The Middle Ground?

This started out as a comment to my friend Helen from Jimmy Moore's LLVLC discussion board over at my personal blog.  Here's the post: When to Eat .  That post was mostly thinking out loud about strategies for weight maintenance.

I see an Eating Timing/Quantity Spectrum:  ad libitum (eat when hungry, stop when satisfied) - to - strictly structured/controlled.  I postulate that in the middle of this spectrum, which is where many in our modern world "live", is where weight maintenance issues arise due to overeating.

I had another discussion about a different middle ground with Peter of Hyperlipid fame in the comments on this thread:  VLC and Insulin Resistance.   I posited that  "Humans seem to do better at the "moderate end of the extremes" if that makes any sense but not so much in the middle. Our appetite signalling and metabolic controls seem ill equipped to handle any significant carb + fat load simultaneously."


I blogged some thoughts on Fats & Carbs  in a companion post.  Basically I envision an Energy Macronutrient Spectrum ranging from VLC/VHF - to - VHC/VLF, and our body's ineffectual processing of mixed fuels and inefficient signalling resulting in overeating of the CF foods in the middle.


I would like to marry these two "Middle Ground = Danger Will Robinson" theories in this post.

How do these two middle ground theories relate?  Firstly, I'm going to leave protein out of the discussion here except to say that IMO, the vast majority of us cannot sustain a proper ad libitum diet without sufficient protein.   It is probably protein insufficiency rather than fat "deprivation" that precipitates LF diet failure.  But I digress ...

On the macronutrient spectrum -- especially if one stays away from the LC or LF equivalents to CF foods -- at either end of the spectrum we can probably happily exist on ad libitum "lite".  By that I mean there will probably be occasions when we eat for reasons other than genuine hunger, but it is pretty difficult to overeat (calorically speaking) either extreme.  This bears out in studying various cultures.   IMHO, it is the moderate end of these extremes that works best.  Too stringently low fat and health suffers because we need fats ... too stringently low carb is just unsustainable for many people, and I have reservations as to the long term healthfulness of a VLC/ketogenic diet.  There's something about your body thinking it is starving while awash in dietary fat for the long haul that doesn't square fully with me.  Again, I digress...

If one wants to exist somewhere in the middle of this spectrum, they probably have to go to the structured/controlled end of the timing/consumption spectrum.  I believe this is why Zone and similar plans tend to measure up rather poorly in diet comparisons.  Lots of calculating involved -- and I'm not so sure Zone prescription for the mix at each meal is best, rather overall mix for the day may be better.  One must go "extreme" on one spectrum in order to balance the "middle" of the other.

But regardless of the plan, if lifestyle forces some eating when you are not hungry on any sort of regular basis, you will likely have to shift to the "structured" side of the intake spectrum.  This is an especially difficult thing for many low carbers to swallow because LC plans tend to be ad libitum.  Consider if you make the same breakfast every day (as many do), you are moving to the middle ... perhaps without even realizing it.  Eating at any time other than when your body tells you to will require at least mindful compensation at other times.  You're in the middle ground on this spectrum and so the advantages of living on the edge of the carb/fat spectrum diminish.  Now the "naturally thin" seem to have better compensation mechanisms.  If they eat a big lunch, they'll spontaneously compensate by eating a small dinner or none at all.  Most of us don't seem to be able to do that without a degree of mindfulness.   FWIW, I think this is why many successful LC'ers tend to plateau out at higher weights than originally desired.  Ad libitum in a modern world is difficult to be true to.

Trying to "live" in the middle of both spectra, which I contend to be most Western diets complete with convenience/prepared foods and liquid calories, is a recipe for disaster ... and we are seeing the results.  CF foods are bad enough if we try to listen to our appetite/satiety signaling because they are weak on a satiety:calorie ratio.  But throw in that these foods are frequently consumed when we are "told" to eat (never skip breakfast!  never skip a meal!  it's break time!) and often in portions larger than we would self-select, and we're totally mucking it up in the middle.

Separating Fats & Carbs

Just some musings on carbohydrates and fats, but with a scientific basis so put it here.

Personally I believe the obesity epidemic can be blamed primarily on two phenomena:

1.  The abundance of high calorie foods high in fats & carbs (I'll call them CF) in ever larger portions, and

2.  Liquid calories loaded with sugar and/or fat

To prevent obesity my solution is simple:  Keep the fats and carbs separate.  If you're going to eat carbohydrate, eat it with lean protein and/or in whole form so you get sufficient fiber.  Go easy on the fat.  If you're going to eat fat, chances are it is attached to protein, forgo the carbs.  If you simply must eat CF foods, rely on portion control/calorie counting and not on satiety to determine how much you eat.  Keep the total caloric load low, perhaps in the 2-300 cal range, to keep the unnatural assault on your metabolism to a minimum.  

My reasons for this are twofold:

1.  Our paleolithic ancestors, from whom we differ very little genetically, did not have access to foods that were rich in both lipid and carb content simultaneously.  I don't envision Paleo dude saved up his tubers to cook in rendered wild boar fat to plate tuber fries with his boar ribs and a side of some veggie also cooked in boar fat.  It seems far more likely that  Paleo dude ate the tubers if in abundance perhaps even delaying the need for a hunt, or saved those tubers for a rainy day when a kill was available for the eating.   Paleo dude was mostly an opportunistic eater in a scarce world.  Obesity was not a problem nor did Paleo chick worry over a little belly roll.  We are programmed to store energy in its most efficient form (lipid) in amounts that are seemingly unlimited.  There would have been no evolutionary advantage to not being able to store energy, or not wanting to partake in this energy source during times of abundance to save for times of scarcity.    There is no physiological reason to limit lipid intake on any given day.  I see no reason to doubt Eaton's work indicating that Paleos ate a relatively low fat diet.  Further underlining the need for taking it while they could get it -- e.g. overconsumption one day if necessary -- and weak signaling at best.  Bottom line, our metabolisms seem designed to switch between fuels depending which was more available, not deal with being bombarded by mixed fuels.

(2) As outlined in Nutrient Fates After Absorption  dietary intake of protein and carbohydrate share the following in common:

(a) they invoke an insulin response

(b) they are on the order in terms of quantity with the body's storage capacity (nitrogen "pool" and glycogen)

(c) their intake stimulates their metabolism (protein synthesis, oxidation)

(d) their absorbed form is as metabolic substrate (amino acid, glucose)

As such, our hormonal signaling is tightly attuned to intake of these macronutrients to maintain levels in a relatively narrow window.  Dietary fat, OTOH, is

(a) once absorbed, packaged as triglycerides in chylomicrons and transported mostly to the adipose tissue for immediate storage.

(b) as chylos, the absorbed form is not the metabolic substrate for lipids, that being free fatty acids (NEFA/FFA).

(c) in quantity, orders of magnitude less than total stored lipid even in the leanest of humans

(d) can virtually be stored without limit thus eliminating any need to limit intake in one feeding

Circulating NEFA levels are controlled indirectly by release from storage.  Dietary fat does not significantly contribute directly to the levels of this energy source.  My take-away message from the post/article is that our appetite/satiety signals are finely attuned to intakes of carb and protein out of necessity to maintain structure and storage/circulating levels within a relatively narrow range.  Our metabolisms change remarkably within 24-48 hrs of deprivation.  Lipid storage, even on a lean person, can last weeks (or more).  Even gorging on fat is a drop in the bucket of the amount of lipid we store (again, even in the lean), so there's no need to limit this in the short term.  Fat mass regulation seems almost independent of dietary fat when you think about it.

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So, whenever I hear the query "Why do we overeat", in many cases it is a passive process.  Our bodies were not made to handle the caloric punch of CF foods, so we tend to eat more calories before the stop signals go up were we consuming just carbs (usually with lots of fiber) or fats (usually with lots of protein).

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Over on the personal blog ( When to Eat ), Helen wondered about separating carbs and fats on a daily basis -- e.g. alternating high fat day(s) with high carb day(s).  This was actually the impetus for this post because my reply became too lengthy for the comments feature here to handle.  In any case, here are my thoughts on that:

Let's say during the day I have a fatty breakfast and a carby dinner or a carby breakfast and a fatty dinner.  Either way, if I'm consuming basically maintenance-caloric levels of these foods, my metabolism will do a bit of switching up within its normal mode.  After carbs, lipid oxidation will be down-regulated and the carbs burnt off or converted to glycogen (see that Nutrient Fate link), but as the glucose is "cleared", lipid oxidation ramps up again.  After fats, lipid oxidation remains as it was.  If there's no to minimal carb in the meal, insulin is likely low so NEFA are released from the fat cells to replenish the IMCL being "burnt".  The metabolism is "normal".  

It takes a few days, however, for the body to transition to a "fat burning" (low carb) metabolism.  Our bodies are inefficient during this transition -- spilling ketones, etc.  This can probably be used to our advantage to get a little more out of weight loss, but is it healthy?  I don't have the answer to that and I'll try to put it on my "to do list" to look into.  My educated guess is that so long as you're not overdoing it caloriewise this is probably OK as diacylglycerols and ceramides shouldn't build up.  It takes a while for IMCL to accumulate anyway on an HF diet.  I don't know if it will accumulate if one's "average" diet is HF, even if some days are LF.

From a weight loss perspective, I do feel this switching up was probably responsible for the whooshes I would experience upon returning to LC after carb cheats.  Was this healthy?  Who knows.  I look at it as a trade-off in the end.  Whatever I did to get here, I'm way better off for it now.

I worry more, however, over the transition from a HF day to a HC day.   The switch gets flipped back almost immediately.   I've posted that as little as a single high fat meal can induce IR, and impaired glucose tolerance (IGT) the following day.  If one is not efficiently burning lipids in short HF stints, this could potentially turn the HC day into a "diabetic day".  I've played with a glucose meter to see about this for myself.  Perhaps the fact that I don't eat particularly high fat (as a % or on a gram basis) version of LC, I've not had issues with tolerating carbs.   Meters are cheap, and you can get strips relatively inexpensively too.  Rather than guess, or look to studies to see, testing one's own response to this is probably better.    But I do think alternating days like this has a greater potential for creating issues than mixing it up "separately" throughout the day.  If one experiences a degree of IGT, I think a good bout of exercise between the last high fat meal and the first high carb meal might be all that's needed.

Companion post to follow ....

Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet

Thanks to Leon for finding this :)

Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet

Basically they took two groups of rats and fed them (ad libitum) either a ketogenic diet (KD) or regular chow (CH) for 8 weeks.  Then they switched the diet of the KD group to CH (KD:CH) and continued to feed the rats for an additional 8 weeks.  As this was a rat study, the rats gained weight/grew for the entire 16 week duration of the study.  

The diets:  KD = 5% carb/15% protein/80% fat             CH = 60% carb/23% protein/17% fat

Now I'm not a rat, but I do find these results both interesting and a bit surprising.  Here are the graphics for caloric intake and weight:

caloric intake: 

Surprise #1:  The KD rats consumed pretty consistently fewer calories (although the difference is not noted with an * for statistical significance) for the first 8 weeks and yet gained consistently more weight.  I'm not sure if this difference was stat.sig. either, but it was mentioned in the results:

After 8 weeks of consuming a ketogenic diet, KD rats had increased adiposity and plasma leptin levels, and reduced insulin, as compared to CH controls. 

So much for the insulin-induced fat accumulation theory once again.  And so much for the metabolic advantage -- if anything, this demonstrates an advantage for the high carb diet.  But CS, doesn't this violate calorie balance?  Nope.   I'm sure there's a TEF or RMR change in the KD rats vs. the CH ones that would explain this seemingly nominal discrepancy.  Furthermore, the KD rats had significantly more epididymal fat (one type of visceral fat) than the CH rats.  Is this a good thing for a rat? .....

Surprise #2:  Initially after the switch, the KD rats didn't go on a soaring blood glucose fueled carb binge.  They actually reduced caloric intake significantly in the first week after the switch.  Presumably these animals had a bit of insulin resistance and blood coursing with postprandial glucose during this first week of the abrupt switch.  And yet this didn't send the rats into a carb frenzy.

After that "honeymoon", however, the KD:CH rats increased their caloric intake over the rats who just ate the regular chow diet the whole time.  This increase is consistent but does not become statistically significant until the last three weeks of the study.  Is this an overcompensation for metabolically "starving" for extended periods?

The hormone level results are totally antithetical to the whole insulin/fat accumulation theory.  KD rats had significantly higher leptin and lower insulin levels than the CH rats.  However this would predict lesser adipose accumulation in KD vs. CH right?  Not the case.  The leptin remained elevated for several weeks (4) following the switch for the KD's.  REPEAT:  lower insulin in KD correlated with increased adiposity (visceral at that).

From the discussion:

Whereas KD rats had significantly increased fat pad weights and plasma leptin levels as compared to CH rats, resuming the chow diet prevented a further increase in adiposity and leptin over time. Rats that consumed chow for the entirety of the study increased fat pad weight and leptin to resemble those of KD:CH rats by the end of the study. In addition, plasma insulin levels in KD:CH rats were not different from CH rats one week after returning to the chow diet, although it was significantly increased after 8 weeks of consuming chow after the ketogenic diet.

If I had my druthers:
1.  A third group kept on KD would have been interesting.
2.  Since they started to see this significance towards the end of the study, why not extend it a bit longer?

Personal aside:  Since I adopted my "cheating" method for LC weight loss and maintenance, this result is consistent with my experiences with going off LC.  In the past, I never "gave up" on LC, just strayed from the strict version of it and never got back to it.  I think there was a small honeymoon period whereby everything still fit and I didn't seem to gain so there was no big motivation to jump back gung ho on the wagon.  (I have no idea if the scale said so or not, but I'll go by size and ignore if there was any water fluctuation in there).  However after that brief period I didn't binge but the pounds sure piled back on fast.  The first 100 lb swing occurred in no more than 2 years but could have been mostly accomplished in one!  The second, in roughly the same time frame.  So fast that before I knew it I was back past where I started. I experienced weight losses in the wakes of some of my cheats during my 10 months or so of rapid losses.  I think because for long weekends or a few weeks (vacation) I probably ate less eating higher carb.  But now I'm a smarter cookie.  I know that I cannot continue like that because whatever the cause, I lose my sensitivity to how much I'm eating after a while of consistent carbs.  

The New Low Carb v. Low Fat Study ~ Comments on What Others Are Saying

In response to my previous post, The New Low Carb v. Low Fat Study ~ Much Adieu About Not a Helluvalot!, LynMarie Daye commented as follows:

Have you seen some of the criticisms of this study? I came across a couple of blog articles suggesting that the researchers are biased against low carb diets and manipulated the data to get results more inline with their beliefs. I would love to hear your thoughts on this.

Another Biased Study? Maybe...

The Diet Wars: The Saga Continues

I decided to comment in a separate post because the comments features here are limited (and no auto-save).

First Tom Naughton's analysis raises many of the same questions that I have over the actual dietary interventions in the study.  Absent food diaries of what the participants were ACTUALLY consuming at the various time points, we have no idea what we're really comparing at each timepoint.  While I, too, don't see where the low fat/calorie restriction group increased their intake, I simply cannot abide that they didn't.  It would also have been instructive to know the caloric intakes of each group and the actual carb intake.  Naughton concludes:  "So in theory, we’re comparing a low-calorie weight-loss diet that lasted for two years with a low-carb diet that reached maintenance level within a year. Strange design for a study in which weight loss was listed as the primary outcome."    I would have to disagree with this conclusion as I believe the actual dietary intake -- particularly in the second year -- probably differed from plan for both groups.  It had to, or the participants in the LFCRD would have continued to lose.   Naughton does say this very same thing later on.   Naughton goes on scrutinize the potential bias of the researchers.  I'll not go into the whole "it's not the calories" nonsense that permeates the low carb community.  I think y'all know where I stand on that by now, but I don't see how this would have influenced the results of this study.  

Which brings me to the statistics that are questioned by both Naughton and Bowden (w/Dr. Richard Feinman contributing in the comments).  I'll admit to having been lazy not delving into their whole analytical methods in my first reading although that legend on the weight loss graph of "predicted" losses really struck me as "off".  I can't for the life of me figure out why they chose the methods they did -- without at least reporting and comparing to the data for just those who stayed in the study AND reported for assessments.  The authors presented some numbers in order to reach a certain statistical significance/power for their outcomes (weight and LDL), and with the dropout rate, they still seem to have the numbers with the remaining participants.  Perhaps if they excluded all but those participants who attended each assessment for the entire study they fell short?  Still, it appears that they not only included those no-shows who remained "in treatment" in their analysis, but also those who dropped out entirely.  I think a case could be made for predicting a value for a missing timepoint for a person who otherwise remains in the study, but to include a prediction for a total drop-out??  

In any case, where data were missing due to attrition, a statistical model was applied to predict what the value would be.  I, too, would rather see the data for those that at least complied enough with the study to show up for five assessments. It will be interesting to see if/when actual data is published what the values are.  It is MORE than suspicious to me that this was not included in the original publication.  But it is premature to presume bias in the statistical model used to skew the predictions.

So, now onto just the commentary by Dr. Jonny Bowden. 

First, since we just discussed the statistics, I would add that if we're going to discount the weight loss outcome on the basis of some bias in the model of biased researchers (who are biased because they believe in caloric balance), then we cannot hang our hats on any of the other predicted outcomes either.  These were every bit as "predicted" as the weight based on a model constructed by the very same (biased??) researchers.  Either their methods are valid, or they are not.  There were 30% more predicted values in the LC group vs. the LF group at the two year mark, where values would have been predicted for 32% of the LF sample and 42% of the LC sample.  

And yet Bowden makes the following statements:

And- hold on to your hats—at all time points throughout the 2 years,including at the finish line, the low-carb group had a significant increase in HDL (“good”) cholesterol, approximately 23% increase to be precise.

There’s not a drug on earth that’s been able to do that. ....

... Second, you may have noticed that those improved cardiovascular risk factors showed up for the low-carb group (only!) after six months, but that after that, there was no difference between the groups in those risk factors—both had improvements. (Except of course, for the very important improvement in HDL cholesterol, which was seen only in the low-carb group and was sustained throughout the two years!)

As I've stated before, the percent game for HDL masks the fact that the changes in HDL are not all that impressive.  The mean increase was 7.75 points for folks with starting value in the mid-40's.  Considering that 2/3rds of the participants were women, their endpoint mean HDL hasn't improved into that "protective" range.   Bowden is flat out wrong claiming that improvement in HDL was only seen for the LC'ers.  In fact, the low fat group also saw an increase of 4.64 points -- a little over half the improvement seen in the LC'ers.   The absolute difference being only 3 points -- is there any difference in terms of risk factors for this small a difference?   Furthermore, HDL increased in the LF group during the second year while it declined somewhat in the LC group.  Absent actual dietary intake records to assess compliance with the plans, what conclusion can we really draw from these data?

Bowden makes a mountain out of a mole hill regarding designating weight loss as a primary outcome and the CVD risk factors as secondary outcomes.  So what?  There was a difference in the secondary outcomes, and this HAS been reported in the headlines.  The LC community seems to have jumped hook-line-and-sinker for these relatively modest improvements and claimed vindication for the healthfulness of long term low carbing.  This study offers no such support.

Bowden goes on to state:

“Averages” often conceal real differences—for example within the low-carb group there were some folks who really stuck to the program, and I’m willing to bet that when the raw data are released, you’ll see a number of individuals who not only maintained their weight (or kept losing) but also maintained the significant gains in cardiovascular risk factors that were dramatically seen after six months.

I have made this statement myself many times in response to comments made about a study where personal or anecdotal evidence counters the results of some study or other.  So the fact that LDL went up almost 8 points on average for the first 3 months of induction doesn't mean that MY LDL would go up that much or wouldn't render a massive reduction impossible.  But Bowden seems to imply that these averages only conceal differences for the low carbers.  Surely within the low-fat group there were some folks who really stuck to the program and who not only maintained but lost more after the 6 mo/1yr mark!!   In the end, the means are still our best comparison for the population at large.

Now Bowden skirts clear of coming out and blaming upping the carbs for the reversal of the 6 month improvements in triglycerides, but Naughton fell into that trap a bit as other LC bloggers have.  Essentially there's that almost wistful air of "what if" they had NOT ramped up the carbs.  Unfortunately, unless more information is forthcoming, we do not know how far they ramped up the carbs, but it is important to see that there was no change in the trigs from the 3 month to the 6 month assessment during which time they were presumably "climbing the rungs" on Atkins.   Naughton mentions that most successful low carbers end up somewhere under 100g/day.  I think that is high for the more hardcore wing of the "movement".

Low carb in the various studies comparing weight loss and other factors seems to follow a predictable pattern "on average" -- greater early losses and a greater regain.  Does this mean everyone will follow this?  No.  But neither does it mean that low fat dieters necessarily regain either.

In the end I find myself annoyed at the "if only this or that, but look at the results anyway".  If only we look at those who followed LC stringently.  Yeah, well, if only.  But in the real world --  where doctors and nutritionists are trying to advise strategies beneficial to the greatest proportion of the population -- we can't just say LC works better, you just have to stick to it.   Because CRD's work when they're stuck to all the same.

Bowden starts to sum up with:  "If you had your choice between two diets- both of which produced weight loss, but one of which did it with less hunger and better cardiovascular outcomes, which would you choose?"  


Bias?

Melatonin a "cure" for the middle aged middle?

Came across this while on another one of my trips around the internet looking for something totally unrelated ... funny how that happens sometimes?

Anyway, thought I would "bookmark" it here with a little comment:

Daily Melatonin Administration at Middle Age Suppresses Male Rate Visceral Fat, Plasma Leptin, and Plasma Insulin to Youthful Levels

Yes, it is a rat study, but as the intro states, endogenous melatonin production decreases with age in both humans and rats.  Basically regular melatonin supplementation reversed the increases in  insulin and visceral fat associated with aging.

I don't know about any of you, but this middle aged (well I guess technically not yet, but ...) chick is going to look into this further!

In addition, if you scroll down the page, there's a list of articles that cite this study. I plan to check out a few of these.

Mass MUST be conserved

Note:  This has been in my draft "hopper" for a while.  I thought I might as well dust it off and post it.  ;-)

I've been thinking for a while about the whole caloric balance arguments and theories of obesity, etc.  I keep coming back to a simpler model of it all to which there really can be no argument.  That is that matter is neither created nor destroyed.  What goes into a vessel must come out of that vessel or the vessel will weigh more.

Intake:  macronutrients, water, oxygen, minerals and other micronutrients -- mostly oral ingestion and inhaling.
Outgoing:  excretory products -- mostly expiration and urine, but feces (containing mostly unabsorbed intake) and perspiration as well.

Metabolism, bioenergetics, whatever ... it all boils down to the rearranging of atoms and molecules for some purpose.  In the end, forget the purpose and just look at the atoms themselves.  We cannot convert an atom of oxygen to an atom of carbon.  If we take in XX carbon atoms in the form of fat, carb or protein, they are either excreted or they stay in some form in our carbon-based lifeforms.  Same for everything else.

As it turns out, it is the macronutrient mass balance that pretty much "rules".  Once we ingest a carbohydrate, fat or protein -- it is broken down into simpler carbs, free fatty acids and amino acids and absorbed.  Anything that passes through undigested/absorbed is a freebie.  Once it gets into "circulation", you own it.  Our bodies are ruthlessly efficient and even recycle things we temporarily excrete!

But once we "own" something, it will add to our net mass/weight unless we get rid of it somehow.  How do we get rid of carbon we don't need/use for structure?  We exhale most of it as CO2, and some more in urea that also serves as an export route for nitrogen through urine.

In any case oxidation/breakdown is the primary route *OUT*.  So here is where mass balance ties in with the caloric balance.  If we don't oxidize intake, we retain it and gain weight.  Plain and simple.  The "little stuff" like H2O and CO2 can get out.  The former is mostly our solvent in which all our bodily chemicals are dissolved, etc.  The latter is the byproduct of oxidation.   But what of bile and concurrent secretions from the liver into the intestine?  The vast majority are recycled (re-absorbed), so this is not a major excretory route.  Ketones?  I'll give you that one, but this has been determined to be a small amount in the non-adapted person, and even more negligible in someone who is keto-adapted.

Hormonally driven theories of fat accumulation fall flat when one considers mass balance.  What goes in must come out or be accounted for.  IF a zero carber consumes 2 pounds of only rendered pork fat one day, those fatty acids MUST go somewhere.  Those carbon atoms, etc. cannot be created nor destroyed.  Therefore, no amount of hormonal response or lack thereof can render the mass balance LAW moot.

But CS, what of futile cycling and uncoupling?

1.  Futile cycles:  We have many of these in our bodies that are seemingly futile -- IOW there does not seem to be a purpose to do work.  But they have a purpose, often to maintain body temperature.  However such cycles consume ATP which was made in ETC, Krebs, glycolysis, beta-oxidation ... IOW "burning" macronutrients.  If a futile cycle uses a certain amount of ATP, this will be reflected in expired CO2 = mass out.

2.  Uncoupling:  This is our body's "pressure relief valve" if we're running a bit too fast for our ultimate needs.  It's like expending energy to drive your car up a hill, but if there are too many cars up there, we release the parking brake on a few and let them roll back down.  How do we account for this?  ATP is used to in the metabolic equivalent of driving up the hill.  This is "wasted" when we release the brake.  But the wasted ATP is accounted for in the manner described in #1.  When we need more cars back on top of the hill, more ATP will be expended to do that, corresponding to more expired CO2.

Bottom line, these two processes are "mass dissipating", but there's nothing magic about it.  They both seemingly "waste" ATP, but I contend this is part and parcel of keeping our engines running smoothly and is largely accounted for in our basal metabolic rate (that, incidentally, is determined by our CO2 expiration rate).

So ... how do we get fat?  We ingest a greater mass of carbon based macromolecules than we excrete on a chronic basis.  If we don't store that excess as triglycerides in adipose tissue as we are supposed to, the lipids will either remain elevated in circulation, or accumulate elsewhere.

Adiposopathy v. Obesity ~ I

I just came across the following article, and haven't quite digested the whole thing just yet.  Still, it is interesting so I thought I would share it here.  This post will be about the most curious topic in this paper, but I hope to revisit this in a series of future blog posts (hence the "I" in the title).  

Adiposopathy Is a More Rational Treatment Target for Metabolic Disease than Obesity Alone

Near as I can tell, the lead author, Harold Bays, is the doctor who coined the term "adiposopathy" or "sick fat".  

Adiposopathy is pathologic adipose tissue dysfunction that may be initiated and/or exacerbated by fat accumulation (adiposity) in genetically susceptible patients [1••].  Adipocytes are metabolically active and adipose tissue is an important endocrine organ (Table 1) [2••]. Abnormalities of adipocyte factors contribute to dysmetabolism (Fig. 1), and adiposopathy [1••,3•] promotes some of the most common metabolic diseases encountered in clinical practice, including type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia.

This is a summary paper focusing on the fact that it is dysfunction of the adipose tissue rather than the amount of adipose tissue that is responsible for Metabolic Syndrome.  Thus explaining your "metabolically obese thin people" and "metabolically normal obese people", etc.   The focus, as the title implies, is MetS treatments that target the fat cell dysfunction rather than simply the person's fat mass.  

Sick fat appears to be related to adipocyte hypertrophy -- an enlarged fat cell:

It has been known since the 1970s that adipocyte hypertrophy increases the lipid/protein ratio of the adipocyte (through a relative consistency in protein content coupled with increased fat content) [13], decreases the responsiveness of adipose tissue to insulin [14], and increases the risk of metabolic diseases such as T2DM [15] and dyslipidemia, even if adipocyte hypertrophy is found in only slightly overweight individuals [16]. In fact, adipocyte hypertrophy is more closely linked to metabolic abnormalities, such as insulin resistance, than is an increase in total body fat [17].

An increase in fat cell size represents a failure of adipose tissue to adequately proliferate and differentiate [18] (as found with obesity and T2DM [19]) and, therefore, a failure to inadequately accommodate a further increase in energy influx [20]. Adipocyte hypertrophy may indicate a resistance or inability to store triglycerides beyond some maximal amount [21]. 

(This is consistent with the Critical Visceral Fat Theory I blogged on previously.)

For this post, I want to focus on the discussion of one of the pharmaceutical treatments:  PPAR-gamma agonists.  (Here's a LINK to general information on these drugs --  thiazolidinediones or “glitazones.” -- Actos and Avandia).  I'm not promoting pharmaceutical therapy, and Avandia has seen a lot of negative press of late, but nonetheless I find the mechanism of action of these drugs to be interesting.

These compounds appear to "cure" sick fat by stimulating the proliferation of new, small, young adipocytes and/or promote the death (apoptosis) of dysfunctional hypertrophied large fat cells.  Since SCAT has a greater ability to differentiate, and VAT cells are more metabolically active, this seems to have differential effects on the two types of adipose tissue.  These drugs tend to cause fat mass gain in SCAT, and loss in VAT, but appear to be most effective in the patients who are fatter to begin with and who gain more fat.  Yes, you read that right.  

From an adipose tissue metabolism standpoint, PPARγ agents have been shown to reduce free fatty acids [23••,91], increase adiponectin [92–94], and reduce leptin [93] (although not consistently so [95]), with unconfirmed effects upon resistin [95,96], IL-6 [97], and tumor necrosis factor-α [95,97]. Thus, it appears that many of the favorable effects of PPARγ agents upon glucose metabolism and adipocyte function may be most related to improvements in free fatty acid metabolism

I've seen diabetics list these meds in their treatment regimes and yet be on weight loss regimes.  In some ways this seems counter productive.  One way to try to cure sick fat is to try to reverse the dysfunction by emptying out the cells.  Another, it appears, would be to replace sick adipocytes with healthy ones.  While weight gain may be the last thing a person wants, I know I probably would resist it were I diabetic, it is interesting to consider.  

ASP Deficiency & Obesity

Came across this (yes rodent) mouse study recently:

Acylation-stimulating Protein (ASP) Deficiency Induces Obesity Resistance and Increased Energy Expenditure in ob/obMice*

Here is where dietary fat leading to obesity seems to come into play.  I consider it indisputable fact at this point that accumulation of fat in adipose tissue has far less to do with insulin "trapping" fatty acids in than it has to do with ASP-mediated sequestering of triglycerides into adipose tissue.   I encourage any new readers to start here.  

Basically, dietary fat is transported from the intestines to fat tissue as chylomicrons.  Chylo stimulate ASP (and are the major stimulator of ASP action, insulin does have an effect but many fold lower).  ASP stimulates both glucose transporters and the esterification of free fatty acids.  ASP's role is to clear dietary fat from the bloodstream.  The "energy" form of fats is free fatty acids (NEFA/FFA) and levels of this are controlled through inhibition of release from adipose tissue by insulin.

The whole excess carb is transported into fat cells by insulin and converted to fat theory of obesity has also pretty much been dispelled as a major contributor in humans.  (Check out my DNL posts)

OK, so what of this study?  Here's the abstract:

Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. In mice, C3 (the precursor to ASP) knockout results in ASP deficiency and leads to reduced body fat and leptin levels. The protective potential of ASP deficiency against obesity and involvement of the leptin pathway were examined in ob/ob C3(−/−) double knockout mice (2KO). Compared with age-matched ob/ob mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance; associated with decreased body weight (4–17 weeks age: male: −13.7%, female: −20.6%, p < 0.0001) and HOMA (homeostasis model assessment) index (−37.7%), suggesting increased insulin sensitivity. By contrast, food intake in 2KO mice was +9.1% higher overob/ob mice (p < 0.001, 2KO 5.1 ± 0.2 g/day, ob/ob 4.5 ± 0.2 g/day, wild type 2.6 ± 0.1 g/day). The hyperphagia/leanness was balanced by a 28.5% increase in energy expenditure (oxygen consumption: 2KO, 131 ± 8.9 ml/h; ob/ob, 102 ± 4.5 ml/h; p< 0.01; wild type, 144 ± 8.9 ml/h). These results suggest that the ASP regulation of energy storage may influence energy expenditure and dynamic metabolic balance.

Do these mice violate the first law of thermo or caloric balance?  Apparently no!  Their reduced ability to sequester dietary fats into adipose tssue is countered by an almost 30% up-tick in energy expenditure.  This is probably the futile cycling seen in rodent models (that is not seen at the same magnitude in humans).  A reasonable mechanism would be that the mouse body's think the mouse has drastically overfed itself due to higher circulating triglycerides upregulating the futile cycles to waste excesses.  But at the same time, since the fat cells aren't adding the usual excesses of triglycerides to its fat tissue, leptin is not secreted at usual levels.  Leptin should tamp appetite, thus decreased amounts would account for the almost 10% increase in caloric intake.  

I do not know what this all means in the scheme of things for development of human obesity, but it at least seems plausible that this may be the mechanism by which high fat -- in a hypercaloric SAD context -- diets induce obesity.  In humans, a high fat diet does increase fatty acid oxidation but this is a delayed (days/weeks) adaptation rather than the immediate stimulatory effect as seen for carbs and amino acids.

Diabetes progresses on LC/HF Diet

The long-term effect of low-carbohydrate/high-fat diet on the development of diabetes mellitus in spontaneously diabetic rats

First the disclaimers:
1.  It's a rat study
2.  The OLETF rats used are a strain that become spontaneously diabetic and mildly obese -- however to the best of my knowledge this strain was not created by genetic manipulation (e.g. it's not a "knockout").  More here.


My excerpts will be from scattered around the article.

The long-term effect of low-carbohydrate/high-fat diets on the development of diabetes mellitus was studied in Otsuka Long-Evans Tokushima Fatty strain (OLETF) rats. Four groups of spontaneously diabetic (type 2) male rats at 10 weeks of age were pair-fed semi-purified powder diets containing different amounts of carbohydrate (80 %, 60 %, 40 %, 20 % of total calories) for 30 weeks. The carbohydrate content was isocalorically substituted for the fat content in the diet. At the onset of experimental feeding (10 weeks of age), an oral glucose tolerance test (OGTT) was normal in each group.

This was a fairly long term study for rats -- 40 weeks total.  The first 10 weeks were simply to grow the rats. Although this is a spontaneously diabetic strain, the OGTT done at the start of the dietary intervention showed these rats were all still normal -- had not developed diabetes.  


The rats were divided into four groups, diets contained the same calories, and although not mentioned, protein content was held constant as well.  Only the carb/fat proportions were altered from LC (20%) to HC (80%) carbs in 20% increments with fat reduced proportionally.  I'll call these LC (20%), MLC (40%), MHC (60%) and HC (80%)


Some background -- emphasis mine.

Many epidemiological studies have already been performed to evaluate the relationship between dietary modification (low-carbohydrate/high-fat diet, LC/HF) and the development of DM. However, their results are contradictory. Some show negative associations, while others show positive associations [5, 6]. Even in animal experiments, some researchers studied the effect of high-fat feeding on the development of DM [7, 8]. However, the experimental duration of the test diet feeding was too short (less than 2 months) in most studies [9, 10]. Moreover, the experimental animals were allowed free access to the test diets in most of the studies. In general, diabetic animals select LC/HF as opposed to a high-carbohydrate/low-fat diet (HC/LF) [11]. In the previous studies, the animals consumed more LC/HF. Therefore, compared with the animals that were kept on the HC/LF, the calorie intake was higher in those fed LC/HF. From the results of the previous studies, it is difficult to draw any conclusion about the effect of LC/HF on the development of DM.

 

This is interesting that ad libitum, rats gain MORE weight on LC than LF because they eat more.  This is counter to low carb dogma.

After 15 weeks of the test diet feeding there was no significant difference in the glucose tolerance among the 4 groups, although most of the rats were diabetic. The body weight increased with the decrease of the carbohydrate intake and increase of the fat intake (p < 0.05), and the difference increased in proportion to age (p < 0.05). The severity of diabetes mellitus was also increased along with the lower carbohydrate intake and higher fat intake, when the carbohydrate intake was less than 60 % (in energy).

So even with isocaloric intake, THESE rats gained MORE weight on low carb than high carb.

On the other hand, there was a significant increase in the 20 % group in the postload plasma insulin levels as compared with the other 3 groups at 40 weeks of age. Fasting plasma free fatty acid levels were increased in the lower carbohydrate content groups (20 % and 40 %) as compared with the higher carbohydrate content groups (60 % and 80 %) at the end of the experiment.

This is to be expected, and is so often ignored.  Since these rats were only mildly obese, the elevated NEFA is probably an indication of some degree of insulin resistance in the fat cells.

Impairment of insulin secretion may be the cause of glucose intolerance induced by low carbohydrate intake rather than insulin resistance. These findings suggest that low-carbohydrate/high-fat diet aggravates diabetes mellitus in genetically diabetic rats, and that the development of diabetes mellitus is associated with the activation of the glucose-fatty acid cycle.

 25 Weeks (15 Weeks Dietary Intervention)

40 Weeks = End of Study

The authors conclude that IGT is due to impaired insulin response (e.g. compromised beta cell function) and not skeletal muscle IR.  I would have to question this because if you look at the tables above, we see that the LC group has a significantly higher insulin response to the glucose challenge at 30 min vs. all of the other groups.  At 60 min, both the LC and MLC groups have higher insulin than the MHC and HC groups (insulin levels correlate inversely with carb), and at the 2 hour mark, only the LC group seems to have abnormally elevated insulin compared to the other groups.  To me their results are consistent with IR -- in the fat tissue resulting in elevated NEFA, and peripherally resulting in the rats having to produce more insulin.

IF I'M READING THESE RESULTS INCORRECTLY, I WELCOME COMMENTS ON WHERE I'VE GONE WRONG.

Again, we have to remember this is a rat model, and one in which the males of this strain are predisposed to diabetes.  However there is a strong genetic component to the development of T2 diabetes in humans.  This study seems to indicate that while the LC'er may have better glycemic control, this is achieved at the expense of elevating the other circulating compound that results in dysfunction and damage -- NEFA's.  

Bottom line:  This study demonstrated that in genetically predisposed rats, diabetes developed and progressed further in those rats fed a LC diet than those fed a HC diet.  

Weapons of Lean Body Mass Destruction: The Role of Ectopic Lipids in the Metabolic Syndrome

Just a "bookmarking" post to share an interesting article.

Minireview: Weapons of Lean Body Mass Destruction: The Role of Ectopic Lipids in the Metabolic Syndrome

Very Low Carb and Insulin Resistance

In response to my recent post -- Can low carb cause central adiposity? -- James Krieger posted a link to a recent study indicating I may well be on to something.  So I thought I would post this study separately (I don't have access to the full text on this one).

Longitudinal adaptations to very low-carbohydrate weight-reduction diet in obese rats: body composition and glucose tolerance.

Longitudinal effects of a very low-carbohydrate (VLC) and a calorie-matched high-carbohydrate (HC) weight reduction diet were compared in dietary obese Sprague-Dawley rats exhibiting impaired glucose tolerance and insulin resistance. Obese rats were divided into weight-matched groups: 

(i) VLC rats consumed an energy-restricted 5% carbohydrate, 60% fat diet for 8 weeks,

(ii) HC rats consumed an isocaloric 60% carbohydrate, 15% fat diet, and

(iii) HF rats consumed a high-fat diet ad libitum.

HC and VLC rats showed similar reductions in body fat and hepatic lipid at the midpoint of the weight-reduction program, indicating effects due to energy deficit. At the end point, however, HC rats showed greater reductions in total and percent body fat, hepatic lipid and intramuscular lipid than did VLC rats, suggesting that diet composition induced changes in the relative efficiencies of the HC and VLC diets over time.

Yes ... this is a rat study with all the issues inherent in trying to extrapolate to humans, but let's not forget Dr. Eades' favorite c57bl6-mouse that he says provides evidence for the so-called metabolic advantage of low carb diets.  In that study, the growth rate of ketogenic diet fed mice was stunted to that of the calorie restricted diet vs. three other diets.  I'll try to remember to update with a citation, but in one longterm study on epileptic children treated with a ketogenic diet, their growth percentiles (height AIR) declined following treatment.  But I'll leave a dissembling of this study and the conclusions Eades draws from it for another day.  

It is important to note that these were not genetically obese rats, but rather were made obese through diet and then put on weight loss diets.  In this study, the VLC and HC rats lost the same for a period of time but the metabolisms of the VLC rats apparently became more efficient indicating an adaptation.  Anecdotally, most low carbers seem to plateau out well above their goal weight.  The various long term studies of LC diets seem to follow a similar trajectory of rapid initial losses followed by regain that would be consistent with the findings of this study.  My own metabolism is in the tank as I do seem to become very efficient during long strings of low carbing.   It would be an interesting study to recruit a number of long term weight loss success stories and compare the metabolisms of VLC'ers to LF'ers.  

Back to the study:

HC rats showed marked improvement in glucose tolerance at the midpoint and end point, whereas VLC rats showed no improvement. 

This ties in with what I've been saying now in many posts regarding "curing" diabetes with low carb diets.  Whatever the glycemic issues of the VLC rats before diet and weight loss, the underlying metabolic impairment persists.  

 Impaired glucose tolerance in VLC rats at the end point was due to insulin resistance and an attenuated insulin secretory response.

So, again, a VLC diet may not only mask symptoms of IR and impaired insulin production, but could potentially sustain the underlying issues and/or further complicate matters by reducing the insulin response.  

Glucose tolerance in energy-restricted rats correlated negatively with hepatic and intramuscular lipid levels, but not visceral or total fat mass. These findings demonstrate that adaptations to diet composition eventually enabled HC rats to lose more body fat than VLC rats even though energy intakes were equal, and suggest that the elevated levels of hepatic and intramuscular lipid associated with VLC diets might predispose to insulin resistance and impaired glucose tolerance despite weight loss.

This paragraph reads a little vaguely to me b/c they lump the VLC & HC groups into one when they talk about the energy-restricted rats.   It sounds like they are saying that VLC rats had higher hepatic (liver) fat and intramuscular lipid (IMCL) compared to the HC rats and this correlated with impaired glucose tolerance/IR.  But visceral and total fat mass was not associated with IGT so it wasn't just the lesser VAT/SCAT fat loss of the VLC group that was responsible for the observed IGT and IR in these rats.

So, yes, this is a rat study.  But it is adding to concerns over long term low carbing.

Can low carb cause central adiposity?

This is mostly a post of a personal nature, but I thought I would put it here on the science side of things because I'll try to tie observations and anecdotes in with some scientific backing/references.

Personal background for my interest in this:  

As a child I had a rather boyish body until around age 12 or so.  At that age my shape (butt and thighs) started coming out (not fat though), but I was a rather late bloomer.  I didn't gain my "puberty weight" until I was 16 or so -- perhaps 20 lbs -- again mostly in my butt/thighs.  Anyone remember Tracey Gold from Growing Pains?  That would be pretty close (pre-anorexia) to my shape.  I lost the weight then yo-yo'd most of my 20's on various diet plans (none of which were low carb).  Although cycling as high as the 200-210 range and as low as 145 during that time, my general body type did not change.  I would always gain or lose weight mostly in my butt/thighs only getting the back and belly bulges at top weights.  My midriff was always  one of my better assets at the bottom of weight swings.  Probably TMI, but my breast size pretty much went up and down about 1.5 cupsize with weight/size.  In 1997 my weight hit up against an all time high and I was wearing 16's.  Well dressed at my high weight I was Delta Burke-ish.

It was then I discovered Atkins and, coupled with a very active job, I lost 40 lbs in a few months getting down to size 8 jeans.  This was the beginning of my body shape transformation.  I lost proportionally more weight in my thighs this time, but not in my waist.  This time tummy weight either remained or perhaps even shifted.  When I went off LC I regained weight rapidly and blew right on through my former upper limit.  I gained it everywhere, but most prominently in the belly like I never had before.  One more cycle of loss and regain a few years later and let's just say that my belly stuck out considerably more than my 40/42D+'s!!  You know, all my life I had difficulty finding clothing that fit at any weight -- my waist was disproportionately small compared to my thighs.  Pants that fit my thighs gapped at the waist.  And when I was heavier, it got worse as larger sizes, especially true plus sizes, tended to just get bigger in the waist.   But since that first low carb weight LOSS, pants have fit me better at every size.  Sometimes I even had extra room in the seat!

This body type was not only foreign to me, but in the past I could always write my weight off as not particularly unhealthy b/c I carried most of it well below the waist.  Now, I carried it around the middle and upper arms and less so proportionally in legs and backside.  Today, after losing the weight I fit (even too big) pants I wore 15 years ago when I weighed some 40 lbs less.  My chest size has gone down from the 40-42 mark to a 36, but I still must shop the "full cut" lines for D cups.  Fifteen years ago when I wore the aforementioned pants I was a 34C in a regular cut.

So, why am I telling you all this info?  Because this is one of my root causes for concern over the healthfulness of LC eating.  Today, the largest remaining fat "depots" are my belly, breasts, and upper arms (although that seems to be more skin).  I wonder over the hormonal implications of having larger breasts when I'm now officially menopausal.  And I worry over my central "obesity" although somewhat comforted that it appears to still be sub-Q vs. visceral.  I don't know if I'm some sort of odd-ball in this regard, but even if so, is this seemingly permanent shift in my fat distribution dangerous, benign or even beneficial?  

In this regard, I've looked to some of the women in the low carb community.  How are they looking after years of low carbing?  I was not encouraged.  Back in early 2009 I came across some pictures of Laura Dolson, Dr. Mary Vernon and Dana Carpender.  All overweight or downright obese.  Although I've never seen the pictures, in their recent book,  MD Eades developed a belly despite low carbing requiring a 6 Week "Cure".  A cruise through various LC forums and blogs will unearth numerous success stories with either stalling out 20+ lbs north of goal and/or weight regain.

Recently I came across some more recent pics of Dana from Jimmy Moore's 2010 Low Carb Cruise, and thought to myself that these were comforting.  I chanced by her blog, read back a bit, and noted that she's now at a low weight for herself and wearing size 10/12's.  Her book was about a 40 lb weight loss on low carb, but she's blogged over the years about weight fluctuations.  In any case, I was flabbergasted when she posted some gymsuit pictures of herself on her new blog:  My Total Gym Transformation.  Kudos to Dana for her honesty in posting these.  But yikes!  If this is the result of 15 years of "fighting the low fat lie" and eating low carb, am I the only one for whom the side pics registered cause for concern?

And then I look at Jimmy Moore.  Obviously not a woman, but a long term low carber who has been steadily gaining weight (and having only short-term success to date at losing it) for almost 3 years now.  One can look at pictures from Jan 2010 here and here.  Now it is difficult w/o seeing pics of his original weight loss progression, but when I look at the before/afters, on his various websites, at over 400 lbs Jimmy seemed to distribute his weight fairly well around his body.  Sure, he had a belly, but in this pic of Jimmy +30 from low weight at 260 lbs, despite remaining rather consistently low carb, one can see where he's gaining ... and the 2010 pics seem to indicate most of it is going to the worst place from a health perspective.

Now I've hesitated making this post as I don't want to be seen as picking on or criticizing these nice folks, but if we can't scrutinize LC "celebs" and look to them for long term prospects, who can we look to?  In the end my thinking is that they "put it out there" so I'm not out of line commenting here in my little ol' blog.

Considering all of the information I've gathered on the etiology of insulin resistance, I think the above may well be two examples of how long term low carbing can increase insulin resistance and perhaps body fat distribution that may be influenced by whatever few carbs one might consume.  I also consider that the extreme carnivore wing of the LC community tends to be the only ones that get truly lean.  My thoughts on this are that they are probably very insulin resistant but it doesn't lead to overt problems because they eat essentially no carbs so their body's inability to handle them normally is not challenged.  It is also very difficult to overconsume on meats, especially when dairy is omitted or extremely limited.

From a recently referenced article:

VAT may influence central SCAT

Mauriege et al found that adrenoreceptor sensitivity was increased in SCAT cells of individuals who have a higher VAT accumulation compared to those with a low VAT deposition [112]. SCAT adipocytes from women with visceral obesity exhibit higher lipolysis rates in vitro than those obtained from women with little VAT [113]. Mauriege et al also demonstrated that among men with high levels of VAT, SCAT adipocytes are more sensitive to β-adrenergic lipolysis which may further exacerbate an impaired insulin action, a potentially important factor in the etiology of metabolic syndrome associated with visceral obesity [112]. Moreover, an increased truncal SCAT mass and an increased amount of VAT mass can independently predict insulin resistance [114]. Together, these findings support that VAT may enhance central SCAT lipolysis and accelerate release of peripheral FFAs.

So the fact that at least a goodly portion of my trunk fat appears to be SCAT, this may indicate excess VAT. The measurements in the Eades recent book offer me little insight into the matter.  Another way to read this is that the trunk fat is an indicator of a degree of IR independent of whether or not my VAT is out of whack.

Later in this same article estrogen is discussed:

Estrogen

Estrogen promotes the accumulation of peripheral gluteo-femoral SCAT, which may be protective [131]. The abundant presence of peripheral fat mass in generally obese women is associated with increased plasma adiponectin, and the loss of estrogen with menopause is associated with an increase in central fat [132]. This accounts for the progression in many overweight women after menopause from a predominantly pear-shape or "gynoid" habitus to the apple or "android" shape. Contrary to popular belief, menopause does not seem to independently cause a gain in total body weight; the increases in BMI that often accompany menopause are usually consistent with normal aging [133]. However, even without weight gain, body fat distribution changes; postmenopausal obese women tend to accumulate abdominal fat along with deterioration of risk factors, even if total body weight and BMI do not change during menopause transition.

After menopause, when ovarian function declines, adipocytes become the primary source of endogenous estrogens [134], and compared to "gynoid" or pear-shaped women, those with central obesity (apple- or "android-" shaped) have lower plasma SHBG and higher estradiol [125,135]. This suggests regional differences in the enzymatic conversion of steroid hormones in VAT versus SCAT [125,136-138]. In ovarian hormone-deficient women, SCAT adipocyte size, lipoprotein lipase (LPL) activity, and basal lipolysis were not found to be significantly greater compared to regularly cycling premenopausal women. However, in the ovarian hormone-deficient women, omental (VAT) adipocyte size was significantly higher, and the omental/SCAT LPL activity ratio and VAT lipolysis were also significantly higher [139]. 

Perhaps my belly is now the inevitable result of my "change of life".  But I am a bit young to have gone through all of this.   I wonder sometimes if LC didn't perhaps accelerate this by influencing estrogen rather than vice versa?  I suppose I'll never know.  But it is worth repeating that the first shift in fat distribution occurred in my early 30's during weight LOSS through low carb.

I would appreciate any input from other (particularly female) low carbers if they have experienced similar as well as any thoughts on whether or not I should be concerned by this as much as I am.

The New Low Carb v. Low Fat Study ~ Much Adieu About Not a Helluvalot!

So the LC Hills are alive with the sound of music to the ears of low carbers once again.  A 2-year NIH funded study pitted a classic lowfat CRD against a DANDR stye low carb diet.  DANDR fared equally with low fat on most measures and even posted a modest sustained improvement in HDL.

Here's the summary:

Background: Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss.

Objective: To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program.

Design: Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936)

Setting: 3 academic medical centers.

Patients: 307 participants with a mean age of 45.5 years (SD, 9.7years) and mean body mass index of 36.1 kg/m2 (SD, 3.5 kg/m2).

Intervention: A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low–glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; 30% calories from fat). Both diets were combined with comprehensive behavioral treatment.

Measurements: Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study.  

Results: Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The lowcarbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years.

Limitation: Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high.

Conclusion: Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years.

Primary Funding Source: National Institutes of Health.

OK.  So let's start with the good here:  Following Atkins FULL plan (increasing carbs out of Induction), even with a bit of an extended induction period (12 weeks vs. 2 weeks) results in nominally improved biomarkers (HDL in particular) in the short and longer term vs. low fat.  IOW, Atkins as prescribed won't kill you and might actually be a bit more beneficial to the cardiovascular system.  This is GOOD news, but I think some are taking it to mean more than it does.  They studied DANDR as prescribed (IOW carbs were increased up the 5g rungs) in obese patients (BMI avg. ~36), excluding any with dyslipidemia (highly correlated with insulin resistance/pre-diabetes) and overt diabetics. 

Less than 10% of the original respondents eventually made the study, and 25% were excluded in the last step.  Granted only less than 15% who made it to the eligibility assessment were excluded for "cause", but these would have been obese persons essentially unaware of their dyslipidemia and/or diabetes.  It is not unreasonable to assume that a large portion of the 3140 who didn't "pass" the prelim phone screening were excluded because of these criteria, and it would also not be unreasonable to assume that a good portion of the 355 who missed their in-person screenings may have decided they wouldn't pass the next step because of missing these criteria.  Of course nobody can say for sure, but abnormal lipids are prevalent in the obese.  So, although I can see wanting to exclude overt diabetics,  I have reservations as to the exclusion of those with lipid abnormalities.  After all, the "risks" associated with obesity are associated with those very biomarkers, and improvements in health (CVD risk among them) associated with weight loss were what was being studied after all.  So I'm left to wonder if the sample studied by Foster et.al. is even representative of the obese population as a whole.  I'll update with a citation when I find it, but I recently read an article stating that up to 20% of the obese are   "metabolically normal" -- so basically this study, whatever its implications, only pertains to this subset of the obese population.  But what of the more-likely obese person with deranged lipid metabolism to begin with??  Hopefully that will be another study on another day.

In any case, here are the starting stats:

.  

Two thirds of the participants were women and the average starting weight was ~103.5 kg for each group which equates to just over 225 lbs.  In one year the average weight loss is not encouraging and would still have the average weight of the participants over 200 lbs.  Here is the breakdown of the weight losses:

If the numbers in ( ) are +/- 1 standard deviation we see SD's of around 1 to just less than 2 kg -- IOW, weight loss was not highly variable amongst the groups.  Weight losses are hardly all that significant in this study (depressing, really).  Now although not statistically significant, the weight losses of the LC group follow a familiar pattern.  Slightly more in the first 6 months followed by a slightly greater regain for low carb vs. low fat.  

When one looks at the "crown jewel" finding of this study, HDL, we see that both groups started with levels in the mid-40's.  Here's the stats (remember low fat on left, low carb on right)

Yes, the low fat diet had the predictable (and not desirable) effect of actually lowering HDL initially, while the LC group only showed increases.  But we're talking an absolute difference in level of around 3mg/dL  at the 1 and two year marks.  I don't find that all that remarkable.  

OK, so some general comments on the study itself.  I have a copy of the full study (thanks J) complete with Appendix and nowhere does it list reported dietary intake for the two groups.  The dietary prescriptions provided are also vague.

Low-Carbohydrate Diet

Approximately half of the participants (n 153) were assigned to a low-carbohydrate diet, which limited carbohydrate intake but allowed unrestricted consumption of fat and protein. During the first 12 weeks of treatment, participants were instructed to limit carbohydrate intake to 20 g/d in the form of low– glycemic index vegetables. After the first 12 weeks, participants gradually increased carbohydrate intake (5 g/d per week) by consuming more vegetables, a limited amount of fruits, and eventually small quantities of whole grains and dairy products, until a stable and desired weight was achieved. They followed guidelines described in Dr. Atkins’ New Diet Revolution (15) but were not provided with a copy of the book. Participants were instructed to focus on limiting carbohydrate intake and to eat foods rich in fat and protein until they were satisfied.  The primary behavioral target was to limit carbohydrate intake.

Ummm ... stable and desired weight?  If the whole point was just to lose around 10% bodyweight I guess they achieved this in the first year.  But I would venture a guess that most 225 lb'ers desire to lose more like 30-40%.  In any case, a few days of food diary analysis at each assessment point should have been included so that the actual carb (and caloric) intake is known.  Did all participants procede up the rungs?  What was the final carb count after 6 months when this group began to regain?  Even fewer details are given for the low fat group:

Low-Fat Diet

The remaining 154 participants were assigned to consume a low-fat diet, which consisted of limiting energy intake to 1200 to 1500 kcal/d for women and 1500 to 1800 kcal/d for men, with approximately 55% of calories from carbohydrate, 30% from fat, and 15% from protein.  Participants were instructed to limit calorie intake, with a focus on decreasing fat intake. However, limiting overall energy intake (kcal/d) was the primary behavioral target.

Here food diaries should have been analyzed to measure compliance, no?  One is left also to wonder if at some point this group didn't also increase caloric intake once a "stable and desired weight" was achieved.  Otherwise we are to believe that two years of maintained caloric restriction resulted in regaining some of the weight after one year?

This is a serious criticism here.  When the comparison of outcomes between two dietary interventions is the primary focus of a study, an accounting of the actual dietary intake of the participants is paramount ... don't you think?  The authors felt compelled to provide details of the behavior modification program that was given to both groups in the Appendix, but failed to provide any details on the actual diet consumed.  In previous comparison studies -- cited by this study -- those being Gardner et.al.,  Shai et.al., and Dansinger et.al. -- dietary intake and compliance was monitored and reported in far greater detail.  Self-reported food diaries may not be perfect, but should be a minimum requirement in order to draw any conclusions on dietary differences.  The authors further muddy the comparison waters by prescribing an exercise program (walking 4X 20min beginning week 4 ramped up to 4X 50min by week 19) and behavior modification program (SAFE - 75-90 min counseling sessions every other week for first 20 weeks then every other month for the duration of the study) but, there appears to be no effort to assess compliance/attendance with either program.

All of this leaves me with serious doubts over drawing any conclusions from this study.  It was either poorly planned, executed and/or reported.  Reminds me in a way about this NEJM study from 2009 -- not much differences in weight loss (and even more pathetic losses) probably due to poor compliance.  If you cannot at least try to demonstrate compliance to one plan or another, how are comparisons even meaningful?   One would hope that if the assessments missing in the article were indeed carried out that this data/results would be disclosed in a revised publication.  In any case, I don't know about y'all here, but when I read results like this -- all this to lose a measly 25 lbs in a year only to put 1/3rd of it back on in the next year -- it is rather discouraging.

Now many in the LC community are pointing to the improved triglycerides during the <g phase and I'm hearing a lot of "if only they hadn't ramped up the carbs".   If only they had used a more rigorous LC diet rather than this "less potent" form as one blogger referred to the diet as.   Fair enough, but that is NOT what Atkins laid out in DANDR ... and that is the point, right?  If DANDR "by the book" isn't the quintessential low carb diet, what is?  Neither the original nor DANDR even encourages staying at Induction (biologically zero) level carbs.  At least the New Atkins cautions that "for some" lifetime maintenance means staying <50g or even lower.  If true low carb living is at these levels shouldn't that be a disclaimer going in??  Or is this the unspoken dirty little secret of the low carb community -- wink wink??  I'm beginning to think it is.  Most of the outspoken long term low carbers seem to go lower and lower as time goes by.  Indeed my own method was <20g most days except for planned cheats, but when I stalled out the advice was almost uniformally about cutting out what few carbs I still ate (not a consumer of "product" here except for the occasional LC wrap).

Now, were the "headlines" I'm seeing heralding this study supportive of low fat dogma, the study authors would surely be derided as idiots, accused of lapses in scientific integrity, bias, etc.  But the authors do at least address some of the issues I've mentioned here, so I'll quote those here:

Our study also has several limitations.  First, the comprehensive behavioral therapy program used in this study makes it difficult to extrapolate our results to  general weight management in the community. However, the clinically significant weight losses achieved at 24 months underscore the need for providing patients with long-term behavioral support, whether by registered dietitians or other allied health professionals (32, 33). Our protocol was based on an Atkins version of a low-carbohydrate plan, which prescribes an increase in carbohydrate intake over time; thus, the effects of longer than 12 weeks of severe (20 g/d) carbohydrate restriction could not be assessed.  Finally, our findings should not be generalized to obese persons who have obesity-related diseases that were excluded from our study population, such as diabetes and hypercholesterolemia.

Bottom line: this study did not look at the long term efficacy/ramifications of the VLC WOE.  We can only postulate that the lipid profiles would be any better (or worse).  So this study offers absolutely no "vindication" as to the healthfulness of long term VLC eating.  Indeed it doesn't seem to tell us much more than the three studies done previously, Shai in particular, except perhaps the age/gender makeup was different.  But speaking of the gender makeup of the study group -- ~1/3 male, 2/3 female:   I wonder (a) why the gender split wasn't more reflective of 50/50 of the population, and  (b) no attempt was made to assess gender differences (if any).

Attrition:    At the 1 year mark, attrition was similar between groups - about 1 in 4, but at the 2 year mark, attrition may not have been statistically different, but while LF had ~1 in 3 drop out, LC had ~2 in 5  (32% and 42% respectively).  I would like to address attrition in this study in more detail, especially since this study refutes (further) erroneous claims made by Westman, Volek & Phinney in The New Atkins that LC diets are easier to stick to and losses are easier to maintain.  Here's what is reported in the study:

There were no statistically significant differences between the 2 groups in attrition, defined as not undergoing an assessment at a specific time point, independent of the reason. Attrition included participants who withdrew and intermittent missingness at each time point. In the low-fat group, 6%, 12%, 25%, and 32% of participants did not participate in assessments at 3, 6, 12, and 24 months, respectively.  Values for the low-carbohydrate participants were 9%, 16%, 26%, and 42%, respectively.

The differences may not be statistically significant according to their methods used, and I'm not privy to the raw data so certainly can't do my own analysis.  BUT there are two types of error in statistics:  sampling error and non-sampling error.  The attrition is consistently greater for the LC group at all time points.  If we're going to play the percent game with HDL (23% improvement sounds better than the absolute value for example), then one can say that 50% more dropped out/failed to report in the LC group vs. LF in the first 3 months, and the drop-out/ftr rates at 6 months and 2 years are 25% and 33% higher respectively in LC vs. LF.    This difference in attrition at least implies LC was more difficult to stick with.  Therefore attrition differentials could contribute a significant amount of "non-sampling error" to the results.  (See this post for a more complete discussion of sampling and non-sampling error.)

I've crunched down the attrition graphic from the study (left out reasons for discontinuing):

Note that the "attrition rate" is combined for those that dropped out of the study AND those who remained "in treatment" but missed their assessment.   The numbers are small, but the differences are noteworthy.  You have more than 3X as many participants not reporting for "duty" -- yet remaining in the study -- in the LC group vs. the LF group at 3 months and twice as many not assessed in the LC vs. LF group at 6 months.   Obviously the values reported can only be reported for those active and present for assessment.  How many of the 10 no shows in LC/3mo showed up and were "counted" in the 6 mo assessment?  Were the no shows all different participants or were any subjects "kicked out" for missing more than one assessment and not included in the data analysis.  At two years, the % attrition may not be a statistically significant difference, but the endpoint data is missing for 23/153 =  15% of the LC group that is considered "In Treatment".  This value is just under 8.5% for the LF group.    What effect might this have on the outcomes?  We cannot quantify it, and the authors do acknowledge the high attrition rate for both groups as a limitation of the study.  But where small differences are seen, it is quite possible that attrition changed the "makeup" of the samples.  On the positive side, those persisting on LC are likely the better adherents so this makes the HDL outcome promising.  On the other hand, we can only speculate about what the 10 additional 2yr no-shows and 8 additional 1yr-to-2yr dropouts in LC vs. LF group had on the ultimate outcome and the touted persistence of HDL improvements irrespective of weight regain.  

This study, in the end, illustrates mostly how difficult it is to reverse obesity.  Even with a significant amount of support the weight losses are not all that impressive for either group, and they regained on average 1/3rd of the weight loss.  It would be nice to know -- in raw numbers -- the number of participants that lost/maintained/gained weight from 3mo-to-6mo, 6mo-to-1yr, and 1yr-to-2yr.  This would have no consequence on any of us individually, but combined with an analysis of compliance with program between subgroups may elucidate a best (or better) strategy for weight loss and maintenance.

I'll leave you with the actual conclusions of the authors:

In conclusion, this 2-year, multicenter study of more than 300 participants revealed that neither dietary fat nor carbohydrate intake influenced weight loss when combined with a comprehensive lifestyle intervention. Both diet groups achieved clinically significant and nearly identical weight loss (11% at 6 months and 7% at 24 months), and persons who received the low-carbohydrate diet had greater 24-month increases in HDL-cholesterol concentrations than persons who received the low-fat diet. We found no differences between the groups for changes in bone or body composition. These long-term data suggest that a low carbohydrate approach is a viable option for obesity treatment for obese adults.