NuSI ... or Just Do It!

Imagine if you will, that a decade or more ago someone told you that if you really wanted to build your journalism career tearing down scientists, you needed to look at diet and nutrition research.  You picked up a copy of Atkins and lost a couple of pounds.  You began cultivating your schtick that simple obesity (the kind of the epidemic) was not about overeating or sedentary behavior, it was something else.  And you received three-quarters of a million dollars to research and write a book.  The book was a best seller and garnered you a cult following in certain circles and you were off to the races giving talks around the globe.  

There were doctors and others who bought into your hypothesis, spreading the word as fact and growing the movement.  But a following from one segment of the population remained elusive:  scientists.   Rather than address the reasons why (serious holes in your hypothesis), you double down and trash scientists more openly and frequently.  You also publish a second book with a dumbed down, even less scientific, hypothesis.  By all indications, this book falls far short of expectations ... and still the scientists are not coming around.  Worse still, many who had believed your hypothesis was plausible, at least worthy of investigation, were abandoning it.

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Why We Get Fat ... Lessons from a Cafeteria Rat

{Original publish date:  2/25/11}

Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose Inflammation: Comparison to High-Fat Diet

(Hat tip to Beth for bringing this to my attention)

This study used male Wistar rats

{eek ... I'm having flashbacks to a former career!}

This rat is not a genetic mutant predisposed towards obesity, but is often used in diet induced obesity (DIO) studies, as they will fatten considerably on a high fat diet.

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High Protein Diet Induces Sustained Reduction in Ad Libitum Intake Despite Diurnal Leptin Compensation

I've written several hundred posts on this blog.  There are some, especially from early on in 2010, that I would really like my readers to see, and I sure don't expect folks who are just finding this blog now to go back and read everything to find some that I feel are key.  I refer to this study quite often because I think for those finding themselves gaining a little bit each year and not wanting to hop on some "diet rollercoaster", there is merit to -- especially for us women -- upping the protein as a percentage in the diet.  So when I was compiling graphics for the 24 Hour Leptin Profiles post, this study was the first I knew to go to for a graphic.  So, I'm bumping the original, adding a little emphasis to the text but not changing it, and I'll add some commentary on leptin at the end.  

---

Original Publish Date:  4/30/10

A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations

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Grey & Kipnis ~ Hyperinsulinemia and Diet Paper

It appears that the website that formerly hosted the full text PDF of the Grey & Kipnis study I cite quite frequently here has been taken down.  I'm sad to see this.

I've linked to that hosted copy so many times it would be impossible to go back and change them all at this point.  Instead I'm posting this up if anyone ever needs to find the reference in an older post, and I'll use my new Google docs host link in all future posts.  

Here it is:

Effect of Diet Composition on the Hyperinsulinemia of Obesity

The Essential Carbohydrate?

I would ask each and every reader to try as best you can to check their nutritional biases at the door here as best you can  and let's just talk semantics.  

What does essential mean?  

Something that is essential is something that we cannot do (or in the nutritional context live) without.  By this definition, it is clear that yes, for most humans, carbohydrates are non essential.  However, even this is too simplistic, because without looking very far, we can identify a group of humans for whom carbohydrates are "deadly" essential.  As in imminent death kind of essential.  Relatively rare as is their number, I'm talking about people with glycogen storage/breakdown disorders.

Now, let's look at the other macronutrients.  Well, we cannot live without protein.  Therefore it is essential.  No argument.   However, proteins are comprised of 21 distinct building block amino acids of which only 8 are actually identified as *essential*.  A strict interpretation of this fact might be that ... eh ... 13 amino acids, or the majority are non-essential.  We don't need them.  They can be made by the body from other stuff.

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Chris Masterjohn on Cherry Picking (and the Metabolic Advantage of Fructose)

... at least in rodents ;-)

Let Us Honor Ancel Keys, Our Patron, As We Cherry Pick Studies to Bash Fructose (Revised and Extended)

Hats off to you Chris!

Metabolism v. Fat Burning

I was reading Alcohol Revisited on Low Carb by Dana Carpender and something she said jumped out at me:

No doubt, however, that alcohol can be fattening, not only because of the calories it contains, but because it slows metabolism - to quote a medical journal article I read, "Alcohol profoundly inhibits lipolysis." In English this means that alcohol slows fat-burning to a crawl. Like carbs, your body burns alcohol preferentially. Don't expect to burn any fat until you've burned through all your alcohol calories. 

First of all, Carpender makes the all-to-common mistake of equating lipolysis with actual fat-burning.  As I summarized in Lip-ocabulary , lipolysis is the breaking apart of triglycerides to glycerol and free fatty acids.   This occurs constantly in our bodies, inside the fat cells by hormone sensitive lipase (HSL) to release FFA's continually as part of the triglyceride/free fatty acid cycle, and in the capillary beds by lipoprotein lipase (LPL).  To further complicate the matter, lipolysis is not stimulated systemically in the same manner.  LPL can be activated in fat tissue so as to release FFA's temporarily so that they can be taken up into the adipose tissue, while it is reduced in muscles that don't need the fuel at the moment.  In any case, we continually recycle up to 60% of FFA back into triglycerides (storage form) both in fat cells and peripheral tissues.   Bottom line, lipolysis rates are not necessarily predictive of ß-oxidation - e.g. "fat burning".

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Metabolic Advantage, Obesity and Eric Jequier

Since I had the whole metabolic advantage thing on my mind writing my last post, and "Anonymous LC Author" mentioned Feinman and Jequier, I was reminded of something that's bothered me for a while now regarding citations of Jequier's work. 

A calorie is a calorie violates the second law of thermodynamics argues for the potential of a metabolic advantage in low carbohydrate diets.   Oddly enough, they ultimately make a first law argument for the MA, but that's a subject for another day.

It was this paper that introduced me to the work of Eric Jequier after which I stumbled upon the subject of my most popular post to date, Nutrient Fates after Absorption referencing this Jequier paper:  Nutrient effects: post-absorptive interactions.  But the Feinman & Fine paper cites a different Jequier paper to which the TEF values of macronutrients can be ubiquitously traced in LC circles.  That paper being:  Pathways to Obesity.  

Surely that paper is all about how we eat too many carbohydrates, right?  One might think so given that Jequier and his reported TEF differences are so often cited by those advocating for the supremacy of  low carb and/or those fingering carbohydrates as the cause of obesity.  But when one takes a closer look we see he feels quite differently:

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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.  

Of Thermodynamics, Chemistry, Biology and Biochemistry ~ Feinman Reply

In response to, this post:

Fred Hahn said...

I am posting this comment on behalf of Dr. Richard Feinman, professor of cellular biology at SUNY Downstate. 

"I never had to go through steam tables but I still teach bioenergetics in biochemistry courses where we think thermodynamics has a lot to do with human metabolism. 

Like most chemists and even some physicists, I would be willing to admit I don't understand the field that well but if you have a problem, feel free to write to me directly. 

I think it is touching that people get excited about thermodynamics but I expect polite discourse. 

Richard Feinman 

Professor of Cell Biology 

SUNY Downstate Medical Center 

feinman@mac.com

Here's the discussion at Eades' blog that resulted in my steam table comment:

Jim B, March 6, 2010 at 9:41 pm

In the last year, or so, I have experienced a re-education on thermodynamics. In the last 20 years or so, there has been a mojor change in the way the subject has been taught.

For over a century, the field was taught with primary emphasis on the heat engine, and a rigorous and nearly total exclusion of modern physics concepts – in particular quantum mechanics.

By introducing quantum concepts of “states” of a system, and the ability of people to “count” or enumerate the possible states of a system, the whole field can be made easier to understand.

Under the old system, it was often easiest to rely on memorization and pushing equations around to survive and answer test questions — but still to not UNDERSTAND what is going on.

The new system is much more rational. Less memorization is called for.

IRREVERSIBILITY

If you drop a book onto a table, all of the potential energy of the book is converted into heat in the table (and to pressure waves of the sound which ultimately end up as heat). The conversion of potential energy to heat is essentially perfect.

Yet, the heat in the table and the sound waves in the air never come back focused in time and space to recreate the conditions that existed on the falling book impact and then propel the book back into the air.

However, it is possible to convert electricity into potential energy at nearly perfect efficiency with a friction free electric motor(with superconducting wires) and a pulley and weight. It is possible to take the same weight and pulley and an electric generator (frictionless and superconductive wires) and nearly perfectly convert potential energy into electrical energy.

Heat – is impossible to convert perfectly into any other form of energy.

Heat = Thermal

Thermodynamics = dynamics of heat. conversions…. as the origin of the word.

The study of the strange way heat stubbornly resists efficient conversions to work or other forms of energy.

[ ... snip]

Reply

mreades, March 7, 2010 at 12:42 pm

Maybe I should go back and give it another look. I still get hives when I think about the steam table problems I had to do in my thermodynamics course in engineering school.

Reply

Richard Feinman, March 7, 2010 at 12:54 pm

Jim B,

What are the sites on the internet you had in mind? I did not find my thermodynamics courses so bad as difficult to understand (although I may still not know enough to distinguish). The reason that the subject is so elusive is that it is not a molecular science which is what we are good at. Rather it is physics of aggregates, that is, ensemble properties which we don’t have good intuitions about. Arnold Sommerfeld put it well.

He was one of the great physicists in the development of quantum mechanics but was considered an expert on most areas of physics. His take on thermodynamics along the lines of your description:

The first time I studied it, I thought I understood it except for a few minor details.

The second time I studied it, I thought I didn’t understood it except for a few minor details.

The third time I studied it, I knew I didn’t understood it but it didn’t matter because I already knew how to use it.

I've got to say it is sad that someone of Dr. Feinman's education could participate in this thread without demonstrating a MASTERY of chemical thermodynamics (no steam tables need apply) since he teaches a related topic.  I've studied thermo at both the undergraduate and graduate levels in physics, physical chemistry, biochemistry (and moreso in the offering from the chem dept vs. bio dept), electrochemistry, diffusion, advanced chemical kinetics, and metallurgical thermo.

So I'm "touched" that Dr. Feinman responded indirectly, but not by his condescending reply.  And I'm troubled that he doesn't seem to be versed enough in chemical thermodynamics to at least interject into that discussion that steam engine thermo is totally irrelevant to biochemistry.  I would also have to differ a bit with the first commenter quoted, Jim B.  There's no "old way" vs. "new way" to learn thermo -- it's just that it is different in different contexts. Likely, the first time most scientists and engineers encounter thermo is in a physical science class hence steam engine.  In that context we don't even associate entropy with "randomness", we deal more with the concept that heat cannot be completely converted to other forms of energy.

Entropy is a rather simple concept in Chemistry.  Although it may be difficult to understand how it is determined, the spontaneous "urge" towards a disordered state is a concept easily digested.  Free energy calculations are straight forward -- no calculus involved either.

There's also a trend in posts of people equating/confusing heat production with entropy.  This is in error.  Heat is an "out" term in the energy balance equation for a human being.  Even if we are put in a hot room, our bodies actively try to keep our body at appropriate temp ... we don't try to convert heat to other energy forms.  Heat is enthalpy, not entropy.  Indeed all of the enthalpy "H" terms are all called "heat of ____"  formation, solution, etc.  Just because heat is required (endothermic) or released (exothermic) in a chemical reaction this does not necessarily correlate with entropy changes.

I think the reason Atwater's calorie values tend to hold up pretty well is that they were determined for humans.  I have no doubt that any single individual might be able to eat a few more or have to eat a few less calories on extreme macronutrient restricted plans as they may well possess a genetic/biologic makeup that processes one or the other more efficiently, but genetic defects in these processes are rare.  But it seems highly unlikely that differences in efficiencies and entropy losses for energy production in humans are considerably different for the macronutrients.  I say this because the bulk of the production of our major "fuel", ATP, is generated in the SAME "engine" -- Krebs & ETC.

I will do a follow-up post in response to this because I've wanted to address the 2nd Law paper (What is someone who admits not understanding a field doing writing a paper on it anyway?) and Feinman's comments in that Eades blog post for a while now.

Brown Fat and the MYTH of Diet-Induced Thermogenesis

Brown Fat and the Myth of Diet-Induced Thermogenesis

INTRODUCTION:  The concept that brown adipose tissue (BAT) is a thermogenic tissue initially came from morphological changes in the tissue when animals were exposed to the cold (Smith and Horwitz, 1969). The physiological basis for the enormous capacity of BAT for heat production during cold exposure awaited the ingenious application of radiolabeled microspheres to measure blood flow in BAT and other tissues (Foster and Frydman, 1978). That production of heat occurred by uncoupling mitochondria was firmly established with the elegant experiments of Nicholls on physiology of BAT mitochondria and Ricquier’s identification of a unique cold-inducible protein in the mitochondria of BAT (Nicholls and Locke, 1984). The presence of large amounts of differentiated BAT in human neonates and species like sheep that require active thermogenesis at birth to protect the newborn from cold exposure on a snow-covered pasture in spring argues that BAT evolved primarily to function as a thermogenic system to protect body temperature (Casteilla et al., 1989).

What is a matter for debate is whether BAT thermogenesis burns off excess calories in a state of positive energy balance o maintain energy homeostasis as a major physiological function.  This concept emerged from experiments in the 1970s when Rothwell and Stock observed that rats fed a cafeteria diet (composed of junk foods high in fats and sugars) gained less weight than expected from caloric intake, and they proposed that excess unaccounted calories were being burned off by the induction of BAT thermogenesis (Rothwell and Stock, 1979).  Accordingly, BAT thermogenesis was proposed as a mechanism not only for protecting body temperature, but also to protect against obesity and the development of insulin resistance.  The data for diet-induced thermogenesis dovetailed with evidence that cold sensitivity and obesity phenotypes in ob/ob mice were associated with defective BAT nonshivering thermogenesis (Trayhurn et al., 1977). This idea that obesity was caused by a defective BAT set in motion a major effort by clinicians to find obese individuals with a slow metabolism. Prentice has commented on the depth of frustration experienced by clinicians when they failed to find obese humans with slow metabolism (Prentice and Jebb, 2004). Prentice blamed research investigating energy expenditure in the ob/ob mouse for this fruitless phase of obesity research in humans, concluding that the fundamental phenotypes of obesity and body weight regulation in ob/ob mice and humans were different. It is now well established that energy expenditure increases as a function of body mass in humans, and accordingly severe obesity is associated with an increase in energy expenditure (Leibel et al., 1995). Moreover, in the interim it became clear that ob/ob mice have neither reduced energy expenditure nor defective BAT per se. Energy expenditure in ob/ob mice was underestimated from the erroneous calculation of energy expenditure in studies comparing lean and obese mice, a problem that persists with a frustratingly high frequency to this day (Butler and Kozak, 2010).  Perceived defects in brown fat did not come from intrinsic defects in Ucp1 induction, but from secondary problems related to excessive white fat in morbidly obese ob/ob mice and regulatory problems arising from downregulation of b1- and b3-adrenergic receptors in ob/ob mice and other models of obesity that attenuate induction of Ucp1 and lipolysis (Robidoux et al., 2004). That none of the phenotypes of energy balance in ob/ob mice are due to modulation of Ucp1 expression was established with experiments showing that phenotypes of energy balance including food intake, adiposity, and oxygen consumption do not vary between ob/ob and Lep / .Ucp / mice under basal and leptin-stimulated conditions (Ukropec et al., 2006). Accordingly, the basic phenotypes relating to energy expenditure and obesity in mouse and human models of leptin null mutations are in agreement (Farooqi et al., 1999), and the data do not implicate BAT.

CONCLUSIONS:  Would it matter to our concepts of energy balance if there was no diet-induced thermogenesis? Probably not, since as I have argued from the phenotypes of several genetic models of thermogenesis, no compelling case can be made for diet-driven thermogenesis. Expenditure of energy to balance food intake would come principally from physical activity and maintenance of body temperature in individuals in harmony with their environment; this would exclude most modern humans.  The realization this past year that significant levels of BAT continue to exist in adult humans has opened the door to research that will aim to determine how this remarkable thermogenic system may be associated with the obesity epidemic and to discover new ways to utilize the potential to expand and activate BAT thermogenesis to prevent or reduce obesity in individuals. Similar excitement about the potential contribution of variation in BAT to slow metabolism and increased susceptibility to obesity occurred 30 years ago. The effort that flowed from this excitement and energy faded because we failed to understand that the function of BAT in mammals is to maintain body temperature in the face of a cold environment and not to maintain a normal body weight free of insulin resistance in the face of an obesogenic environment.

BOTTOM LINE?  The  title of this review says it all.  Those proposing a metabolic advantage for LC diets involving futile cycling of fat have no leg to stand on for that aspect.

Before The New Atkins

Westman, Volek and Phinney were among the contributers (and Westman headlined) the following, partially Atkins Foundation funded, review:

Low-carbohydrate Nutrition and Metabolism

I can't recommend reading this highly enough.

I've listed the references in a separate post, numbered (the formatting farkled the last few but I'll let you count ;) )

For a non-gimmicky discussion of how low carb diets REALLY work for weight loss, this is where it's at!

A calorie is a calorie!

Is a calorie a calorie?
Andrea C Buchholz and Dale A Schoeller
 

Wanted to post this here for my own organization.  This review looks at the results of various studies comparing high protein (OK, OK, yeah Atkins is high fat not high protein ...) low carb diets to low fat.  Their ultimate conclusion is, basically, yes.

 

Given the Eades/Colpo dust-up over at their respective blog/sites, this whole thing has come up again.  I think it's important to remember that food calories are a measure of metabolizable energy.  The 4/4/9 P/C/F numbers are averages that were determined for mixed meals.  But this should be accountable for in excretory products, because not only do we have thermodynamic laws, there's ultimately a conservation of mass issue.  Changing the proportions of macronutrients doesn't change the way(s) they are metabolized, though in the case of protein its use is changed.  A fatty acid that goes into the fatty acid spiral will produce the same amount of ATP whether or not carbs are around.  If it didn't, then there would be some FA fragment floating around that has to go somewhere.  The only macronutrient that seems to change in the presence or absence of carbs is protein.  Protein is thermogenic.

 

If a metabolic advantage exists, it would show up consistently, and increase with time.  As pointed out in this study, most of the extra weight loss at 12 weeks was already accomplished at 6 weeks (and could be attributable to water weight).  Furthermore, the Atkins trajectory for weight loss in one famous comparison study, "The  A to Z Weight Loss Study" is in the opposite direction from 6-to-12 months.  See below (click to enlarge)

I'm not sure if this is statistically significant, but if you look at Atkins vs. Learn, most of the difference is in the 1st two months and after 12 months, the difference is not much more than it was at 2 mo.  Further, if there's a significant advantage at 2 months, one should see that difference in loss triple for 6 months, and be 6X as great at 12.  This clearly doesn't happen. 

In most studies, it is degree of compliance to any plan that correlates best with weight loss.  It just so happens that LC's less structured plan and appetite suppression of protein assists greatly in this endeavor.