The setpoint hypothesis revisited

The homeostasis 

(hō’mē-ō-stā’sĭs): The ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes.

Humans are warm blooded and the enzymes that make us, require a certain temperature to operate optimally. The water and ion concentration of cells must remain at a certain level to allow for normal cellular processes to occur. Homeostatic processes make us able to adapt to environmental changes. Feedback mechanisms are responsible for maintaining particular levels of processes. Most processes allow for some variation, but if pushed too far in one direction the process may break down.

Body temperature is maintained by thermoreceptors communicating with our hypothalamus, by sweating, vasoconstriction and dilation, hairs standing on end, shivering, shifts in metabolism and other. All of these factors work in unison and affect each other and by doing so maintain our body temperature at around a rough mean.

During energy restriction we get hungry, our thyroid hormone levels decrease, non essential processes like that of reproduction is down regulated, and energy expenditure goes down. It is difficult to make people gain weight by overfeeding and it is difficult to make people lose weight by underfeeding. The feeding always affects energy expenditure. Thus body weight or some level of cellular mass is required for survival and the body is self regulating to make sure sufficient tissue mass is present for survival and eventually reproduction.

None of this justifies the use of the term “setpoint” in body weight regulation.

The set point 

“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.” 

Stephan Guyenet 

Although I have much respect for Stephan Guyenet and appreciate his very fine blog, 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.

When it comes to the body fat setpoint, I rather like the lake comparison. A lake can for those less informed seem to have a set point of water level. Despite rather large fluctuations in temperature, evaporation and water going into and out of the lake, the lake maintains it water level because the factors mostly responsible for the level influence each other. This does not mean that it is difficult to change the level, nor does it mean the lake «attempts to defend against change.» Build a damn dam and the water level will go up. Drain it, and the level goes down. It’s not very hard, you just have to push the right buttons.

If our fat mass changes through life and in various situations and in fact is not that difficult to change, then why the hell say it’s a set point? It’s obviously not very set, is it? Most of the time we are gaining and losing fat at pretty much equal speeds, although with constant variations around the mean. The fact that the fat storing and fat using process does not spiral out of control either way, that most of us don’t get very lean or very obese, would mean that there is a control mechanism, a feedback loop or a set point. But all the body’s processes are regulated. We are self regulated and all processes work best around a given mean determined by the nature of the very process and the processes it affects or is affected by.

A homeostatic process must have a level to operate on. It’s the way the world works. The level can usually be changed by modifying the factors that make the process.

Stephan Guyenet claims that one criterion for the cause of modern fat gain is that it “…has to cause leptin resistance or otherwise disturb the setpoint.”

What I don’t understand is, why can’t we say disturb the “regulation of body weight”, “the metabolism” or “the process.” Why “disturb the setpoint”?

The language

“..the body doesn’t want to lose weight. It’s extremely difficult to fight the fat mass setpoint, and the body will use every tool it has to maintain its preferred level of fat: hunger, reduced body temperature, higher muscle efficiency (i.e., less energy is expended for the same movement), lethargy, lowered immune function, et cetera.” 

Stephan Guyenet 

Whenever body fat setpoint is discussed it seems the body is at war with one of its processes. Why turn it into fight? Obviously it is not that difficult to “fight the fat mass set point”. I’ve asked people who’ve lost weight who said it was easy. What’s more is that they have stayed lean with ease. The setpoint hypothesis was invented mostly because people didn’t lose weight by eating low fat and that they often regained lost weight. Now, I could try to change the water level of a lake by drinking the water through a straw, and when failing I could conclude that the water level is “extremely difficult to fight”, but it wouldn’t be a very good conclusion.

I believe firmly that our language is a great obstacle for scientific progress. The main reason is that it is very hard to imagine things that cannot be put into preexisting words. Also our minds operate within the boundaries of our language and language will limit the things we can imagine. I think quantum physics is a good example of an area in which the language simply is not sufficient. The electrons can be in several places in the same time. Some things are both particles and waves. Matter consists mostly of empty space and so on. On top of it all, once words are set, once something is described in a particular way, it usually stays that way.

In Guyenets posts about the body fat setpoint, the word setpoint is often given with quotation marks, like in the above quote. I can only assume that this means that the word setpoint is not an accurate description of what he is talking about, that it is not actually a set point, but that it is used for the lack of a better word.

Guyenet also writes extensively about leptin. Leptin is an interesting protein, but it is just one of those signaling molecules involved in the homeostatic regulation. Of course weight will change if we or nature messes with leptin, its receptors in the hypothalamus or any other involved part. But the existence of leptin does not justify the use of the setpoint term.

Body fat mass can be quite easy to change so why the hell do we need the setpoint? I feel the word contributes nothing to our understanding and if anything just complicates the matter more than necessary. How about adding a muscle mass setpoint and a bone mass setpoint? How about a hair growing speed setpoint or a saliva setpoint? Does it help our understanding?

I do not think the use of the word setpoint is neutral. It affects out thinking and I am afraid its existence is a net negative contributor to the science of body weight.

On the website of one of the leading obesity clinics in Norway we are told that the clinic bases its work on the setpoint theory. They call it theory, but talk about it as an undeniable fact. This is a problem because the hypothesis rests on the assumption that weight loss is inherently difficult and that the body (in the words of Guynet) “will fight” that weight loss. It is not a very positive attitude. Remember that the setpoint hypothesis saw light of day partly because losing weight through traditional (eating less) methods did not give the expected (based on thermodynamics) results and that people constantly regained lost weight. The clinic thus operates on the assumption that it may take years of hard work to change the setpoint downwards and that it takes a very short time to change the setpoint upward (that the body «gets used» to a new higher level of fat mass).

What if the obesity clinic, instead of basing its treatment on setpoint theory (forcing overweight people to starve and doing insane amounts of exercise), said that weight loss does not have to be difficult and lasting weight loss is possible? What if they read some real science, pushed the right buttons and stopped torturing people? The studies are out there. It really does not have to be difficult. The metabolism must be altered, mostly through changing the hormonal milieu and reducing inflammation thus achieving a homeostatic regulation at a lower amount of body fat mass. And there is little evidence it has to take years to do so.

The conclusion

«When something seems ‘the most obvious thing in the world’ it means that any attempt to understand the world has been given up.» 

 Bertolt Brecht 

If the point of this rambling is lost on you, let me try to sum it up.

The body fat “setpoint” is just a word used to describe a level of a self regulating biological process.

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.

9 kommentarer om “The setpoint hypothesis revisited”

  1. «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.»

    After losing 34 lbs of fat, I can maintain my weight even though I can eat anything I want and as much as I want. I only have to follow two rules:

    1. The food has to pass the paleo test
    2. Carbs have to be under 75 grams per day


  2. Where does body recomposition fit into set-point hypothesis?

    By exercising after eating, my weight remains fairly constant, but my waist is shrinking and I can now wear jeans that haven't fitted for 10 years.


  3. Jake, that is exactly what I meant with «determined by what we eat.» Some foods just changes the whole fat inn fat out equation.

    Nigel, I guess those small fluctuations in fat mass that happens with body recomposition is either within the setpoint or you are changing the setpoint. Must be something happening with your muscle mass setpoint also or something. Bah..the word just confuses me more and more. Shrinking waistline is good though. Congrats!


  4. Please note that the scientific, non-colloquial, definition of theory is a system of principles that integrate known (undeniable) facts. Therefore a theory is not not about facts.

    Now, if they called it the setpoint hypothesis, which is what it really ought to be called as it is not a proper theory and barely passes for hypothesis, then it would be unreasonable to act as if it were incontrovertible fact.

    Just sayin.


  5. Very good post. The lake analogy is appropriate. Perhaps the most important principle here is that almost all biochemical reactions are connected in feedback. This sometimes appears as a set point; the equilibrium constant is the ratio of backward and forward rate constants. However, as in the lake analogy, concentrations can have an effect although there is resistance to change. That is why small changes in diet do not have an effect — even if you could measure changes in your own diet of 100 kcal/d it would not do any good. But you can reach a new equilibrium, that is a new «set point.»

    You are right about the language. What's wrong with the idea of a setpoint is that it is the analog of «the little man in the brain» idea in neuroscience. Your body doesn't «want» to do anything. It is not «protecting» anything. Nothing is «set.» The matrix of rate constants for biochemical reactions can be quite strongly interconnected so as to allow only a narrow range before harm sets in, as blood glucose, but that is not universally the case.

    I have the sense of having just written a lot of words saying exactly the same thing you did and yet there is probably some hidden additional brilliant insight.

    Richard David Feinman


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