a meal with the high glycemic Carb and so and then that would trigger insulin and insulin could help drive the glucose to to into being stored as fat or as glycogen. And so that's been a major hypothesis. I think Gary Tops has really talked about that, David Ludwig, and there's evidence in support of that. But what we found out was that when you eat glucose, that it when the glucose levels go up. High glycemic foods again are culprits, that some of that glucose gets converted to Fructo, especially in the liver. And now I told you how important the liver was for fruc dose. So when you're eating, you know, drinking glucose solutions or drink or eating a lot of high glycemic CARBS, the glucose goes up in the liver and in the blood and that triggers the production of fructose. So now you have another mechanism that could drive obesity, not just insulin but fructose. And and so what we did is we gave glucose to mice that couldn't metabolize fructose. They had a normal insulin response and they love glucose, but instead of getting fat like really control rats who became, you know, the the normal rats fed glucose would became quite fat and they became prediabetic in the whole bit. But they had high fructose levels and they're in their liver and when we block the fructose we found that we could significantly reduce the development of obesity. They still became a little obese, but they were they were protected from insulin resistance and they were protected from fatty liver very well. And then we did a study with soft drinks and kind of showed the same thing. So what what we think is is that the main mechanism by which soft drinks cause obesity is through the fructose content. It's not just the fructose that you drink, but the glucose is being converted to fructose as well in the liver and it's the fructose that's driving a lot of the obesity and fatty liver. There is some being driven by insulin and it you know, when I discuss this with Gary, he pointed out that, you know, when these animals fructose makes an animal insulin resistant and prediabetic and it's the fructose that does it. Right. But once you become insolent resistant, your insulin levels tend to be high in the blood and although the fat is reason, the insulin resistance in the fat is to glucose, not to not other mechanisms. So when you become insolent resistant, glucose can't get into the fat tissue, but the insulin is still working on the fat tissue and blocking the degradation of facts. So fat accumulates. So Insulin, even with the fructose pathway, insulin turns out to be playing a role in the obesity. But it's work not working because glucose is stimulating it is working because fructose is causing insulin resistance. So the insulin levels go high and then the insulin blocks the fat from being burned in the in the fat tissue. So we've got a couple you know. So I mean this is really deep signs. But the bottom line is sugar, which contains glucose and fructose, can cause obes, the Metabolic Syndrome Fatty liver, and it's primarily the fructose that's responsible. But the fructose can come both from the Diet but it can also be made in response to high glycemic carbs and you know melody. This really points out to how important carb restriction is, low carb diets, Keto diets, in terms of blocking this mechanism. So if you really want to lose weight, you know intermittent fasting... a great way of removing the you know, your exposure to these carbs, and a low carb diet or Ketodiet would be another way to reduce the exposure to not just the fructose we eat but like from high glycemic carbs that can convert fructose in the body. So so what you've championed really makes a lot of sense to me. So is that the Polyo Pathway, the that Glucose to fructose conversion? There's only one way that animals can make fructose and they make it through a thing called the poly all pathway. Sorry for the complicated name, but this pollyall pathway is Converts Glucose to fructose and it can be activated a number of ways. So the number one way is by a High Glucose. So like die in diabetes when you have a High Glucose, your making fructo. So almost everybody who has diabetes, especially if it's not well controlled, they're making fructose. Okay, and when you eat a high glycemic carb it's sort of like trying to create a diabetic state in your transient diabetic state in your liver, because the glucose levels go up high and that converts the Gluecost to fructose, I mean activates the polyole pathway and it converts the Bluecoast of fruit does. So this is the main way that we make frucose. But interestingly, this pathway can get turned on and stressed. So like in a heart attack. It was shown that in the heart you start making fructose. Can you believe that when there's low oxygen you can start making fructose and sort of like being turned on in situations of survival, you know, and if you're dehydrated, if you get dehydrated, fructose production can increase. So inside of you. So they're but usually it's you know, these are kind of small amounts with just mild you know, but the dehydration pathway may be much more important as a mechanism for stimulating fructose. And we kind of learned about that when we realized that most people with obesity have an elevated hormone in their blood called Vasopressin, which is a marker of dehydration. And it's like in canny if you just measure vasopressing, that blood tests called Copeptin. But if you measure it in a population, people who are overweight almost always have a high copeptin and if you if you're lean and you have a high Copeptin, you're quite an increased risk for developing obese to your diabetes. And what makes the Copeptin go up is if you're dehydrated. There's a scientist named Jody stookey I think you should invider hunt your podcast. She's really an unbelievable character who has championed, you know, studies looking at how well are populations hydrated, and it's kind of you know, we we tend to most people are not drinking enough water. It's especially true for people who are overweight or obese. It's depending on what kind of measurement you use, it can be like five or tenfold higher risk for dehydration if you're overweight or obese. And so this is, you know, something you might say, well, how can that be? You know? Well, it turns out that to become dehydrated there's two ways you can do it. You can drink too little water or you can eat too much salt and both have the same effect on your blood. So when you when you drink too little, the concentration goes up in your blood and that trip triggers thirst and the condition we call dehydration. So when you're dehydrated, if you lose in water, like vomiting or diarrhea or sweating. As you lose water, the salt concentration goes up in the blood and and it creates thirst, stimulates this vasopress and harmone and you are dehydrated. But if you eat salty food, like really salty food, which we love, I mean salted popcorn, gotta much of my kids life. You know, when I was a kid was was trying to making popcorn and going to the movies and eating popcorn and and getting really thirsty from it. And then we drink soft drinks to quench our thirst and the course soft drinks are not quenching. They actually dehydrate you more and so you're still thirsty. So you drink more and more soft drinks and you eat more and more popcorn and you're raising the salt concentration in your blood and that activates this polyall...

...pathway and so the polyall pathway makes fruit dose and then fructose, as it's metabolized, sucks the water out of the blood into the tissues as it makes glycogen. And so fructose will rapidly make glycogen and fat. You know, it's sort of interesting melody. Whenever I would eat popcorn, the next day I would gain like two pounds and I always thought it was water, but it may not be it. I think it's likely glycogen and that what happened was I just activated this massive glycogen deposition into my into my my liver, which is not great. But yeah, and and if it was just water, you'd expect the weight to come down like the next day, but it tends to come down slower when you eat that kind of salty food. It takes you have to like go back to your low carb, low salt or intermittent fasting type of diet. The big thing we found was that salt can be a cause of obesity and and when we gave animal salt it took a lot longer. So, you know, was sugar. It's kind of quick, you know, not the first few weeks. It's not a two week thing or three week thing. Was Sugar, it's aid if you're giving it to a mouse or something. I mean it takes to two or three months, but if you give salt, you have to give weight twice as long, for four or five months before you they really become start becoming fat. So there's a different process and salt is slower and more secret. It's kind of like a stealth mechanism for obesity. Hi, friends, I'm about to tell you how you can get forty dollars off one of the most life changing revealing biohacking experiences that I have had. That would be the NUTRICENCE CGM program. You Guys Know I love continuous glucose monitors. Monitoring and understanding your blood sugar levels is so, so important for metabolic health and longevity. Did you know that the majority of chronic illnesses actually stems from an inability to manage your blood glucose levels? If you know how your body is actually responding two different foods, amounts of sleep, stress, fasting, exercise, wine, anything else you're doing in your life, then you can truly make changes to achieve your health goals. So, whether that's managing your weight, eating foods that make you feel good, having energy throughout the day. Optimizing a longevity understanding your blood glucose is key. Here's the problem. True, you can check your blood at the doctor or you can randomly check it with a glucometer at home where you prick your finger. The problem is that's just a snapshot. It's a single picture of that brief moment in time and if I've learned one thing from wearing continuous glucose monitors, it's that your blood sugar can change a lot, even from minute to minute. You really need to get a sense of how your blood sugar is changing all throughout the day when you wear a continuous Glucose Monitor, which is painless to put on, I promise. I have a lot of videos on my instagram of how to put them on, so definitely check those out. It gives you a picture of your blood glucose levels seven for fourteen days. And what I love about the Nutricens CGM program is it has a super awesome APP that helps you interpret the data and really understand what's going on. And the APP not only does it track your data, but you can log meals, see macronutrient breakdowns and so much more. It even gives you an overall score for each of your meals based on your body's response, so you can really find what meals are working for you. And each subscription plan includes one month of free support from a registered DIETITIAN. NUTRICENCE Dietitians will actually help you identify what you should be paying attention to, what that data actually means. They can really hold your hand if you're new to the space, or if you're already knowledgeable, then they can provide you even more advanced tips and recommendations. It is so, so helpful. They'll make sure that you adjust your diet and lifestyle to find what you enjoy doing so that you can have long term, sustainable changes. Nutri since also has a private facebook group for members where you can find support from other members and learn about their experience. I love wearing a CGM. I just think it is so profound. Even if you just do it once for fourteen days, I think you will learn so, so much. It's helped me realize, for example, how low car versus low fat affect my blood sugar levels, how Berberine has an amazing effect at lowering my blood sugar and so much more so if you'd like to get a continuous gloul close monitor. Go to NUTRICENCE DOT IO Melanie. That's in Utri Sein Se dot Io melaniem Ela and ie, and the cupon code Melanie Avalon will get you forty dollars off any subscription. That that's nutricence dot Io Melanie with the Cubun Code Melanie Avalon for forty...

...dollars off any subscription. If you haven't tried to continuous Glucose Monitor, you are missing out. Now is the time and I'll put all this information in the show notes. All right. Now back to the show. So you're talking about all of these different markers or factors that correlate to Metabolic Syndrome and OB city. So we talked about the hieric acid levels, we're talking about the dehydration and all within nature wants us to be fat. You talked about how it relates to this basically this survival switch, which is creating a state in our body that would be preparing for a sort of hibernation and that in animals, you know, their body activates all these pathways so that they can store up all this fat and then when they're hibernating. You talk about how a hibernation sort of mimics metabolic syndrome. A question about that. So these animals that are hibernating or migration, you talk about how happens with birds that are migrating, which was so cool. I had no idea about that. Those situations with animals who are hybrating and birds that are migrating and the similarity and their bodies to metabolic syndrome. Oh when also the humming bird is their form of quote, Metabolic Syndrome? All five things, like the abdominal B city, the triglysides, the low HD, all the blood pressure and the high fasting blood sugar. Or is it a little bit different? There is a little variation. It's not exactly the same. So, for example, bears, they become hungry left and resistant, they start foraging, they put on fat, they block burning the fat and they increase the fat production, and so they do almost everything right. And but no one's really measured their blood pressure to see if their blood pressure goes up. So that's not been proven that the blood pressure goes up or their hdl. Yeah, and the also they I don't think there's studies looking at the HDL. If you give fructose to a mouse. They do show the all the whole things that hdl falls, even the HDL. Yeah, Oh, wow. I was wondering if the HDL was like the thing. That might be a little bit different. Well, in the rat, in the rat it's been certainly reported that fructose drops HDL, increases vldl and treglycerides and so I mean, oh, in the fructest yeah, yeah, so it can do the whole thing. But in in these animals in the wild, there's some variability. So it turns out birds they get almost all of these same things. They get insolent resistant fat. They get a very, very prominent loop fatty liver, which is more than you see like in the mammals. But you know, it's interesting. Birds Black this year case just like we do. So we're when it comes to the yaric acid pathways. We're a little bit more I like the bird in terms of the the fact that it doesn't have your a case and we don't have your case. Your case is an enzyme that degrades uric acid and most mammals cavo it. But we lost that gene years ago and probably to help us survived by kind of enhancing this sugar pathway, the fructose pathway, but anyway there is this survival switch. Most of the animals show pretty much the majority of these same features. Some of them have not been studied and there may be some exceptions, you know, but they're all. You know, it's a pretty consistent story that these animals will before they hibernate or before they migrate or before they nest, they have to rapidly increase their weight. Some of them seem to do it by eating fructose and then others we don't really know the mechanism, but we think it's because they somehow activate fructose production in their body, but that's something we want to prove. We haven't actually proven it yet. But like bears. Yeah, bears, for example, will eat a lot of fruit dose in the fall and we did do a study in hibernating bears and they do get high blood levels of fructose, you know, when they're preparing for hibernation. Because I was thinking a lot about that, like if the FRUCTO signaling is required to start this preparation for hibernation, and so, evolutionarily, what would have come first, like how do we evolve to instigate this hibernating pathway? Like did we eat the fruit first and the fruit made us fat and then that was like a happy chance that made us be okay for winter? Or did we learn to gain weight and then associate it with fruit? I'm not particulate in this. Well, I'm curious. So, for example, with the animals that are not eating fruit toes, but they're still turning on the survival switch and hibernating, like, why take that extra step to make fruittoes when they could just store...

...the fat? Like, why would you even go that route? You know, you're asking a really good question that I can't totally answer, but it seems like very early on and evolution, there was a distinction made between the kind of nutrients and the biology of their effects. So it seems to me that glucose was was really designed as being the immediate energy that animals use to to do things, you know, in the immediate sense, and fruit dose seems to have been a fuel that was used to to preferentially store calories. It seems like, you know, Mother Nature kind of figured this out. So, for example, trees, a lot of trees, will the fruits will ripen in the fall the fruit will ripen in the fall and that's when the sugar content goes up, and so the trees sort of time the fruiting of the tree to a period of time when the animals need want to have fructose just to store the extra fat and preparation for the fall and winter. And so there seems to be like a timing where they and then in turn, the when the animals eat the fruit, they disperse the seeds to help the tree. So it's kind of like a symbiotic thing. There's a there's even a fish. I you know I've commented on this and other podcast there's a fish called the Pacu that lives in the Amazon and when the Amazon floods, if the fruit yeah, eats the fruit out of the tree. So and the trees have it time. You know the I read these I read these papers going all the way back to like the late eighteen hundreds. It's really interesting. But it's been noted that the you know, that the timing of the floods, that times with the with the fruiting and the ripening of the fruit and the fish. You know, everything's there perfectly and then the fish eats the fruit, gets fat from it because they so many. So they get a big dose of fruit dose because they're really eating a lot for their body weight, and then they they get this fat and then they quit eating and the Amazon recedes and when it recedes back to it's regular river, they there. They can go months with eating very minimal food in the red and they kind of wait until, you know, the flood again and then they go out there and get more fruit. So it's really I mean. So there seems to be some longstanding relationship that has developed between how these animals survive and nature, and we kind of disrupted that. And this is one reason I like intermitten fasting. Is is intermitten fasting sort of goes back to the way nature wanted us, you know, where we would, you know, put on a little fat, then you need to burn it off and when you hibernate you actually remove the food, you no longer have the food available and then your body transitions into a point where it's burning the fat. And so there's an argument that intermitten fasting is a great way, you know, has a evolutionary basis to it. Well, that actually brings me to a huge question I have for you. So I'm excited you brought that up and I actually first thought about this not in your most recent interview with Peter a tea, but that first one that I listened to in two thousand and twenty, and it's something that you touched on as well in this interview, which was the role of fructoes in the the cells and how it's energy to pleading, and I don't think you mentioned this in the interview, but in your book you talked about how it's converted to is it ATP and amp so my question is, and how this relates a fasting is the benefits of fasting, Cali restriction and or restriction are often attributed to ampk. How is it different? So amp activated kind as how is that different? Because when I first heard you talk about fructose creating an energy deficit in the cell, normally that's what we want, is an energy deficit. So how is that not activating AMPK? How is that not a good thing? Okay, so let's go through that. So it's a complicated question. So, if it's okay with you, I like to do is kind of take you through how the fructose works and it's relationship with AMPK. Okay, and I'm so excited I'm ready. So fructose lowers the ATP level in the cell, but not to zero, not to alarm that the cell is going to die, but it drops it like ten twenty percent, which is kind of like a warning. So it drops it only ten to twenty percent. The way it does that it first consumes some ATP is the fructose is metabolize and it consumes the enzyme...

...that metabolizes fructose doesn't so rapidly that there's this immediate drop and energy associated with metabolism or breaking down a fructose. So there's you know, it costs calories to make calories and so or to cost energy to make energy, and so some energy is used up as the fructose is burned. So there's this immediate drop. That immediate drop figures because of there's a fall and not just ATP but also phosphate, and that triggers an enzyme that call ampd amonase, and that ends, I'm sweeps away amp when the ATP is used. It makes atpn amp and then normally the amp would then be remade back to ATP. So there's it's kind of normal shuttle where ATP goes to ATPN amp and then they get re remade back to ATP. But when you when you drop the phosphate in the cell, it's activates an enzyme that takes away the amp and makes uric acid, and so it specific to fruked us. So glucos doesn't do that. And so now you don't have enough amp to kind of reconstitute ATP and at the same time you're removing the ampn making the uric acid, and then the uric acid goes into the energy factories themselves. That actually localizes to the mynochondria and and brings with it an enzyme that causes Oxidat of stress, and you get this big oxidatu stress in the MONOCHONDRIA. That slows down the MYNOCHONDRIA and it slows down both the fatty acid oxidation and the creb cycle or citric cycle. So it makes it makes the Mitochondria make less ATP. Coming out of that, the ND G, instead of being made into ATP, tends to be shutted into fat. So fat is a storage energy. So instead of making immediate energy, it shifts it to storage energy. And one of the ways that the uric acid also works, in addition to working on the monochondria is that inhibits the amp kinnees. So this there's a thing that's activated that helps burn fat and Burns Fat and it Burns Glucose, basically, and it's called AMPK, and low ampk characterizes diabetes and things that increase a PK can be used to kind of treat diabetes. And as stimulating ampk is a good thing because it causes burning the fat and when the uric acid goes up in the cell it blocks that. So you don't you you end up not being able to burn fat so well, and glucose levels go up in the blood as well, because it ends up stimulating this thing where you start making glucose, the liver starts pouring out glucose, and so so what what's happened is when you eat fructos, you are resetting the energy to a lower level and you're inhibiting amp kinnees. Now, when you are starving and you have zero energy, you need to activate amp K to make ATP because you don't have enough to survive. Even though you may have no fat, you'll try to burn whatever fat you have, you'll try to burn whatever glucose you have. So you're trying hard to make ATP when the level gets really low. And so when we eat fripped us, it's like we're preparing for starvation, not actually being in the extremes of starvation. And so when you're in the extremes of starvation you want to activate ampk to help you survive, but when you're trying to store fat, you actually want to inhibit ampk to help you store fat and to raise glucose levels and so forth. So that's sort of the difference. When an animal hibernates, and we did this study, the enzyme that is storing fat we call Ampdm Andase it's levels fall and amp kindness goes up, and the amp kindas then allows the animal to burn the fat while it's hibernating. And when you're fasting you're actually stimulating amp kinnees, and so that's good because it helps you burn fat. And so amp Kinne's can be is a good guy if you're wanting to lose weight, and if you're wanting to gain weight, it's it's a bad guy. You want to in hi it. If so, does that help? So basically,...

...when you're taking in the fructose, it creates like a little miniature. We're going to be starving soon. Let's store energy. Compared to if you're actually starving or actually fasting, your body's like we have to generate energy. So it starts burning energy, right, right. So, so immediate energy is what you need if you have if you're about to die. But if you get a warning sign that things are not good, you actually you know, you think could happen in the future, then you want to store energy. So what if you combine those? What would be stronger? So what if you're fasting? You're actually starving, but then you have like a little bit of fructose? What would that do? We've actually done some studies on this and then there's a beautiful paper in the literature on this too. So when you're starving, it's sort of interesting. Or like even on a Kido Diet, your uric acid may go up, even though you're burning fat and uric acid is supposed to block the burning of fat. When you're starving, the process to burn fat becomes stronger than than the ability of uric acid to block it. We think the uric acid is actually helping still bring raise glucose or to increase glucose output from the liver. So we do think that it's still kicking into help, but it's not. When you're truly starving, the AMPK kindne's pathway just takes over and is stronger, and you can actually show that. And there is an interesting there is a paper that took starving animals and they had hiuric acid and when they gave them fructose, the fructose was turned completely into glucose. So it went the other way and the fructose became an immediate fuel. And of all things that you know with starvation, uric acid tends to go up because what happens you start breaking down muscle. The way it works with starvation is once you want to run out of fat and glucose, you start breaking down your muscle using that as an energy source and that rapidly leads to death. But at that stage uric acid goes up in the blood from the breaking down of muscle. The uric acid is may actually be helping to drive glucose up, but anyway. So if you give any kind of energy in a starving animal, it doesn't matter so long as it's a calorie. The animal use it to try to make ATP so kind of re routes the system, and so starvation is such a critical, near fatal and sometimes fatal event that animals will will do everything they can to take any source of calorie and try to use it to survive. But when the way we eat fructos, we're using it more like as a warning sign. It creates a warning sign that we could that we could lose, we could be in trouble, and so it's preferencial using this pathway that will lead to fat accumulation and inhibition of a PK. So I think a really practical takeaway from that, and I'm not advocating going on severely. Hi, friends, so what I'm about to say may include some disturbing content, so if young ones are listening, you may want to skip ahead. On Valentine's Day, two thousand and twenty two, I experienced sexual battery by a man at a massage parlor. I felt so helpless and so scared while it was happening and afterwards I was really, really scared to tell anybody. I'm so glad that my friends encourage me to tell the police and I'm so glad that the police believed me and that the man is now in jail and ever since sharing my story, you guys have been so supportive. So many people have applauded me for telling the police, saying that something like that had happened to them too, and they never told anybody. I started looking into the statistics and they are pretty shocking. So sexual assaults are most likely the most prevalent crime in the US and they are also the most underreported. Every sixty eight seconds, an American is sexually assaulted, so I was one of those. Every nine minutes that victim is a child. Meanwhile, only twenty five out of every onezero perpetrators will end up in prison, and only five percent of sexual assault reports filed have ever been proven false. Eighty two percent of all juvenile sexual assault victims our female, ninety percent of adult rape victims are female, and in two thousand and nineteen over six hundred and fifty two thousand, six hundred and seventy six women were raped and nearly one million women were victims of sexual assault. I believe this is a huge, huge problem happening in our society. It's one of the crimes where there's not usually evidence. It's not like a physical object was stolen or somebody outwardly injured or killed, it's basically your word against the perpetrator, and so it can be really, really scary to tell somebody...

...and stand up for yourself, but I want to encourage you that we can change this, we can speak up. So if something happens to you, I encourage you. Please, please, tell somebody. I promise you you're not crazy. The thing that really convinced me to go to the police was it wasn't so much about me, but about stopping this man from doing this to somebody else. If you feel like someone crossed a boundary, they probably did. People don't usually question things that are appropriate and normal, and as parents, I encourage you to have these conversations with your children and whatever time and way you feel comfortable. I think we can make change here. It's just about spreading awareness and taking a stand and speaking out. So thank you, everybody so much for the support. I love you all. You are amazing and let's change this. So, like I always say, you got this. Okay, back to the show restricted diets, but I think that dismantles the myth. There's this idea that if you, you know, are eating too low calor of a diet, you'll inter starvation mode and they'll reach a point where you won't lose any more weight. But it sounds like if you actually are again, not advocating this is a dietary approach, but if you actually are starving, you are going to burn fat. You know, like that pathway is going to overtake the storage promoting pathway. Yeah, the way. Yeah. So the way it works is that the fat and the glycogen that center that we've stored, they are preferentially used when we're starving and eventually when they go get used up, then the muscles are broken down and that's really the very end stage and that's when people really die rapidly. There is a very, very strong mechanism when you starve to drop your energy metabolism. So if you not get enough calories, the body tries to respond by reducing how much it will spend. So it's not like hibernation, but they there's a real move to reduce, to slow your metabolism, especially when you're at rest, and so that can be quite significant. So if what happens is that people, when they start losing weight, they find they have to eat less to stay at the same weight. So let's say, you know you're normally eat one thousand eight hundred calories or a day, and now you want to lose weight. So you lose ten pounds, but your body adapts to that by trying to lower its metabolism and and now to eat this to stay at the same way. You know, this new way you have to eat less calories a day and this can make it very difficult. And the way that you can get around that is if you can improve your Mitochondria. The MINOCHONDRIA, you know, are your energy factories and they make ATP and as we get older they work a little bit less well and as we get overweight. Chronically being overweight also wears them down, and so what you need to do is to try to keep the energy factories strong, and there's certain foods that do that. Vitamin C's good for that, by the way. Dark chocolate's good for that. But the best way is to have an exercise program and to try to exercise and what we call zone to where you raise your heart rate enough so that you are getting the muscles working but you're not going into exhaustion very quickly and you don't build up lacktic acid in your blood. And so the classic teaching is to exercise until you have trouble talking as soon as you if you can still talk while you're exercising, but just barely, that's perfect. And if you can't talk, you're probably going too fast and if you can talk easily, you're probably exercising too slowly. And so, you know, get on a stationary bike or whatever, walking or jogging, but that's what that's what they recommend. And then by improving your Mitochondria, then when you lose weight you can still eat your sixteen hundred calories a day without having to worry about regaining the way. So I have so many more questions but I want to be super respectful of your time. But one last question I could ask would be because you touched on the Vitamin Sea, because I think listeners might be a little bit nervous right now about fructose and fruit, and fruit is high in vitamin sea and some other, you know, Nu Trans that possibly might counteract these issues. All of these studies on fructose, do we find any of this with whole fruit? Yeah, so I've done studies on whole fruit, both political studies as well as we've done research studies on the components and fruit and natural fruits, whole fruits contain substances that block fructos effects. And but it's when the fruit is not super ripe.

And and so fruit contains vitamin C and it contains potassium and it contains flame and alls and all of these are substances that actually block some of the effects of fructos. So does fiber, and so it's like the plant doesn't really want the animal to eat the fruit when it's start. They want to wait for the fruit to ripen so the seeds are are maturing and can and concede well, and the early when the fruit is in the early face and immature fruit, it's tends to be very high and stuff that's very good for us. And then as the fruit ripens, what happens is the vitamin C content goes down and the sugar content goes up and by the time it falls off the tree or you know, when the animals start eating it, it doesn't have much vitamin C anymore and it's at or flavanols and this mainly fructose rich and then they eat a lot of them and Bingo they can activate this pathway to gain weight. But we thank God. We tend to like tart fruit. We tend to like fruit that is often high in vitamin C and these flavanols like Ludiole and Quersatin, and David promoter has pointed out that some of these flavanols not only block fructose but they block uric acid. Yeah, they can lower uric acid and we've actually done studies like what if we give vitamin C, we can temper, we can reduce the effects of fructose to gain to cause obesity in animals, and if we can do something similar, we can. I've given potassium. So like some diuretics that are used in hypertension are known to cause metabox syndrome as a side effect and they tend to raise uric acid and lower potassium. And if we lower uric acid or raise potassium, we can block the effects of these directs cause met about syndrome. And since fruits have a lot of potassium, I'm thinking that's probably a protective mechanism as well. And so there's there's a lot of good things about fruit. And when we did a loaf, we did a diet in people in Mexicans who are overweight, where we put them on a low sugar diet with fruit supplements, or we put them on a low fructose diet. So they're there were basically low fructose for added sugars, but they could get natural fruit in the other group was just low fructose across the board. So that, you know, and what we found was that when they had natural fruit supplements they like the Diet more and they lost weight just as well and they had improven in their metal box syndrome just as well. And so, you know, eating natural fruits are good and you know, I don't think you want to eat a bowl of grapes at one setting. You don't want to eat lots of fruit at the same setting, but like a natural fruit is a great way to go. I would recommend, you know, one with each meal. You know, a nice apple or something like that would be a good thing to do. Also, there's the amount of FRUC dose in the fruit and some fruits have, you know, very little fructose, some have more. In my book I kind of talked about which one's tend to be better, you know, and figs in particular are very rich and sugar. So it's not all fruits are good, but but anyway, there's a science to this. So I think you know, if you're interested in and you want to read more about it, you can. You can do so in my book. Yes, listeners, get nature wants us to be fat. We only, like briefly, barely touched an echo of everything that is in this book. So thank you so much for your time. I've been looking forward to this for so, so long. It was incredible. The last question I ask every single guest on this show and it's just because I realize more and more each day how important mindset is. So what is something that you're grateful for? I'm grateful to be able to have the opportunity to do research and to take care of my patients. You know, I was very lucky that I chose this path to become a doctor and I'm still a clinician and practicing physician and I'm very grateful for being able to try to help people, both my patients and to do research where we can try to understand the causes of disease. You know, I'm grateful that covid is finally empty. Yep, it's a nice, nice thing. Well, thank you so much. I am so, so grateful for your work. I'm just in awe of everything that you're doing. It's incredible. I can't wait for listeners to get your book. If it's okay with you, I feel like I'm probably going to email you some other questions I have, but thank you so much. Any links you want to put out there for listeners to best follow your... Okay. Well, I do have a website. It's Dr Richard Johnsoncom. We post lots of little stories there, so that would be a good site for us. Awesome. While put that in those show notes again, the show notes aren't Melanie avaloncom. Slash fructos and thank you so much, Rick. This was amazing. I'm just so happy. Thank you for coming on the show. Thank you, Melanie. Bye. Yeah, bye. Thank you so much for listening to the Melanie Avalon biohacking podcast. For more information, you can check out my book what when wine? Lose weight and feel great with Paleo style meals, intermittent fasting and wine, as well as my blog, Melanie avaloncom. Feel free to contact me at podcast at Melanie Avaloncom and always remember you got this.

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