This is a transcript of the Gastropod episode, The End of the Calorie, first released on January 26, 2016. It is provided as a courtesy and may contain errors.

TARA HAELLE: I don’t really buy into this “a calorie is a calorie” thing.

DAVID WISHART: In the end, and I guess this is sort of treating it as a chemist, a calorie is a calorie is a calorie. It’s a unit of energy.

SUSAN ROBERTS: I think all calories are not the same when it comes to how satisfying they are.

MARION NESTLE: You can’t count calories anyway. It’s not really possible for anybody who’s just an eater to figure out how many calories you’re eating.

RICHARD WRANGHAM: The calorie is the only darn thing we’ve got in this game at the moment, isn’t it? But it gives us a sort of unfair sense of precision. The calorie is a somewhat dangerous item because it leads us to thinking that we’ve solved the problems when in fact we haven’t.

NICOLA TWILLEY: Hello and welcome back! This is the first episode of a new season of Gastropod, the podcast that looks at food through the lens of science and history. I’m Nicola Twilley.

CYNTHIA GRABER: And I’m Cynthia Graber. And I bet you listeners have no idea what we’re going to be covering in this episode.

TWILLEY: Seriously, if you can’t guess already, then go get yourself a coffee and take this again from the top.

GRABER: Yes, that’s right, we are not easing into things this season. We’re stepping boldly into one of the thorniest food controversies of all—the calorie. What the heck is it? If you’ve ever tried to lose weight…

TWILLEY: Hello New Year’s resolutions.

GRABER: You’ll know that the standard advice is that you have to eat fewer calories than you burn. But we wanted to know: Is a calorie the same no matter what type of food it comes from? And is one calorie for you exactly the same as one calorie for me?

TWILLEY: Or me. We’ll hear from all of the folks you just heard and more on this show, as we visit the special rooms where calories are measured and the labs where scientists are busy proving that the numbers on our food labels are off—sometimes by quite a bit. So is the calorie broken?

GRABER: Listen in for more. But first, this week’s show is a special episode brought to you in collaboration with Mosaic, that’s the online publication of the Wellcome Trust.

TWILLEY: If you have ever wrestled with counting calories, the guy you need to blame is Santorio Sanctorius. He lived in the 1600s in Padua, in what’s now Italy.

GRABER: And he’s a fun character.

NESTLE: We would say a serious case of obsessive compulsive disorder.

GRABER: That’s Marion Nestle. She’s professor of nutrition, food studies, and public health at New York University. She’s also co-author of a book called Why Calories Count: From Science to Politics. And she wasn’t kidding when she said our man Santorio Sanctorius was a little OCD.

NESTLE: Well, he weighed every single thing he ate or drank and every thing he excreted. Everything.

GRABER: Every day. For thirty years.

NESTLE: He developed a special weighing chair, because these things were very difficult to do. and every day he sat in his chair and weighed himself. I mean he must have been extremely compulsive. And at the end of that, he did a kind of calories in, calories out kind of thing—he didn’t know what a calorie was. But he could see that what he ate had a big effect on what he weighed and what he excreted.

TWILLEY: That was really the first step toward understanding the relationship between what we eat and what our bodies use, store, and get rid of. But it was vague. There was no unit of measurement. No calorie, in other words.

GRABER: More than a century later, French scientist Antoine Lavoisier took the next step. With a literal guinea pig.

NESTLE: Well, he looked at heat energy. I mean one of the things about calories is they’re a measure of heat.

TWILLEY: Lavoisier had already figured out the chemistry of combustion, and he had a hunch that something similar was going on inside our bodies—that we burn food as fuel. As it turns out he was right. It’s a little complicated, you can’t just picture a log fire in your stomach, but the chemical reaction that unlocks energy from food is equivalent to burning.

NESTLE: The heat that you get when you burn a food in a chamber is the same as the heat you get if you’re putting a guinea pig in a chamber.

GRABER: Lavoisier’s idea was that as the guinea pig burned all the food that it had eaten, its body would give off an equal amount of energy as heat.

NESTLE: And so he figured out that if he measured the heat, he could develop some kind of measure of the caloric value of food.

TWILLEY: Two and a half centuries later, I still have trouble wrapping my head around that one, but it is true: we burn food for the energy we need to stay alive. And the end product of all of those reactions in our bodies that keep us alive is heat. So if you measure one, you get the other.

GRABER: And to measure that heat, Lavoisier created a weird-looking contraption—it looks like an urn that you might use to get coffee in at a conference, with a spout pouring water out at the bottom. But in this case, the urn had a guinea pig hidden inside.

NESTLE: So the guinea pig’s in a chamber, the chamber is surrounded by water. As the guinea pig gives off heat, that heat is transmitted to the water, they can measure the change in temperature of the water, which is measurable. And then figure it out that way with some clever calculations.

TWILLEY: Lavoisier called this guinea-pig-inside-a coffee-urn gizmo a calorimeter. Because “calor” means heat in Latin. But he never used the word calorie. In fact, he got guillotined in the French Revolution shortly after the whole guinea pig thing.

GRABER: He didn’t have time to take his research to the next level, unfortunately. It took another few decades until a German researcher did use the c-word. And he, finally, meant a specific unit of energy in food.

TWILLEY: To be even more specific, the calorie was defined as the amount of heat energy required to raise the temperature of one gram of water by one degree centigrade, from 14.5º to 15.5º, at sea level. Good to know, right?

GRABER: That’s just what I was thinking. I know when I look at a doughnut I wonder how many bathtubs of water is that doughnut gonna heat up by one degree.

TWILLEY: This all sounds completely random, but we are not joking with you, people. This is the calorie. That’s what it is. And what’s even weirder is we measure it in almost the same way that Lavoisier did, today. But with humans as the guinea pigs.

GRABER: That’s right. We now stick humans in a box, feed them donuts, and see how much they heat up. At least, that’s what the first human-sized calorimeters were like.

NESTLE: While we were writing this book, we went to Penn State and visited—they have a calorimeter museum there. And it’s this really quite large room, in which there are desks and tables and then on a platform is this room that looks like a shipping crate, kind of, except that it’s made out of wood and it’s quite beautiful, and it’s connected to all of these pieces of equipment. It’s not used anymore. But you can imagine putting somebody in there for several days. They never stayed in for very long. But they stayed for several days while these measurements were being taken.

GRABER: That seems like a long time to be in a shipping crate!

NESTLE: And many of the original measurements that were made using this thing were really important measurements in science.

TWILLEY: The one at Penn State is a museum piece—it was built in 1902, and it worked the same way as Lavoisier’s coffee urn. It was a little wooden room with a stepladder to get into it and a tank-full of water as a kind of insulating layer around it.

GRABER: The US Department of Agriculture—they do a lot of food research, including calorie research—scientists there were actually using similar human-sized calorimeters even just a decade ago, measuring the heat that the person inside gave off.

TWILLEY: And they still use little rooms today, but now they’re covered in tons of sensors that measure exactly how much oxygen the person in the room breathes in, and exactly how much carbon dioxide they breathe out. And the USDA scientists can work backwards from that to figure how much energy you’ve burned.

GRABER: We actually traveled to Beltsville, Maryland, to visit the USDA calorimeters in person.

GRABER: This is literally a walk-in cooler.

BILL RUMPLER: We bought this from Norlake, which is a walk-in cooler company, yeah. Because unlike a lot of them, they’re nice—they’re sealed fairly tight.

TWILLEY: Bill Rumpler is a USDA researcher. He’s the one that tricked out the walk-in coolers to turn them into calorimeters.

GRABER: So we have a fold-up bed, a treadmill, a TV, a toilet?

RUMPLER: Yeah, and then there’s the access ports. In the doorway, we have an airlock for passing food in and out. Or passing out non biohazardous material. Like a urine or blood sample, we wouldn’t pass out through the food locker. We have a blood port, which a person can stick arm out through. We can hook up a catheter or just simply pull their blood samples. They have Internet access, we have a couple of different ways people can exercise in here.

TWILLEY: There are three of these rooms. They’re about 10ft by 10ft, and they’re pretty stark—fluorescent overhead lighting, vinyl floor tiles, white walls, lots of exposed pipe and sensors. It sort of reminded me of a low security prison.

GRABER: People are shut in here for 24 to 48 hours. I imagine it gets kind of boring.

RUMPLER: I had a woman years ago that was in my study that brought her sewing machine and she sat and made clothing while she was in there.

GRABER: Got to come up with something.

TWILLEY: You’re allowed to bring, like if you, your hobby is knitting, you’re allowed to bring?

RUMPLER: We discourage sewing machines now, because she made a mess. But yes we encourage people to bring like their knitting or their books to read, if they have some sort of non-destructive craft.

TWILLEY: For each experiment, they have a different schedule, and the people in the calorimeters have to stick to it precisely. So the most recent one, they had dinner from 6:00 to 6:45. And then they had four and a quarter hours of quote low activity—that’s reading, computer, TV. And then they had to get in bed and stay in bed between 11pm and and 6:30am. No exceptions.

GRABER: It seems like a crazy set-up. But this is what scientists have used to figure out how many calories people burn from a particular meal. Or how much of an impact different kinds of exercise have on burning calories. Or whether snacking between meals has an impact on how much energy you use overall.

TWILLEY: Bill told us that they’ve had more than 2,000 people coming through these rooms for various experiments over the years. And they’ve discovered a lot about how we burn calories and what order we burn fats versus carbs and all of that.

GRABER: Those little rooms tell you how many calories a person is burning. But if you want to know how many calories were in the food to start off with, you need something called a bomb calorimeter.

TWILLEY:  And that works on the same principle—there’s a can with water around it to measure the heat. Except that this time instead of a guinea pig or a human body, the food itself gets put in the can and set on fire. David Baer works with Bill at the USDA facility—he’s a research physiologist. And he gave us a demonstration of their in-house bomb calorimeter.

DAVID BAER: Uh, this is a little holder—and we take the food, make a pellet out of it, this is a pellet press. So we make a little pellet, and we put this here—and then there’s a wire that goes from these electrodes, onto the top of the sample, and then this gets placed in here. It locks in, and then it gets filled up with oxygen, and then once it’s all, the temperature is all equilibrated, it will fire, and we’ll get a display print out of the temperature change and the calories that are in the sample.

GRABER: If I freeze-dried and ground up a cheese sandwich, the bomb calorimeter could tell me just how many calories are in that cheese sandwich. That’s the baseline—kind of the ultimate maximum amount in the sandwich. But to get the number on the label, you have to do a whole other set of calculations.

TWILLEY: And the dude we have to thank for those numbers, the ones on the labels, is Wilbur O. Atwater.

GRABER: I love his name. We get some great names on this show.

TWILLEY: It’s time for a Wilbur comeback I think, any expectant parents in the audience? Our Wilbur was also a USDA scientist, and he is known as the father of nutrition science for an amazing set of experiments he did at the turn of the twentieth century.

NESTLE: I think Atwater was just an extraordinary scientist. And I cannot imagine that anybody today could do the kind of experiments he did in quantity and quality.

GRABER: Marion Nestle is a huge Wilbur fan. So anyway, Wilbur wanted to know if humans work like bomb calorimeters. So he measured potential calories in more than 4,000 foods in a bomb calorimeter. That’s like me incinerating my cheese sandwich. Then he fed those foods to people, and collected their excrement. And then he burned the feces in the bomb calorimeter to see how many calories it contained.

TWILLEY: And that told him how many of the total calories that were in the food originally did not get digested. How many calories were lost, basically—that came out the other end untouched. And he did that whole process with 4,000 different foods.

GRABER: It took him a few years.

TWILLEY: By subtracting the lost energy from the potential energy in all of these foods, and then crunching all those numbers together, Wilbur arrived at something we now call the “Atwater Values.” These are three numbers that represent the available energy—the calories—in each gram of protein, carbohydrate, and fat in your cheese sandwich.

NESTLE: And the tribute to the quality is that the Atwater values have held up to this day. So that you still see on food packages 4 calories per gram for carbohydrate and protein and 9 calories per gram for fat. And those are approximations, they’re not exactly right for everything. But boy they’re close.

TWILLEY: Like Marion says, those numbers are the foundation of every single calorie count you see on a label today. Although, bizarrely—

NESTLE: The FDA allows five different ways for food companies to calculate calories. One is they can use a bomb calorimeter. Nobody does that. Really nobody does that.

TWILLEY: They mostly use Atwater Values, like everybody else. Or they pull from some lists that the USDA put out, updating those values to take into account undigested fiber and a few other quirks.

GRABER: These five different counting methods means that the exact same foods might have slightly different calorie counts on the labels at the store. You can check this out for yourself. Nicky and I went to a supermarket near the USDA offices.

TWILLEY: Spaghetti is the most generic. Let’s do spaghetti.

GRABER: OK.

TWILLEY: So we have spaghetti: 56 grams, 210 calories.

GRABER: And this one is—56 grams, 210 calories.

TWILLEY: Barilla. Spaghetti. Where is it? 56 grams, 200 calories.

GRABER: So there is a difference—but only a ten calorie one. Overall, labels don’t vary by a huge amount.

NESTLE: Well, I would say probably within 10 percent. And that’s not considered to be very much in calorie determinations. I used to laugh a lot when food packages used to have calories as “454 calories.” Oh come on, give me a break, you can’t measure it that accurately. So what you want is you want some ballpark figure that’s going to work all right. And these work all right.

TWILLEY: Close enough is Marion’s mantra, at least when it comes to calories. Yeah, the number on your package is not precisely the number of calories you’ll actually get from the food —but it’s close enough.

GRABER: But not necessarily. In the past couple of years, scientists have been showing that in some cases that gap can be huge.

TWILLEY: To find out more, we followed David Baer into the USDA kitchen. It’s down the hall from the calorimeter rooms.

BAER: So if you want to take a look in here, this is our research kitchen. We can feed 60 or 70 people a day. Everything’s weighed out to the nearest gram. So right now we’re working on a dinner, getting that ready. Dinner tonight is meat loaf, mashed potatoes, corn, a homemade brown bread, a homemade chocolate chip scone, vanilla yogurt, and a treatment, which is yellow.

TWILLEY: The treatment is the thing they are testing—in this case, it’s tomato juice.

GRABER: But for a previous series of studies, the treatment was nuts—pistachios, almonds, and walnuts.

BAER: It is really a mathematical approach and basically we feed a pair of diets to each of our research volunteers. One of those diets is—we call it a base diet. And the other diet contains the food of interest.

TWILLEY: And what David and his colleagues do is they just repeat what Atwater did—they measure the total energy in the quote food of interest, they measure the total energy in the base diet, they measure the energy left over in the feces.

GRABER: And they measure the total energy the people burn. Although for this nut study, they didn’t have to lock people in the rooms—the subjects could go about their daily lives. The scientists instead used other markers they could test in blood and urine.

TWILLEY: And using all those numbers, they can figure out exactly how many calories our bodies can get from the food they’re testing—in this case, the nuts.

GRABER: And to really see that difference, the base diet that the volunteers eat has to be exactly the same. Exactly, exactly, exactly. And it’s complicated—they have to make it exactly the same taking into account people’s different sizes and genders.

BAER: We don’t tell people it’s 2,600 calories or anything like that, we just tell them it’s a level. And then everything is weighed out. So on each of these labels is a gram amount of the food that’s in there. And, you know, to get 96 grams of brown bread, it’s a couple of big slices and then some smaller pieces to get us to the exact weight.

GRABER: Wow. But so like 5ft 4in woman and 6ft guy would have different amount of food that you’d give them in this lunch?

BAER: Yes, they’d be getting different amounts. They’d be given an amount to maintain their energy level, their body weight.

TWILLEY: The thing I love is that, you know, here it’s like half a waffle, that’s how precise it is. If you were at home you’d just have the damn waffle.

GRABER: That and the bread crumbs. I mean, you’re getting like the little extra crust you have to eat…

TWILLEY: So you’ve got people eating precisely the same thing. Now you have to add the nuts.

BAER: Generally 1.5 oz or 3oz of nuts in the diet. And they come to our research center to receive all their meals, and after about nine days of adapting to the diet, we’ll give them a little capsule that contains a marker. And we’ll look for that marker to show up in their feces. And that’s when we know to start, we’ll start collecting their feces. And so we have different jugs and collection apparatus that we give to people and we give them coolers and when we’re collecting feces we’ll give them dry ice so the stuff stays nice and cold.

GRABER: Yes, if you participate in a USDA study, be prepared.

TWILLEY: The food is free, but you have to carry your poo around in a cooler.

GRABER: So okay, that’s the feces. What about the nuts?

BAER: So the first study that we did with tree nuts was a study with pistachios. And we found that when we actually measured the energy, the calories in a serving of pistachios, it was about 5 or 6 percent less than what you would see on a food label or in the USDA database. As that study was going on we started to prepare to do a study of almonds.

GRABER: And there they found that the difference was closer to 30 percent—way more than five or six.

TWILLEY: 30 percent! So if you have a handful of almonds as a snack and the label says 100 calories, you’re only getting 70.

GRABER: They’ve most recently done a similar study with walnuts. For walnuts, the difference was 21 percent.

TWILLEY: And they’re not sure why. David thinks it has something to do with the internal structure of the nuts—how the fat is sort of wrapped up in other plant material.

GRABER: That hypothesis does seem to fit with the findings of another group of scientists. They’re looking into­ how cooking changes the structure of food and finding that those changes make a big difference in how many calories our bodies can get from it.

MID-ROLL

TWILLEY: So we set out on this adventure because we wanted to know whether a calorie is always a calorie—whether we should just put our faith in the number on the label. And David Baer at the USDA has shown that, at least in the case of a specific kind of food—

GRABER: Nuts.

TWILLEY: We shouldn’t. Our bodies can’t get as many calories out of almonds as the label says.

GRABER: But what if what we do to our food before we eat it also changes the number of calories our bodies can get out of it?

TWILLEY: That’s the question that Richard Wrangham has been looking into. He is anthropologist at Harvard University and the author of an excellent book, Catching Fire: How Cooking Made Us Human. And the way Richard got curious about this whole calorie thing was somewhat unusual.

WRANGHAM: Oh well, I had a kind of absurd introduction to the problem because I was studying the feeding behavior of wild chimpanzees. And I tried to eat everything that chimpanzees ate, and I even tried to go for days at a time eating only what they ate. And I discovered that it left me incredibly hungry. Even though what chimps eat is not the same as what hunter gatherers eat, it led me to the thinking that there’s something very different about living as a wild animal eating raw foods, and living as a human. And then you know I realized that every human eats their food cooked. So I started developing the idea that humans have something special about them. We need cooked food. And then I was astonished to discover how little was known about the process of cooking in terms of its impact on physiology and nutrition of foods.

TWILLEY: Wilbur Atwater, for all his brilliance, never really tackled that question.

GRABER: So in the past few decades, Richard and his colleagues at Harvard have been figuring out just what cooking does to different foods.

WRANGHAM: When my colleagues and I first produced a paper saying, look, it seems as though cooked food produces more energy for humans than raw food does, we were met with the response, well, no, cooked food is only as good as raw food.

TWILLEY: And Richard’s critics pointed out, look, if you feed people raw potatoes and look at their poo, there’s no starch in it, so they must have digested it.

WRANGHAM: So we needed to do these experiments and now what we’ve got is very clear replicable experiments showing that mice grow better when eating cooked sweet potato than eating raw sweet potato.

GRABER: And they think they know why. They think it’s because cooking changes the structure of the starch and so it can be absorbed in the small intestine, which is the next thing after the stomach. But the starch in raw sweet potato can’t be absorbed by the small intestine, it passes on to the large intestine. And that starch gets broken down by bacteria. And those bacteria eat some of the calories themselves, so not as many calories make it to us.

WRANGHAM: And the net result on a variety of carbohydrates from grains and tubers is that something like 30 to 40 percent increase is the typical increase in the number of calories that you are able to get from eating your starch cooked as opposed to eating it raw.

GRABER: Forty percent is a big deal, but we’re talking about starch ­and you’re probably not eating raw potatoes, so this might not seem so relevant. But Richard and his colleagues have found the same thing is true for meat.

TWILLEY: So a steak tartare, where you’re eating beef raw—your body will get fewer calories from that than from the exact same amount of cooked mince.

GRABER: And peanuts. You get more calories from roasted peanuts than from raw ones. But, one note of caution, most of the research has been done with mice.

WRANGHAM: None of this research has been done experimentally on humans.

TWILLEY: Side bar, some of it has actually been done on pythons.

WRANGHAM: Pythons are wonderful because pretty much all they do is just sit and digest.

GRABER: Still, Richard is sure these are big differences. And the same will be true for us humans, as well.

WRANGHAM: If you’re looking for a percentage, I feel very averse to giving any. Because we’re still at a very early stage with this and different foods are going to differ in all sorts of ways. I think it’s going to be more in the range of 20, 30, 40, 50 percent reductions than 1 to 2 percent. But it is going to depend a lot, of course, on the foods and the complicated thing here is that many of the foods that we deal with are foods that have been amazingly predigested in a sense.

TWILLEY: This is the craziest part for me. Richard has shown that normal cooking makes more calories available, but what about the kinds of intense processing that corn goes through to become a Dorito? What does that do to the calorie count?

WRANGHAM: Yeah, I mean heat extrusion, when you put food at very high temperature and squeeze it, is all increasing the relative number of calories you get compared to the Atwater convention. And my sense of the way that the food industry has been going over the last many decades is increasingly turning our food basically to mush. To the maximum number of calories you can get out of it.

GRABER: We don’t know exactly how big of a deal this is—but we are actually beginning to cast some doubt on whether a calorie is always a calorie.

TWILLEY: Based on David Baer’s work at the USDA and Richard Wrangham’s work at Harvard, we now know that the internal structure of food makes a difference to how many calories our bodies get from it. And we can change that structure by cooking.

GRABER: So there is a difference between different foods. Six ounces of beef can have a different calorie count depending on whether you eat it as a well-done burger patty or as steak tartare.

TWILLEY: So far we’ve been looking at whether differences in the internal structure of food can change how many calories are available to us from it. But what about differences between people? Can that have an effect?

GRABER: Scientists already know that different people have different metabolisms. Some people can’t seem to gain any weight, and some people have a really hard time losing it. Your metabolism also slows down as you get older, so you literally need fewer calories to survive.

TWILLEY: More muscle means a faster metabolism. Gender has an effect on how your body uses calories. How much fat you’re carrying already has an effect.

HAELLE: And then once you’re not active, your body’s metabolism slows down more. That’s the only explanation I have, because it doesn’t make sense that I would count calories and try a diet that had worked for me previously and there’s absolutely no response.

GRABER: Tara Haelle is a science writer. You heard her at the start of the show complaining that, at least for her, one calorie that she eats is not the same as a calorie for other people. She’s had two kids. And while she has certainly gone up and down in her weight over the years, she thinks the birth of her second kid just completely screwed up her metabolism. After her son was born, she had to finish up a major writing project—and then she tried to lose weight.

HAELLE: That was when I, again, tried counting calories three different times. And nothing. Nothing. I tried Atkins again. Nothing. When I say nothing, at this point I was 250 pounds, and over a period of probably four months of attempting calorie counting, then doing Atkins, and then going back to calorie counting, I didn’t see, like, I didn’t even drop to 247. There was about the two pounds up and down natural variation of the body, and nothing else.

TWILLEY: This is such a common challenge. You count calories and somehow you still don’t lose weight. For a while, researchers thought the blame could be pinned on genetics.

BAER: There used to be this concept of thrifty genes and people who were really metabolically efficient. And then when you start to tease apart all the parts, there certainly is variation among individuals. I hesitate to give a number as to what that variability is, but so far nobody has really found a very thrifty sort of an individual that just needs fewer calories.

GRABER: So it’s true, as David Baer says, there’s a little bit of variation—some people genetically just need fewer calories to make their bodies work. But most people say this genetic difference isn’t huge, and it can’t be blamed for the obesity epidemic.

NESTLE: Genetics matters, as genetics matter in all things. But how much is a matter of argument. And the overall argument about genetics is that the prevalence of obesity started to rise quite sharply in the early 1980s. Genetics did not change in that ten or twenty year period.

TWILLEY: So Marion says genetics can only account for part of that rise. But there is one big difference between people that scientists are starting to realize could be responsible for making some of us gain more weight from exactly the same amount of food. To find out more, we went to San Francisco to visit Peter Turnbaugh. He is a professor in the microbiology and immunology department at UCSF.

PETER TURNBAUGH: So I think most people think about a calorie in terms of the amount of energy they can get out of their food. If you’re eating a box of Cheerios you’ll have a number on the label that says the number of calories that you’ll get out of a given serving.

GRABER: But Peter thinks those numbers might be wrong. And that’s because they ignore the tiny creatures that live in our gut.

TURNBAUGH: Our gastrointestinal tract is home to trillions of microbes. And those microbes play a very important role in helping us to digest our food. And so that concept of the calorie needs to not just take into account the absolute amount of energy that’s possible to gain from a food, but also the variation between us in terms of how good our own bodies and our microbes are at liberating those calories.

GRABER: Microbes! You know we can’t go too long on this show without talking about them.

TWILLEY: I wonder sometimes, like, if our listeners played a microbe drinking game. If you had a shot every time we mentioned them, you would be on the floor about five minutes in.

GRABER: Be careful. But really, our gut microbes might be making the difference.

DAVID WISHART: And the gut microflora is probably one of the most distinct things. Like everyone has a heart, everyone has a brain, but the microflora for each person is as distinct as their fingerprint.

TWILLEY: That’s another David, David Wishart. He’s a professor in biological sciences and computing science at the University of Alberta, in Canada.

GRABER: We’re going to talk to him more later in the show. But the question is, can those differences in our personal gut microbes really make a difference in how much energy each of us gets from food?

TURNBAUGH: So what we did was look at lean and obese humans. And we found that there were changes in the types of bacteria that were found in their gut. And so that suggested then an association between the types of bacteria that are found in an obese versus lean individual.

GRABER: And then they did what they call a transplantation experiment. They took microbes from obese humans and microbes from their lean twins and used those to colonize some specially-bred microbe-free mice.

TURNBAUGH: And what was really exciting and possibly disturbing LAUGHS is that although we did see an increase in body fat in mice colonized by the lean microbial community, we saw about twice as much increase in body fat with mice colonized with the obese donor. And so that suggests that some of those changes in the types of microbes that are found matter in terms of the amount of energy that we’re gaining from our diet.

TWILLEY: Other scientists are starting to confirm these findings in really interesting ways. There was a study that came out just last month about Risperdal, which is an antipsychotic drug that a lot of people complain makes them gain weight. The scientists gave risperidone, which is the active ingredient in the drug, to mice. And the microbes living in those mice’s guts changed. Over the two months of the study, the mice packed on another 10 percent of their body weight again. That’s like me gaining a stone—

GRABER: Fourteen pounds

TWILLEY: —in just two months!

GRABER: Here’s another shocking study. It’s a case study about a woman who needed a gut microbe transplant to kill a nasty antibiotic resistant infection she had—it’s a bug called C.diff. You might have heard of these transplants—they’re also called fecal transplants. Anyway, the donor was her teenage daughter, who’s overweight. So the transplant did kill off the C. diff. Which is amazing. But the woman gained more than 40 pounds as of the time the study was published last year. She hadn’t changed anything else but her gut microbes. And she couldn’t lose the weight.

TWILLEY: This is all really compelling evidence that depending on your gut microbes, a calorie really might not be a calorie. And that gives Tara Haelle some hope. Because she says, maybe we’re finally going beyond the dogma that a calorie is always a calorie.

HAELLE: And then there’s the question of: Is a calorie a calorie for my body. And that’s a different question because like you just said, if you eat 1000 calories, but your microbiome is only extracting 800 calories from, then a calorie is not a calorie, a calorie is 80 percent of a calorie.

TWILLEY: But the problem is, we have no idea how to use this information yet.

TURNBAUGH: Yeah that’s sort of the million dollar question, is how do we take this really complex system and figure out what’s happening.

GRABER: Our gut microbes can change quickly—if we’re traveling, if we change our diet, if we take antibiotics. We don’t really have any idea how big an impact it all has.

TURNBAUGH: We’re not at the point where we can tell people the best way to do it or even what the goal is in terms of the optimal set of microbes but we know that at least it’s very plastic and very malleable and so, you know, if we’re able to figure this out, at least there’s the chance that you know someday you might be able to tailor your microbiome.

TWILLEY: It is so frustrating. We know the calorie is broken. But we don’t know how to fix it yet. And meanwhile, while Tara does see hope for the future, right now she’s completely melting down trying to lose weight, because the best advice medicine can give her is to count calories.

HAELLE: And I do have to say that I’m kind of pissed at the scientific community for not coming up with something better for us. I feel like this is not a priority, and the prejudice that exists against obese people, and the implication that it’s their fault that they got themselves there, and all of that. I do feel sort of a resentment towards the medical community for not finding ways to actively help more. And at the scientific community for not figuring out sincerely what the fuck is going on.

TWILLEY: Amen.

GRABER: Eventually researchers hope that we can use the microbiome to help out people like Tara. But for now, all we know is that it’s really hard to count calories and come up with an accurate number. Even nutrition guru Marion Nestle struggles with it.

NESTLE: Well, some people think they can do it, and I’m sure there are people who can do it better than I can. I’m terrible at it. If you cook at home and weigh every single thing that you put into your cooking very carefully and then calculate how much protein, fat, and carbohydrate it has, you could come pretty close. But if you’re not measuring and you’re not measuring the amount that you’re actually eating—because remember, the biggest source of error in calorie determination is portion size, so much bigger than anything else that you don’t worry about anything else—you can’t really tell. And in a restaurant it’s out of the question. So you’re at a complete loss.

TWILLEY: So here’s what I’m thinking, Cynthia. It’s impossible to count calories. It is totally tedious, the numbers on a lot of menus are wrong, the numbers on labels are off by up to 20 or 30 percent, for some foods anyway. And then your gut microbes mean that you have no idea how much energy you’re actually absorbing at the end of it. Can we just ditch the calorie?

GRABER: We actually did pose this question to everyone we spoke to. Nobody was quite ready to completely give up on the calorie. But Susan Roberts—she’s director of the energy metabolism lab at the Tufts USDA Nutrition Center—she’s spent decades studying obesity and working with people who are trying to lose weight. And she thinks there’s a better unit of measurement than the calorie: How full does the food made you feel. How long can you go before you want to eat again.

ROBERTS: If you go to let’s say Dunkin Donuts and you have some of those sugar coated doughnuts, which I used to do when I was 50 pounds heavier than I am today, two hours later you’re probably going to be starving hungry. If you have a bowl of steel-cut oatmeal, with just a little bit of sugar, much more slowly digested carbs, you’re not going to feel the same hunger. So just counting calories is not going to be sufficient to help somebody lose weight and keep that weight off. Because if they eat hunger-promoting calories, they’re not going to be able to keep it up.

GRABER: She even designed a diet based on this principle of satiety. Of feeling satisfied with your food.

TWILLEY: That’s also what Harvard professor David Ludwig suggests. He uses a satiety index rather than a calorie count. Adam Drewnowski, an epidemiologist at the University of Washington, has a different replacement for the calorie: a nutrient density score. His system ranks food in terms of nutrition per calorie, rather than simply overall caloric value. Leafy greens score very high.

GRABER: We’re not saying that either of these are THE solution.

TWILLEY: Definitely not. There isn’t enough research yet to justify replacing calorie counts with satiety scores or nutrient density numbers on our food labels. It’s just that there are other ways to measure food, other than the calorie. And maybe some of those other ways of measuring our food could be more useful, if we’re trying to lose weight or be healthier overall.

GRABER: And there’s nothing stopping us from changing the way we think about food—from calories to one of these other methods—right now, while we wait for more research. But what about the future? As Peter said, someday scientists expect to be able to understand our gut microbes well enough to be able to use them to control how many calories we get from our food.

TWILLEY: And there’s another, even more futuristic approach. Up in Alberta, David Wishart is working on something called metabolomics. It’s a totally different way of looking at how our bodies interact with food.

WISHART: Even though we might be eating an orange, and there’s lots of, thousands of chemicals in an orange, those compounds actually get transformed by our liver, and by our gut and the bacteria that live in our gut, into thousands of other compounds. And that’s the—that’s the food metabolome.

GRABER: This is complemented by what he calls the human metabolome. That’s all the compounds that our body produces.

TWILLEY: This is some pretty weird science. David is building two databases of all of these different chemicals—one for the chemicals in our food and one for the chemicals our body produces—and he’s already up at 30,000 and 40,000 in each.

WISHART: But the latest estimates are that there’s anywhere between 1 and 2 million compounds. Many of which we have no idea what they are, what they look like. So it’s incredibly large. And incredibly complicated. And in some respects it’s a more challenging project than, say, the human genome project.

TWILLEY: All of these different chemicals have different effects, and then they interact with each other, and really, we have no idea what’s going on.

GRABER: Yeah, but they’re starting to figure some of it out. For instance, they’ve already found that high ­fructose corn syrup seems to interact with compounds in our bodies in ways that end up increasing the production of fat cells and causing inflammation.

TWILLEY: As he gradually figures out all these chemicals and how they interact—David expects different interactions can change how the body extracts energy from food.

GRABER: But, again, it is super, super early stages of this research. Still, it hints at the idea that eventually, some day, we could have personalized nutrition based on how each unique person’s body interacts with food. And, in fact, last month a study out of Israel did just that. They showed that different foods cause different people’s blood sugar to spike, and some of it was really surprising. Like a tomato might make one person’s blood sugar go sky high and not somebody else’s. So they designed new diets for all the test subjects that keep their blood sugar down. Some people could have white bread, some couldn’t. Some had chocolate, others didn’t.

TWILLEY: And the point is, the same thing could work with counting calories. The Israeli researchers point out that these kind of personalized diets could be designed to respond to the different ways we each get energy from food. David agrees.

WISHART: Yeah, I think that’s exactly it. I think you could get to the point where it’s personalized nutrition. I think it’s an ambitious goal but it’s one that would be a wonderful thing to have.

TWILLEY: In fact, David can picture a future where we all have a little device that would monitoring our own unique set of microbes and the particular interactions between the chemicals in our foods and our bodies and all the quirks of our own personal metabolism, and then it could come up with specific recommendations, tailored just for you

WISHART: Yeah, I think it is possible to imagine you could get all of those pieces of information and maybe telling you whether you’re not active enough, or whether you need to repopulate your gut with a probiotic or with some more olive oil….

TWILLEY: Apple or Google is not going to be coming out with this anytime soon, though. For now, calories still count.

GRABER: Basically, even with all the individual variation and the different structures of foods that we’ve been talking about, the bottom line is you do have to eat less than you burn. That’s physics. So if you’re gaining weight, yes, to lose weight you have to reduce calories. Marion Nestle could not emphasize this enough when we spoke to her.

NESTLE: Once the foods are in the body, it’s really calories count. And so from the standpoint of health, what you eat matters a lot. From the standpoint of body weight, you can lose weight on chocolate bars, McDonalds, potato chips—you can lose weight on anything. Absolutely anything. And this has been shown over and over and over again by people who think they’ve just discovered it for the first time. See! I can go to McDonalds and lose weight. Well of course you can, if you reduce your calories below expenditure. Really, that’s all it takes.

TWILLEY: Marion is right. But, as we’ve found out, she’s also kind of wrong. For maintaining or losing weight, how full certain foods make us feel or how our unique collection of microbes process food, maybe even all of those millions of chemical interactions that David Wishart is studying—that really does matter. And then there’s a bigger point. Which is that the calorie is just one thing we can measure about our food. And maybe it’s not the most helpful.

NESTLE: There’s a cultural argument that calories are reductionist. They reduce the cultural value of food which is cultural, historical, political, economic, and all its other complexities to one measure of calories.

GRABER: Those arguments have always been around. Food is so much more than its calorie content. When Wilbur Atwater was studying calories in the early 1900s, he and the USDA were trying to make sure people weren’t starving. But now for many of us, we have just too many calories floating around.

TWILLEY: The calorie made sense as a way of thinking for that first generation of nutritionists. But we’re in a different context today.

GRABER: We are—but we’re also not ready to totally ditch the calorie.

WRANGHAM: The calorie is the only darn thing we’ve got in this game at the moment, isn’t it. But it gives us a sort of unfair sense of precision.

GRABER: One way calories are still useful is as a relative measurement. Spinach has fewer calories than a cookie. That grilled salmon dish likely has fewer calories than a cheeseburger.

TWILLEY: I feel like the exact opposite of a diet guru here, but there is no better solution right now. This new science around the structure of different foods is exciting, the new science around the microbes in our guts is really exciting, the new science of metabolomics is really complicated and exciting. But none of it is ready for primetime yet. Richard Wrangham agrees.

WRANGHAM: And so the calorie does need a reboot, but no one’s come along and yet found out how to do it.

GRABER: Thanks this episode to Marion Nestle. We have links to her book, Why Calories Count, at gastropod dot com. And she’s just written a new book called Soda Politics.

TWILLEY: Thanks also to David Baer and Bill Rumpler for showing us around the USDA calorimeters in Beltsville, to Peter Turnbaugh in his lab at the University of California, San Francisco, to Richard Wrangham, who sat down with us in the anthropology department at Harvard University, to David Wishart of the University of Alberta, and to Susan Roberts of the Tufts USDA nutrition center. We have links to their labs and papers on our website at gastropod dot com.

GRABER: Special thanks to Tara Haelle and Beau Nash, who shared their personal stories of calorie counting with us. And don’t miss our feature length story about the calorie, which we wrote for Mosaic, the online publication of the Wellcome Trust. We have a link at gastropod dot com, along with pictures of those crazy calorimeter rooms.

TWILLEY: We’ll be back in two weeks with an episode you will not want to miss—all about the history and science of aphrodisiacs. It’s gonna be a fun one!