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Monday, November 28, 2016

Are the Super-Obese the Ones Who Are Metabolically Adapted?


The current theme of metabolic research seems to have settled on physiological changes, post-weight-loss in the obese, that set the person up for almost assured failure and regain.  It has been reported that the super-obese (usually a term for BMI>40) tend to have REEs that are higher than would be predicted by standard, generally accepted models such as Harris-Benedict or Mifflin-St.Jeor.  This is both what was seen in the Biggest Losers "before" weight loss, and was reported in comments on this blog by Dr. Yoni Freedhoff, who measures REE in the obese he treats.  

In order for a super-obese person to fully reverse their obesity, they will need to lose large amounts of weight -- 100, 200 or more pounds.   To do so, most will need to dramatically cut calories to lose at a rate that is motivating enough to sustain a fairly lengthy time period.  Even "fast" weight loss, reported by many, and especially gastric bypass patients, occurs over several months to a year ... or more.

It is well documented that REE will decline in most, and it will decline more precipitously in response to more drastic cuts in intake.  The individual variation in this response is often glossed over.  It has also been well documented that REE returns to normal levels once maintenance calories are consumed.  This is something that has now been replaced by the results after 6 years for 14 former contestants on The Biggest Loser.  The abysmal media reporting on that study has now placed a *fact* into the general discourse that the reason obesity is so difficult to reverse is a physiological one -- as the New York Times blared, "Their Bodies Fought to Regain Weight".  This was followed by an editorial by a neuroscientist, cautioning in the subtitle "The problem isn't willpower. It's neuroscience. Why you can't -- and shouldn't -- fight back. ".

In this blog, I will discuss how what Kevin Hall actually says about the Biggest Loser study clashes with interpretations, and where we agree.  I will then address where we disagree.   His bottom line appears to be that metabolic adaptation is defined as measuring REE when obese and then calculating what it should be at 100, 150, 200, etc. lbs lighter.  He focuses on change in REE being greater than would be predicted for the individual based on their super-obese metabolic starting point.  I disagree that this is an appropriate measure, and especially how this interpretation has been portrayed in the media.  As it turns out, the "after" subjects did not have depressed REEs when compared to others at that weight!  

I propose a "what if it's all been a big fat super-obese lie" question.  What if -- instead of the body fighting to maintain some re-set super-obese setpoint by "adapting" to calorie restriction and weight loss with a depressed metabolic rate  ... What if it is the super-obese who are exhibiting a metabolic adaptation to their chronically overfed state?

Some Background:

I tweeted out my last post, Is Metabolic Adaptation Real?, as follows:

A back and forth ensued with Kevin Hall, the NIH researcher who was principal on the Biggest Loser Regain study.  Before I get to that, I have to say a few words about The Obesity Society (TOS) which published that study (Persistent metabolic adaptation 6 years after “The Biggest Loser” competition) and another by Rosenbaum and Leibel (Models of energy homeostasis in response to maintenance of reduced body weight) in the July 2016 edition of their journal, Obesity.   Along with these two studies, the journal editors Eric Ravussin and Donna H. Ryan (both from Pennington) penned an editorial:  Energy expenditure and weight control: Is the biggest loser the best loser?   I think this gets my award for the most tone deaf, defeatist pile of I-don't-even-know-what-to-call-it published in recent years ... and that includes a long list of dubious studies and editorials from science journalists, diet doctors, PharmDs,  and phoned-in PhDs.  

Now TOS appears to be comprised of both doctors who treat obesity and researchers.  The purported purpose of their joint shindig with ASMBS (bariatric surgery group) is to marry research findings with practical treatment applications for this "disease".    So it is especially painful to see Ravussin and Ryan flat out misrepresent what either of those two studies showed ... not knowing Ryan, I would say Ravussin especially, as he has been principal researcher on countless studies.   I'll tackle that editorial one of these days, if I can contain my anger 😮 , but here's the major point to this post -- point 3 of 6 in the editorial:
The major drivers for weight regain are probably physiological responses to weight loss: (a) the persistence of a very low RMR, 700 kcal/day in absolute value and still 500 kcal/day after adjusting for the lost weight; (b) the lower energy cost of all weight-bearing activities; and (c) the likely persistence of increased orexigenic signals in concert with decreased anorexic hormones.
And yet, as I was reminded in my Twitter exchange with Kevin Hall, point (a) was not even made in that study!   Here's the exchange expanded and screen capped to the best of my ability.  There may be a tweet or two missing, but it includes the important stuff (you should be able to click and enlarge to read).  

So it just so happens that the expanded tweet in this exchange is the most relevant.  From the paper -- in the Results part of the Abstract even, not buried in the discussion!
Weight regain was not significantly correlated with metabolic adaptation at the competition's end (r = −0.1, P = 0.75), but those subjects maintaining greater weight loss at 6 years also experienced greater concurrent metabolic slowing (r = 0.59, P = 0.025).
How can you read that and then blame regain on this so-called adaptation?  I just don't see how that is!!   

Defining Metabolic Adaptation:

The remainder of the Twitter exchange goes more to the point of what metabolic adaptation is.  As I understand Hall now, he is talking about for the individual, from their super-obese starting point.  He is saying that the REE measured at the reduced weight is lower than would be predicted by their weight loss.  He is saying it is lower than how it would be predicted from baseline.

I could see if they did some calculations using the actual weight loss (and composition) into some model -- e.g. for each pound of fat lost RMR could be expected to decline 5 kcal ... or something like that.  This would make sense.  But this is not what they did!  Here is the original study of the Week 6 and 30 data.
To account for the altered body weight and composition, the predicted RMR at wk 6 and 30 was calculated according to the following equation developed using baseline data:
RMR (kilocalories per day)
= 1241 kcal/d + 19.2 (FFM) + 1.8 (FM) − 9.8 (age) + 404 (for males) (R2 = 0.85)
They are using a regression equation developed from baseline data for just those widely divergent super-obese contestants!  According to Hall, the RMRs measured at baseline were a little high compared to established models like Mifflin-St. Jeor.   Now established models have few data points up in the super-obese range, but there were several of the women in particular transitioning from the mid-high 200s to the mid-high 100s.  In the study, instead of using something like M-SJ with caveats for how well this targeted their baseline metabolic rate, they rather implemented a regression line that included men weight more than 400 lbs.   The average baseline RMR was over 2600 cal/day!!!!

I wonder had they created a regression on just body weight age and gender, if this regression would have over-predicted at all.  After all, they lost more than 80% of their weight as fat mass, "preserving" the lean -- that's almost a 10X calorie factor in their regression used!  But that aside ...

I had first noticed that something was "off" back when the original study came out.  Before I had even looked at what the existing models would predict for those contestants, it clicked when revisiting another study bearing Hall's name: the first of his recent LC vs. LF metabolic ward studies.   Below left are the baseline characteristics -- the "before" -- subjects in that study.  As you can see, they are slightly more obese on average than TBLers at 30 weeks (on right).  And they have a slightly lower average metabolic rate.  Before.  In all their diseased glory [/snarkasm].

And this is the baseline data for reference 15 in the TBL Regain study

Their BMIs were closer to the average of TBLers after the 6 years, and yet the women (so not as good a comparison to the mixed gender group in both Hall studies) had metabolic rates considered to be "adapted" or depressed in TBL.  At the time I noticed this, I looked at several other studies.  Let's add in the info for the Paleo/Nordic study that I'll be linking to in a moment (again, just women).

Here we had a BMI similar to 30 weeks, and REEs are well below the average in TBLers, though this population was also older.

Another Expert Weighed In - Dr. Yoni Freedhoff

A few years back now I addressed the topic of appropriate caloric intake.  After seeing measurements in study after study after study ... and recalling how relatively little I used to eat growing up a lean kid.  The LC-community and general "you aren't eating enough" nonsense over what constitutes "starvation" calories is so very warped.   Dr. Yoni Freedhoff commented on that post, and there was a short exchange to confirm his comments:

Freedhoff has actually measured the RMRs of, no doubt, countless patients at this point, and I see no reason for him to distort things on this topic (unlike someone like Fung who makes all manner of stuff up, so I cannot take anything he says about people he supposedly treats seriously).    By and large, the super-obese tend to burn more calories at rest than predicted by standard equations.  This is also what Hall and colleagues saw in the Biggest Losers.  

So what Hall is saying is that the reduction in metabolic rate, based on a likely higher-than-normal RMR, exceeds that predicted for the weight loss alone.  What I'm saying is that this is not what we should be focusing on when looking at metabolic adaptations in obesity.  It's been acknowledged that the RMRs measured "after" were NOT significantly reduced compared with predictions of validated models.    

A 150 lb woman who used to weigh 275 lbs does not have a lower metabolic rate than a 150 lb woman who never became obese.  Does it happen to some individuals?  Yes, and perhaps.  But the totality of the scientific evidence simply does not support the idea that the body "fights back" and defends the higher weight by becoming uber thrifty with calories.    

Super-Obese Metabolic Adaptation Makes Sense!

What if all of this adaptation talk is obscuring the reality that the super-obese eat a ton of food.  They do.  I did.  This is extremely easy to do in our obesogenic environment, especially if you eat out or take out a lot, which was my nemesis.   It's not always a lot (volume) of food, or what is considered a huge portion these days, but it is very easy to consume north of 3000 cal/day with not a lot of food, especially if your diet contains one or more of the following:  soda, sugary/fatty coffees and chais, ice cream shake smoothies, booze.  It is very easy if you do any snacking at all on the usual suspects.  

Obesity -- the storage of surplus energy -- is NOT a pathological process in most individuals.  Certain individuals can store that fat in different ways and disproportionally in certain regions, and some of this is genetic disease (one lady I chatted with on Twitter has lipedema and lymphedema).  At some point, adipose tissue can become "sick" leading to development of other issues, but we have tests for the ensuing hypertension, dyslipedemia and hyperglycemia and a name for it:  metabolic syndrome.  But obesity in and of itself is the body behaving normally.   Now 30 lbs looks different on different people, but I would only need to gain 30 lbs to go from the highest normal weight for my height by BMI (24.9 = 145 lbs) to obese by BMI (30 = 175 lbs).  On my body, even back starting from normal weight, that was not pathological fatness.   Policies and paradigms are being established based on the super-obese (rates of which are sky-rocketing far in excess of obesity-in-general, while overweight has remained fairly constant), and this really is misguided in my opinion.

When you chronically eat in excess of your needs at a normal weight, you burn fuels according to a heirarchy that is based on the body's ability to store the components of that food.  Alcohol, protein, carbs and then fat.  Chronic long-term excesses are stored in adipose tissue, and on the SAD or even the so-called "low fat" (30%) diet, these excesses come largely from dietary fat.    At some point, it seems the body begins to store even some of that protein (see this post).  The obese have higher levels of fat stored within muscle cells (intramyocellular lipid/triglycerides IMCL or IMCT) -- not only have they filled up the bank, they are filling up the wallets and purses and tucking stuff under mattresses!   The fat tissue is likely somewhat sick, but this doesn't even appear to be the overt case for many of the TBL contestants in that study.  Still, all stores are perpetually topped off and the limits of adipose storage are being pushed.  

In such a state, in the presence of continual high energy intake, it would make sense for the obese individual's body to bump up the RMR to "throw off" some of that excess energy it no longer has any place to put!  The respiratory quotients -- RQ: a measure of substrate utilization -- were reported to be a bit low at baseline.  Lower RQ indicates burning of fat.   

So we have a mechanism and the evidence to support the idea of a super-obese metabolic edge.  When you are no longer eating in persistent surplus for anything resembling a normal weight, why would you expect to maintain this "edge"?   Maybe that edge was around 500 calories ... which for the Biggest Losers was 13% of their average baseline TDEE (and intake) of 3900 cal/day.  Maybe it was only a few hundred in some.  Maybe the predicted RMRs were further "inflated" because of the retention of FFM and the regression equation used.

Moving Forward ...

Our national and global dialog on obesity is horribly broken.

The bottom line I got from the two studies on Biggest Loser contestants is that they got obese, as all do, (as I did), consuming a LOT of calories.  They still had a high TDEE at 30 weeks when their average BMI was reduced from almost 50 to just at the threshold for obesity.  Their average RMR at 30 weeks was not low for their final body sizes, and averaged a respectable 1750 calories/day.    I reject using that 6 year study for any scientific conclusions regarding metabolic adaptation because there were too many variables that were not controlled for or even considered.   In the end, there was NO CORRELATION between adaptation and regain.   So where did the New York Times get its headlines?

As noted by Hall himself, these participants are not representative of the population as a whole, and their results not generalizable.  This is why I called the study I blogged on a "better study".  It was done on a more generalizable population (albeit only women).  But it was also done with greater monitoring of the subjects throughout almost a year.    What it showed should be comforting to the mildly to moderately obese population that is thinking about doing something to reverse their weight status.  The only thing more daunting than facing a period of time dedicated to losing a lot of weight, is doing so with the fear that it will all be for naught anyway and you're destined to put it back on!

Whatever "metabolic adaptation" seen for losses of 100, 200 or more pounds likely do not translate to the mildly obese, many of whom (especially if shorter) need to lose as few as 30 lbs to become not just overweight, but normal weight.  I think the idea of losing a "metabolic advantage" from being super obese makes far more sense squared with the entirety of the evidence.   That is likely the biggest issue the super-obese face.  At my heaviest I was weight stable eating whatever I wanted and didn't seem to gain more.  Perhaps this is the biggest hurdle in reversing super-obesity.

It is simply not true that dieting causes your metabolic rate to permanently tank so that once you've been obese -- of any magnitude -- you will forever more need to eat even less than you did before you became so, or your thinner counterparts who never became obese.   This is not to say that some will experience slowed metabolic rate, but it's not a given that your body is trying to defend an obese state.   

Whatever the metabolic hand you've been dealt, wouldn't it be nice if at least a diagnosis of this "disease" came with automatic testing for metabolic rate??  Take the guess work out of it for people.  Measure before.  Measure during (if a lot of weight, several times).  Measure after.  This is mighty empowering to those who choose to face reality.  The broken metabolism, stretched rubber band, holding a beach ball under water stuff ... not so much.

It seems to me that The Obesity Society is leading the way in pushing this disease model for obesity, and doing so by pushing the narrative in their peer-review journal.  Ravussin was a co-author on the first two metabolic studies involving the Biggest Losers.   If space were an issue in the discussion, surely he was involved in some initial brainstorming over the results before nuances got cut out?  

It seems unconscionable to me that we are not having an honest discussion about this.   It's bad enough that you have predatory diet-promoting doctors selling all manner of hope and "solutions" to the obese under the guise of new or *better* science.  The Ludwigs and Hymans of the world, laughing along with Gary Taubes, blaming low calorie diets for obesity, and promoting olive oil dressing in avocados on Dr. Oz to keep hunger at bay, because fat won't make you fat, and carbs are starving you internally and keeping you from burning fat.  That is bad enough.

It is worse when you have a society of professional cheerleaders wanting to hang a disease label on you and then distort facts to convince you that it's OK because (a) it's not your fault -- none of it, ever--, and (b) there's nothing we can do for you anyway except bandaids (anemic weight loss drugs) and sutures.  Don't mind us while we argue amongst ourselves over the role of diet and exercise in all of this, right?   This goes against all of what the scientific evidence has shown all these many years.  We can no longer accept that a 350 lb person claiming to eat 1350 calories/day is being truthful -- perhaps they are lying to themselves and thus don't intentionally lie to everyone else, but that is another issue.   We know that the ability to burn fat is not suppressed, because they can burn it like crazy under certain circumstances.  They have enough mitochondria and access to plenty of fat.  Even The Biggest Losers -- whom countercults insist is "doing it wrong" in every way -- didn't actually break their metabolisms!

The medical establishment is simply not ever going to be able to solve the non-medical aspects of this, and seem largely disinterested in solving the problem for the small percentage who are truly suffering from a genetic disorder.  But cheer up, we're upping our empathy game and awareness.  It's all good!   We can manage this together ... whatever that means.  You just have to believe a distortion of the scientific evidence.  😒

presented at Obesity Week 2016

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