A Chemical Hunger – Interlude A: CICO Killer, Qu’est-Ce Que C’est?


[
PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]


Runner up titles: Son of CICO, 2 CI 2 CO, Revenge of CICO, CICO 2: Judgement Day, CICO Returns, CICO! Here We Go Again, CICO’s Bogus Journey 


Calories In Calories Out (CICO) gave us more trouble than any other section we worked on when writing A Chemical Hunger

Part of the problem is that CICO means different things to different people, and covers a number of loosely related hypotheses. We found it hard to disentangle these when we were writing Part II. A number of times we circled back to our section on CICO and tried to reorganize it, or re-write it entirely, but we weren’t able to figure out a way to clarify the argument to our satisfaction. 

But feedback on the posts has proved extremely helpful, and we think we can now do a better job explaining what we meant. Special thanks to commenters-on-the-blog Richard Meadows and Grat Ivar, to fellow bloggers Alvaro de Menard and Stephen Malina, and commenters on MetaFilter and Hacker News, for helping us clarify our thoughts on this.

Linear Relationships

One way to interpret CICO (or one sub-hypothesis) is that it claims there is a strictly linear relationship between calories eaten/burned and weight change. This is specified if we take “weight gain = calories in – calories out” literally. Essentially, this hypothesis says that overeating by the same amount should always lead to the same amount of weight gain.

This is clearly false. The overfeeding studies provide extremely strong evidence against this version of CICO, since people gain very different amounts when overfed by the same amount, the difference appears to be mostly genetic, and some people actually lose weight, even when overfed by moderate (1000 kcal/day) amounts. Many people still believe something like “for every extra 3500 calories you eat you always gain one pound”, but all available evidence comes down very strongly against that.

At low levels of overfeeding, people at normal weight often don’t gain any weight at all. We liked how sdenton4 on Hacker News put it: “It’s pretty obvious the body has other ways to dump excess calories than turning them into fat stores.” 

Willpower

In Part II, we quote Stephan Guyenet as saying, “This model [CICO] seems to exist mostly to make lean people feel smug, since it attributes their leanness entirely to wise voluntary decisions and a strong character. I think at this point, few people in the research world believe the CICO model.”

What does Guyenet mean here? A common interpretation tied up in CICO is that differences in willpower explain the difference between obese and lean people. The idea is that weight gain is easy and weight loss is hard for everyone. This interpretation says something like, everyone would be 300lbs if they didn’t use their willpower to eat healthy foods rather than cake — you have to control yourself. From this perspective, people who are obese lack willpower and people who are thin/fit are virtuous resisters of temptation.

The overfeeding studies also provide strong evidence against this hypothesis, since they find that it is hard for most people to gain weight and easy for them to go back exactly to the weight they were before the overfeeding. We think this leaves “willpower” explanations dead in the water. Most skinny people have no trouble staying that way.

While not everyone means this when they say “CICO”, many people do, and we wanted to address this aspect of CICO because it is a common misconception. There’s also a strong moral reason to argue against this aspect of the hypothesis, because the idea that obesity is the result of lapses or weakness in willpower has been used to justify many cruel and ineffective positions. People who believe that obesity is the result of laziness and weak willpower believe that people with no moral fiber can be recognized on sight. As a result, they do things like treat overweight and obese people with disrespect, make jokes about them, don’t hire them, don’t give them proper medical treatment, etc. They think that shaming and social stigma are effective interventions against obesity. Some think that overweight and obese people should feel ashamed of their weight. This is as horrible as thinking that cancer patients should feel ashamed and responsible for falling sick. 

In addition, placing the blame on willpower and moral failing, and treating individual responsibility as the appropriate intervention, means abandoning the search for the causes of obesity. If you think obesity is largely the result of willpower, then there’s no mystery or need for a solution. But in fact obesity is not the result of willpower, and obesity remains very mysterious. Let’s quote that article from The Lancet again: “unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures.”

Calories Lead to Weight Gain

Another interpretation is something like “calories matter for weight gain”. Other things being equal, you generally gain weight when you eat more calories and you generally lose weight when you eat fewer calories.

We are not trying to argue against this at all! If you eat 400 kcal/day, you will lose weight (there are studies on this). If you eat 10,000 kcal/day, you will gain weight (there are studies on this one too). But the amount of calories you eat matters much less than most people think, and there isn’t a strong linear relationship between calories consumed and weight gained (see above).

You can lose weight by consistently eating at a calorie deficit, but people who do this either struggle to maintain their lower weight or gain it back. For two people who are the same height, one might weigh 150 lbs and the other weigh 200 lbs. If the 200 lb person loses 50 lbs, it will be hard for them to maintain a weight of 150 lbs, but easy for the person who weighed 150 lbs to begin with. Why is that? And why has the number of people struggling with their weight grown so dramatically since 1980?

There may be some people with exceptional willpower and incredible support systems that can lose lots of weight and keep it off — in the same way that stage magicians with incredible willpower and lots of training can learn to hold their breath for 10+ minutes underwater. The question is why they would need to use their incredible willpower in the first place! Maybe willpower can be a solution, but it’s not the cause — it doesn’t explain the differences between 1980 and today.

What about those Calorie Intake Numbers?

A bunch of readers zeroed in on this paragraph:

It’s true that people eat more calories today than they did in the 1960s and 70s, but the difference is quite small. Sources have a surprisingly hard time agreeing on just how much more we eat than our grandparents did, but all of them agree that it’s not much. Pew says calorie intake in the US increased from 2,025 calories per day in 1970 to about 2,481 calories per day in 2010. The USDA Economic Research Service estimates that calorie intake in the US increased from 2,016 calories per day in 1970 to about 2,390 calories per day in 2014. Neither of these are jaw-dropping increases.

People pointed out that this is about a 20% increase in calories, which doesn’t seem to match our description of the increase as “quite small”. So let’s take a second to unpack our reasoning.

First of all, this was a smaller increase than we expected. We know that even a small daily change adds up over time, but we expected the change in daily calorie intake since 1980 to be much larger. 

Partly this is because once you gain weight, you burn more calories (because it takes more energy to move and maintain physiological function) and you need to eat more calories to maintain your weight. Studies show that people with obesity eat and expend more calories than lean people. From this study, for example, consider this sentence: “TDEE was 2404±95 kcal per day in lean and 3244±48 kcal per day in Class III obese individuals.” From this perspective, the average daily consumption per Pew being 2,481 calories per day doesn’t seem like much — that’s about what lean people expend daily. Obese individuals generally burn 3000+ kcal/day, and while not every modern person is obese, it does make the increase from 2,025 calories per day in 1970 to about 2,481 calories per day in 2010 look relatively small.

This is something of a chicken and the egg problem. We could weigh more because we eat more calories, but we could also eat more calories because we weigh more, and we need to eat more calories to continue functioning at that weight. You may say, “but if you eat less at a higher weight you will dip into fat stores to make up the difference”. Not if your set point is too high you won’t! If you eat less than you need and your body wants to defend your current weight, you will crave food and feel tired and stupid. Sound familiar?

In addition, there’s some evidence that back around 1900 people ate more than they did in 1960, without much more exercise, and they weren’t obese — though take this one with a grain of salt, since for the obvious reasons, we don’t have great calorie data from back then. This is mentioned in the paragraph immediately following the one quoted above:

If we go back further, the story actually becomes even more interesting. Based on estimates from nutrient availability data, Americans actually ate more calories in 1909 than they did in 1960.

For the sake of argument, let’s accept that an increase of 400 kcal/day is a meaningful amount. Let’s further assume that the 400 kcal/day increase is entirely responsible for the increase in the rate of obesity since 1980. Even if the increase is meaningful and driving the obesity epidemic, we have to ask, why are people eating more now than they used to?

Just because calories are causally involved doesn’t mean they’re the “first cause”, the cause we should be looking for. Imagine there were an evil dictator that went around force-feeding people. These people would gain weight (per the overfeeding studies) and in some sense the calories would cause the weight gain. But if we’re being reasonable, the insane dictator is the cause, and the calories are just the mediator. 

We know people do eat a bit more today than in the 1970s. So the question is something like, in this case, what is the insane dictator? When we say “not CICO” part of what we mean is “not willpower”. 

Miscellaneous

Another point worth mentioning is that there seem to be different kinds of weight change.

One is the kind of weight change that happens around your set point. For most people, changing your weight by 5-10 pounds in either direction will be relatively easy. This may be possible through diet and exercise; the amount of weight change may even have a close linear relationship with the amount of calories you add or remove from your diet! In this limited sense, CICO may be a useful guideline. 

This is very different from major changes in fat mass! All available evidence suggests that it is very, very hard to lose more than 10 or so pounds and keep it off, probably because it involves fighting your lipostat’s setpoint. 

Another kind of weight change has to do with changes in muscle mass. Altering your body composition to have lower fat/higher muscle percentages can occur without changing your set point and result in significant visual differences. We suspect that weight gain and weight loss work differently in bodybuilding because that involves weight change driven by increases in muscle mass, not fat mass. We’re perfectly willing to believe that people can gain and lose muscle mass in a reliable way based in part on caloric consumption, but that’s not the focus of A Chemical Hunger

Cutting fat gained when increasing muscle mass might also be relatively easy, because that’s more fat than you “naturally” had before the gains. More body fat should lead to more leptin, but your body had you at the leptin level it wanted you at before, so the leptin-based part of the lipostat will help you lose that fat mass. But changing fat mass alone seems pretty dang hard.


20 thoughts on “A Chemical Hunger – Interlude A: CICO Killer, Qu’est-Ce Que C’est?

  1. Jim says:

    This article really dances around it, but it would probably be helpful to explicitly frame this in the context of the first law of thermodynamics. Calories-in-calories-out is unquestionably true – the carbon atoms either stay in the body or they don’t. It’s just that there are so many psychological and biological factors that subtly affect both ends of the equation, and the “calories out” part only happens invisibly via respiration.

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    1. Sniffnoy says:

      Right, the usual counter to CICO isn’t “CICO is false” but rather “CICO is trivial”. Sure, gain = CI – CO is true, but the problem is that CI and CO aren’t independent. Increasing CI doesn’t necessarily lead to weight gain… because CO goes up along with it, in ways that are not obvious (e.g. fidgeting instead of deliberate exercise). The falsehood isn’t gain = CI – CO; the falsehood is that we can just set CI and CO, rather than having to look to what is determining CI and CO, and relating them to one another (i.e. the lipostat and whatever is affecting it). Don’t get a statement being trivial or useless mixed up with it being false!

      Liked by 1 person

  2. gleamingecho says:

    “At low levels of overfeeding, people at normal weight often don’t gain any weight at all.”

    Doesn’t this mean they’re not being overfed? What is the definition “overfeeding” being used here?

    Like

  3. Fred says:

    Something that I though you’d be interested in, SMTM:

    CPAP use in those with obstructive sleep apnea (and maybe in those without it, but no one studies that) leads to, on average, an increase in BMI, and the increase is in proportion to the amount that CPAP is used. This was unexpected by many and some theorize it is because a decrease in “calories out” due to more restful sleep and easier breathing while asleep. I think it’s something else to do with CPAP.

    This increase in BMI finding just feels very intuitively wrong to a lot of people who are probably thinking something like, “If my sleep and sleep breathing are fixed the I’ll have the energy to exercise and the will power to eat better and will have normalized leptin and ghrelin levels so I don’t have to fight against as intense of cravings.”

    Indeed, Leptin and ghrelin levels do normalize with CPAP use and fatigue and sleepiness often go away with CPAP use. There also is a decrease in calorie expenditure during sleep, but I have wondered whether CPAPs emit obesogenic compounds. They have DEHP in the tubing and BPA in the masks. Philips’ PAP machines were recently recalled because a foam that they use was breaking down and may have been off-gasing. Perhaps there were obesogenic flame retardants in it. I’ll have to see what brands of PAP are used in the BMI/CPAP studies to see if there is any hint of a brand effect.

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    1. Huh, that’s a great idea. An extra 8 hours of exposure every day to a medical device is a lot, and we have some data in an upcoming post that implicates medical devices more broadly, so this seems plausible. Please keep us posted!

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  4. Jack Peterson says:

    You ask me, “Why is this football stadium packed full of people?” I respond, “Because more people went in than went out.” My explanation is correct, but also useless: it doesn’t explain _why_ more people went in than went out. IMO, (any version of) CICO as an explanation for obesity is useless for the same reason.

    Liked by 1 person

    1. Mahmud says:

      One way to frame it is, people may have a somewhat clear way of addressing who is allowed in (those with a ticket) but have no clarity as to when and why some choose to leave or don’t. It’s the some choosing to leave or stay, and that too at different times that confuses us more than anything. Why we give too many or too few or just the right amount, or whatever amount of tickets we sell is it’s own mystery. But the bigger mystery is why the ticketed attendees stay or leave at times we can’t control.

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  5. Lamson Nguyen says:

    Interesting series so far. I’d like to see you address extended and intermittent fasting.

    On Thu, Jul 15, 2021 at 8:50 AM SLIME MOLD TIME MOLD wrote:

    > slimemoldtimemold posted: ” [PART I – MYSTERIES][PART II – CURRENT > THEORIES OF OBESITY ARE INADEQUATE][PART III – ENVIRONMENTAL CONTAMINANTS] > Runner up titles: Son of CICO, 2 CI 2 CO, Revenge of CICO, CICO 2: > Judgement Day, CICO Returns, CICO! Here We Go Again, CICO’s Bogus ” >

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  6. Tim says:

    I know this is anecdotal, but at the start of the pandemic (March 2020), my wife and I started the Keto diet – which for us meant 20g of carbs per day, and little to no sugar. My wife wanted to lose over 60 pounds. Fast forward to today and my wife lost between 50 to 60 pounds. Astonishingly, it wasn’t even that hard once you get past the habits of your pervious diet. With plenty of food substitutions to choose from, we never felt that we were going hungry or depriving ourselves. And I wouldn’t describe our willpower to be particularly great, as I mentioned we found passable substitutes for most cravings.

    So I’m a big fan of Keto, yet now I wonder. Was it the lack of carbs or sugar, or is there something about eliminating breads, pastas, or high fructose corn syrup? Or more precisely, something about eliminating what those foods are contaminated with? I look forward to your next article!

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  7. Brian says:

    I’m enjoying this so far — I suspect that one driver of the increase in obesity has to do with some kind of endocrine disruption, and I’m interested to see what you turn up. But I do have some disagreements with what you’ve presented here. In no particular order:

    – I think that focusing on exercise (actually leisure exercise) is missing the big change in activity levels between (say) 1900 and now: people used to have, on average, much more physically demanding jobs. Technology and labor-saving devices really have saved a lot of manual labor. So while leisure exercise has increased over time, total caloric expenditure due to physical activity has almost certainly decreased.
    – I’m not sure which is wrong (probably both to some degree), but clearly the estimate of caloric intake (about 2400/day on average over the whole population) and the estimates given for TDEE (about 2400/day in lean study participants, increasing up to about 3200/day in the morbidly obese) can’t both be right — especially since it seems in that study that the vast majority the participants are female, and women have on average substantially lower TDEE than men.
    – I think you are right that it’s mostly not about willpower. But I don’t think that the fact that some people have an easy time staying thin and others a hard time disproves it. You can easily have a model that there are some people who (for whatever reason) don’t need extra willpower (or adverse circumstances that force them to eat less or move more against their inclination), and others need varying degrees of willpower/adversity in order to stay thin and otherwise become fat. As willpower and adversity (as concern food and energy expenditure) decrease generally, this will affect people to various different degrees.
    – You mention that there is not a linear relationship between calories consumed and fat gain/loss. This is certainly correct, though a lot of people seem to find a pretty consistent relationship when they start actually measuring their food intake. But my understanding is that the discrepancy between the theory-CICO and reality is that people change how much they are moving around in response to caloric changes, not that there’s anything mysterious going on. (Of course this is consistent with the lipostat being the major driver, here.)
    – Surely body composition changes would trigger the lipostat to respond just as much as straight fat loss, since the lipostat measures fat mass (or even body fat percentage?), not weight? So I’m not sure how the fact that body composition can change at the same weight is an argument against the possibility of fat loss. Maybe I’m missing something.

    Anecdotally, I managed to lose over 30 pounds in the last four months by changing how much I ate, and I mostly didn’t feel that hungry overall. I did change the overall composition (more veggies and satiating foods like fish; less pasta and milk), but I didn’t cut anything out entirely. About 10 pounds of that weight I’d gained in the previous year, the rest gradually in the preceding years. I’m now at the lowest weight I’ve been in about 10 years; I’ve gone (so far) from borderline-obese to just barely overweight. Sure, one data point isn’t proof of anything, and it could go up in smoke in the future, but at the moment it’s not taking any herculean effort, just being conscious about diet composition, portion size, and when I eat.

    One last thought. I wonder how much analogy there is between increasing obesity on the one had, and IQ and the Flynn effect on the other. We know of lots of environmental things that affect IQ: nutrition, pathogens, stress, cultural exposure to abstract thinking. These probably account for the Flynn effect. But within a community, IQ is highly heritable. Similarly, as we look at changes across time, we see e.g. the effect of availability of calories, lower levels of required activity, endocrine disruption, hyperpalatable foods. But if we look between individuals, maybe (I don’t know) the majority of the differences will be in how people respond to those environmental factors (both in their habits and in e.g. how their lipostat responds), not the environmental factors themselves. And if you are advising an individual who wants to lose weight…. CICO (using whatever technique makes that easiest).

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    1. Mahmud says:

      “– I think that focusing on exercise (actually leisure exercise) is missing the big change in activity levels between (say) 1900 and now: people used to have, on average, much more physically demanding jobs. Technology and labor-saving devices really have saved a lot of manual labor. So while leisure exercise has increased over time, total caloric expenditure due to physical activity has almost certainly decreased.”

      Herman Pontzer appears to have thoroughly debunked the notion that exercise truly causes fat loss. He managed to prove, against everyones expectation, that the Hadza, pound for pound burn the exact same calories as sedentary westerners……

      “Anecdotally, I managed to lose over 30 pounds in the last four months by changing how much I ate, and I mostly didn’t feel that hungry overall. ”

      I’ve cut from 160 to 140 over the same period using roughly the same strategy+ long term fasting. Since I am south asian I need to have a lower BMI and am aiming for the 19-20 range. Will probably update here to see how it goes. My current plan is to cut down to like 10% body fat and just regularly force my body to stay there until it just gets used to it. Don’t know how long that will be but it shows me I had an intuitive view of the “set point” slimemold has mentioned as the best (but still yet incomplete) theory that we have.

      I tend to go for meat, fiber(psyllium husk) and water as my method of feeling fuller on fewer calories. Perhaps this is the trick? As Muslims say, a third of the stomach for food, a third for water and a third for easy breathing.

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  8. anon says:

    People think the “calories out” part is BMR + Activity and the only way to increase your CO (other than changes in muscle mass) is to move more.
    They don’t understand or severely underestimate how variable your basal metabolic rate is.

    Perhaps biggest evidence that the BMR is dropping in the population as a whole is that the average human body temperature has been dropping since the industrial revolution. More dramatically, there was a well documented drop in body temperature by 0.5C in an amazonian population between 2004 and now. What happened between then? They got increased access to store bought food.

    So that got me thinking, what else could the body do to lower its BMR? I think the brain is another big one. Anyone who tried fasting or keto knows the mental fog and headaches you can get when the body runs out of readily available glucose. Talking about intelligence and IQ can be a controversial and touchy subject, but we know that obesity affects the brain in a negative way. So could obese people perhaps be starving their brain of glucose?

    Of course this last part is pure speculation on my part. But whatever is making us overweight and obese better well explain why our BMR is dropping.

    Like

    1. Mahmud says:

      Controversial, but I know African American women have quicker gestation times, this appears to affect the childs brain size(from the little I’ve read, quicker gestation = smaller brain size) and in the end, their IQ and test scores. Also, African American women are statistically way more overweight and obese than the general population.

      I fear strongly that being of lower SES has forced them into a recurring cycle-eating packaged foods with endocrine disruptors, getting overweight as a result, giving birth quicker than they should to children less healthy than they should be. This cycle only perpetuating itself…….if it’s even so much as slightly plausible the feds should intervene with the might of all power invested in them and turn ruthless against any and all source of possibly dangerous chemicals. Big Government vs Big Chemical.

      This may go some ways in explaining why the racial gap in a lot of measurements has basically been stagnant or worsening for the past 50 years. Something happened in the 70s-80s to everybody in the world.

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  9. I contend you focus too much on extreme overfeeding & extreme starvation.

    A famous rule of thumb (at least in fitness circle) is that the “ideal” rate of loss is 0.5%-1% body weight per week. Another common figure that matches those is a pound or 0.5kg a week.

    In episode 2, you said that a 3kg *additional* weight loss over three months is a “very moderate benefit”. By the heuristic above, you expect to sustain a loss of about 6kg over three months. 3kg is 50% of that!

    Most people get sustainably lean slowly, or get fatter slowly. I’ve seen this happen in both directions around me: People cleaning up their diet, as a lifestyle change and not a punctual diet. Family members that were relatively lean in early adulthood becoming fatter with time without significant lifestyle changes, being able to easily lose weight on a diet, but then gaining it back over time as they didn’t make long term diet changes.

    The key to CICO is constant vigilance (or much more easily, radical lifestyle/environment design). But if you don’t go into extreme scenarios, the numbers work.

    I ran a N=1 experience on ICO when I was cutting in 2019. Here’s the data: https://docs.google.com/spreadsheets/d/1kwGo8YRcEdPJotxaWLlc72pz6YvdU2ymKw_gFa_dKkY/edit?usp=sharing (Everything should be easy to interpret, W is weight, and is measured in kg.)

    As you can see, I lost pretty much as much weight as I expected. I didn’t get more muscular during the experiment (this was not me getting into fitness). You can contend this was fat I put on while exercising, but that doesn’t matter too much because then I also lost the fat I had when I started exercising.

    There’s two points to explore:

    (1) Set points. I think everyone that has played with its weight has felt them. And yet… my own experience showed that they weren’t really there as much as I felt in my bones. I wonder also to which extent the set point is not just a consequence of a control mechanism that has us eat more to maintain the set point. If you track everything, you basically prevent this mechanism from working (not easy!).

    Moving your set point is clearly feasible still. Ultimately, this is what a bypass or a gastic sleeve achieves. I reckon it’s also possible in a way that’s less radical (at least I’ve seen people do it).

    (2) Metabolic adaptations. These definitely exist. They are more extreme for extreme interventions, for sure. I think they explain in great part the “snap back” after extreme overfeeding and extreme staravtion.

    Metabolic adaptations also exist for slow diets (albeit they are milder)! The recommendation is to tackle them with week-long refeeds (which is what I did in my experiment above).

    So I think CICO works pretty well, and it can reliably make people leaner.

    That’s not to say it’s the only explanation for the obesity epidemic (the contaminant argument is pretty compelling, though I don’t think it explains 100% of the phenomenon).

    That’s not to say either that it’s a bulletproof way to lose weight. Clearly, it’s much harder for some people because their control system makes it harder for them to move away from the set point.

    Clearly, part of that is genetic, and I think the willpower debate is pretty sterile, because in the end that’s pretty much unknowable, and admonishing people to have more willpower doesn’t help.

    But if you can “implement the numbers” (which is the hard part), I’d be surprised if CICO doesn’t produce results — it might not be exactly the predicted weight loss as it was in my case, but I would find it very surprising if it’s not more than 60% of it.

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  10. First time comment. Background; retired cognitive behavioural therapist from mental health nursing.

    My initial reaction, after the obvious one of something interesting to read, was idiosyncratic response to drugs. Assumming that that one agrees that there’s no such thing as junk food, only junk diets? So obesity is a phenotype expression of the person’s genotype where a once adaptive gene has become maladaptive in out current obesogenic environment.

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  11. Heikki Levanto says:

    “Calories in” seems to be fairly well understood thing, and easy to measure. I guess most of the variability happens on the “calories out” side of the equation. I don’t know if there are any studies of the caloric content of feces, but I suspect there might be some variation. Some calories must be there, as they say, 50 billion flies can not be all wrong.

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