Will NuSI clear the bar?

Gary Taubes is out with a new article in Scientific American ... rehashing the same old same old, and essentially getting paid to write a press release for NuSI.  

What Makes You Fat: Too Many Calories, or the Wrong Carbohydrates?

Rigorously controlled studies may soon give us a definitive answer about what causes obesity—excessive calories or the wrong carbohydrates

We get the rehashing of how WWII stopped Bergmann and Bauer's Lipophilia Hypothesis from becoming the working hypothesis for obesity, and yet another primer on calories vs. carbohydrates.  We again are asked to ignore the obvious -- that Americans are definitely eating more, on average, with no concurrent need for those calories, and likely moving a bit less as well.   The obesity epidemic that supposedly was instigated by the low fat craze is blamed on the fact that much of our additional caloric load is in the form of carbohydrates.  This is not supported by one of Gary Taubes' own paradoxical cultures, the Pima, who did not eat a low carb diet prior to the 1900's, let alone billions of humans all over the globe.   Or .... despite the "modern paleo's" insistence, the paleolithic diet in the literature -- both cited for the basis of the diet and that used in clinical trials.  

But most importantly, this does not even pass the smell test based on every assessment of the American diet circa 1970 and 2000+.  There are minor differences between NHANES and some other studies, but generally the macronutrient composition of the SAD has changed very little.  More importantly, they all point to us eating on average somewhere in a 300-500 cal/day range more.  (I seem to recall one study even putting that surplus in the 600 range).  While protein has stayed roughly constant as a percent, fat was reduced by 3-4% as carbs were increased by the same percentage.  A generous "rounding" of the dietary changes would have protein at 15% and a swing from carb/fat from 45/40 to 50/35.    We could even go further than that and look at 55/30 as the "prescribed" SAD.   Of course we would have to ignore the fact that Americans are not eating less (in absolute amounts) of any macronutrient (there's one that has men eating a few grams less, insignificant), but:

Iff* the obesity epidemic is due to some hormonal effect brought on by the macronutrient composition of the diet, we should be able to see this studying a macronutrient change within  the range -- even an exaggerated one as above -- that has been associated with this obesity epidemic.  This would seem to be plain logic.  If you say A causes B, then that is what you should test.    *Iff = if and only if

So the press release begins:

Why do so many of us get so fat? the answer appears obvious. “The fundamental cause of obesity and overweight,” the World Health Organization says, “is an energy imbalance between calories consumed and calories expended.” Put simply, we either eat too much or are too sedentary, or both. By this logic, any excess of calories—whether from protein, carbohydrate or fat (the three main components, or “macronutrients,” in food)—will inevitably pack on the pounds. So the solution is also obvious: eat less, exercise more.

The reason to question this conventional thinking is equally self-evident. The eat less/move more prescription has been widely disseminated for 40 years, and yet the prevalence of obesity, or the accumulation of unhealthy amounts of body fat, has climbed to unprecedented levels.

I would point out that the publication of Atkins' first book -- all in all his books read by millions and tried by countless more -- dates to just about 40 years ago, to no greater long term success.

But of the any-macro strawman, while it doesn't add to fat mass, excessive protein does "pack on the pounds" as shown in the recent Bray study blogged on HERE.  This metabolic ward RCT involved overfeeding roughly 40% of weight stable calories (around 950 cals) on one of three diets by protein content:  low (5%), middle (15%) and high (25%).  It was relatively small (n=25, LP=8, MP=9, HP=8) and overfeeding lasted 8 weeks.  I constructed the table below of the results:

Try as Richard Feinman may, he could not convince JAMA of his carbophobic agenda and they rejected his letter.  This was likely because all of the surplus calories were in the form of fat and/or fat and protein, and as you can see from the table, the carb consumption actually decreased slightly.   So here is a metabolic ward study demonstrating that when you eat surplus fat calories, you add fat mass, and if you consume sufficient-to-surplus protein along with that caloric surplus, you add fat mass and lean mass to really pack on the pounds.  No carbohydrate induced additional fat-trapping insulin required.  Indeed, the lowest insulin-stimulating diet, LP, resulted in a trend, if anything, towards higher fat mass gain (not stat.sig.).

This is but one study, I'll discuss a few more.  But the long term success rate of weight loss diets does not invalidate the calorie law (I will call it such as I am not aware of any metabolic ward study where subjects failed to gain weight on a caloric surplus or lose weight on a caloric deficit regardless of composition).  But back to the NuSI-is-funding-a-study promo ... pre WWII blah blah ... hormones ... carbs ... insulin ... blah blah ...:

After a decade of studying the science and its history, I am convinced that meaningful progress against obesity will come only if we rethink and rigorously test our understanding of its cause.  ... [plug for NuSI] ...  The investigators will follow the evidence wherever it leads. If all works out as planned, we could have unambiguous evidence about the biological cause of obesity in the next half a dozen years.

Almost a year ago, now, I wrote a blog post entitled NuSI Again: A Bar Too High, Occam's Razor and Rabbit Holes.  I've already discussed the Occam's razor part -- that being the "obvious" calorie connection.  But let's refresh about how NuSI is setting the bar very high.  Gary Taubes has been overusing the term rigorous in relation to science a lot lately.  Anyone who has read this blog even a little, or read this post on Taubes' blog or listened to even a smattering of his lectures on YouTube is well aware of the disregard and contempt in which he holds obesity researchers specifically, and pretty much all scientists in general.  

Is it fair to say that I think they are all idiots? A surprisingly good question.

Certainly one subtext of my talk (and my work) is that a journalist is getting it right and sixty-odd years of nutritionists and obesity researchers got it wrong (with maybe a half dozen exceptions who were marginalized for their beliefs.) So, yes, it was fair to say that I think a large body of otherwise very smart people, Ph.D.s and M.D.s all, were operating with suboptimal intelligence. Certainly in a pursuit — science — in which the one goal is to get the right answer, getting the wrong answer on such a huge and tragic scale borders on inexcusable.

~ Gary Taubes

OK ... fine words from someone who wrote three PhD theses worth on cherry-picked, often outdated, and even more often misrepresented science.   Interviewer: "There is a problem lying behind the calorie issue, is what you are arguing", Taubes responds:

Yes, well, this is one of the many arguments against. But the alternative hypothesis…I spent about 10 years studying this. My background was in rigorous science, I started out in physics, but I moved into nutrition and was stunned at how bad the science was. And I started going back in time to try and find some baseline experimental data that you could believe in.

So in the course of my research I ended up reading the European literature prior to World War II. Science is effectively a European invention, done best in pre-World War II Germany and Austria. ...

Rigorous science?  But the NuSI founders, Taubes and Dr. Peter Attia, do make an attempt to summarize the so-called "bad science" they intend to replace with the "good" HERE.

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(3/31/2019

EDIT #1  3/31/19:  This has long since been removed from the NuSI website.  You can access a copy HERE instead.

EDIT #2: In a reddit AMA with Taubes, when confronted with a lengthy list of scientific research countering TWICHOO, Taubes shares the origin of NuSI's review of the literature.

"Ok. I obviously don't have time to go through this list, but I can say that we (NuSI and Stuart Buck, the director of research at the Arnold Foundation) recently tried to assess all the relevant studies to see if any of them settled the energy balance vs. carbohydrate hypothesis definitively. Our list of the relevant studies is posted at NuSI along with an assessment of each trial. Here's the URL: http://nusi.wpengine.com/wp-content/uploads/2012/09/Summary-of-Diet-Studies-Condensed.pdf"

In other words, Stuart Buck and perhaps some underlings at LJAF or NuSI conducted a literature search. 

/END EDITS)

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So all of these studies ...All meaningless and useless.  No DEFINITIVE answers.  Perhaps that's true, but tons and tons of evidence explicitly refuting the plausibility of  what I call TWICHOO (Taubes Wrong Insulin-Carb Hypothesis of Obesity).   Please read the Bar too High post for details regarding the 7 points of discontent NuSI lists on this research page.  But these boil down to:

• Free-living studies are useless (except when you need to quickly replace your smashed G3P theory with a carbs v. calories analysis using such a study, Shai).
• Metabolic ward studies are expensive and thus are short and small in number. 
• The low carb diets tested aren't low carb enough and/or studies do not vary carb content.  

Interestingly, and why I discussed it previously, one of the studies they have nice things to say about in their summary is that Bray overfeeding study.

Well-performed over-feeding study that addresses the effects of overfeeding on fat and protein, but not the relevant question -- the effect of carbohydrates on weight regulation. The carbohydraete content of all three diets was equivalent - roughly 40 percent of calorie. The trial also assumes that overconsumption of calories is the fundamental cause of fat/weightt is gained. This is also a hypothesis to be tested. 

Well, it's true that this study didn't look at carbohydrate overfeeding, but so what?  Surely this demonstrates that eating too much, or adding fat and/or protein on top of a baseline maintenance diet caused fat gain.  And yet, there was another overfeeding study that did make the summary cut, Horton et.al. Fat and carbohydrate overfeeding in humans: different effects on energy storage.  Here's what they said about this study:

Hypercaloric diet, 14-day trial, adding 50% excess carbohydrates or fat to a baseline diet that could already be carbohydrate-rich. Neither diet would reduce insulin levels below baseline. 

Neither diet would reduce insulin levels below baseline?  Are they still trying to prove the you-can't-gain-fat-without-eating-carb nonsense?  While it is not specified in the study, that "could" was easy enough to ballpark from information in the study.  Baseline diets were determined from two weeks of careful logging of the usual diet.  For the lean subjects, calories were ~2650/day assuming 15% protein and the 36% fat reported, works out to around 100 g each of protein and fat and ~325g/day carbs (did I mention these were the 9 lean subjects?).  The obese consumed ~3350 cal/day assuming 15% protein and 33% fat reported, works out to about 125g/day each of protein and fat and ~430 g/day carbs.   This would mean that the lean subjects were overfed around 1300 calories of fat only (~145g) or carbs only (~325g) for a total carb intake of  750 g/day.  The obese worked out to ~1650 cals, 180g fat or 415g carb overfeed, a whopping 850g carbs/day in the carb overfeed!   

Apparently nothing in the abstract where the study authors state that 75-85% of the excess carb energy was stored while 90-95% of the excess fat energy was stored was of interest to whomever compiled the NuSI research summary.  But further:

Carbohydrate overfeeding produced a very different picture. Progressive increases in both carbohydrate oxidation and total energy expenditure were seen with carbohydrate overfeeding. Both were evident on the first day of overfeeding and reached maximum by day 7. The increased energy expenditure seen with carbohydrate overfeeding was approximately double that which could be explained by the combination of increased TEF and increased body mass. Thus with carbohydrate overfeeding, more of the excess energy was oxidized and less stored in the body than was seen during fat overfeeding. 

This was a pretty well designed study but did suffer from the limitations of metabolic ward studies -- size and duration.  Definitive answers?  No.  Some answers?  Yes.  Pointing towards calories or carbs as culprit?  The calories have it, because you gave obese subjects an insulin tsunami and they gained less calorie-per-calorie than the same subjects gained from the fat bombs.

Back to our press release.  Under the heading "rigorous experiments" Taubes suggests that 20 years of experiments have indicated that low carb advocates are on the right track and his borrowed long-defunct hypothesis is indeed correct.  He then waxes poetic and expands this to diabetes, heart disease and even cancer!  Carbs kill and NuSI is going to prove it.  *SIGH*  He then goes on to discuss how the causes of obesity are difficult to test because it takes a long time for obesity to develop.  (True, but they can get significant weight gain in reasonable timeframes nonetheless).  Thus NuSI will first test their hypothesis in the context of weight loss .... by ... drumroll please ... manipulating macronutrient composition in a weight-maintaining isocaloric state.  

NuSI is actually funding a study about to get under way!

• It is going to be a metabolic ward study. Good. 
• Sixteen subjects. Eh ... more than some, but far from large enough to render the proposed study superior to any of the multitude of prior metabolic ward studies already in the books. 
• Overweight and obese subjects.  
• The baseline diet will be 50% carb (15% sugar), 35% fat, 15% protein -- The caloric level of this diet will be "carefully manipulated" until they are sure this is a weight maintaining level, and then ...
• The ISOCALORIC study diet: "The total carbohydrate content of the new diet will be exceedingly low—on the order of 5 percent, which translates to only the carbohydrates that occur naturally in meat, fish, fowl, eggs, cheese, animal fat and vegetable oil, along with servings of green leafy vegetables." They will keep calories and protein constant ... meaning this will verge on the NuttyK at 80% fat.  
• " The idea is not to test whether this diet is healthy or sustainable for a lifetime but to use it to lower insulin levels by the greatest amount in the shortest time."
• Metabolic rate, etc. will be determined in a metabolic chamber.  Good.
• Unspecified study duration - both the duration on the baseline maintaining diet and on the study diet.

It sounds to me like they are trying to prove some sort of metabolic advantage -- inefficiency -- of a very extreme form of the low carbohydrate diet.  Not answering the question of how we get fat.  They plan to do this with a diet, I might add, that is virtually impossible with real, whole foods and requires large amounts of refined fats.  Even bacon is like 60:40-70:30 fat:protein as are eggs, so you're talking a lot of butter, cream and/or oil.  They do know that the Buttertons are fictional, right?  How is this superior rigorous science in action?  Some questions, comments:

• Do they really expect to see weight loss?   
• If they saw weight loss, of what relevance to real life situations would this have?  Even the Inuit ate diet averaged around 50% fat and almost 45% protein (three times what this study diet will contain).
• Will they do a full metabolic workup including liver function?  Body composition including intramuscular and organ fat content?  That might make the cost of the study worthwhile and answer some of the real questions about extreme LCHF diets.
• There is no mention of food quality on the baseline diet.  Will the 15% sugar be in the form of soda, juice drinks and candy or will it be mostly from fruits as the current dietary guidelines clearly stipulate?  This is important, because NuSI's mission is supposedly to revamp the guidelines that have inadvertently caused an obesity epidemic in their eyes.  In this case it likely won't matter as they will have to include refined dairy fats and oily dressings in the test diet to make it palatable to normal people (that haven't convinced themselves that swigs of bacon fat are delicious).   Still, if the test diet is going to be meat/poultry/fish, cheese, eggs and fats, the baseline diet should include a range of whole carb sources like beans, tubers, fruits and real "whole" grains and not just white flour pancakes with syrup, sugary low fat milk and such.  

I realize health is not the issue here ... only it should be because the purpose of NuSI is to solve the burdens the obese place on the world.  Supposedly this means they care as much about health as changes in weight.  Or not?

In Conclusion:

This study will not clear the bar NuSI set.   It will also not provide any more information than is already available from existing metabolic ward studies such as Grey & Kipnis (request access) and Leibel/Hirsch et.al.  Even the recent Ebbeling et.al. study (link to blog post) was well compliance-controlled (albeit with some design flaws that marred the conclusions that could be drawn) even though it was not a metabolic ward study.  The macros varied widely but in the end, when calories were cut and subjects adhered to the restriction, they lost weight.  When calories were increased to a degree, they maintained weight regardless of the macro composition of the new weight maintaining caloric levels and despite differences in metabolic rate ascertained by their methods (likely measurement error or otherwise compensated for elsewhere).  

Similar happened in Weigle (also link to a blog post) although the time frames were too short, perhaps, to see the effect of protein-for-fat swap.  Calories aren't given but in this study subjects ate 50% carb throughout, 15/35 P/F to weight maintenance then 30/20 for two weeks calorie matched to weight stable, then ad libitum for 12 weeks of the 30/20.  By spontaneously cutting about 440 cal/day subjects lost weight -- if one presumes 2500 cal/day to start, we're talking a reduction of carbs from just over 300 to around 250g/day.  Just another of seemingly infinite studies demonstrating that calories and not carbohydrates are what counts in the weight gain/loss game.  Protein seems to be the only macro that alters body composition (and often in conjunction with specific activity).  

In the press release Taubes writes:

One drawback to this rigorous scientific approach is that it cannot be rushed without making unacceptable compromises. Even this pilot study will take the better part of a year. The more ambitious follow-up trials will probably take another three years. As we raise more funds, we hope to support more testing—including a closer look at the role that particular sugars and macronutrients have on other disorders, such as diabetes, cancer and neurological conditions. None of these experiments will be easy, but they are doable.

There is absolutely nothing more rigorous about their proposed study than many of the metabolic ward studies that preceded them.  Nothing.  Where would the results of this pilot study lead them?  Let's just say for the sake of argument that these people lose a statistically significant and clinically significant amount of weight on this diet over, say, an 8 week period.  Would they continue the study for a longer period?    Is this of any practical relevance to the current obesity epidemic?   If you think so, check your skirt, your bias is showing.

I keep coming back to the obvious.  Occam's Razor.  Humans never ate such a diet so it would be interesting to see if this even meets the ethics threshold, especially if it is going to last a significant amount of time.   It will, however, be a way to spend some millions of dollars, get paid to write more press releases, draw a salary from the non-profit and pretend to be doing it all in the furtherance of saving the human population from itself.