Watch Kevin Hall talking about his research on weight regain in the “Biggest Loser” show participants. I was kicked out of my office during the shoot (my office is next to Kevin’s) for making too much noise (I was having a heated discussion with my fellows). Here is the accompanying article.
Harvard surgeon and author Atul Gawande presented four BBC Reith Lectures in 2014 about various aspects of medicine. It is impossible to read or listen to Gawande and not come away profoundly moved. You can download the episodes directly from the BBC or from CBC’s radio program Ideas. Here is an interview with Gawande on the new Medical website Stat.
Chow, C. C. & Hall, K. D. Short and long-term energy intake patterns and their implications for human body weight regulation. Physiology & Behavior 134:60–65 (2014). doi:10.1016/j.physbeh.2014.02.044
Abstract: Adults consume millions of kilocalories over the course of a few years, but the typical weight gain amounts to only a few thousand kilocalories of stored energy. Furthermore, food intake is highly variable from day to day and yet body weight is remarkably stable. These facts have been used as evidence to support the hypothesis that human body weight is regulated by active control of food intake operating on both short and long time scales. Here, we demonstrate that active control of human food intake on short time scales is not required for body weight stability and that the current evidence for long term control of food intake is equivocal. To provide more data on this issue, we emphasize the urgent need for developing new methods for accurately measuring energy intake changes over long time scales. We propose that repeated body weight measurements can be used along with mathematical modeling to calculate long-term changes in energy intake and thereby quantify adherence to a diet intervention and provide dynamic feedback to individuals that seek to control their body weight.
Science writer Gary Taubes has a recent New York Times commentary criticizing Kevin Hall’s recent paper on the differential metabolic effects of low fat vs low carbohydrate diets. See here for my recent post on the experiment. Taubes is probably best known for his views on nutrition and as an advocate for low carb diets although he has two earlier books on the sociology of physics. The main premise running through his four books is that science is susceptible to capture by the vanity, ambition, arrogance, and plain stupidity of scientists. He is pro-science but anti-scientist.
His first book on nutrition – Good Calories, Bad Calories, was about how the medical establishment and in particular nutritionists have provided wrong and potentially dangerous advice on diets for decades. He takes direct aim at Ancel Keys as one of the main culprits for pushing the reduction of dietary fat to prevent heart disease. The book is a great read and clearly demonstrates Taubes’s sharp mind and gifts as a story teller. In the course of researching the book, Taubes also discovered the biological mechanisms of insulin and this is what has mostly shaped his thinking about carbohydrates and obesity. He spells it out in more detail in his subsequent book – Why We Get Fat. I think that these two books are a perfect demonstration of why having a little knowledge and a high IQ can be a dangerous thing.
Most people know of insulin as the hormone that goes awry in diabetes. When we fast, our insulin levels are low and our body, except for our brain, burns fat. If we then ingest carbohydrates, our insulin levels rise, which induces our body to utilize glucose (the main source of fuel in carbs) in favour of insulin. Exercise will also cause a switch in fuel choice from fat to glucose. What is less well known is that insulin also suppresses the release of fat from fat cells (adipocytes), which is something I have modeled (see here). This seems to have been a revelation to Taubes – Clearly, if you eat lots of carbs, you will have lots of insulin, which will sequester fat in fat cells. Ergo, eating carbs makes you fat! Nutritionists were so focused on their poorly designed studies that they missed the blatantly obvious. This is just another example of how arrogant scientists get things wrong.
Taubes then proposed a simple experiment – take two groups of people and put one group on a high carb diet and the other on a low carb diet with the same caloric content, and see who loses weight. Well, Kevin Hall anticipated this request with basically the same experiment although for a different purpose. What Kevin noticed in his model was that if you cut carbs and keep everything else the same, insulin goes down and the body responds by burning much more fat. However, if you cut fat, there is nothing in the model that told the body that the fat was missing. Insulin didn’t change and thus the body just burned the same amount of carbs as before. He found this puzzling. Surely there must be a fat detector that we don’t know about so he went about to test it. I remember he and his fellows labouring diligently for what seemed like years writing the protocol and getting the necessary approval and resources to do the experiment. The result was exactly as the model predicted. We really don’t have a fat sensor. However, the subjects lost more fat on the low fat diet then they did on the low carb diet. This is not exactly the experiment Taubes wanted to do, which was to change the macronutrient composition but keep the calories the same. He then hypothesized that those on the low carb diet would lose weight and those on the low fat, high carb diet would gain weight. Kevin and a consortium of top obesity researchers has since done that experiment and the results will come out shortly.
Now is this surprising? Well not really, for while Taubes is absolutely correct in that insulin suppresses fat utilization the net outcome of insulin reduction is a quantitative and not a qualitative question. You cannot deduce the outcome with formal logic. The reason is that insulin cannot be elevated all the time. Even a continuous grazer must sleep at some point where upon insulin falls. You then must consider the net effect of high and low insulin over a day or longer to assess the outcome. This can only be determined empirically and this is what Taubes fails to see or accept. He also commits a logical fallacy – Just because a scientist is stupid doesn’t mean he is wrong.
Taubes’s recent commentary criticizes Kevin’s experiment by saying that it 1) is a diet that is impossible to follow and 2) it ignores appetite. The response to the first point is that the experiment was meant to test a metabolic hypothesis and was not meant to test the effect of a diet. My response to his second point is to stare agape. When Taubes visited NIH a few years ago after his Good Calories, Bad Calories book came out I offered the hypothesis that low carb diets could suppress appetite and this could be why they may be effective in reducing weight. However, he had no interest in this idea and Kevin has told me that he has repeatedly shown no interest in it. (I don’t need to give details on how people have been interested in appetite for decades since it is well done in this post.) I came to the conclusion that appetite control was the primary driver of the obesity epidemic shortly after arriving at NIH. In fact my first BSC presentation was on this topic. The recommendation by the committee was that I should do something else and that NIH was a bad fit for me. However, I am still here and I still believe appetite control is the key.
The prevalence of near sightedness or myopia has almost doubled in the past thirty years from about 25% to 44%. No one knows why but it is probably a gene-environment effect, like obesity. This recent paper in PLoS Genetics: APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans, sheds light on the subject. It reports that a variant of the APLP2 gene is associated with myopia in people if they read a lot as children. Below is a figure of the result of a GWAS study showing the increase in myopia (more negative is more myopic) with age for those with the risk variant (GA) and for time spent reading. The effect size is pretty large and a myopic effect of APLP2 is seen in monkeys, mice, and humans. Thus, I think that this result will hold up. The authors also show that the APLP2 gene is involved in retinal signaling, particularly in amacrine cells. It is thus consistent with the theory that myopia is the result of feedback from the retina during development. Hence, if you are constantly focused on near objects, the eye will develop to accommodate for that. So maybe you should send your 7 year old outside to play instead of sitting inside reading or playing video games.
Just out in Cell Metabolism is Kevin Hall’s most recent paper that shows that low carb diets have no metabolic advantage over a low fat diet. In the experiment, a group of 19 individuals spent 22 days in total in a metabolic ward where their diet was completely specified and metabolic parameters were carefully measured. The individuals were put on both isocaloric carbohydrate reduced diets and fat reduced diets where the order of the diets was randomized over subjects. The short version of the result was that those on the fat reduced diets had more fat loss than the carbohydrate reduced diet although the cumulative difference was small. The body composition changes and metabolic parameters are also matched by the detailed NIDDK body weight model. You most certainly do not lose more fat on a low carb diet.
The results do show that a calorie is not exactly a calorie meaning that the macronutrient composition of the food you eat can matter although over long time periods the body weight model does show that macronutrient differences will always be small. Ultimately, if you want to lose fat, you should eat less and exercise more (in that order). It’s your choice in how you want to reduce your calories. If you like to go low carb then by all means do that. If you like low fat then do that too. You’ll lose weight and fat on both diets. The key is to stick to your diet.
This experimental result is in direct contradiction to the argument of low carb aficionados like Gary Taubes who claim that reducing carbs are particularly beneficial for losing weight and vice versa. Their reasoning is that carbs induce insulin, which suppresses lypolysis from fat cells. Hence, if you ate carbs all the time, your fat would get locked away in adipocytes forever and you would become very fat. However, the problem with this type of reasoning is that it doesn’t account for the fact that no one eats for 24 hours each day. Even the most ardent grazer must sleep at some point and during that time insulin will fall and fat can be released from fat cells. Thus, what you need to do is to account for the net flux of fat over the entire 24 hour cycle and possibly even longer since your body will also adapt to whatever your diet happens to be. When you do that it turns out that you will lose more fat if you reduce fat.
Now this was only for a diet of 6 days but experiments, funded by Gary Taubes’s organization, for longer time scales comparing the two diets have been completed and will be published in the near future. I’ll summarize the results when they come out. I can’t say what the preliminary results are except to remind you that the model has held up pretty well in past.