Last month, I was honored to get the opportunity to interview preeminent obesity researcher, Dr. David Ludwig, author of the new book, Always Hungry?, which is being released this week. Below is a lightly edited transcript of that interview. Enjoy, and please check out Dr. Ludwig’s book, and spread the word.
Dr. Ludwig: The basic message of Always Hungry? is that overeating doesn’t make you fat. The process of getting fat makes you overeat.
Something has triggered our fat cells to take up and hoard too many calories, leaving too few for the rest of the body. We then get hungry and metabolism slows down. Cutting back on calories – the conventional approach – only makes that situation worse… In other words, obesity isn’t a state of excess; it is a state of depravation. And the challenge is to develop an approach that takes into account this underlying biological problem. A century of research clearly demonstrates that obesity is more of a biological issue than one of will power.
We know from work on experimental animals that if you change a gene or give an animal a special diet or certain drugs, it will naturally gain weight. And another set of genes, dietary conditions or drugs makes the animal lose weight. We don’t think that the rats in these experiments get fat because of a lack will power. And yet we make that assumption about people.
Body weight is controlled by biological mechanisms that evolved over millions of years, and ignoring these causes us to stigmatize people. This book is aimed at addressing the underlying biological drivers, with a special focus on the fat cells.
Adam: It’s amazing to listen you talk about this, because it’s so resonant with my own personal belief. For seven years, I’ve been trying to promote the theory that obesity is a biological problem – that it’s really a problem with the fat cells. [See here and here and here] In your book, you use the phrase “obedience training for the fat cells” to refer to what dietary interventions should be. I just love that phrase; it’s perfect.
Dr. Ludwig: Thanks. By the way, it is very easy to demonstrate this. With Type 1 diabetes, the beta cells in the pancreas don’t make enough insulin. Without insulin therapy, the patient invariably loses weight, no matter how much they are eating – 5,000, 7,000, 10,000 calories a day. With adequate insulin administration, people with Type 1 diabetes regain weight to their previous trajectory. And if you administer too much insulin, they will predictably gain weight.
In experimental animals, insulin administration produces low blood sugar, hunger, overeating and weight gain. If you restrict their calories to prevent weight gain – which is the essence of conventional treatment for obesity – the animals still gain an excess amount of fat tissue.
Adam: Right. Exactly.
Dr. Ludwig: In this way, preventing weight gain by calorie restriction doesn’t solve the basic problem. And since that problem – not having enough calories in the blood – goes unaddressed, you feel miserable.
Adam: Exactly. Another analogy: a pregnant woman grows a baby in her body not because she’s eating “excess calories” but because of biological causes. There’s nothing she can do about this growth inside her. If she starves herself, she will still grow the baby, because the baby will find the nutrients and calories it needs to survive. The starving pregnant woman, however, will be tired. She will be hungry, she will be lethargic…
Dr. Ludwig: Yes. As long as the baby is growing, she will experience increased hunger, and there is also evidence that women who are pregnant move less to conserve energy. Eating more and moving less doesn’t make the baby grow; the baby growing makes the pregnant woman hungry and fatigued.
Similarly, if fat cells have been triggered to suck up too many calories, we get hungry and metabolism slows down. Until we address that basic problem at the fat cells, cutting back on calories creates a battle between mind and metabolism that we are destined to lose.
Adam: Exactly. One great thing about the Always Hungry? title and your whole philosophy is your focus on the biological drivers that determine things like palatability. You addressed this in the book. We tend to blame obesity on hyper palatable food. The industrial flavor-makers in New Jersey are doping our food with chemicals to make it taste good; as a result, we are overeating this food and getting fat because of it.
But as you point out, a lot of the foods we consider “hyper palatable” are very processed carbs that deliver big insulin and blood sugar hits. So how do you disambiguate whether these food make you fat because you overeat them or because they stimulate too much insulin?
People like Gary Taubes and Mark Friedman and others have argued that the biological drivers of hunger are what are critical. It’s not “in your head,” and the psychologist is not going to fix them. Because if your fat cells are like “we need XYZ,” they’re going to get XYZ and keep up yelling at you until you give them what they want. Is that basically correct?
Dr. Ludwig: Yes, exactly.
Adam: The other thing I really love about your approach – and I don’t mean, to sound too much like a shill here – is how you’ve separated this concept of “fat cell centric” thinking from the low carb diet and even from insulin-centric thinking about obesity.
There is an overlap between “fat cell centric thinking” and “low carb diet centric thinking.” But I think that the more people study this, the more they realize these are two different ideas. The low carb diet – or really any kind of diet – is just a kind of mechanism. It’s a strategy to do “obedience training for the fat cells.”
By contrast, what people like you and me are saying is that diets work, when they do, not because they make you eat less and move more, but because they fix the fat tissue.
People can do well on all sorts of diets. Blogger Denise Minger wrote a provocative piece recently arguing that extremely low fat diets might help with insulin sensitivity in some people… Different strategies might be deployed, but first we need to pay attention to what really matters, which is those fat cells! Right?
Dr. Ludwig: Yes, and the most important thing we can do is cut back on processed carbohydrates, which stimulate more insulin secretion than any other food calorie for calorie. I like to describe insulin as the ultimate fat cell fertilizer – sort of a Miracle Grow for your fat cells. We don’t want those kinds of miracles!
Beyond that, people do differ in how their bodies respond to specific foods and nutrients. Some people seem to do best with very little total carbohydrate. Others can tolerate a lot of carbohydrate, as long as it’s in a slow acting natural form (that is, low glycemic index). There’s undoubtedly considerable individual variation in what’s optimal for each person. And then we need to think about the non-dietary influences on the fat cell.
Dr. Ludwig: Sleep deprivation, stress and too much sedentary time adversely alter fat cell behavior through hormonal and autonomic inputs. So we want to think about treatment broadly, and that’s the focus of the program in Always Hungry?
Adam: That’s great. I think that’s exactly the right idea, and I particularly like the diagram that you have on Page 45 which shows that fundamental idea so clearly.
I think a lot of researchers think, okay, stress and sleep deprivation do play a role. But the conventional line of thinking is: when you’re stressed, you’re going to eat more. Food will be more palatable.
They say the same thing with sleep. If you don’t sleep, your hormones will get messed up, which will cause you to be sedentary or eat more. So even though they recognize the importance of non-dietary factors, like stress and sleep, their thinking is still filtered through the calories-count paradigm.
But if these researchers could only absorb your diagram on Page 45, they would get it. Oh! Okay! Insomnia and stress mess up the fat tissue, and that’s really the root problem.
Another thing to consider in the mix is medication. Something like 100 million Americans are on various medications, like anti-depressants, statins and diabetes meds. A lot of these, from what I’ve read, make you fat and diabetic. Obviously, our addiction to refined carbs is a huge deal. But this pill popping seems important, too. Right?
Dr. Ludwig: Yes. Ironically, the primary medications for Type 2 diabetes only add fuel to the fire. The problem in Type 1 diabetes – what we use to call juvenile diabetes – is insulin deficiency. So insulin treatment is necessary and lifesaving. In Type 2 diabetes, the fundamental problem is insulin resistance. There can be problems with the beta cells that make insulin as well, but just giving insulin, without attention to diet, will promote weight gain and increase insulin resistance over time. Other drugs, including statins, can also increase risk for Type 2 diabetes.
Adam: My dad has diabetes. He didn’t have it before he took a statin. I have no idea what caused what, but the relationship between statin use and diabetes is certainly disturbing.
On a more personal note, before I discovered meditation 5 years ago, I took an anti-depressant for about a month. While still on an insulin-lowering low carb diet, within two weeks, I had gained something like 10 pounds. So I was like WHOA. I did research online, which seemed to show that the drug I was on could be an insulin secretagogue. So I stopped it, and I immediately lost all that weight.
Later, I went online later and looked up the relationship between these drugs and weight gain. There are hundreds of forums devoted to this subject. And the stories are so sad. Like, a woman will say since I started taking Prozac, I’ve gained 20 pounds. But I’m eating 1,200 calories a day and going to gym. I don’t know what’s going on!
Meanwhile, scientists show that these drugs stimulate insulin – that Miracle Grow. Yet patients have no idea about the connection. Their doctors just say well, maybe you’re lying or maybe you need to starve yourself more.
And I find this contempt for people struggling with overweight so damaging. Your message in the book that obesity is biological is such an important message for people to hear.
I don’t know how to change our culture, so that people understand this model. What do you think? How are we supposed to advance this revolution and get people to think more fat-cell-centrically?
Dr. Ludwig: The nature of scientific change is that evidence accumulates slowly until reaching a tipping point, and then change happens fast. My mission has been to do the research, to contribute to the knowledge base, while also maintaining a focus on the clinical realities. I am also a practicing endocrinologist with a focus on obesity and diabetes. Based on recent discussions with scientists, public health experts and patients, I think we are reaching a tipping point.
We have gone from an almost universal acceptance of the low fat diet as the obvious way to prevent obesity and chronic disease to the 2015 Dietary Guidelines Advisory Committee recommending no upper limit on dietary fat. This change, if translated into the USDA Dietary Guidelines, will allow us to refocus on more effective approaches to disease prevention.
Beyond low fat diets, our focus on the calorie balance view of weight control has become the fundamental impediment. Which isn’t to say I’m arguing against the first law of thermodynamics, from which the calorie balance model arises. I and others argue that the model does not lend itself to effective obesity treatment. Calories in, calories out [CICO] well describes the energetics of a toaster. But humans aren’t machines. We are biological systems that respond and adapt to change.
Take fever as an analogy. You can think of a fever as just a problem with heat balance – too much heat in, not enough heat out. That’s of course correct, but it’s not very useful. From that perspective, all you need to do to treat a fever is to take a cold shower. Imagine that you have a fever, and you get into a cold shower. If you are capable of staying long enough, your temperature will drop, but your body is going to fight back intensely with severe shivering and blood vessel constriction, and you will feel miserable. That’s why the heat balance view of fever is not useful clinically, but a biological view is – such as using Aspirin to change the body temperature set point. We need to be thinking in the same way about the body weight set point.
Adam: Absolutely! I had written something similar a few years ago… that metaphor is a good way to get people to understand the distinction.
What’s particularly cool about what you’re doing is that you’re working with real people who have weight issues. I imagine it’s gratifying to help people who’ve been dieting and failing their whole lives, who discover your program and feel in control again. How does that feel for you?
Dr. Ludwig: Well, we have to recognize that the correct treatment for excess weight is critically important. If we don’t get it right, we set up our patients for failure. But even having gotten biology right, we still must contend with the toxic environment that makes a healthy lifestyle inconvenient, at least in the short term. Of course, the diseases caused by bad diet (like diabetes) are much less convenient over the long term. But we all need to be working together to create a better environment where the healthy choice is the easy choice.
Adam: That’s true. I wonder what can be done in terms of fixing things. You mentioned in the book that leptin therapy can be useful for people who have rare genetic obesity. The blogger ItsTheWoo, who also thinks fat-cell-centrically, has written a lot about the leptin-insulin dance.
I wonder what other therapies could be useful. Obviously, diet is important. But what about drugs like Metformin?… If pharmaceutical companies understood that this is a biological problem, they could start to develop drugs and therapies specifically to lower insulin or to improve insulin sensitivity. Do you think those things are going to happen?
Dr. Ludwig: We’re going to need to develop a sophisticated understanding of how pharmacological modification of hormones could be useful in some situations, especially when severe problems have already developed, like pre-diabetes. But food is ultimately our most powerful hormonal modulator.
We published a study in 2012 in JAMA, where we put people on low fat, low carb and intermediate Mediterranean diets, each for a month at a time. We found that leptin levels dropped the most on the low carb diet, but energy expenditure increased the most, and that combination of high energy expenditure and low leptin levels suggest improvements in leptin sensitivity.
Obesity is a state of leptin resistance, so just adding leptin doesn’t really help. That’s why Amgen – which invested many millions into leptin treatment – didn’t directly profit from that investment. The key is to improve leptin sensitivity. There are drugs in development that could do that, although the history of drug treatments for obesity has been a sorry story. Let’s not forget food as our most powerful medicine.
Adam: It’s truly amazing what you can do with diet… To that end, what’s going on in the current research that really excites you?
Dr. Ludwig: Well, we have a follow up of our JAMA 2012 study, being funded primarily by NuSI, the Nutrition Science Initiative. We are putting 150 adults on one of three diets varying in carbohydrates: From 20% to 40% to 60% carbohydrate; and fat varies in the opposite direction – 60%, 40%, 20%. All three diets have the same amounts of protein, 20%.
After an initial weight loss of about 10% to 15% — which will stress the system — we random assign the participants to one of these three diets for about 5 months. We will be able to assess what the relatively long term impact of these diets are, not just on metabolism, but also on body composition. Do you store less fat, calorie for calorie, on one diet than another? That’s a critically important question which, when answered, will materially help clarify these hypotheses.
Adam: Assuming that it does show a distinction, what you think would be the response of the research community? In your book, you mention that there’s not enough funding for critical studies on obesity. But what would happen if you did show a significant effect? Would researchers say okay, I want to try to replicate this? Would it shift the conversation?
Dr. Ludwig: You know, science requires replication, validation and assessment of questions with multiple different designs, so no one nutrition study could ever answer these questions completely. One always has to make tradeoffs in a study design. Our study is a feeding study… we are giving people everything they eat for an entire academic year. That lets us ask very precise questions about how food alters biology. But we also need to look at what happens in the ultimate context – people choosing foods on their own and making adjustments… in real life. In addition to interventional studies, we need high quality observational studies, because randomized clinical trials in nutrition cannot be conducted for 50 years. And some of the most important outcomes are truly long term.
Ludwig. Yes indeed.
Adam: I mean, I’m convinced enough to say okay, I’ll control my carbohydrate. This morning, I’m going to have stir-fried vegetables and meat and a small bowl of oatmeal – so it’s not like I have no carbs. But I do wonder what the long term effects are [of a low carb diet like mine]. Obviously, we can point to traditional cultures that don’t get obesity and diabetes and argue that, if we model our diets on their diets in some fashion, we might live longer. But, like you said, we can’t fund a billion dollar study to last 50 years to see mortality outcomes.
In that sense, what’s nice about the calorie idea is that it gives people comfort, even if it’s false comfort. Taking care of yourself becomes math. It’s bookkeeping. Counting calories gives people a sense of control and lets them ignore the reality that biology is messy and non-linear and that we don’t totally have a handle on it. I think that’s scary for some people… so as much as obesity is a science problem, it’s also a marketing problem.
Dr. Ludwig: Yes. You know, the calorie balance view is appealingly simple, as is the low fat diet: don’t want fat on your body? Don’t put fat into your body. Similarly, people can say if you don’t want calories on your body, don’t put calories into your body. That’s simple but not very useful.
It’s like if somebody has too much carbon-dioxide in their blood for a biological reason, and you just tell them to breathe faster to blow off the CO2. It might work for a short time, but it’s impossible to keep up over the long term. And so we need to think in a more sophisticated way about body weight, just like we do about body temperature, the regulation of gases in our blood, and all other fundamental bodily functions.
Adam: Absolutely. Yeah, I just wonder if there’s a way to sloganize this. One thing I came up with a while back was: count insulin, not calories. But even that is not totally accurate, because there are factors other than insulin –leptin and LPL and things like that. So I don’t know the way to sloganize [the fat-cell-centric model].
Low carb can be sloganized: Don’t eat carbs. Same thing with Paleo: eat like a caveman. Same with vegan: don’t eat animal products. And these ideas – incomplete or misguided as they might be – easily spread because they’re simple.
All this is to say that the conversation you’re seeking to advance with Always Hungry? is THE conversation the research community needs to have if it’s to have any hope of solving the obesity and diabetes epidemics. I’ve read a lot of books and articles on this topic, and I can’t recommend what you’ve done here enough. Great diagrams and analogies and writing style in general. You also have a certain cache, because you’ve personally carried out original research in this area. Many people who write about this topic – me included – don’t have that experience, so our perspectives, while valid, are less direct. Anyway, I hope people read and really absorb what you’ve written, because it could help a lot of people.
Dr. Ludwig: Thank you and pleasure talking to you.
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