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Monday, August 29, 2011

Fat Metabolism in Formerly Obese Women: Part I Resting Metabolic Rate

Wow!  Many recent events and blog posts about the web have hit a lot of my deja vu "memory nerves".  This has had me going to the draft bin looking for what it is I'm reminded of.  This one was sparked by being linked to a series discussing hunger and satiety over at gnolls.org.  I'm going to link you to Part IV as that is where the paper I'm discussing in this post/series is cited, but J. Stanton  has links to other installments.  

So, most of this current post has been in my hopper since February!  But this article/study has actually been "on my plate" longer still, as the PDF was downloaded to my HD back in June 2010 after reading James Krieger's  piece on the ease of regain.   I'm going to break this up into three parts:  
  • Part I dealing just with resting energy expenditure and its contribution to our overall "metabolic rates".  
  • Part II will deal with the resting metabolism in terms of contributions of fat and carbohydrate
  • Part III will address expenditure and substrate usage during and after exercise.  





Fat metabolism in formerly obese women
Ranneries, et.al.  AJP-Endo, 1998.

Overview:
An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C).
Measured:
  • Lipolysis in the periumbilical subcutaneous adipose tissue
  • Whole body energy expenditure (EE)
  • Substrate oxidation rates (glucose, fatty acids)
... fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.
Subjects:
FO*  n=7:  Body weights in excess of 120% normal weight when obese.  Body weights reduced by conventional CRD to 110% normal weight, weight stable for at least 2 months.eight.  Weight losses were in excess of 10% bw and ranged from 15-20kg (33-44 lbs).
C  n=8:  Never obese subjects who were matched in terms of various parameters such as weight, BMI, body composition, etc.   These were well matched as can be seen in Table 1.
*Note:  Average weight of all subjects was around 140 lbs.  Which means that when obese, the FO's weighed in the 170-185 lb range.  When I put the average height and these weights into a standard BMI calculator using the average weight as baseline and adding 15 or 20 kg, the FO were not technically obese on average (BMI <30), or borderline.  I'm trying to figure a way that each of the 7 individuals could be technically obese (e.g. each with individual BMI of at least 30) given this information.  But I do think it is worth noting we weren't talking morbid obesity here and likely most of them were sub-200 lbs to start.  
All subjects were fasted overnight, and had not engaged in strenuous activity for three days prior to the study.  They also consumed a 15% protein, 30% fat, 55% carb standard diet (provided to them free of charge) during those three days.  They "sat quietly" for 15 minutes prior to the baseline measurement which is the only data I'll be discussing in this installment.



Differences in Resting Energy Expenditure, REE:

Note:  REE is often referred to as basal metabolic rate, BMR, or resting metabolic rate, RMR

The results:  
Control:  4.88 ± 0.74   (n=8)               Formerly Obese:  3.77 ± 1.07  (n=7)

The average REE of the formerly obese group was thus 23% less than that of the controls.   Let's do the calculation for basal energy expenditure per day.
 

Wow!  That's a pretty whopping (and depressing) difference of almost 400 cal/day.  This is perfect fodder for the HAES/Dr. Linda Bacon's of the world to demonstrate just how futile an effort losing weight is.  And don't be fooled, low carbers out there, you are not immune to this metabolic adaptation either.  Because if you've lost weight you've done it by establishing a sustained caloric deficit, even if you did so without conscious effort.  

The REE also seems to be rather high for the control group in light of average intakes of around 1550 cal/day for American women in the 1970's.  But I would remind readers that the controls were not lean, they were matched to the FO's who were still at 110% of normal weight.  

I would also note that while REE is generally ~60% of TDEE, this is perhaps a book-keeping error in that the energy we expend in activity -- e.g. walking for an hour -- includes that we would have expended at rest.  I note that the caloric levels of the diet provided to all subjects for the three days prior to the study was:
... computed from equations in which FFM and FM are used to predict 24-h energy expenditure (EE) based on previous measurements in our respiration chambers and multiplied by 1.12 to account for a higher free-living activity.
In other words, my REE calculations for calories per day are essentially equivalent to the TDEE (total daily energy expenditure) for a very sedentary person.  I would note (as bolded), that the factor used for "accounting for free-living activity" -- e.g. not being confined to a metabolic chamber -- amounts to only 12% increase.  Using that factor, we can surmise the TDEE's are 1879 and 1453 cal/day for C and FO respectively.  So a never obese woman can consume almost 1900 cal/day to weigh on average just under 140 lbs, while a formerly obese woman must consume under 1500 cal/day to maintain that same weight.  Still not comforting, but we -- especially us women -- have GOT to get away from formulaic expenditure estimates based on just total weight, and this notion that 1500 cal/day is some sort of starvation ration.  It is not!

Continuing with a look at the data, I note that the variability is also considerable.  Those "±" are for the standard deviation.  It is unfortunate that the individual values were not presented in such a small study, or at least the range of values (min,max) wasn't presented.  With such small samples trying to derive this sort of thing is an exercise in futility.    However one thing that did jump out to me was the considerable difference in the variability of the data with SD of 1.07 for FO (n=7) vs. only 0.74 for C (n=8).  

Why does she keep pointing out the n's here?  Because here is the formula for standard deviation for a sample.  The ∑ term is the "sum of the squares of the deviations".  To manually calculate the SD, as those of my age in science/engineering programs actually had to do innumerable times during the course of our studies, you first calculate the mean (that's the x with the bar over the top).  Then each individual deviation is the individual value (x) - mean.  Some of these will be positive and some negative, however when we square them all values become positive. Then we add them up, hence "sum of the squares of the deviations", let's use "d" for individual deviation.
  I note SD-squared is a statistical value itself, called the variance.
We obtain:   C:  3.83     FO:  6.87
And let's standardize that per data point: Giving:    C:  0.358        FO:  0.981

Now, let me be the first to point out that this isn't normal statistical practice because the investigators had the individual data points and could have provided them in tabular or graphic form.  But since we don't have that to work with, I'm just manipulating things backwards to give you an idea of the variability of the data sets.  Clearly we have much higher variability for the FO than the C.  This is somewhat evident in the differing SD's of 1.07 and 0.64 for FO & C respectively, but I believe expressed as an "average" of the 0.981 and 0.358 for FO & C respectively, it is more representative of the variation in REE amongst FO vs. never obese.  I'll address this in some thoughts at the end of this post.


There are some caveats mentioned by the authors that are easily overlooked when one focuses on tabulated data but are also important to the interpretation of the data.  I'll break it out in bullet point form with comments interspersed:

  • REE did not correlate significantly with FFM (r = 0.54, P = 0.06), which could be attributed to the low variability in FFM among the subjects (REE = 4%). 

Because there is a well established correlation between fat free mass (FFM, aka lean body mass - LBM) and REE/RMR/BMR,  we would expect to see one in this study.  However the fact that we do not is easily attributed to the study design where subjects of similar weight and body weight distribution were included.

  • A positive correlation existed between REE and VO2 max  (r = 0.62, P = 0.02).
  • Most of the difference in REE between FO and C could be accounted for by differences in VO2 max 
The controls had higher VO2 max  than the formerly obese.  The study said nothing about the exercise status of the groups, however it was stated that the weight loss was achieved through conventional energy restriction.  Therefore we can presume no formal exercise.   
  • After adjustment for differences in both FFM and VO2 max the group difference was attenuated
FO: 4.07 ± 0.65      C: 4.64 ± 0.81 kJ       (P = 0.19)

I often leave statistical notations like P-values out of posts to keep them more readable to the general audience.  However I'm including them here because this is probably the most important piece of information as regards metabolic adaptation in this study.  The term "adjusted for" means essentially controlling for those parameters.  When the expenditure was essentially "standardized" to some baseline FFM and VO2 max , the difference between groups was more than just "attenuated" as the authors state, it is essentially statistically obliterated.  Common P-values for demonstrating statistical significance are 0.05, 0.02, 0.01, 0.001.  These correspond to the probabilities (multiply P-value times 100) that the difference could have been produced by random selection.   The smaller the P-value, the more sure the researcher is that the results they are reporting are due to the variable being investigated.  Here, a P-value of 0.19 is statistically untenable.  In other words, REE/FFM/VO2 max was statistically the same in FO v. C although were this the presentation, there may have been some wording to the effect that they were similar but trended towards being lower in the formerly obese.

I would love to see the pooled data of the 15 subjects here.  It sounds like if we treated these women as individuals, the predictor of REE would be a combination of the long-established FFM correlation and VO2max.


Implications for the Formerly Obese Individual and Long Term Maintenance ... Some Thoughts

Many who read here also read at many of the blogs out there that I do.  There's no need to name names here, but I think we can all agree that the comments of late have been swamped a bit more than usual with long n=1 accounts.  I'm certainly among those who are trying to reconcile the results of all of these types of studies with our personal experiences.  One tendency, that is all-too-human, but should be resisted at all costs, is to tend to believe the validity of those studies that agree with our personal experiences and write-off as flawed any of those that are in conflict with same.  I'm going to be doing a post on some realistic ways to view these studies to assist in your personal journey or dietary/lifestyle strategies and what may work better for you.  

Clearly here we see that the variability in the FO group (however it is looked at, but let's look at mean and SD of 3.77 ± 1.07) we see that as a percentage, the SD is 28% of the mean.  This is often called the CV = coefficient of variation.  We also revisit the change in mean REE.  That is if we take the C = 4.88 value as some sort of baseline energy expenditure, the 3.77 for the FO is 23% lower.  See where I'm going here?  I would not be surprised to find that one FO subject had a higher REE than all of the controls.  Note, I'm not speculating that this occurred, just that mathematically it is entirely possible and would not require some fluke. So if someone has lost a lot of weight and they are able to maintain eating 2500 cal/day, I say hooray for you and don't look a gift horse in the mouth, but your personal experience is not in conflict with the results here.  Also even if you've never been obese and you have to eat only 1500 cal/day or you start gaining, I say "I'm sorry", but you also don't render these results moot.  This is also part of the reason for my tedious somewhat unorthodox backwards stats in the main part of the post.  To show the variability in a different way that perhaps gets it across.

So what does the REE data from this study tell us, and how can we use it to our advantage?  Well for starters, it is yet another one in likely thousands of studies that demonstrate metabolic adaptation -- that sustained caloric restriction (intentional or otherwise) and substantial fat loss leads to reduced metabolic rate.  Not in everyone to the same extent, but almost invariably.  There are obesity clinics and the like where you can get your REE measured by a 10 min COtest.  If you are obese and can't lose, it would behoove you to have that measured so you know the starting point.  If you've hit a long plateau, you might not want to know the answer ... but I would also recommend such a test if you're frustrated by trying all sorts of things and not seeing more results.  I say "you may not want to know", because you may well be one of those folks for whom the REE drops more than average.  In any case, that "is what it is" and knowing what you're working with is better than flailing around in the dark.  

Studies like this also stress how you can't go back.  No no no.  You'll never ever be able to eat like you used to and maintain your more slender self.  And it may not be fair, but if, like most of us, your weight loss has slowed in later stages and plateaued out, you will have to keep doing what you're doing to maintain.  Your body has achieved its new energy balance point!  And, you may not ever be able to eat like you could have had you never gotten obese.  Lots of things in life are unfair .....

What if you're not happy with that?   Well first, before you let panic set in, I think we need to keep in mind a few things about this study.  Before we get too depressed about it's implications for the "damaged metabolism" let's consider the time frames here.  These women were only weight stable after significant losses for at least 2 months.  If they lost weight by conventional energy restriction we're talking a minimum of 4 months (2 lb/wk) to as long as 11 (1 lb/wk) ... and that's for steady losses with 100% compliance.  A mere minimum 8 weeks after "reaching goal" seems insufficient.   Also, again here the individual data would be so much more helpful  even though the numbers are too small to draw any meaningful inferences.  I would love to find a study following reduced obese over a few years measuring REE with maintenance.  I don't do accurate enough record keeping to really say, but I'm pretty sure my metabolism has rebounded a bit over the past years.  I would like to see the energy balance phase to be at least as long as the weight loss phase to compare REE with weight matched controls.  I suspect that the results would differ from what we see here.  

Still ... what have we always known is correlated with metabolic rate?  Lean mass.  What did we learn from this study that was somewhat hidden by the focus on FO vs. C?  That REE is highly correlated with VO2 max. What is VO2 max?  Well, for sure when one does a Google search on this the overwhelming links direct you to sports and fitness sites.  Most simply it is a measure of maximum oxygen usage and related to endurance.   How do you increase it?  Training -- increasing duration of (that old chronic cardio) and/or intensity of activity.  If anyone wants to continue their pipe dreaming that switching to some sort of "fat burning" metabolism will improve their mitochondrial function in spectacular fashion irrespective of activity, I'll not stop you.  But for the rest of you, exercising to increase VO2 max seems like a more rational and, more importantly, effective approach.  Forget the calories burned in the exercise itself, calorie restriction seems to have an impact on VO2 max that manifests itself as a reduced REE.   

I've discussed here before several studies analyzing weight reduction by exercise only, exercise plus diet, diet only, different types of exercise, etc. etc.  It seems clear to me that whoever you are, if you've become obese -- the more obese the worse the problem -- then following prolonged energy deficit accompanying weight loss your REE will be lower.  One tool in that toolbox to prevent regain?  Move more ... period.  And perhaps a strategy to maximize increasing VO2 max  has a whole lot more merit to it than certain gurus would like you to believe.

In Part II  I'll revisit this exercise angle in the context of substrate partitioning in the resting state.

19 comments:

Duffy Pratt said...

Have their been any studies to show whether different weight loss programs might lead to different changes in basal metabolism. What you say here seems to indicate that basal metabolism may not lower as much if weight loss is achieved by increasing exercise? What about other factors? Will the speed of weight reduction make a difference? Is there a difference based on the type of food one eats to lose weight. You seem to suggest that all sustained weight reduction programs will lead to the same, or similar, results. It doesn't seem obvious to me that this should be true, and I'd be interested in hearing about any studies that show it is true (or false).

Also, your recommendations about increasing VO2 Max are very, very simplistic. Only a very limited range of exercises will have any significant effect on VO2 Max. Mostly, they involve repeated sustained interval training (typically 2-5 minute intervals) that are done just below a person's anaerobic threshold. This is very intense exercise, and I don't think anyone is likely to study its impact on the obese, largely because this kind of intense, sustained effort is probably beyond the capabilities of the average obese person.

Light aerobic exercise will have some benefit on VO2 Max, especially for people who are out of shape. Weight lifting and other forms of exercise will have basically no effect on VO2 Max, even though it might help increase metabolic rate by the increase of lean tissue.

markgillespie said...

This recent study which says the same thing regarding VO2max was posted on Lyle's forum recently:

Obesity (Silver Spring). 2011 Aug 11. doi: 10.1038/oby.2011.262. [Epub ahead of print]
Lower Than Predicted Resting Metabolic Rate Is Associated With Severely Impaired Cardiorespiratory Fitness in Obese Individuals.
Miller WM, Spring TJ, Zalesin KC, Kaeding KR, Nori Janosz KE, McCullough PA, Franklin BA.
Source

eulerandothers said...

'Weight lifting and other forms of exercise will have basically no effect on VO2 Max, even though it might help increase metabolic rate by the increase of lean tissue.'

I don't know about increase of lean tissue and a corresponding increase in metabolic rate - which would be useful for someone who remains a couch potato and hopes that lifting weights a few times a week will allow them to burn more at rest.

I think that weight lifting and other forms of exercise build muscle strength and that makes it easier to be active EVEN during the time not spent in the gym. Climbing stairs, walking all the way across the parking lot, moving furniture, pushing a rotary lawn mower: all of these things are daunting when you don't have muscle strength.

Princess Dieter said...

I found tracking my food intake invaluable to the sad, sobering realization that I way below average in caloric burn. I kept using those calorie level tools, and they didn't jive with my tracking. After over a year of tracking what I ate (I am no longer religious, but I may do that again now that I'm way lower in size), I realized I needed noticeably fewer calories than the calculators estimated. I'd gain at levels of so-called "maintenance". At one point, I was noticeing that I'd MAINTAIN at 350 to 400 calories FEWER than what the general calculators said was maintenance for my size.

Now, I didn't like that, and one person does not a study make. It was just what I needed to learn and accept to finally lose weight more steadily. I had to cut calories DRASTICALLY lower than I desired. Then I lost at a steady pace.

I know I'll never be able to eat even at the level my never-obese sisters do. One sister used to maintain at 2000 calories AT MY AGE. She's 11 years older and has had to cut back a couple hundred calories, as she started gaining on her usual, happy 2000 daily. No more for her.

Me, I'd regain on 2000, and I'm 183 lbs. I should not be gaining weight at that level, but I will and do. I have to assiduously stay well under. And that's why I don't aim for a thin weight. I could not sustain it. I'd have to eat near-anorexic calories. Sheesh.

But some of us have to face the nasty little truths. I was morbidly obese, and obese for 2+ decades. I ain't normal, metabolically. Maybe never will be (after all , my thyroid ain't coming back to life). BUT....I can figure out what is maintain-able. What I can live with and what I cannot and find the weight I can sustain with some strategy, but not hair-pulling-crazy low-low cals.

Sucks, the unfairness of life, yes?

Evelyn aka CarbSane said...

Hi Princess! Yes, unfair but as some doctors and others will remind us, it's "reality" right? I get very annoyed every time I hear "we can't know the calories in our food" and "we can't know how many calories we expend". Poppycock. The calories in various databases and on labels work pretty darned well, and if one does careful tracking for a long enough time, they can sure as heck figure out how much they can eat.

I think this can be as freeing as it is limiting in some ways as I believe eulerandothers has commented here about. If I know I can eat 1600 cal/day to maintain, then I can eat 1600 cal/day of junk food if I want and know that I won't gain weight, or 1000 cal and lose. And then I can decide if I want to eat 1000 cal of calorie dense food that doesn't fill me up as much or 1000 cal of nutrient but not calorie dense food and not be hungry.

@Duffy: I've got a number of studies on exercise and diet and metabolism that I've blogged on previously and will be referencing in Parts II & III. Less easy would be to provide you with a list of studies on changes in BMR with diet alone. I've yet to come across a study demonstrating either a better preservation of lean mass with LC v. LF, and every study I've ever read that compared diets has shown similar reductions in BMR when measured. If I'd come across one that showed a difference it sure would have caught my attention!

Evelyn aka CarbSane said...

Thanks Mark, I'll look into that!

Evelyn aka CarbSane said...

Here's the link to the article Mark cites. If anyone has access (Mirrorball perhaps?), I would be very interested in the full text!
http://www.nature.com/oby/journal/vaop/ncurrent/full/oby2011262a.html

justjuliebean said...

Well, here's my n=1. I should be able to follow your math, but stats are a bit far out of my realm, so anecdote it is. I used to be resentful about how much I could eat, but I seem to eat much more than your average "dieter", I'd be surprised if I ever eat under 2000 kcal/day, unless I'm ill, or it's the day after Thanksgiving, etc. I don't know how true it is about people, especially overweight/obese, underestimating their calories, or if I'm different, but I try to be honest, at least with myself. You certainly seem to believe that 1500 kcal is a reasonable amt of kcals, and I've not heard you refer to this chronic underreporting. Do you not believe it? Granted, I'm 5'5, and I do spend some quality time at gym, and ride bike for transportation, but I've been obese, and my currently lifestyle isn't really dropping me below BMI = 26, so obviously I haven't figured something out yet. OK, this is off-topic by now, but I'm curious that you don't really account for underreporting, which is supposedly such a global phenomenon? And I wonder if there's some kinda habituation going on with low-cal eating, maybe if I started eating much less, my metabolism would just shift downward, and I'd still be hanging at BMI = 26, just eating less? Just wondering why it seems that I eat so much compared to other FOs

Evelyn aka CarbSane said...

@jjb: I'd be willing to bet your VO2max is higher from the exercise/activity. Unfortunately I never received a reply back from the source of that information on the intakes. If underreporting was involved, it could probably be presumed to be uniform so the increased intake corresponding with the obesity epidemic explains it. I do also believe that an epidemic of "dieting" may well contribute by reducing BMR, especially with yo-yo dieting.

I think if you ate less you'd lose weight. But you'd have to eat less for the rest of your life to stay thinner. Be happy you have more wiggle room than some on that count!

eulerandothers said...

'I think if you ate less you'd lose weight. But you'd have to eat less for the rest of your life to stay thinner.'

This is a part of the Weight Watchers' program. It's a shock to find out that, when you have lost 5 pounds, say, you suddenly are assigned x number fewer Points Plus to 'spend' each day. Man, that's a pisser! Brutal.

I know that at around 2000 calories a day, I lose, steadily, a little less than 1 lb a week. If I'm eating more than that, on average, I'm not losing, on average (I'm up and down and weight loss is erratic, unpredictable and climbing up, not down).

If I'm going to be 50 pounds lighter than I am, I sure should be able to eat just around 2000 calories a day? That doesn't make sense to me. The very fact that I have 50 pounds less on my frame means my metabolism is so stoked I can eat just what I'm eating now? Time will tell, I guess, but I really doubt that.

If I've been EXERCISING all along, now, that would make more sense. But, then, I've been burning calories with exercise, too. My lifestyle changed, in that case! I don't think I can be a 'couch potato' after that without repercussions on the scale.

Diana said...

Maybe there is a way around this: build up lean body mass as much as possible.

http://www.sciencedaily.com/releases/2011/08/110829114706.htm

Admittedly this does take a lot of effort but (OK, n=1 here), the thinner I get the easier it is to move my arse. And the more I want to. I'm never gonna climb Denali, but I see Mt. Washington in my gunsights.

Diana said...

Forgive me if I am repeating myself - I got caught in the Hurricane and I am still not quite on this earth.

On eating less forever - I realize this isn't a practical approach for everyday life, but here's a little n=1. I ate much more than I have eaten for the past 3 months last week, for that matter, than I usually ate (apart) from binges, ever. Three solid meals a day. Some of the stuff "very bad" carbs - including trail mix, Twix bars, yoghurt covered raisins, pasta, ice cream....beer.

I honestly don't know how many calories a day I was eating but I wouldn't be surprised if it was 2200-2500, a lot for me. And bad, bad stuff, Low Carb no-nos.

I maintained my weight of about 140 pounds. I'm not skinny (yet) but the point is, I did maintain. I was doing hard trail work, and one day I took an 8 mile hike, rather difficult.

So what's the relevance? You CAN eat more - if you do hard labor in return, not gym stuff. Modern people associate exercise with the gym. I say, 'bah humbug', that's for sissies.

If you work your ass off, you can eat more. If you really work your ass off, you can eat more and lose weight. (But you risk injury.)

eulerandothers said...

'the thinner I get the easier it is to move my arse. And the more I want to.'

Ditto. Make that n=2!

Diana said...

@euler - wanna hike Mt. Washington w/me next summer?

Sorry - I did repeat myself. I got home 2 days later than expected due to hurricane.

eulerandothers said...

'wanna hike Mt. Washington w/me next summer?'

I'm pretty sure you are a good hiker and I would have a hard time keeping up with you!

My Blog said...

Hmmm, I do not think 1500 calories is too small. I recently started tracking calories because my Paleo diet was not performing the magic it was supposed to. Well, aside from it being a very healthy and nourishing diet (that I still eat), it turns out you can eat too much grass fed beef and almond butter. LOL! Anyways, I started tracking religiously (because I'm a perfectionist) and with my Crossfit workout several days a week, I still feel satisfied with about 1500-1600 calories a day. I am 5'7" and about 150#. Down from 162 at the beginning of summer. Anyways, I guess I'm just agreeing with your post :)

Evelyn aka CarbSane said...

Welcome to the Asylum MB! It's interesting to see a slightly taller woman (I presume since this post was about women) reporting this sort of intake for a change.

Jamie said...

Thanks for the welcome :)

I updated my google name, so that I'm no longer "my blog" :)

Jamie

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