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

BUMP!

In addition to blogging on several topics raised during Stephan Guyenet and Gary Taubes recent appearance on the Joe Rogan Experience podcast, I've decided to bump some of the past content on this blog relevant to some topics discussed and/or research studies mentioned.  I'll include a little commentary with each.

At around the 12 minute mark, Stephan makes a great opening play, and then gets distracted or flustered into fumbling the football.  Stephan asks what it is about the food environment, etc. that causes obesity, and distills it down to the simplest of questions (paraphrase):

Q:  What is the most fattening diet on the planet?
A:  Human junk food.

Nail.  Head.  Boom.  He then calls out some numbers from the research summary he posted on his blog in advance of the podcast.   The study I discuss in this blog post is the one included in "#52" that he's discussing in the podcast.    Joe seemed perplexed by this idea that we couldn't replicate the junk food fattening with sugar or even fat alone.   Joe seems fixated on junk food = sugary "bullshit diet".  He gets very confused, despite Stephan laying it out fairly well.  Give just sugar/refined carb or give just fat, and the rats don't get AS obese as they do when you give them a mixture of sugar/fat and FLAVOR in human junk foods.    Yes, Joe, soda is just sugar and is a junk food, but junk foods are  also things like donuts, cookies and ice cream or pizza, fries and Doritos.  Carb + fat + flavor. 

While the CAF rats are indeed rats, this study does a fairly good job in demonstrating that it's not just the macros.     Four diets:  Standard Chow (mostly grains, 12% fat) , Low Fat Refined (35% sugar, 10% fat) diet, High Fat diet (45% fat, as lard and soybean oil) and CAF -- a wide assortment of junk foods from sugary breakfast cereals, to Doritos, to pork rinds, to wedding cake.   If it's carbs and insulin, why don't the rats on the SC get fat?  If it's just refined carbs, why don't the sugar rats get fat?  If it's just the fats, why don't the lardos get fat?   These two groups of rats did gain more weight, but -- as Stephan mentions -- they don't gain a lot more, and more importantly, they don't overeat energy.  The CAF rats, meanwhile, consumed over 30% more food/calories and got a whole lot fatter. 

Gary's Response:  We're looking at this wrong.  Calories are the wrong way to look at this.  

SIGH

Other blog posts discussing this study:

• Why We Get Fat ... Lessons from Obese Humans & Cafeteria Rats (3/9/11)
• Why We Get (Sick) Fat (and Sick Livers) - Lessons from a Cafeteria Rat (3/8/11)
• Taubes' Rat Problem  (I think this one is most relevant to current topic).
• Revisiting the "Cafeteria Rat" Study -- Why Doesn't Everyone Get Fat?  (7/1/12)
• Lessons from the Cafeteria Rat: Adiposopathy ~ How/Why Does Fat Get "Sick" (8/1/15)

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{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 designed to be predisposed towards obesity.  It is, however, often used in diet induced obesity (DIO) studies.

Guyenet v. Taubes ~ Topic 1: "Just 10-20 Calories a Day"

Unless you've been living under a "rock" in the world of nutrition, you're aware that Stephan Guyenet "debated" Gary Taubes on the Joe Rogan Experience podcast.

It took me several days broken up to watch/listen to the whole thing. In a nutshell, it was Science & Substance (Stephan Guyenet) versus Stories & Slander (Gary Taubes).

Rather than summarize, there were several points made that I'd like to address. In no particular order. I'll include this intro with links to prior topics as this series progresses.

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The $12M NuSI/Ludwig Study ~ Part V: Intake, REE and TEE Measures

Summary:

Continuing on with discussion of:  Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

Previous posts in this series:

Part I: Critique of the Study Design

Part II: $12 Million for 12% Weight Loss?

Part III: Some "Early" Lessons

Part IV: Insulin Resistance Does Not Hamper Weight Loss

This post should perhaps have come first, but it has taken a while to look deeply at the data for the primary outcome -- total energy expenditure measured by doubly labeled water -- and related outcomes of intake and resting energy expenditure.

In this study, all participants were paid to participate, AND provided free food for ~8 months.  Said food was professionally and meticulously prepped, weighed, measured, individualized to provide each subject with some pretty exact caloric level and macronutrient composition.  The test phase (in other words, the study proper) involved maintaining a consistent weight (to within ±2 kg), for a considerable length of time:  20 weeks, assessed at the midpoint and the end.

In the previous study, a roughly 300 calorie/day increase in TEE was observed during 4 weeks of isocaloric feeding, producing no weight loss.  This was essentially dismissed as "not enough time to show weight loss"  {paraphrase}   ....  So in the current study, the average change in TEE masks the often wild swings of up to 2000 calories per day between 10 week maintenance time points.  If this increase (or decrease) in expenditure is truly real, the subjects would HAVE to have adjusted intake accordingly over the course of several weeks in order to maintain consistent weight.  

This post is about the massive discrepancies between intake and TEE data (also compared with REE), and the inexcusable near-dismissal of these discrepancies in the journal article.

Bottom Line:

Either the DLW-TEE data is (for reasons that can be discussed) unreliable/inaccurate, or the intake data is unreliable. If the TEE data is problematic, how can a result of a difference of means of 250 cal/day be justifiably defended as significant/meaningful, when we see no such difference in intake? If the intake data is problematic, then how can we conclude anything from a "diet comparison", because significant deviations in caloric intake would render the strict macro compositions totally irrelevant. 

Either way, the researchers failed to address this glaring problem with the results study.  Further, the discrepancies in these two data sets are so egregious that it is impossible that both can be considered accurate and reliable.  It has to be one or the other.  Based on the data for Resting Energy Expenditure (REE), the needle points to the intake data as the more reliable measure.

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The $12M NuSI/Ludwig Study ~ Part IV: Insulin Resistance Does Not Hamper Weight Loss

      

Continuing on with discussion of:

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

No summary for this post.  Here are links to earlier parts in this series:

Part I: Critique of the Study Design

Part II: $12 Million for 12% Weight Loss?

Part III: Some "Early" Lessons:  In this most recent post, I discussed the relationship between measures of insulin (both fasting and 30 minute OGTT response) and weight loss during the Run-In Phase.  

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The $12M NuSI/Ludwig Study ~ Part III: Some "Early" Lessons

SUMMARY

Continuing on with discussion of:

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

In Part I, I discussed some issues with methodology, mostly focusing on the reduced Run-In Phase that likely compromised the outcomes irreparably.

In Part II, I highlighted a serious issue with the Run-In Phase, the purpose of which was to produce a somewhat homogeneous "reduced weight state" to test various diets in maintenance of that state.

Ultimately, since randomization to the various test diets occurred after weight loss (PWL) randomization to maintenance test diet would not influence the impact of various BSL (pre-weight loss baseline) measures on the Run-In outcome -- target = 12% ± 2% weight loss -- on a standard composition diet for all:  45% Carb / 30% Fat / 25% Protein.

The researchers appear to have made minimal adjustments, if any, during the Run-In Weight Loss so as to produce a more uniform result.  Rather, the result was a wide range of weight loss (5.6 to 16.0%, roughly 10.5% ± 5%) . 

Thus we have an "accidental" test-within-a-test of the CIH/TWICHOO from these "early" results.

In the end, I offer these scatter plots for all 105 subjects who successfully completed the study, for whom complete data for insulin measures and energy expenditure were available at all time points.

The Carb-Insulin Hypothesis (aka TWICHOO) predicts that weight loss will vary inversely with insulin levels:  The higher the insulin levels, the lesser the weight loss.  The Run-In Phase data supports no such relationship (indeed, if anything, absolute weight loss was greater for those with higher baseline insulin measures.

Meanwhile, differences in weight loss are easily explained by variation in caloric deficit during the calorie restricted Run-In due to coarse estimation of baseline energy expenditure (vs. rigorous measure).

This post expands on some relationships of baseline (BSL) and post-weight loss (PWL) measures as observed during the weight loss portion of the Run-In Phase.

Bottom Line:  Baseline insulin status seems to be irrelevant to weight loss on a "high carb" calorie-restricted diet.  

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The $12M NuSI/ Ludwig Study ~ Part II: $12 Million for 12% Weight Loss?

UPDATE:   12/17/2018     Original Posting: 12/3/2018   

During the writing of a new installment in this series, I revisited the following paper:

A randomized study of dietary composition during weight-loss maintenance: Rationale, study design, intervention, and assessment

Yes, folks, so full of themselves were these researchers, that they felt the need to write an entire paper (submitted approx. one year in advance of the "real study") outlining their amazing study. Regarding this post, focusing on the OUTRIGHT FAILURE TO IMPLEMENT THEIR STUDY DESIGN AS STATED, I stress the following from the previous paper.

ONCE AGAIN, the stated goal of the weight loss run in is 12% ... not 10 or 5 or 15 or whatever ... 12%.  I'm just going to quote the relevant part here (cleaned of references, etc. and formatted for readability, all emphasis mine)

Energy intake was restricted to 60% of estimated needs to achieve a target weight loss equating to 12 ± 2% of baseline body weight, with a minimum of 1200 kcal/d. We asked participants to weigh themselves daily using Wi-Fi scales, and the amount of food provided was increased or decreased as necessary to reach the target weight loss over 9 to 10 weeks. 

Previous studies have indicated metabolic adaptation characterized by declines in resting energy expenditure (REE) and TEE with weight loss corresponding to 10% of baseline weight. With 20% weight loss, REE may not decline further, but TEE may continue to decline at a slower rate due to shifts in non-REE. 

We selected the 12 ± 2% weight loss target to ensure significant metabolic adaptation without imposing greater burden (on participants and the study) of a larger weight loss target.

Only they must not have done this as weight loss in this study was roughly 10.5% ± 5%.  FOR SHAME.

/UPDATE

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SUMMARY

This post focuses on a critical issue with the Run-In phase of the recently released $12 million dollar NuSI funded study led by David S. Ludwig MD, PhD: Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. On occasion I reference the 2012 predecessor: Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance.

Virtually every stipulation leading up to the study, the Abstract and Full Text of the journal article, and continuing through to Ludwig's November 28, 2018 response to Kevin Hall in BMJ,  has stated that the MAIN purpose of the Run-In phase was to achieve 12%  ± 2% weight loss.  The study was intended to test the so-called Carb-Insulin Hypothesis during 20 weeks of weight-stable maintenance on diets of varying carbohydrate content.


OUTCOME:

With only 10 weeks of 60% calorie restriction during Run-In, the subjects who completed this phase averaged 10.5% weight loss (std.dev. 1.7%), ranging from only 5.6% up to 16.7% weight loss.  This doesn't change much for analyses of just those completers for whom complete energy data are available (same mean, SD = 1.5%, range 5.9% to 16.0%).

This indicates an unacceptable variation in the post-weight loss (PWL) "biological state", and to use this as the baseline "anchor" for diet comparisons is negated by either Study Design and/or execution thereof.

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The $12M NuSI/Ludwig Study: Part I: Critique of the Study Design

SUMMARY

The results of the $12 Million Dollar NuSI-sponsored study, headed up by Dr. David S. Ludwig, are finally out.  

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

While the good doctor is making the rounds touting them as evidence in support of the Carb-Insulin Hypothesis (TWICHOO in these parts), a review of the raw data made available to the public casts grave doubts on his victory lap.  This study built upon the "promising" results of the 2012 study:  

Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance  

This post focuses on comparisons of Study Design between these two studies, some improvements, and the ultimate failure that renders the primary outcome data suspect, if not outright useless.  (And I don't say that lightly!)

Improvements:

• Study size
• Length of time on one test diet (20 weeks) vs. 4 weeks crossover on each diet w/o washout
• Protein held constant between test diets
• Macro extremes the same -- e.g. LCHF = 20% carb/60% fat , HCLF = 60% carb / 20% fat
• Post weight loss (PWL) assessment of TEE
• Intake adjusted to maintain weight

Detrimental Changes:

• Drastically altered run-in phase 
• Shorter in total:  16 weeks vs. 20 weeks
• No monitoring period before gathering baseline data.
• No baseline intake assessment
• Shorter weight loss phase:  10 weeks vs. 12 weeks
• More varied weight loss and no minimum loss established to be included in the test phase.  In previous study, all subjects had to achieve at least 10% loss, averaged 13.5%.  Current study, losses ranged from 5.6% to 16.0%
• Only 2 weeks for weight stabilization vs. 4 weeks.
• Added ad libitum snacks for those who needed to increase caloric intake in maintenance but could not tolerate the larger meals necessary.
• Assessing post weight loss DLW-TEE during the same two weeks immediately following weight loss that are designated for stabilizing reduced weight.
• Changing protocol to anchor TEE changes to this flawed PWL measure of TEE instead of baseline per original protocol.

Why Aren't We Taking Anti-Obesity Drugs?

This post was prompted by the following article on Medscape

Why Aren't We Prescribing Pills for Obesity?

It is written by Caroline M. Apovian, MD 

I'd encourage you to read this whole thing first, as I'm genuinely interested in that response. Additionally I'm curious as to whether or not your response changes after reading this blog post (or other sources I'm about to link to).

"Real Food Keto" Quips

Rather than formally reviewing Real Food Keto -- an abomination of a book written by Jimmy Moore and his "Nutritional Therapy Practitioner" wife Christine Moore -- I've decided to compile a collection of my tweets here in a blog post.  I'll sort from most recent, with the newest before the "page break" after each update.  Feel free to comment here, but I'm also embedding tweets if you wish to go respond on Twitter.   Some may include additional commentary, others just the tweet. Enjoy!

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This book is littered with nonsense about how low stomach acid causes everything from ass itching  to zygomycosis.   No doubt there will be more of these tweets coming!

Fun #RealFoodKeto "facts" from @livinlowcarbman and his NTP wife.

FACT: Lemon juice (mostly citric acid) gives it a pH ~2.  Add some to neutral water (pH 7), the lemon water will be less acidic (e.g. higher pH, closer to 7) but will not become alkaline (pH >7)#LCHF-raud pic.twitter.com/QX7gJ1x6qS

— Evelyn (@CarbSane) October 31, 2018

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Swan Song

[no I'm not retiring the blog]

TLDR:  Rather than dragging things on by dismissing more black swans, Gary Taubes could eat crow and go quietly into the night.

After a long hiatus from any meaningful new content, and monumental blows to TWICHOO (Taubes Wrong Insulin Carbohydrate Hypothesis Of Obesity -- c'mon, it has a much better ring to it than the Ludwigian version),, Gary Taubes has gotten back to blogging a bit.*

He has apparently been reading (in fits and starts, in other words, probably not really reading) obscure books about obscure cultures from long, long ago.  Mind you, that in five years plus of arduous and comprehensive research put forth in Good Calories, Bad Calories, there was no mention of the Yahgan people he's about to discuss.   One wonders why not.  Heck, this is right in his time period of excellence for nutritional research and reporting!  (Uttermost Parts of the Earth, this is to a 2007 version of a book Taubes states was published in 1948).  But alas, no Yahgan (I also checked Wikipedia's alternate spellings), among the conventional-wisdom-challenging by Taubes circa 2007.

It's OK really, nobody expects you to track down every obscure culture, especially one that counters your hypotheses.  Shhh... look away ... no paradoxes to be found here!

Fast forward to 2018.  Currently, Gary Taubes has been  thinking about black swans as he engages in a bit of light Summer reading.  Perhaps no longer needing to devote so much time to NuSI has opened up a lot of free time for such endeavors.

(*something I still hold out hope of doing more of myself)

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