Set Point ~ Settling Point Part II: Substrate Balance & Body Composition
Continuing the discussion of Point 9 from this paper, and Part I,
Although less obvious than the fact that energy intake must be equal to energy expenditure, weight stability also requires that the substrate mixture oxidized be equivalent, on average, to the composition of the nutrient mix consumed. When “substrate balance” is not achieved, changes in body composition occur, which in time are bound to elicit adjustments in food intake.
The contributions made by carbohydrate and by fat to the fuel mix oxidized is reflected in the ratio of CO2 produced to O2 consumed. This ratio is known as the “respiratory quotient” or “RQ.” It varies between the values of 1.0, when CHO is the predominant fuel, and 0.7, when oxidation of fat provides most of the body's energy. The ratio of CO2 produced to O2 consumed during the biological oxidation of a representative sample of the diet consumed is defined as the “food quotient” or “FQ”. Stable body compositions will only be sustained if the average RQ matches the average FQ of the diet.
The composition of the fuel mix oxidized and hence the average RQ are influenced by the size of the body's substrate reserves. The steady state of weight maintenance thus tends to become established for a particular body composition in a given individual living under a particular set of circumstances. This corresponds to a “settling point” . Such a view accommodates the fact that circumstances cause weight stability to occur for various degrees of adiposity.
There's something about this paragraph that just doesn't sit right for me. Clearly there are examples of folks eating anywhere in the spectrum of fat intake, carb intake and even protein intake who are of similar body composition. And there are also many examples of folks who dramatically change the composition of their diets without seeing any major changes in weight or degree of adiposity. Although humans don't continue to grow in height, we can and do grow in size under certain circumstances and we add both lean and fat mass. I suppose that the composition of our excesses may influence the proportion of added mass that is lean and fat, and body builders go to great extremes trying to build lean mass. But how can this FQ/RQ balance explain how a Kitivan (% C/F/P ~ 70/20/10) and Mark Sisson (20/55/25) might have similar physiques? And how to explain the many studies like Grey & Kipnis, for example, where macros were varied between extremes with weight maintenance?
I believe that this is because of the heirarchy of fuel selection as described in Nutrient Fates After Absorption. We all burn carbs for energy first, then protein, then fat. I used to believe it went carbs, then fat, then protein, and that protein made a poor energy source, but my mind was changed on that when I learned of all the ways amino acids can feed into the Krebs cycle without needing to be converted to glucose. At no time do we ever just burn carbs or fats, but our oxidation rates of the macros are always changing. For protein, intake is ultimately limited by nitrogen balance. Although no absolute maximum is known, it is impossible to get one's complete daily nutrition from very lean meats b/c the limit is somewhere in the 250-350g range and likely a lower range if one is consuming this much protein daily. While we use proteins to build lean tissue, we simply don't sequester and store excesses in those tissues in the same way as we do lipids in adipose tissue. As any natural ectomorph who has ever tried to look like Hans and Franz will tell you - grin.
For the most part, despite claims to the contrary, most of us eating "typical" Western diets, or according to the USDA Food Pyramid (or now My Plate) are eating carbohydrate amounts significantly less than our storage capacity. Indeed it seems that our brains consume at least 100g/day of glucose and likely closer to 150g when we're not in metabolic starvation mode and "running on ketones". So if you subtract that out, many of us don't even eat our liver's glycogen capacity more (~100g) let alone our skeletal muscle glycogen capacity (estimated to be up to 600g but at least 300g). So I envision that the Kitivan cycles their glycogen significantly, and although not in "excess" calorie-wise, if they consume "excess" carbs compared to what can be oxidized/stored immediately, these probably enter the DNL cycle described in this post, and/or the liver does ramp up it's own DNL and adds a few more grams of triglycerides to circulation.
Indeed Kevin Hall and Carson Chow, Gary Taubes' two favorite young biophysicists at NIH, in their The Dynamics of Human Body Weight Change, work with a two compartment model by treating carbohydrate as a constant over the long run because even wild fluctuations in this component only comprise a pound or two of non-water mass. Hall & Chow's paper is heady and even possessing the math background to understand it all, I'm not inclined to wake up that portion of my brain any time soon. One thing I glean from the paper, however, is that the protein content of the diet may well be the factor that determines body composition. I also get the overarching message from the paper that given a particular starting point there are various "set points" for body weight and composition depending on the environment. IOW, those "shifting set points" or what Flatt rather describes as "settling points". A distinction without a difference perhaps? They also discuss how their models won't apply to an infant. I would say that the models that would apply to an adult human would not apply to a growing child/adolescent either. And many studies and anecdotal observation seem to demonstrate that caloric restriction - and perhaps protein insufficiency or sufficiency - during periods of growth does influence basal metabolic rate and body composition - favoring partitioning to fat vs. lean. This is what happens in mice with mild caloric restriction and even rats on a ketogenic diet! It is important to point out that rodent studies do not translate well to humans for two reasons: (1) rodents are hindgut fermenters and so extracting calories from carbs is less efficient than fat, and (2) rodents continue to grow through adulthood.
So where does this leave all of us? If I'm understanding Stephan's comments in Part I correctly, set point is not a singular value (or range) determined by genetics. It is influenced by environment. And this appears to be how Hall & Chow couch it as well. Given a certain start point and inputs body weight will "settle" at different points. Stephan writes:
Proponents of the "settling point" idea often leave out the fact that we have already characterized a negative feedback loop that homeostatically regulates body fatness. It's not just an abstract idea; we know what the machinery is that carries it out.
The modern idea of the setpoint is not quite what you described, and that's the source of a lot of confusion. The argument "my weight changed, therefore there's no setpoint" doesn't hold water, because the setpoint is not a genetically determined level of fat mass that never changes throughout life. It responds to prevailing conditions, including food reward and hormonal state (e.g., menopause).
Also, the mechanism itself can probably be damaged, resetting it at a higher level. All you need is a bit of leptin resistance, and your setpoint will increase accordingly.
I can see where Stephan is coming from but I guess ultimately it doesn't seem to apply if that makes any sense. I mean, yes, processed food is high on that "food reward" scale, but I don't see how this necessarily explains the obesity epidemic in a practical sense. And it doesn't explain why most of the guys I went to college with didn't gain much weight in the same obesogenic environment that most of the women did. Yes, my first "pudging" coincided with puberty, but I still don't get how a set point is even relevant if it couldn't take the perturbation of BK lunch a few days a week. Was that all it took to develop a bit of leptin resistance in a very active, unusually muscular adolescent female? If so, we're all doomed! Doomed I say!! < /melodrama> Why did my body not do just a little bit to defend my set point?
In this regard I do believe that "settling point" is a better theory to work with, and I think even the fanatic low carbers will agree with this one b/c Gary Taubes tells us that LC will "correct" the situation to the degree possible. Therefore by changing the dietary environment, you are creating a new "settling point". I'm going to bust your balloons again and say, perhaps the higher protein content of an LC diet may influence this somewhat (so eat more fat to minimize this benefit - grin) but in the end, what determines a "settling point"?
You guessed it! Calories In - Calories Out = Energy Stored.
How to lower CI? Well, low carb works for many, but surprise surprise, so does low fat! Or we can adopt a bland diet or even take it to the extreme of drinking tasteless sugar water and olive oil a la Shangri La or plain boiled potatoes, etc. Or we can count calories, exercise portion control, etc. etc.
As much as I like to get into the nitty gritty of the science of it all, in the end it really just boils down to that. I guess we can agree or disagree on what is more "effortless" for weight loss. If never eating starch is sustainable for the long haul and produces weight loss, great. If eating boiled potatoes and plain hamburgers ad libitum is sustainable, great. It truly is finding what works for you ... and I submit that eating just bland foods or never eating starch, etc. is far from effortless. Resettling is difficult, it is not, however, impossible.
And perhaps this is where genes play a part. I am very taken with that study I cited in which it appears that different genes call for a different macronutrient balance. Maybe that is why low-carb works great for some, not for others.
This is not "eat right for your blood type". And it most certainly DOES NOT invalidate CICO/ELMM. But I do think it adds a crucial piece to the puzzle.
"The composition of the fuel mix oxidized and hence the average RQ are influenced by the size of the body's substrate reserves."
OK, fine, but let us analyze which alleles this body possesses, and how they are expressed. Maybe your body has the allele that enables you to eat more carbs, and mine, a more protein-based diet.
"There's something about this paragraph that just doesn't sit right for me."
That's exactly what bothered me about the paper. I agree with your take on it 100%-- the body is good at adjusting RQ to match diet composition. What matters for fat accumulation is total energy balance (roughly speaking). This is ignored by low-carb advocates who point out that carbohydrate ingestion suppresses fat oxidation, and suggest that this would lead to body fat accumulation.
Regarding the setpoint vs. settling point debate, I'm not feeling very particular about the terminology. However, I still think the homeostatic mechanism, whatever you want to call it, is relevant to common obesity. Rudy Leibel showed that weight reduction of just 10% in obese women leads to reduced energy expenditure, reduced sympathetic tone and reduced thyroid signaling. Leptin replacement to the pre-weight loss level reverses this phenotype.
I feel this is good support for the idea of a higher leptin-dependent setpoint (or whatever you want to call it) in human obesity.
As with all biological phenomena, the response to an obesogenic environment will differ between individuals. Some people, for genetic or other reasons, have homeostatic mechanisms that are more resistant to the influence of junk food, menopause, age or whatever. Same with lung cancer and smoking or any other disorder-- if 10 people smoke the same amount, only one or two will develop cancer.
There are clearly genetic susceptibility factors for obesity. Studies show that 40-70% of BMI variability is heritable. GWAS studies have found a number of susceptibility genes-- most of them are expressed in the hypothalamus (all known nondysmorphic monogenic obesity phenotypes are due to mutations in the leptin signaling pathway as well). A recent study supports the idea that genes primarily determine the response to an obesogenic environment rather than dictating body fatness, and that genetic factors are less relevant when the environment is not obesogenic:
I do not see this as necessarily supporting a set point because how did the person get obese to begin with? And would a weight matched person who was never obese have the same circulating leptin as the supplemented reduced obese? I would think now.
Why would a lean force-fed male who gains say 20 lbs fat over a couple of months revert back, but a 15-16 year old girl who gains those same 20 lbs over a period of a couple of years not have her feedback system prevent that in the first place?
Overfeeding studies are almost never done with low fat or low carb diets, they are usually accomplished with lots of liquid calories, and fatty/carby high energy foods (like mashed potatoes loaded with cream and butter). There's a reason they use heavy cream vs. oil - or worse, lard - to overfeed humans on fat! So how to explain food reward in all of this?
Y'know, with respect to that last paper, we saw that with the CAF rats too! There was FAR more variability in the weights of those rats as compared to any of the other diets. They had the same genes, but give 'em crap food and SOME got very VERY obese, while others barely bigger than the standard chow rats.
You asked "how did the person get obese to begin with?"
The current model, which I feel is well supported, is that the setpoint increases due to a reduced sensitivity to feedback signals, primarily leptin. There is a lot of debate still over what is increasing the setpoint, but I feel that reward/palatability is a strong candidate. There are almost certainly other factors as well. Exercise improves leptin sensitivity in rodents for example.
Supplemental leptin does cause fat loss in obese people, it just doesn't return them to the lean state.
You asked "Why would a lean force-fed male who gains say 20 lbs fat over a couple of months revert back, but a 15-16 year old girl who gains those same 20 lbs over a period of a couple of years not have her feedback system prevent that in the first place?"
Because the fat gain is due to different mechanisms in each case. In one case, the setpoint has not changed, while in the other, it has increased gradually. The feedback system is not keeping the girls' weight stable because it has gradually been altered by environmental factors.
I feel this explanation is consistent with Leibel's study, among others, which together show that both lean and overweight/obese people seem to "defend" their current body fatness against (short-to-medium term) changes, and that this process is leptin dependent.
There will always be individual variability in the degree of susceptibility to the various obesity factors.
On a related note, I have no problems this time maintaining a singificant and relatively rapid weight loss. Wonder why that would be .....
Maybe it was my evil ovaries ;-) <-no need for a response there, just funnin'
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