You Will NEVER Eat Sugar Again After Watching This! | Dr. Robert Lustig

Let's come back to fructose. We mentioned it was one of the three culprits when it comes to liver fat, along with branched-chain amino acids and alcohol. Let's talk about physiology of fructose entering the body, the liver, and beyond. You consume fructose. Okay, first thing is something sweet hits the tongue. Message goes tongue to brain, sugar's coming. Message goes brain to pancreas, sugar's coming, release the insulin. Now, if something sweet turned out not to be fructose, but to be, say, an artificial diet sweetener, you still get the message, release the insulin. Okay, so keep that in mind. Okay, sweet alone generates the insulin, you know, part of the insulin response. Now, the rise in the blood glucose will be the rest of the insulin response, but, you know, the sweet alone will have primed the beta cell to release insulin. So you get that even before the food gets to your stomach. And we can prove that because there's a phenomenon called the cephalic phase of insulin secretion. You take a patient, you admit them to the hospital overnight, they wake up in the morning, they're fasting, their blood glucose is 70, everything's fine, right? You bring a tray of food into the room, and you let them look at it. You let them smell it, but you don't let them eat it. Got it? And then you take the tray out of the room. What happens to the blood glucose? Nothing, because they didn't eat anything. What happens to the blood insulin? It went up. The more obese, the higher it went up. But the insulin went up, not because the glucose changed, not because they ate anything, not because there were calories to work on. The insulin went up because the brain thought the food was coming. Cephalic phase of insulin secretion, well-known, dates back to the 1970s. A guy at University of Indiana by the name of Terry Powley did this work way back when. I actually worked on a disorder of that brain to pancreas connection called hypothalamic obesity. That's how I got into the obesity business in the first place. Kids with brain tumors that basically destroyed that area of the brain that controls energy, metabolism, energy balance, and food intake. And so these kids would become massively obese after their brain tumor. And I was at St. Jude Children's Research Hospital, and I was charged with figuring out how to help them, okay? 350, 400 pounds, okay? These were kids who were normal weight and height until their brain tumor. And then all hell broke loose. And I had to figure out what to do for them. And what we did was we gave them a drug that suppressed insulin release because we postulated that their problem was that the brain thought they were starving because that area of the brain was dead. And so their vagus nerve, which was telling the pancreas what to do, was telling it generate more insulin because we can't see the leptin level. We can't see that energy balance is normal. We think the patient is starving, therefore, release more insulin. And so the insulin levels would go sky high, and that would drive everything into fat. But we couldn't fix that because that area of the brain was dead. So what we did was we basically stopped the pancreas from making extra insulin. And lo and behold, they started losing weight. But even more importantly, they started exercising spontaneously. These were kids who sat on the couch, ate Doritos and slept. And now, because we got their insulin down, they had energy to burn instead of to store. And so they started being much more active. And the parents would say, oh my God, I got my kid back. And the kids would say, this is the first time my head hasn't been in the clouds since the tumor. We reversed their metabolic mayhem by getting their insulin down. And that's just at the level of the tongue. Okay, so now the fructose goes further down, gets into the stomach. Okay, it doesn't do anything in the stomach, but then goes into the duodenum. And then the question is what happens to it there? And several things happen to it there. The first is that your intestinal cells can actually turn fructose into fat, intestinal de novo lipogenesis. And so about 10% of the fructose load will get turned into fat in the intestine right away and get absorbed through the lacteals and into the lymphatic system and come out. And it's their chylomicrons and they get circulated and they go to the liver and they get cleared, just 10% of the fructose load. But that leaves 90% of the fructose load still there. And what happens then? So there's an enzyme in the intestine and it's called TXNIP, thyrodoxin inhibitory protein, thyrodoxin inhibitory protein. And this enzyme basically ratchets up the ability to absorb fructose. So if you've never seen fructose and you get a big bowl you don't absorb it. And the reason is because you haven't activated this enzyme yet. And so you end up with bad diarrhea. And pretty much anybody who goes crazy on Halloween knows about bad diarrhea. It's because they hadn't activated enough of their TXNIP. But if you had Halloween every day, then you wouldn't get diarrhea. You'd get fat instead. And it's because you ratcheted up your TXNIP. This is work from Richard Lee at Harvard of this whole TXNIP thing. Okay. That increases fructose absorption at the level of the intestine. And then that fructose goes to the liver and the GLUT5 transporter in the liver will suck that fructose out of the portal system to a point. There's a limit to how well that GLUT5 transporter will work. If you overstimulate, if you basically drink a 20 ounce Coke, which has way too much fructose for that GLUT5 transporter, then the liver will grab what it can, but it can't grab enough. And so you will end up with a serum fructose level that will be present in the peripheral circulation. So normally your fructose level in your blood is zero because it doesn't make it past your liver. It goes intestine to liver and goes, you know, and that's it. But if you overwhelm your liver's capacity, then you will end up with a fructose level. So what happens if you do that and you drink that 20 ounce Coke? Turns out there are fructose receptors on beta cells and that makes them secrete more insulin because they have to clear it. And that's like a real disaster because now you've got everything going wrong. But what happens in the liver to the 85% or so that gets cleared by the GLUT5 transporter? Goes into the cell, fructose gets converted to fructose 1-phosphate by the enzyme fructokinase. And fructose 1-phosphate then gets chopped up into three carbon fragments and then they get turned into pyruvate at the level of the mitochondria. They do not get turned into glycogen. So fructose does not go to glycogen. Glucose does go to glycogen. Fructose does not go to glycogen. Fructose goes to the mitochondria. And that's the reasons why the mitochondria get overwhelmed because there's too much pyruvate at the level of the mitochondria for the mitochondria to handle because there was too much fructose coming into the cell in the first place. And so that's when the mitochondria go, ah, ah, ah, don't do that, and send that pyruvate off to become citrate, then acetyl-CoA, and then that acetyl-CoA becomes malonyl-CoA, and the malonyl-CoA then gets added two carbon fragments at a time, and you end up with fatty acids. That's how you end up with triglyceride. That's how the fructose becomes triglyceride. It goes to pyruvate first, then tries to enter the mitochondria, can't, gets thrown off as citrate. The citrate becomes acetyl-CoA, then malonyl-CoA, and then fatty acids. Then those fatty acids get packaged with like a microsomal transfer protein, and now you have a VLDL. Now you have a triglyceride molecule. And that triglyceride molecule can leave the liver and increase your serum triglycerides and serve as a substrate for either obesity or cardiovascular disease, or that triglyceride molecule won't make it out of the liver at all and will precipitate as a lipid droplet, and now you have fatty liver disease. And when you have fatty liver disease, that generates the insulin resistance. And now your pancreas is going to make more insulin to make the liver do its job. So you've got the high insulin, you've got the fatty liver, and you have the metabolic mayhem. If you enjoyed that clip, you're going to want to head over here and catch the full episode. I'll see you over there. Insulin is a bad guy. I can't say it any simpler than that. Yes, glucose is bad, too. I'm not saying it's not. Insulin is worse. Insulin is associated with all of the diseases.