Is It Really Just Calories In, Calories Out? Metabolism, Insulin, Hormones and Why Counting Fails

0:00 [SPEAKER_00]: Calories in calories out is real. [SPEAKER_00]: Calories unit the same way that a second is a unit and an inch is a unit. [SPEAKER_00]: You can no more argue that calories in calories out is real than you can argue that an inch is shorter than it is. [SPEAKER_00]: That part is settled. [SPEAKER_00]: The people who tell you that it's not really about calories are usually honest something real, but they draw the wrong conclusion from it.

0:19 [SPEAKER_00]: Now, last episode, we went after Willpower, and we said something that made a lot of you mad. [SPEAKER_00]: We said that the equation is true and close to useless as advice, because your body defends its weight below your awareness. [SPEAKER_00]: And telling someone to just eat less and move more is like reading the final score and calling it a game plan.

0:34 [SPEAKER_00]: A lot of you not at a long and plenty of you wrote back with the opposite complaint. [SPEAKER_00]: You didn't think that the equation was useless. [SPEAKER_00]: You thought it was wrong. [SPEAKER_00]: It's not calories. [SPEAKER_00]: You said, it's my insulin. [SPEAKER_00]: My thyroid, my cortisol, my rectum metabolism.

0:46 [SPEAKER_00]: It's the kind of food, not the amount. [SPEAKER_00]: So today we're going to take that seriously and we put every one of those on the table and test it. [SPEAKER_00]: You know the guy that I'm talking about. [SPEAKER_00]: He's in the comments under every before and after photo. [SPEAKER_00]: He's done his own research and he already knows that for a fact, your weight has nothing to do with how much you eat.

1:03 [SPEAKER_00]: We're going to keep running in hand today because the thing about that guy is that he's not stupid and he's not entirely wrong. [SPEAKER_00]: He's just wrong about the exact part that he's loudest about. [SPEAKER_00]: Here's the whole episode in a sentence so you can hold on to it the entire way through.

1:17 [SPEAKER_00]: Every one of these theories is pointing at something real, and every one of them turns out to be a hand on one of the levers that move the calories in or the calories out, sometimes both. [SPEAKER_00]: Not one of them though, it's a whole and the equation. [SPEAKER_00]: I'm Dr. Jordan Faganbaum, and this is the parable medicine podcast.

1:43 [SPEAKER_00]: By the end of this, you'll be able to take any, it's not calories, it's blank, and sort of out in about 10 seconds flat. [SPEAKER_00]: Real or oversold, and which lever it's pulling. [SPEAKER_00]: And I'm going to leave you with one thing that should end the insulin argument for good. [SPEAKER_00]: There's a class of drug, the one that it feels like everyone you know is on right now, that works partly by prompting your pancreas to release more insulin.

2:03 [SPEAKER_00]: And despite that, it produces the biggest weight loss of any obesity drug we've ever approved. [SPEAKER_00]: Keep that one in mind because we're going to keep coming back to it. [SPEAKER_00]: Now the law underneath all of this is just thermodynamics. [SPEAKER_00]: The change in the energy you've got stored equals the energy you take in, minus the energy that you burn.

2:19 [SPEAKER_00]: You don't gain weight without an energy surplus, and you don't lose weight without an energy deficit or calorie deficit. [SPEAKER_00]: And here's what gets lost with all the shouting. [SPEAKER_00]: The low car researchers agree with that. [SPEAKER_00]: David Ludwig agrees with that, Gary Taubs agrees with it.

2:33 [SPEAKER_00]: Nobody credible in this fight is arguing with the first law of thermodynamics. [SPEAKER_00]: They're arguing about what sets the two sides of it, which is a completely different argument. [SPEAKER_00]: and the two sides are not simple numbers. [SPEAKER_00]: Take the burn side, the thing that people call their metabolism.

2:48 [SPEAKER_00]: You probably picture a single number, you could look up like your height. [SPEAKER_00]: It's really three things stacked together. [SPEAKER_00]: Most of it, roughly 60%, is just the cost of being alive. [SPEAKER_00]: Running your heart, your brain, your kidneys, keeping you at a normal temperature, all of it just to keep the lights on while you sit there and do nothing.

3:04 [SPEAKER_00]: That about 10% is the energy it takes to digest the food that you eat. [SPEAKER_00]: And the last 30% or so is movement. [SPEAKER_00]: And most of that movement isn't the gym. [SPEAKER_00]: It's all incidental, shifting and pacing, twitching, fidgeting, standing and doing all of that all day.

3:18 [SPEAKER_00]: And it turns that dial up or down without asking your permission. [SPEAKER_00]: Last little piece is important. [SPEAKER_00]: The part where your body adjusts the burn on its own without telling you, because it comes back in about five minutes, and it does a lot of work. [SPEAKER_00]: And this is the whole reason for the episode.

3:34 [SPEAKER_00]: Both sides of the equation, the end and the out are outputs of a control system. [SPEAKER_00]: They aren't knobs that you set by hand. [SPEAKER_00]: Last episode, we drew one conclusion out of that. [SPEAKER_00]: Willpower is a weak lover for weight loss. [SPEAKER_00]: And today, we're going to draw a different one.

3:47 [SPEAKER_00]: Every single, it's not calories theory that you've ever heard is a claim about that control system. [SPEAKER_00]: And every one of them lives inside the equation, not outside of it. [SPEAKER_00]: So let's take the four big ones, roughly in the order that you hear them the most, starting with the one about the burn.

4:03 [SPEAKER_00]: The first claim, the burn side is broken, my metabolism crashed, so the math doesn't apply to me. [SPEAKER_00]: Now there are two versions of this, and the data say they're mostly wrong, and the correct version is more useful than the myth anyway. [SPEAKER_00]: Version 1 is that your metabolism falls off a cliff when you hit 40.

4:19 [SPEAKER_00]: present company included. [SPEAKER_00]: Everybody believes this. [SPEAKER_00]: Your metabolism didn't get the memo, though. [SPEAKER_00]: There's a study from 2021 published in science that pulled the best measurements we have on more than 6,000 people aged eight days old to 95 years old.

4:34 [SPEAKER_00]: They used doubly labeled water, which is the gold standard for measuring how many calories you actually burn out in the real world, not hooked up to a machine in the lab. [SPEAKER_00]: Here's how it works. [SPEAKER_00]: You drink water that's tagged with a harmless traceable marker, and then they measure how fast you flush that marker back out.

4:50 [SPEAKER_00]: The faster you clear it, the more energy you're burning. [SPEAKER_00]: You can picture watching dyed water drain out of a tank, and then time in it. [SPEAKER_00]: Adjust for body size, and here's what they found. [SPEAKER_00]: Your burn is pretty much flat from age 20 to age 60, not slowly declining, flat.

5:05 [SPEAKER_00]: It doesn't even start to drop until about 63, and when it finally does, it goes down less than 1% a year. [SPEAKER_00]: pregnancy doesn't spike it. [SPEAKER_00]: Your forties didn't tank it, but there is a caveat. [SPEAKER_00]: This is a lot of different people measured at different ages, not the same person tracked for 40 years straight, but it is an enormous, consistent picture, and there's no cliff in it anywhere near midlife.

5:27 [SPEAKER_00]: The metabolism you're blaming, or somebody else's blaming, is running about the same as it did when you were in your 20s. [SPEAKER_00]: Now, version two of this story is the serious one because this one's real. [SPEAKER_00]: When you lose weight, your metabolism does go down by more than the smaller body accounts for.

5:43 [SPEAKER_00]: We talked about that in the last episode, so I'm not going to do it again, but what I want to do is put a real number on it because the numbers exactly where people go off the rails. [SPEAKER_00]: In an ordinary person who loses about 10% of their body weight, the drop in their resting burn or calorie expenditure, beyond what you've already predict from just carrying around less body mass, runs somewhere around 70 to 130 calories a day.

6:07 [SPEAKER_00]: Researchers had people cut their food in half for three weeks. [SPEAKER_00]: They lost about six kilos. [SPEAKER_00]: The resting burn dropped 260 calories a day on average, which sounds enormous. [SPEAKER_00]: But when the researchers backed out the part that was due to simply having a smaller body to run, the true extra adaptation, the part that's actually your metabolism slowing down was about 72 calories a day.

6:29 [SPEAKER_00]: You've probably heard a much scarier number than that, 300, 400 calories a day. [SPEAKER_00]: Now that's real too, but it's not what you think. [SPEAKER_00]: 85 to 90 percent of that bigger number isn't your organs powering down or your body suddenly set shifting to produce less of a demand on your metabolism.

6:47 [SPEAKER_00]: It's that you move more efficiently. [SPEAKER_00]: After you lose weight, your muscles do the same amount of work for about 20 percent less energy. [SPEAKER_00]: So the adaptation is mostly about how you move. [SPEAKER_00]: In this next one sets up the rest of the episode, there's a study where women 80,000 calories a day and lost less than half the weight the math said that they should.

7:09 [SPEAKER_00]: Sounds like proof that metabolism has cheated them. [SPEAKER_00]: But when researchers took the gap apart, only about a third of it was metabolic adaptation. [SPEAKER_00]: Half of it was that they ate more than what they wrote down. [SPEAKER_00]: The metabolism took the blame for what the food diary was hiding.

7:23 [SPEAKER_00]: So let's put this whole thing together. [SPEAKER_00]: Adaptation is real, it's also bounded. [SPEAKER_00]: It's a couple hundred calories at the far extreme. [SPEAKER_00]: Most of that is just efficient movement. [SPEAKER_00]: And it never once flips the sign of the equation. [SPEAKER_00]: Nobody in any of these studies ate an deficit and gained fat.

7:39 [SPEAKER_00]: Your metabolism is not the reason that the math stopped working for you because it didn't stop working at all. [SPEAKER_00]: Our guy in the comments has already moved on, by the way. [SPEAKER_00]: He's done blaming metabolism and now he's on to hormones. [SPEAKER_00]: Okay, the second claim, but it's really for wrapped into one, it's my thyroid hormone, cortisol, PCOS now renamed PMOS, or it's menopause, and every one of these has real physiology, but not one of them is why somebody is carrying around an extra 40 pounds, well, at least not due to the hormones.

8:08 [SPEAKER_00]: Let's take them one at a time because the details matter. [SPEAKER_00]: Thyroid first, because it's the most common one, and there's a twist in it that most people haven't ever heard about. [SPEAKER_00]: A genuinely underactive thyroid, real hypothyroidism, does lower your metabolic rate.

8:21 [SPEAKER_00]: That part's true. [SPEAKER_00]: But most of the weight it puts on is water weight, not fat mass. [SPEAKER_00]: When your thyroid hormone drops, your tissues start accumulating these big, water-hungry molecules. [SPEAKER_00]: And at the same time, your kidneys get worse at clearing free water, so you retain salt and fluid all over.

8:37 [SPEAKER_00]: That waterlogged state has a name, it's called [SPEAKER_00]: So when you finally treat the thyroid, most of the way that comes off is you letting go of that water. [SPEAKER_00]: And we can measure this directly. [SPEAKER_00]: In one study, they treated hypothyroid patients for a full year.

8:51 [SPEAKER_00]: And on average, they lost about four kilos. [SPEAKER_00]: Then they measured where those four kilos came from. [SPEAKER_00]: Essentially, all of it was from water, which is lean mass, and fat mass barely moved. [SPEAKER_00]: In a bigger real world study, a hundred patients started on thyroid medication, the median weight change was negative one tenth of one kilogram, basically zero, half of them didn't lose anything at all.

9:13 [SPEAKER_00]: Even the American thyroid association says it flatly on their own patient page. [SPEAKER_00]: Most of the weight gain in low thyroid is retained salt and water, usually in the range of 5 to 10 pounds, and treating it brings you back to the weight you were before, not to some lower number.

9:27 [SPEAKER_00]: So a real thyroid problem can add you a few pounds, but most of it's fluid. [SPEAKER_00]: It doesn't build obesity and fixing it corrects the water, not really the calorie math. [SPEAKER_00]: Cortisol is next, the stress hormone, which the internet is absolutely certain is quietly making everyone fat.

9:43 [SPEAKER_00]: In people who don't have cushion syndrome, which is a fortunately rare and generally dramatic disease of far too much cortisol, the everyday version of this claim is weak and it may even run partly backwards. [SPEAKER_00]: The biggest analysis we have pulled long-term cortisol measured in people's hair across more than 26,000 subjects, and the correlation at body mass index came out at about 1-10th.

10:03 [SPEAKER_00]: Let me translate that because a correlation of 0.1 means nothing on its own. [SPEAKER_00]: It means that cortisol explained roughly 1 percent of why people different body size. [SPEAKER_00]: 1 percent. [SPEAKER_00]: and blood in urine court is all did even less than that. [SPEAKER_00]: In a study of 369 people with obesity, there are 24-hour urine courtes all had basically no relationship with their weight.

10:24 [SPEAKER_00]: And the authors wrote in plain language that the data doesn't support a strong link. [SPEAKER_00]: Now, there is a real kernel in the cortisol story and I want to be fair to it because it's not nothing. [SPEAKER_00]: Fat tissue carries an enzyme that can regenerate active cortisol locally, right inside the fat itself.

10:39 [SPEAKER_00]: So the level in your blood can look normal while the level is in the tissue is higher. [SPEAKER_00]: That's real mechanism. [SPEAKER_00]: But when researchers went and measured whether belly fat really visceral adipose tissue that fat around your internal organs, when that actually dumps enough of the cortisol back [SPEAKER_00]: And here's the causation trap that really puts a nice bow on this.

11:01 [SPEAKER_00]: People carrying more fat, clear cortisol out of their system faster, so their bodies produce more of it just to keep the blood level normal, which means high cortisol output can be a consequence of the fat, not the cause of it. [SPEAKER_00]: So cortisol is real, it's effect on your weight is tiny and inconsistent, and if anything, the arrow may point at least partly the other way.

11:21 [SPEAKER_00]: The third one, PCOS, and actually if you haven't heard as of this year, it's got a new name. [SPEAKER_00]: This past May, an international consensus in the Lancet renamed it, polycystic ovarian syndrome, PCOS has become PMOS, polyendocrine metabolic ovarian syndrome, because the cysts were never actually cysts, and the condition was never really just about the ovary.

11:40 [SPEAKER_00]: It's the exact same move the liver people made when fatty liver disease got rebranded as [SPEAKER_00]: Let's run with it. [SPEAKER_00]: Does it break the equation? [SPEAKER_00]: Short answer, no. [SPEAKER_00]: But the details here are worth getting right. [SPEAKER_00]: The best data show that women with PMOS have a resting burn about 10% lower for every kilogram of lean tissue that they carry.

12:02 [SPEAKER_00]: 10% lower. [SPEAKER_00]: That sounds like a broken metabolism, and that's how it kind of gets sold. [SPEAKER_00]: But there's a catch. [SPEAKER_00]: Their total resting burn, the actual number of calories they burn at rest, came out about the same as everyone else's. [SPEAKER_00]: The 10% per kilo difference washes out once you look at the whole body.

12:19 [SPEAKER_00]: And the cleanest test settles it cold. [SPEAKER_00]: Take women with PMOS and women without it. [SPEAKER_00]: Put them on the same diet with the same resources in support. [SPEAKER_00]: And 12 weeks later, they'd lost 18 and a half kilos versus 19 and a half. [SPEAKER_00]: Statistically the same.

12:33 [SPEAKER_00]: So the difficulty in PMOS is real, and it lives on the input side, more appetite, more cravings, insulin resistance that shows up even in lean women with the condition. [SPEAKER_00]: The physiology makes it harder to eat less, but it doesn't make it impossible to lose weight. [SPEAKER_00]: And I'll be pretty straight about the fashionable version of this.

12:50 [SPEAKER_00]: The one that says their fullness hormones are all broken. [SPEAKER_00]: The studies genuinely disagree with each other. [SPEAKER_00]: Some find the hunger hormones are higher, some find them lower, and some find no difference at all. [SPEAKER_00]: The part that holds up is that the appetite burden is really persistent, it's not a magic hormonal off-switch.

13:07 [SPEAKER_00]: fourth, menopause. [SPEAKER_00]: We just did a whole four part series on this and this particular topic is covered in episode three, so we're going to cover the highlights here. [SPEAKER_00]: Here's the single thing you need to know for today. [SPEAKER_00]: The best study we have followed about 3,000 women across their actual menopause transition with yearly body scans for over a decade.

13:24 [SPEAKER_00]: Menopause itself, the hormonal change on its own, added about one and a half kilos of body fat over the three and a half years around the final [SPEAKER_00]: Meanwhile, the average woman gains 10 to 15 kilos between ages 30 and age 60, so menopause is a small slice of the midlife weight gain, and the rest is aging, activity quietly dropping off, and eating the trips upward so slowly that nobody clocks it.

13:50 [SPEAKER_00]: What men pause clearly does is move fat to the midsection, into the deeper, more dangerous visceral compartment around your organs, and that matters for your heart and your health. [SPEAKER_00]: But it changes where the fat sits more than how much of it there is. [SPEAKER_00]: Same equation, just enough on the inputs and the change of address.

14:07 [SPEAKER_00]: So, four hormones and one pattern. [SPEAKER_00]: Every one of them is a real modifier. [SPEAKER_00]: On the burn side or on the appetite side, real, sometimes we're treating, and every one of them smaller than the story being told. [SPEAKER_00]: Okay, the third big claim. [SPEAKER_00]: It's the smartest sounding one on the list, so we're gonna spend the most time talking about it.

14:24 [SPEAKER_00]: The type of calorie matters, therefore accounting the amount is pointless. [SPEAKER_00]: Now, there's a genuine point in here, it's just not the one that most people think that they're making. [SPEAKER_00]: Remember the category error from the top of the episode, a calorie is a unit, so a calorie is not really calorie, read literally is nonsense, kind of like an inch is not an inch, but the careful version of it means something real.

14:45 [SPEAKER_00]: That two foods with the same calorie count can do different things inside of you, and that's true. [SPEAKER_00]: It's an argument about what moves the inputs, so let's take it seriously, both halves of it, the burn side and the absorption side. [SPEAKER_00]: Let's start with the burn side because that's where people overreach.

15:01 [SPEAKER_00]: It is true, for example, that protein costs more to digest than carbohydrates or fat. [SPEAKER_00]: Your body spends something like 20 to 30 percent for every calorie from protein just processing it against a few percent for fat. [SPEAKER_00]: So the claim goes, eat more protein, raise your metabolism.

15:17 [SPEAKER_00]: And technically, yes, that happens. [SPEAKER_00]: But when you measure it, the effect is very small. [SPEAKER_00]: If you put people in a metabolic chamber, [SPEAKER_00]: where you can measure every calorie that they burn and swing their protein intake up two or three times how much they were previously eating.

15:31 [SPEAKER_00]: They're total daily burn barely moves. [SPEAKER_00]: At borderline 50 to 80 calories because their movement quietly drifts down to compensate. [SPEAKER_00]: Protein's real value is not that thermic rounding error, the thermic effect of food. [SPEAKER_00]: And we're gonna do an entire episode on protein, so I'll give you this short version here and say the rest for that one.

15:49 [SPEAKER_00]: Protein earns its key when it comes to reducing your dietary intake. [SPEAKER_00]: It does tend to keep you fuller to some extent, but more importantly, it crowds the higher calorie food off of your plate. [SPEAKER_00]: Now, whether the benefit is mostly from the fullness, like most people say, or really displacing the food, which less people say, my read of literature is mostly from displacing the other higher calorie food, but we're going to cover this in detail on the protein episode.

16:13 [SPEAKER_00]: Now, here's the best test in my opinion of whether the type of calorie is what decides how much fat you're carrying. [SPEAKER_00]: Researchers overfed people by about 950 calories a day for two months, and they vary the protein from 5% of the diet all the way up to 25%. [SPEAKER_00]: Everyone gained almost exactly the same amount of body fat.

16:32 [SPEAKER_00]: It's the same surplus, same fat, no matter the macros. [SPEAKER_00]: What the protein change was how much muscle they built alongside it, and they're total weight. [SPEAKER_00]: So the size of that surplus decided the fat. [SPEAKER_00]: The protein decided how much muscle came with it, but even that's a contention because the way they tested muscle, there's some error bars there.

16:49 [SPEAKER_00]: Now the underrated part, and it's where a calorie is not a calorie is quietly correct. [SPEAKER_00]: The absorption side. [SPEAKER_00]: Think about what that number on a food label actually represents. [SPEAKER_00]: It's the gross energy in the food, measured by literally burning it in a machine, but your body isn't a machine that burns things to ash.

17:07 [SPEAKER_00]: You only keep what you absorb. [SPEAKER_00]: Now, for most of what you eat, a normal mix diet, that label is actually pretty close. [SPEAKER_00]: Within a few percent of what you actually get out of it, the gap only gets big for a few specific foods and the cleanest example is nuts. [SPEAKER_00]: Let's take almonds.

17:22 [SPEAKER_00]: If you're like me, you eat almonds pretty frequently. [SPEAKER_00]: Now, you absorb about a third fewer calories from whole almonds than the label says. [SPEAKER_00]: A serving reads about 170, 160 calories, but you actually get about 130, and the reason is physical. [SPEAKER_00]: The fat is locked inside rigid cell walls, your gut can't fully crack, so a chunk of it rides straight through you and out.

17:43 [SPEAKER_00]: And you can prove it's the food and not the person, because researchers fed the same almonds in different forms, whole, then chopped, then all the way down to almond butter, and the calories people absorbed, climbed the whole way up. [SPEAKER_00]: almond butter landed right on the label, the same nut, same label, but different calories depending on what shape it's in.

18:03 [SPEAKER_00]: And now the limit, because this gets oversold into a free calorie theory of nuts, but it's really only a third for almonds, about a fifth for walnuts, and about 5% for pistachios. [SPEAKER_00]: So while it's real, it's food specific, and it's not a loophole you can build a whole diet on.

18:18 [SPEAKER_00]: Cooking does something similar, but mostly to starchy foods and some proteins. [SPEAKER_00]: Heat breaks down the starch and unfolds protein so you can pull more energy out of it than you could do raw. [SPEAKER_00]: The clearest human example is with an egg. [SPEAKER_00]: Your gut digest only about half of the protein in a raw egg, but about 90% of a cooked one.

18:37 [SPEAKER_00]: Cooking genuinely improves the bioavailability [SPEAKER_00]: of what's in the food, in this case an egg. [SPEAKER_00]: For food that's already easy to digest, like a piece of lean meat, cooking barely changes the calories, so it's a real effect for some foods and a small one for most. [SPEAKER_00]: So here's the bottom line on absorption.

18:52 [SPEAKER_00]: For a normal diet, the calories you absorb are close to what the label says. [SPEAKER_00]: It's a real effect at the margins, mostly whole nuts and high fiber foods, and it shifts a little with how you cook and grind things up. [SPEAKER_00]: That changes the term in the equation, but it doesn't break the equation and for most people, it's not even close to the main story.

19:10 [SPEAKER_00]: The main story is on the intake side, and it's a different thing entirely, so I want to keep them separate. [SPEAKER_00]: Remember that ultra-processed food study from the Wheelpower episode where people ate 500 calories a day more without even noticing? [SPEAKER_00]: that wasn't because they absorbed more from the same food.

19:25 [SPEAKER_00]: It's because they ate more of it. [SPEAKER_00]: Processing does make food easier to over eat. [SPEAKER_00]: It's softer, so they can eat it faster, but it's also more calorie dense, and it's less filling. [SPEAKER_00]: That's calories in effect, not an absorption effect. [SPEAKER_00]: So processing touches both sides a little, but the big one by a mile is how much you eat, not how much you absorb of it.

19:46 [SPEAKER_00]: So where does this leave calorie counting? [SPEAKER_00]: Precise counting was never really on the table, partly because the label is off for some foods and it shifts with how they're prepared, but mostly because people are genuinely terrible at measuring or even estimating what they actually eat, and it's worse than you think, because even the professionals can't do it.

20:02 [SPEAKER_00]: There's a study where they took registered dietitians, people who count calories for a living, more or less, and had them weigh and record their own food for a week, while knowing they were being checked against the gold standard measurement. [SPEAKER_00]: They undercounted their own intake by about 220 calories a day.

20:18 [SPEAKER_00]: The non-dietitians in the same study missed by over 400 calories. [SPEAKER_00]: In another one, when they had dietitians just eyeball restaurant meals, they lowballed them by [SPEAKER_00]: And there's the classic study. [SPEAKER_00]: The people who swore up and down that they ate under 1200 calories a day and still couldn't lose weight.

20:38 [SPEAKER_00]: When they were actually measured, they were under-reporting their food by about half, and over-reporting their exercise by about half. [SPEAKER_00]: Their metabolism was normal, but the math wasn't mathing. [SPEAKER_00]: So the label is a ballpark and your food diary is closer to a creative writing project.

20:52 [SPEAKER_00]: That's not a reason though to give up on the whole idea or concept of calories in calories out. [SPEAKER_00]: But it is a reason to stop trusting the number on the wrapper and trust the trend on the scale over two weeks instead. [SPEAKER_00]: And that right there is the guy in the comments.

21:05 [SPEAKER_00]: The guy who says, look, I'm eating 1,800 calories a day but I can't lose a pound. [SPEAKER_00]: His metabolism is fine. [SPEAKER_00]: It's just that his accounting is off. [SPEAKER_00]: Which brings us to the last one, and it's the only one on the list that actually tries to break the equation instead of just dodging it.

21:19 [SPEAKER_00]: It's not calories. [SPEAKER_00]: It's insulin. [SPEAKER_00]: This is the big one, so we're going to test it the hardest, and it's going to end somewhere you don't expect. [SPEAKER_00]: Here's the claim. [SPEAKER_00]: Stated as strongly as it's smartest people stated, because if I straw a man it, you shouldn't believe a word I say after.

21:33 [SPEAKER_00]: This is the carbohydrate insulin model, built by serious researchers like David Ludwig and popularized by the journalist Gary Taubs. [SPEAKER_00]: It goes like this, carbohydrates raise your insulin. [SPEAKER_00]: Insulin drives fuel into your fat cells and locks it there as long as insulin is elevated.

21:48 [SPEAKER_00]: So less energy stays circulating in your blood, so your body thinks it's starving. [SPEAKER_00]: So you get hungry and you burn less. [SPEAKER_00]: In this picture, the fat accumulation comes first and it drives the overeating. [SPEAKER_00]: Tobs has a great line for it. [SPEAKER_00]: We don't get fat because we overeat because we're getting fat.

22:04 [SPEAKER_00]: The strong version of this says carbs make you fat somewhat independently of calories. [SPEAKER_00]: It's a real theory with real proposed mechanisms, so let's test it. [SPEAKER_00]: Three different ways. [SPEAKER_00]: Test number one, if insulin is the master switch, then cutting carbohydrates which drops your insulin should, theoretically, burn off more fat than cutting the exact same number of calories from fat.

22:25 [SPEAKER_00]: So they ran precisely that experiment, in a metabolic ward where they could control every gram of food that goes into the subject's mouth. [SPEAKER_00]: Same calories both ways, six days on each, and everybody did both arms so each person was their own control or a comparator. [SPEAKER_00]: The result, cutting fat lost more body fat than cutting carbohydrates.

22:43 [SPEAKER_00]: 89 grams a day against 53 for cutting carbs. [SPEAKER_00]: Calorie for calorie, the low insulin diet lost less fat, which is the opposite of what this model would predict. [SPEAKER_00]: Now the fair caveat here, straight from the same researchers, just so we're being honest here. [SPEAKER_00]: Over the long run, those differences shrink towards each other.

23:01 [SPEAKER_00]: So this doesn't prove that keto, for example, can't work for weight loss. [SPEAKER_00]: It just proves that there's no calorie for calorie magic in dropping your insulin level. [SPEAKER_00]: Test 2. [SPEAKER_00]: Does insulin even predict who gains weight in the first place? [SPEAKER_00]: Answer is a coin flip.

23:16 [SPEAKER_00]: In Pima Children, higher fasting insulin did predict more weight gain down the line. [SPEAKER_00]: But in a group of Colorado adults, doubling the fasting insulin predicted 6.3 kilograms less weight gain. [SPEAKER_00]: Same blood test, but the opposite answer. [SPEAKER_00]: In Pima adults, the insulin resistant people gain less weight than the insulin sensitive ones.

23:36 [SPEAKER_00]: So if anything, insulin resistance sort of looks protective. [SPEAKER_00]: The one genetic study that people wave around for the insulin model only works for meal-triggered insulin, explicitly not fasting insulin. [SPEAKER_00]: These are different tests. [SPEAKER_00]: And even then, the whole effect is about three kilos spread across the entire range from low to high levels of insulin.

23:54 [SPEAKER_00]: If you put all that together, what you get is this. [SPEAKER_00]: Your fasting insulin is mostly a readout of the fat you're already carrying. [SPEAKER_00]: It's not a crystal ball for the weight that you're gonna gain. [SPEAKER_00]: Now, a sharp defender of the carbohydrate insulin model will say, fine, forget fasting insulin.

24:10 [SPEAKER_00]: The real claim is about insulin you spike after a meal. [SPEAKER_00]: Now, there's a genetic study that people point to that supports a version of that. [SPEAKER_00]: People whose bodies are built to pump out more insulin in response to food do carry a little more weight on the order of three kilos across the whole range.

24:25 [SPEAKER_00]: I want to take that seriously because it's the strongest card that this model can play. [SPEAKER_00]: But think about what your after meal insulin is. [SPEAKER_00]: You ate so it went up. [SPEAKER_00]: The bigger the meal, the bigger the response. [SPEAKER_00]: carbohydrates drives the biggest spike, protein, a smaller one, and fat barely moves it.

24:42 [SPEAKER_00]: But the headline is that insulin after meal is mostly a measure of how much food just showed up. [SPEAKER_00]: So when you see a bigger insulin response tracking with more weight, most of the time that's one fact showing up twice. [SPEAKER_00]: You ate more, so your insulin went up and you ate more, so your weight went up.

24:59 [SPEAKER_00]: The calories are doing the work and the insulin is riding along with them. [SPEAKER_00]: A passenger kind of looks like a driver in the scenario. [SPEAKER_00]: And even that small genetic signal about three kilos, most likely works in the same unglamorous way. [SPEAKER_00]: If your body runs a little more insulin, it can nudge your appetite up a notch, so you eat a little more.

25:17 [SPEAKER_00]: That's still calories. [SPEAKER_00]: It's still the equation. [SPEAKER_00]: It is an insulin reaching past your mouth and storing fat on its own, which is the one thing the model actually needs to be true if the model is correct. [SPEAKER_00]: And before the big one, a quick story because it's how science is supposed to work.

25:32 [SPEAKER_00]: Gary Taubs and the physician Peter Tia co-founded an nutrition research institute, and they funded these metabolic board studies to test the carbohydrate insulin model. [SPEAKER_00]: The model Taubs spent years arguing for, and the studies came back against it. [SPEAKER_00]: And they published them anyway.

25:47 [SPEAKER_00]: The data won over the hypothesis, even for the people who most wanted the hypothesis to be true. [SPEAKER_00]: That's the whole game right there. [SPEAKER_00]: Now, the one that should end the argument, said everything else aside and look at the drugs that a lot of people in this country are taking.

26:00 [SPEAKER_00]: The GOP ones, some agglutide, Trezzepatide, Ozzampic, Manjaro, the ones you've heard of a thousand times. [SPEAKER_00]: Here's what almost nobody arguing about insulin online has clocked. [SPEAKER_00]: These drugs are mechanically insulin secretotokes. [SPEAKER_00]: That's a fancy way of saying, part of their jobs tell your pancreas to put out more insulin.

26:19 [SPEAKER_00]: The newer one, Tersepatide, adds a second gut hormone called GIP that pushes insulin to, and it loses more weight than the single hormone drug, not less. [SPEAKER_00]: Now to be precise here, because this is exactly where the argument usually gets a little sloppy, these drugs don't crank your insulin up around the clock.

26:36 [SPEAKER_00]: They amplify insulin release only when your blood sugar is already elevated right after a meal, and the ease off once it comes back down. [SPEAKER_00]: That's the whole reason they don't put you into a hypoglycemic hole. [SPEAKER_00]: So they aren't flooding you with insulin the way a pile of carbs is supposed to in this model.

26:51 [SPEAKER_00]: They're making your body's insulin response to food, bigger, and sharper. [SPEAKER_00]: So here's the best version of the test. [SPEAKER_00]: If your insulin response to a meal were the master switch that locks fat away, then a drug that makes the response bigger should, at the very least, not produce the largest weight loss of any obesity medication we've ever approved.

27:10 [SPEAKER_00]: Samagulotide takes off around 15% of body weight on average, turns appetite around 20. [SPEAKER_00]: Remember the passenger in the driver? [SPEAKER_00]: Normally, your after meal insulin and your weight right up together, both pulled up by how much food you're actually eating. [SPEAKER_00]: This drug pulls the insulin up and the food down at the same time and the weight still falls.

27:29 [SPEAKER_00]: The passenger got separated from the driver and it turns out the passenger was never steering and it gets worse for the insulin story when you look at what happens to insulin on these drugs. [SPEAKER_00]: Over time, fasting insulin doesn't climb. [SPEAKER_00]: It falls, and not because the drug is secretly lowering it.

27:45 [SPEAKER_00]: It falls because the person is losing body fat, and it tracks the weight loss step for step. [SPEAKER_00]: So the drop in insulin is a readout of the fat coming off, not the thing that caused it. [SPEAKER_00]: What caused it was appetite in controlled feeding studies, people on some agglotite ate about a quarter fewer calories, and the weight they lost came off mostly as fat.

28:05 [SPEAKER_00]: and the resting burn their energy expenditure held the same. [SPEAKER_00]: People describing the food noise just going quiet, the constant low negotiation with a refrigerator gone. [SPEAKER_00]: The mechanism is appetite reduction, start to finish. [SPEAKER_00]: The intake side of the equation turned down at the source in the brain.

28:23 [SPEAKER_00]: And that's our guy in the comments one last time. [SPEAKER_00]: It was never insulin lock in the fat away. [SPEAKER_00]: The insulin was real. [SPEAKER_00]: The calories that its appetite signal was quietly adding, meal after meal, year after year, those are the ones that showed up on the scale.

28:36 [SPEAKER_00]: So let's cover the whole list because the pattern is pretty clear here. [SPEAKER_00]: Your metabolism didn't crash at 40. [SPEAKER_00]: It adapts a couple hundred calories when you die and lose weight, and most of even that is just moving more efficiently. [SPEAKER_00]: Your thyroid holds water, the 40 pounds came from somewhere else.

28:52 [SPEAKER_00]: Cortisol explains about 1% of anything, and even that may run partly the other way. [SPEAKER_00]: PMOS is a real 10% nudge on the burn that washes out to almost nothing at the whole body level. [SPEAKER_00]: And the type of food changes how much you absorb and how much you eat, which is real, but it is still calories.

29:09 [SPEAKER_00]: And insulin, the one that tried the hardest to break the equation, turns out to be so far from the master switch that the drugs which crank up your insulin response to a meal are some of the best weight loss tools we've ever built. [SPEAKER_00]: Every one of those objections was pointing at something real, and every single one of them was a hand on a lever, not a hole in the equation.

29:28 [SPEAKER_00]: It's not calories, it's blank, gets the blank right, but the not wrong, every single time. [SPEAKER_00]: The insulin is real, the cortisol, the thyroid, all real, they do their work by changing how much you eat and or how much you burn. [SPEAKER_00]: and that's still calories in calories out.

29:43 [SPEAKER_00]: The equation is not the right thing to argue with. [SPEAKER_00]: The whole game is what's pushing on the two sides of it or one over the other, and almost none of that pushing is under your conscious control, which is exactly what we told you last week. [SPEAKER_00]: So what do you actually do with that?

29:57 [SPEAKER_00]: If the inputs aren't a matter of willpower, then you change what you're working with, instead of just grinning your teeth against it. [SPEAKER_00]: More protein and more fiber, so the fullness comes cheaper. [SPEAKER_00]: Get the stuff you overeat out of the house, so the decision is already made before you're standing in the kitchen at nine at night.

30:11 [SPEAKER_00]: Sleep because tired people eat more and they don't feel those satiety or fullness signals as early after a meal. [SPEAKER_00]: And look, if you want to count your calories and weigh your food to the gram, you can do that. [SPEAKER_00]: Some people, a minority folks, will be successful, but just know there's some squish in the equation.

30:27 [SPEAKER_00]: Either way, watch and trust the trend on the scale over the next two weeks. [SPEAKER_00]: None of that's glamorous, but all of it works with the machine instead of against it. [SPEAKER_00]: And it leaves one door standing wide open. [SPEAKER_00]: We just watched a drug that raises insulin strip the fat off of people by reaching into the brain and turning down their hunger.

30:44 [SPEAKER_00]: So next time, the last one in this series will go straight at the drugs. [SPEAKER_00]: What GLP ones do, why they work when will power does and whether taking one is cheating. [SPEAKER_00]: And I'll tell you right now, your answer to that last question is going to depend almost entirely on whether these last two episodes landed for you.

31:00 [SPEAKER_00]: That's next week. [SPEAKER_00]: I'm Dr. Jordan Fagenbaum, and this has been the Barbell Medicine podcast.