Saturday, March 5, 2011

Set Point versus Settling Point

Why are we fat? One term often invoked is “set point” to explain how we regulate our body weight. Set point is seemingly considered by most people to be a fundamental principle.

The problem, or beauty of science, is that words have precise meanings, and every attempt should be made to define terminology with precise meaning. When we delve further into “set point” and into its interpretation, we almost assuredly either have a poorly defined term, or a flawed line of reasoning providing the foundation.

Claude Bernard, in An Introduction to the Study of Experimental Medicine, pointed out that the sight of a phenomenon (in this case, the fact that most people have great difficulty losing weight and eventually put whatever they lost back on) will always awaken an idea of causation. Here, the idea is set point [1], where the brain has a ‘lipostat’ and drives our behavior.

A theory is an explanation. Set point theory is an explanation of the set point hypothesis. In order for the theory to be valid it must be able to explain the observations. Theories can certainly be supported, modified, and rejected based on new evidence. Human Evolutionary theory explains how we went from great apes to human beings, but new evidence is constantly being uncovered and the theory of human evolution is modified to explain the phenomena.

A hypothesis is more of an educated guess, based on observations. This guess, or idea, needs to be testable, and falsifiable, in order for it to be valid. Often there are multiple competing hypotheses to explain observations, and it is the job of scientists and the goal of researchers to eliminate the ones that are incorrect. [2]

A theory should be something that began as a hypothesis, and has been repeatedly tested and supported by those tests as well as the accumulating and historical observations. And the theory remains valid as long as there is no evidence to dispute it. Many people would define a theory as an accepted hypothesis.


According to the set point theory, individuals have a control system which dictates how much fat they should carry. We have a fat thermostat, it has been argued. If we’re 150 pounds and 15% body fat between the ages of 18-25, then our set point can be seen as either 15%, or 22.5 pounds (15% of 150). Another individual might have a fat setting of 50 pounds, in which an individual of the same height and sex might weigh closer to 180 pounds and have a body fat percentage closer to 28%.

Set point theory was originally developed in 1982 [3] by Bennett and Gurin to explain why long-term repeated dieting doesn’t seem to work (MIT Medical). Most of us know that long-term weight loss via caloric restriction and/or physical activity are generally futile. With set point theory, it explains this observation by imagining that we’re fighting our set point, and it’s going to be a losing battle because the set point sends signals to the body to compensate for the weight loss so that we will inevitably put it back on, similar to the heater kicking in overnight in your home to maintain a temperature of 73 because it has a set point, or thermostat, that detects changes in temperature and sends signals to the heater to compensate for the drop in temperature.

So set point is apparently very good at monitoring how much fat we accumulate and how much we weigh based on the observations and the futility of dieting. The Center for Health Promotion & Wellness at MIT Medical point out that the thermostat doesn’t differentiate between dieting and starvation and a person trying to lose weight who begins a diet with a high set point “experiences constant hunger. . . . The body reacts to stringent dieting as though famine has set in.” [4]

And, unless I’m missing a page from the MIT pamphlet, there is no mention about how the body’s set point protects us against ‘overeating.’ Why, for example, do any of us get fat in the first place? According to set point theory, when we eat more than what our set point calls for, signals in the body should help us maintain our weight of 150 and 15% body fat, right? But we know that’s not necessarily the case. We know that many people who are today obese were once relatively lean and gained weight over what their presumed set point was when they were 18-25, where they now weigh 220 pounds with close to 40% body fat.

While set point theory, at first blush, seems like a logical way to explain why it’s so hard to lose weight, set point theory is a horrible way to try and explain why we get fat. In fact, one could argue that the idea of a set point has been refuted in millions, if not billions, of individuals. [5]

The BBC recently ran a program entitled “Why Are Thin People Not Fat?” which should be a feather in the set point hypothesis cap.

In the program, there is mention of a study conducted on prisoners from Vermont, where they were ‘overfed’, to the eventual tune of a daily intake of 10,000 calories. The principal investigator, Ethan Sims, noted that there were “marked differences between individuals in ability to gain weight” (Taubes, 2007). Reportedly, one subject gained less than 10 pounds after thirty weeks on this regimen. [6]

Are these different set points at play?

What should not go without documenting is the affect that the nutrient composition of the diet seemed to have on a number of the research subjects. In other words, the quality of the diet pushed its way into the spotlight, rather than the quantity of calories being fed. From Good Calories, Bad Calories (p. 310):

One potentially relevant observation that Sims and his colleagues neglected to publish, for example, was that it seemed impossible to fatten up their subjects on high-fat, high-protein diets, in which the food to be eaten in excess was meat. According to Sims’s collaborator Edward Horton, now a professor of medicine at Harvard and director of clinical research at the Joslin Diabetes Center, the volunteers would sit staring at “plates of pork chops a mile high,” and they would refuse to eat enough of this meat to constitute the excess thousand calories a day that the Vermont investigators were asking of them. Danforth later described this regimen as the experimental equivalent of the diet prescribed by Robert Atkins in his 1973 diet book, Dr. Atkins’ Diet Revolution. “The bottom line,” Danforth said, “is that you cannot gain weight on the Atkins diet. It’s just too hard. I challenge anyone to do an overfeeding study with just meat. You can’t do it. I think it’s a physical impossibility.”

Getting their volunteers to add a thousand calories of fat to their daily diet also proved surprisingly difficult. Throughout their numerous publications, Sims and his colleagues comment on the “difficult assignment of gaining weight by increasing only the fat.” Those fattening upon both carbohydrates and fat, on the other hand, easily added two thousand calories a day to their typical diet. Indeed, subjects in some of his studies, Sims and his colleagues reported, experienced “hunger late in the day . . . while taking much greater caloric excesses of a mixed diet”—as much as ten thousand calories a day.
Sims and his collaborators did not wonder why anyone would lose appetite—develop “marked anorexia,” as they put it—on a diet that includes eight hundred to a thousand excess fat calories a day, and yet feel “hunger late in the day” on a diet that includes six to seven thousand excess calories of fat and carbohydrates together. It would seem there is something about carbohydrates that allows the consumption of such enormous quantities of food and yet still induces hunger as the night approaches.

Two Chicago psychologist, David Wirtshaffer and John D. Davis, published a paper in 1977 entitled “Set points, settling points, and the control of body weight.” (They also responded to a critique about a year later, in response to Mrosovsky and Powley, who wrote a paper in 1977 arguing that the term set point was a useful concept for describing the fact that body weight is maintained at a relatively constant value and is defended against challenges.) Wirtshafter and Davis believed that the term “settling point” was more appropriate to explain the phenomena. They noted:

“The term set point, which refers to an input variable in a control system, should be used only as an input variable and then only when there is evidence that such a reference variable exists. Since stability of a controlled system can be maintained by a regulatory system which does not contain a set point the use of this term implies a particular type of control and should only be used when there is evidence for its existence.”

The authors pointed to a home heating and cooling system with a thermostat as an example of a feedback system which regulates “an output variable (room temperature) by means of an input set point variable, i.e., the thermostat setting.” They noted that in this case, “as in all set point systems, the value of the set point is independent of the operation of the system and, once adjusted, remains the same until readjusted.”

They went on to explain the importance of understanding that precise regulation can be achieved, “by a feedback system which does not contain an internal set point. . . . The fact of regulation and defense of body weight, or any other regulated variable, does not imply the existence of a set point in the control system.”

“A system may exhibit ‘set point like’ behavior,” wrote Davis and Wirtshafter, “without in fact containing a set point.” Many people who invoke the term set point, are using it in the context of ‘set point like,’ but this behavior blurs the distinction, the authors argued. They argued further that using the term as a convenient description of perceived phenomena is a misuse that leads to considerable confusion.

In science, it’s important that terminology and definitions are clearly defined. There should be as little room for interpretation as possible when we’re dealing with variables. If we don’t, hypotheses and theories will be virtually untestable, and therefore no longer are valid.

“Rats with VMH lesions have a higher body weight settling point than normal rats and animals with LH lesions have a lower settling point than normal rats,” wrote David and Wirtshafter. “The differences between the body weight settling points of VMH- and LH-lesioned rats and normal ones may or may not result from a change in the set point of the system as a result of the lesion. The term settling point is neutral with respect to the reason whereas the term set point is not.”

“Just as the fact that body weight is regulated does not imply the existence of a set point mechanism, so the fact that the level at which weight is regulated changes under certain conditions does not imply that the set point for weight has changed.”

Stephan Guyenet, over at his terrific blog, Whole Health Source, wrote a four part series (Part I | Part II | Part III | Part IV) regarding set point and noted:

Again, this supports the idea that the body has a body fat mass "set point" that it attempts to defend against changes in either direction. It's one of many systems in the body that attempt to maintain homeostasis.

Pal Jabekk, author of Ramblings of Carnivore, countered in a recent blog post:

“OK, so why do we care?

“We care because this has some very important implications for human obesity. With such a powerful system in place to keep body fat mass in a narrow range, a major departure from that range implies that the system isn't functioning correctly. In other words, obesity has to result from a defect in the system that regulates body fat, because a properly functioning system would not have allowed that degree of fat gain in the first place.

“So yes, we are gaining weight because we eat too many calories relative to energy expended. But why are we eating too many calories? Because the system that should be defending a low fat mass is now defending a high fat mass.”

It seems that Stephan may be misusing the term set point if you were to ask Davis and Wirtshafter.

In a different blog post by Guyenet, and the subsequent comments section, Dr. Harris or PaNu wrote:

“Did you happen to listen to Gary Taubes' interview with Jimmy Moore? I was surprised when he referred to set-point theory as "naive". I think a set-point is the only possible explanation for normal people having stable weight without counting anything.”

And Guyenet’s response:

Gary thinks fat mass is regulated by fat tissue. He downplays the evidence suggesting that body fatness is homeostatically regulated by the brain in a manner similar to blood pressure, blood pH, oxygen tension, ion concentrations, and many other things.

That being said, different people have different understandings of what the "set point" means. I use it to mean a level of fat mass that's actively defended against changes in the short term. But it can obviously change in the long term, or else there would be no such thing as obesity. That's why some object to the term, because the "set point" is not permanently fixed.

I actually find Dr. Harris’s assertion that a set point is “the only possible explanation for normal people having stable weight without counting anything” to be naive or misguided and Guyenet’s explanation of Gary’s position as incomplete.

If you replace the words ‘stable weight’ in Dr. Harris's comment with a multitude of outputs, be they body temperature, total body water, blood glucose, for example: We don’t have a thermostat, hydrostat, and glucostat, respectively, rather we have control systems which do not imply a set point, rather they settle at numbers that we can generally predict, and it appears as though a set point is involved.

Peter, who writes at Hyperlipid, joined in on the action with a recent post:

“There is clearly a regulatory set point for the control of breathing. There is also one for blood pressure, blood sodium, potassium, pretty well everything else. I manipulate many of these daily to earn a living. Why not one for bodyweight?”

“At the moment I have an insulinocentric view of metabolism and bodyweight. Insulin appears to explain a fairly large chunk of weight control issues. It doesn't intrinsically need a set point concept, but there is every reason to accept some brain input to determine bodyweight. But the idea that the brain can over ride the obesogenic effect of a diet which requires chronic hyperinsulinaemia to maintain a semblance of health is very hard to accept.” [7]

Nonetheless, people will make the argument that body weight regulation may be achieved indirectly by regulation of total adipose tissue content. That an animal will respond to a lipectomy by regaining the fat lost will be invoked as evidence that the regulation of fat tissue implies a set point. But again, body weight can be reflected by the regulation of fat tissue via a control system without a set point.

Arguments for a set point theory are generally forwarded by moving from a descriptive use of the term to an explanatory one without any additional evidence. In other words, there is an implication of causation from correlation. Proponents assume that regulation of a system implies a set point.

The control of blood glucose, for example, is tightly regulated in healthy individuals. It is regulated through a system involving hormonal, neural, and enzymatic systems, to name a few, which work together to try and maintain constant blood glucose levels. By the same logic invoking set point theory, we should conclude that we have a blood glucose set point. Each one of us ostensibly has a glucometer, like the ones diabetics use to measure the amount of glucose in the blood, and when the glucostat takes a reading that is too high, we compensate to lower our blood sugar and vice-versa. [8]

But we don’t think this is the case, rather we believe that there is a complicated regulatory system in which our blood glucose concentration settles at a particular level.

There are plenty of systems which are regulated by systems that do not imply a set point. The regulation of body weight should not be excluded from this possibility.

Earlier, I mentioned Kurt Harris alluding to a recent podcast by Jimmy Moore with Gary Taubes as a guest, in which Gary referred to set point theory as naive. Here’s what transpired in the podcast (paraphrasing):

Taubes: A very important point in science is that terminology should be very precisely and correctly defined. And when you're thinking 'set point,' you're basically thinking that there's some regulator in your brain, probably in the hypothalamus, that is measuring all these signals from the body, the way a thermostat in a house would. The terminology came from the idea of heating and a thermostat, and how they have set points: you set the thermostat to 70 degrees, and the thermostat measures the air temperature and it tells the heater to go on if it's too cold and it tells the air conditioner to go on if it's too hot. With the set point theory, there's the idea that there's this regulator, this thermostat, in your brain, that's measuring fatty acids, and leptin, and insulin, and adjusting appetite and expenditure to keep a particular set point, or your weight at 150 pounds, and if you put on a few pounds the thermostat kicks in and your body inches back to 150.

In the 1970s there were a couple of Chicago psychologists [Davis and Wirtshafter] who said a more apt description would be a settling point. There are all these forces working on your fat tissue, hormonal and enzymatic forces, that work to put fat in or get fat out, and depending on the hormonal milieu, which is controlled by your diet, and this competition of forces determine how much fat you have. So if your diet remains relatively the same: the same amount and kind of food, your settling point, your hormones, are going to remain relatively the same.

If you look at a surface of a lake, it's going to appear to have a set point. It's going to go up a little during certain times of the year, it's also going to go down a little at others, but you can imagine that there's some regulator deep in the recesses of the lake's brain that says we want to control the level of the lake. But there's not. There's just the water flowing into the lake, the water flowing out of the lake. The rain fall, the evaporation, and different forces on the body of water going in and the water going out that are going to determine the level of the lake, and there's no Wizard of Oz; there's no ultimate regulator of the water level. Just nature and the environmental forces that effect it.

This is also what's going on in the fat tissue. By invoking set point, you're evoking this idea of a regulator in the brain that's controlling it, but you don't need a regulator in the brain. All you need is the competition of forces trying to put fat in and get fat out of the fat tissue. When you change the balance of forces, by getting rid of the sugar and refined carbohydrates for instance, you lower insulin levels, you reduce the forces putting fat in, and fats starts flowing out and your settling point goes down.

If you had a dam in the river going out of the lake, the lake would carry relatively more water than a lake that did not have a dam. You remove the carbohydrates from the diet and it's the equivalent of removing the dam from the rivers below the lake. You remove the dam and suddenly the water gushes out and the water level drops. The excess fat flows out in the case of the person, and the excess water flows out of the lake. You haven't changed the thermostat, or an internal regulator in the brain or in the lake, rather, you have changed the competition of forces, or more specifically, you have removed one of the major contributors to excess accumulation (in the fat tissue and in the lake, as it were).

David Kessler, former commissioner of the FDA, and author of The End of Overeating, wrote a chapter devoted to “Pushing Up Our Settling Points,” and he concluded that it’s more useful to think of the term settling point.

Kessler’s hypothesis? “[T]he point where our weight settles is primarily the result of motivation and availability--how much we want to seek out food and how readily we can obtain and eat it.”

Sounds an awful lot like the toxic environment. [9] Kessler then uses anecdotal accounts to describe how behaviors and emotions get in the way of us consciously controlling how much, and what we eat. Again, think about the settling point in the context of every other biological process, and then think about how ludicrous motivation and availability seem as conscious factors in complex regulatory systems.

We can even use Dr. Harris’s earlier observation about set point, but apply it to settling point as “the only possible explanation for normal people having stable weight without counting anything.” In other words, there are biochemical drives at play that determine our behavior, not the other way around. What Kessler seems to be invoking is the term settling point to explain the calories-in/calories-out model of obesity, which is a good example of misinterpreting a definition in his book, The End of Overeating. [10]

Arguing that body weight is controlled by the brain is nothing new:

Wirtshafter and Davis noted in 1977, “The growing interest in the use of control theory to analyze the physiological substrates of behavior has prompted a number of investigators to suggest that body weight, or some closely related quantity such as total lipid volume, may be regulated by means of a set point control system. Indeed, this conception of weight control has become so popular that it is put forward as established fact in at least one introductory psychology text.” [11]

“The defining characteristic of such a system is that it contains a reference point against which the current state of the organism is compared. Deviations from the set point generate an error signal which activates the system to correct the deviation.”

“In spite of the popularity of this notion there is a real question concerning its value in furthering our understanding of the control of body weight. Postulating the existence of a neural set point in order to account for the constancy of body weight does not explain much; it merely assigns to the central nervous system (CNS) just that property needed to account for body weight constancy.” [12]

It has also been noted that the introduction of a concept such as set point creates the difficulty in explaining others. This is not dissimilar to the concept of the calories-in/calories out myth; the idea that increased intake and/or decreased expenditure are the drivers in obesity.

For example, we know that rats gain a tremendous amount of weight before hibernation, that many species of birds pack on the pounds prior to migration, that women who become pregnant gain body weight and fat, that children going through puberty gain weight and fat, or muscle, depending on the sex, that rats can become obese when fed a high-fat diet, or perhaps that even humans, who are fed a diet high in sugar and refined carbohydrates can be made obese.

“To explain these phenomena within the context of a set point model,” wrote Wirtshafter and Davis, “one would have to assume either that the set point is labile or that is becomes inoperative under certain conditions,” such as the ones mentioned in the preceding paragraph.

“In other words,” Wertshafter and Davis explained, “changes in the set point of a system cannot be inferred from changes in its settling point, nor can the existences of an internal set point be inferred from the fact that a system appears to have a settling point which it will defend.” Remembering the lake analogy here is instructive.

It is getting seemingly easier and easier to “fight” the set point and gain weight in the US and many other countries are not far behind. Most proponents argue that we have a set point, and that it’s relatively easy to fight it while gaining weight, while losing weight proves to be more challenging, where the set point gets more angry and is more willing to engage in physiologic fisticuffs. It’s more likely that the hypothesis, or its interpretation, [13] is wrong.

1. In fact, most people don’t think set point is a hypothesis, rather, just about everyone refers to it at ‘set point theory’ and many think it’s a scientific law: “an analytic statement, usually with an empirically determined constant,” as it was put in Wikipedia.

2. There are virtually an infinite number of hypotheses, many of which are ephemeral, but theories often remain to be tested and modified for long stretches of time, such as the theory of evolution, or many theories in quantum physics or astronomy, where theories can remain to be tested due to our limited capacity to test them. You can be a little more fast and loose with hypotheses, so long as they are valid, but theories can’t be hunches or guesses that are not grounded in science and evidential data. To quip that a proper scientific theory is ‘just a theory,’ is an injustice, and the use of ‘theory’ as a pejorative is actually more aptly, and perhaps ironically, described as ‘just a hypothesis.’

3. At least, according to MIT Medical.

4. Well here’s a news flash: the body is in fact starving on a semi-starvation diet! When we restrict food, it’s a form of starvation. That’s why caloric-restricted diets are also referred to as semi-starvation diets.

5. One could legitimately ask the question: How is set point even a theory and not a refuted hypothesis?

6. Taubes also notes another overfeeding study, led by Claude Bouchard, in which 24 men (twelve pairs of identical twins) were overfed by 1000 calories a day, six days a week, for 12 weeks. “The subsequent weight gain varied from nine to thirty pounds.” Another study noted by Taubes was conducted by James Levine from the Mayo Clinic in which 16 healthy people were overfed by 1000 calories a day for seven days a week, for eight weeks. The weight gain in these individuals ranged from less than one pound to just under nine, a ten-fold variation. Taubes G. Good Calories Bad Calories. 2007.

7. I happen to immensely respect Kurt Harris, Petro Dobromylskyj, and Stephan Guyenet’s intellects and posts immensely, so I’m inclined to believe that the disagreement on set point is a problem of interpretation.

8. “Although I have much respect for Stephan Guyenet and appreciate his very fine blog,” writes Pal Jabekk, “I don’t understand his focus on the body fat setpoint. I don’t understand anyones focus on body fat setpoint for that matter. I’ve never felt comfortable using the “setpoint” word when it comes to body weight regulation. It makes me think of a glowing red number etched into my hypothalamus. “15 kg fat” NO MORE, NO LESS. It does not feel very “organic” to have a set point and I’m pretty sure I am organic. But of course, no one is claiming there is a number etched in my brain.” (Jabekk P. The Set Point Hypothesis Revisited. Ramblings of a Carnivore. February 26, 2011.)

9. "Cheese-burgers and french fries, drive-in windows and supersizes, soft drinks and candy, potato chips and cheese curls, once unusual, are as much our background as trees, grass, and clouds," according to Kelly Brownell.

10. “Overeating” is a misnomer. Take two individuals, Ben and Jerry, both 5-foot-10-inches and 24-year-old males. Both eat approximately 2500 calories a day. Ben weighs 160 pounds and has 10% body fat. He doesn’t consciously think about how many calories he’s eating, how many he’s expending. Neither does Jerry. But Jerry weighs 220 pounds and has been gaining weight steadily over the past year or so. Jerry is ‘overeating,’ but Ben is not? Overeating implies that we have conscious control over what we put in our bodies, so Jerry is overeating and needs to eat less, but to say this is physiologically possible in the long-term, that Jerry can eat 1500 calories a day and get near the physique and body weight of Jerry is naive. And if he couldn't lose the excess weight eating 1500 calories, Jerry is still overeating, despite consuming 1000 calories fewer than Ben?

11. Bourne LE, Eckstrand BR. Psychology: Its Principles and Meanings. New York: Holt, Rinehart and Winston. 1976.

12. One question that warrants further exploration is that if a researcher, clinician, or weight loss specialist truly believed in a set point, why would they ever treat a patient who is overweight with dieting and exercise? It’s like fixing the problem in your overheating house by tossing ice cubes in the living room.

13. “The body fat “setpoint” is just a word used to describe a level of a self regulating biological process,” noted Pal Jabekk. “To call a certain mean level of a homeostatic regulation a set point is unproblematic. As far as I can see, this is how Stephan Guyenet uses the term. But when medical professionals use the setpoint hypothesis to argue that body weight loss by nature is difficult and near impossible, we have a problem. The continued use of the expression seems to affect both medical professionals and researchers in a negative way, because it closes their mind for other possibilities, among them that weight loss from a physiological point of view is easy if you just push the right buttons. That we do not always know what these buttons are does not mean weight loss must be difficult, only that we are ignorant. Many aspects of metabolic regulation are under our control. Most important of all is that the level of homeostatic regulation of body fat called the setpoint, seems to be determined by what we eat.” (Jabekk P. The Set Point Hypothesis Revisited. Ramblings of a Carnivore. February 26, 2011.)

1 comment:

  1. I believe Sherlock Holmes might chime in on this topic with, "it is a capital mistake to theorize before you have all the evidence. Insensibility tends to twist the facts to suit the theory, instead of the theory to suit the facts".