Gary Debunks Taubes II ~ It's the Frucose Stupid, revisited

Gary Taubes had a problem on his hands for his "Alternate Hypothesis" on the cause of obesity. While Why We Get Fat was in the writing stage, a couple of NIH biophysicists remained pesky thorns in Gary's side having challenged him on a lynch-pin of TWICHOO (Taubes Wrong Insulin-Carbohydrate Hypothesis Of Obesity).   Not to mention an equally pesky then-anonymous bunny-eared blogger who posted some pretty damning stuff on the subject, especially when she looked at his seminal reference on the subject from GCBC.  Downplay as he might, try to move on and have everyone forget, as he eventually relented and did, Taubes' original WWGF remains enshrined in the first journalistic effort on the topic: Good Calories Bad Calories.

It wasn't all that long ago that people were shouted down in forums and comment sections of the low carb persuasion for daring to suggest that people could gain weight on low carb.  Remember the meme?  At least you won't gain weight being a fat glutton?  Can't gain weight so long as there's no carb around?  It was all there in black and white in GCBC-- you need glucose to make alpha glycerol phosphate (aka glycerol-3-phosphate) to store fat.  

Well ... he was forced to abandon that one and come up with some more imaginative ways carbs really make us fat after all for WWGF.  Since then his lecture schtick has also evolved to include a new mechanism for obesity -- one that the Japanese don't thwart so brazenly provided you buy that they eat virtually no sugar.  

TWICHOO 1.0:  carbohydrates → insulin spikes → hyperinsulinemia → glucose to fat & fatty acids trapped in adipocytes → fat accumulation/obesity    

... ancillary to this version was this notion that insulin spikes → insulin resistance in muscles first → more glucose to fat in adipocytes. 

TWICHOO X.0:  fructose → insulin resistance → hyperinsulinemia → fat trapped in cells → overeating and/or wasting of lean tissue → obesity      

... in this version, Taubes posits that the "metabolically healthy" can likely eat insulin-stimulating starches to no ill effect so long as they remain insulin sensitive (e.g. don't consume fructose).

There are problems with the evolution of TWICHOO.  A scientist -- as Gary likes to play in journalistic arenas -- is entitled to tweaking and altering their hypothesis in the face of new evidence. Actually, they are compelled to do so. And do so unambiguously they should. This is not what Taubes has done. He's simultaneously jumped on another bandwagon (fructose = bad, bad, evil, and more bad) while never clarifying the gaping holes in his first hypothesis. Version X.0 (the tweaks were subtle so we don't know what number we have finally arrived at, hence the X) has not been completely fleshed out and put forth to replace v. 1.0. Fructose has never really fit into the TWICHOO "it's all about insulin" hypothesis. I'll save the big problem with X.0 for another post -- that being the dietary factor most easily manipulated to produce insulin resistance is fat.  One cannot heed evidence implicating fructose and ignore more compelling evidence implicating fat in this regard. But that's for another day.

Now onto the title of this post.  Around a year ago, Gary Taubes began putting the written finishing touches on TWICHOO X.0 in the wake of making an utter ass hat of himself at AHS11.  Rather than discuss the points Stephan Guyenet made in his follow-up post countering the 1.0 version of his hypothesis, Gary offered up a five part "rebuttal" of food reward.  But he stepped in it in doing so.  In that blog post, he referenced some studies by PJ Havel's group:

The second and third papers, both published in October, were randomized controlled trials in humans — rather than primates or rodents — which is always a nice attraction in nutrition research since there’s no guarantee any animal model really reflects the physiological situation in, well, us.  The second paper reported that overweight and obese older adults (40 to 72 years-old) getting a quarter of their calories from fructose-sweetened beverages used less fat for fuel and actually expended less energy than did the same subjects when they were getting the equivalent calories from glucose drinks. So the calories were the same; the metabolic effects were different. For the fructose, the effects were what we’d expect (okay, what I’d expect) if the fructose beverages were causing or exacerbating insulin resistance, an observation that Havel et al had published earlier. The more insulin resistant these people became, the less fat they used for fuel—hence, we can assume, the more fat they stored—and the lower their basal metabolic rate. 

NEITHER of the papers (I bolded his links and directed the first to the free full text) make Taubes' original case about carbs and insulin.  They just don't.  If it's carbs spiking insulin that leads to fat trapping (that we still hear about 90 some percent of the time, often from people citing Taubes), how do a pair of studies demonstrating that fructose -- a non-insulin spiking carb -- elicits metabolic mahem whilst glucose does not, work in your favor?  By changing your hypothesis and hoping nobody notices I suppose...

Considered together with a third study Taubes wrote:

What can we take away from these studies? Well, these three papers certainly support the contention that the sugars consumed in western diets have very specific deleterious metabolic effects, and that maybe these sugars are the, or at least a proximate cause of insulin resistance and metabolic syndrome, and so, we can assume, obesity and type 2 diabetes and perhaps all the other chronic diseases that associate with these two conditions (cancer anyone?). 

OK ... let's back up the bus here ;-)  I already weighed in on this smoke-and-mirrors game back then with: Gary Debunks Taubes ~ It's the Fructose Stupid!  Of the three, the study entitled "Consuming fructose-sweetened, not glucose sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans" is the most troublesome for TWICHOO.  

Go back to GCBC, in it he wrote:

"Over the years, prominent diabetologists and endocrinologists -- from Yalow and Berson in the 1960's through Dennis McGarry in the 1990's -- have speculated on this train of causation from hyperinsulinemia to Type 2 diabetes and obesity.  Anything that increases insulin, induces insulin resistance, and induces the pancreas to compensate by secreting still more insulin, will also lead to an excess accumulation of body fat. 

What? Yet another "oh nevermind??"  He's taken back the G3P stuff, but never the carbs cause IR stuff that permeates LC theology to this day!  How to reconcile how fructose, that does not directly increase insulin, causes IR.  How Gary?  

There are still far too many who have been misled by Taubes-inspired mouthpieces, if not Taubes himself, that carbs cause insulin resistance.  Many of these same people believe they've pooped out their pancreata by consuming too many carbs in their misguided yoots.  Neither is true for the vast majority if not essentially all people.  The evidence on that is pretty clear folks.  You can fashion more elaborate scenarios about how carbs cause you to overeat and all of that, but the evidence remains.

... Can we get to the present Ev?  OK!!

So just before Thanksgiving, Gary Taubes treated us to a rare blog appearance.  What would happen if…? Thoughts (and thought experiments) on the calorie issue.   I'm beginning to wonder if NuSI is planning on funding actual experiments after all, or if we'll just get more of these "thought experiments" from the likes of Gary Taubes.  

Gary posits we perform an experiment on the holodeck metabolic ward of the Starship TWICH-UCAN.    We find two healthy young male twins in prime energy balance at 3000 cal/day and confine them to the ward for 20 years.   The experiment he proposes is so minor as to be silly.  The twins, I'll call them F&G instead of A&B are manipulated differently in all of 5% of their caloric intake.  Gary wants to feed F&G exactly as before, but with one difference.  Twin F gets 10% or 300 cals as sugar, thus 5% or 150 cal or 37.5g as fructose, while Twin G gets the 10% as glucose, thus 5% or 150 cal or 37.5g glucose.  Yes folks, he's really *thinking* on this one!  Or as he would say in his wannabe-physicist days, he's been all nachdenken über over it.  He specified the scenario, not I.  To demostrate the reason Taubes gedankenexperiment is such a dud, we have to put the rest of the 3000 calories in context.  Let's do a reasonable SAD macro of 50/35/15 for C/F/P to begin with, and let's assume we take the 10% "control" out of the carbs, leaving the rest alone.  So F&P are each consuming 375g carb/day to begin with, of whatever composition, and Gary proposes in tiefe gedanken that we fix the composition of 300g of that at whatever their current carb intake is, leave fat and protein alone, dictate 37.5g glucose to each, and either an additional 37.5g glucose for G or 37.5g fructose for F.  

Come back in 20 years and what do you expect to find?  I'm going to go out on a limb here and say, NO DIFFERENCE DUE TO DIET.  There might be something that goes on in F vs. G, but is there a person reading this who believes that altering the carb composition of 5% of one's diet in energy balance is going to set metabolic mahem in motion??   The ever dogmatic Taubes, perhaps.  The result of his gedankenloseexperiment is as follows:

What happens? Care to guess?  Will A and B still be identical after 20 years of A eating 300 calories of sugar every day that B does not eat?

We know sugar is metabolized differently from the glucose in starch because of the fructose component. Glucose is metabolized by cells throughout the body; fructose is metabolized primarily in the liver. We know the liver will turn some of this fructose into fat and if the fructose is delivered quickly enough (say in liquid form as sugar water), it  likely to cause insulin resistance in the liver, which in turn might cause systemic insulin resistance.  The extra 150 calories of glucose in B’s diet will stimulate more insulin secretion, although for B this will come in the absence of any fructose-induced effects in the liver. One way or the other, A and B will experience different metabolic and hormonal effects, despite eating precisely the same amount of calories in diets that are otherwise 90 percent identical. Their fat cells, for instance, will be on the receiving end of different hormonal and metabolic signals. As Claude Bernard would say, the fat cells would be living in a different  milieu intérieur and this will effect how they change over time.

Cut the french crap Gary.  Do you really believe this will change much?  It might change things ever so slightly.  No where near enough to make a difference, even over 20 years I'd wager.  Perhaps if all of Frick's carbs were designated to come from sugar, and all of Guac's from starch, or at least 90% or so, then we might see a difference.  And before going on, let's address this strawman, shall we?   I don't know how many times it bears repeating, and Lyle McDonald's Energy Balance Equation treatise still remains one of the best on this, nobody claims all calories are identical.  But on balance, unless you are at the uber extremes of macro composition, it all seems to marvelously balance out in the end.  Carbs are about 4 cal/g, as are proteins, and fats around 9 cal/g.  These are and have always been approximations.  If people ate the same exact thing day in and day out and then varied one component, they'd probably react.  If their homeostatic machinery is intact, their metabolisms and such should react to such a change.  After all, isn't that what Taubes and company have been telling us?  That calorie restriction is useless because we'll just turn down the thermostat and burn fewer calories?  Nobody denies adaptive measures.  

The question with this experiment is whether we believe such would be even perceptible switching out 150 cal glucose for fructose.  Gary is so into his new evil sugar manufactured schtick these days, however, that he apparently does.  After going on a bit more on the what if's, Gary proposes his scenario of what he proposes happens:  (I've replaced A with F, B with G, we'll call our twins Frick and Guac)

...  let’s assume two things for the sake of argument. First, the sugar in Frick’s diet causes Frick to become insulin resistant. And second, insulin works to put fat in fat tissue. There’s some evidence for our first assumption and the second assumption is in the textbooks; there’s a lot of evidence for that.

ZZZZZZZZZZZZZZzzzzzzzzzzzzzzzzzzzzzzzzzzzz 

Now as Frick becomes insulin resistant, his pancreas has to secrete more insulin than G’s to handle the equivalent carbohydrate load. So Frick now might have higher circulating levels of insulin than Guac. If he does, this means more calories might be fixed in Frick’s fat tissue than in Guac’s.  Put simply, Frick might now be getting fatter than Guac. And as Frick gets fatter, his body has to compensate for the calories that are being locked away in the fat tissue and for the greater metabolic demands of a heavier body. What does Frick do?

Before we answer that riddle, answer me this.  Whatever happened to the fact that Guac is spiking his insulin more with each meal as a result of consuming glucose?  Back to the holodeck... 

What Frick can’t do is eat more, because we’ve fixed his caloric consumption at 3000 calories per day. One option is he could cannibalize his lean mass to feed his growing fat tissue. This can certainly be done without violating any thermodynamic laws. Now Frick gets fatter while simultaneously losing muscle mass and his weight remains more or less the same. A second option is that Frick’s body merely expends less energy to make up for the calories being locked away in fat tissue and the greater caloric requirement that comes from being heavier.

Again, why isn't Guac's fat being locked away from the insulin his extra glucose is spiking?  Here we have the same old rehashed and unsubstantiated pile of goo theory of obesity which is rather nonsensical. 

Now Frick gets fatter while his energy expenditure goes down. While Guac remains in energy balance throughout the experiment — eating 3000 calories a day to match the 3000 calories he expends — Frick moves into positive energy balance. He’s still consuming 3000 calories every day, but he’s expending less. And the reason he’s in positive energy balance is because he’s amassing fat in his fat tissue and getting heavier (Although a naive observer, wedded to the energy balance, might decide that Frick has become a couch potato and that’s why he’s getting fatter. In this case, the direct effect of the sugar is to make Frick expend less energy and this in turn causes the energy imbalance that makes Frick fat. The causality is reversed.)

Yeah, Gary, this is the funniest one of all, because we all know that the way to turn an active kidlet into a couch potato is to feed him some sugar ... right?  Eh ... when has observation ever swayed Gary's hypothesizing, right?   Now I'm convinced he had one of the Havel studies in his mind when writing this.  Those studies were actually one clinical protocol with two different write-ups.  The overweight subjects ate a regular diet for 2 weeks to establish a baseline weight-maintaining caloric intake.  They were then instructed to consume 25% of this baseline caloric intake as either fructose-only or glucose-only sweetened beverages. But ... and this is a biggie ... the remainder of their intake was not restricted.  Both groups consumed more non-sugary beverage calories, equally and gained weight.   Now the second paper, makes two points:  1.  resting metabolic rate was lower in the fructose consuming group (-.09 from 1.19 = -7.6%) and fat oxidation rates were lower.  Ding ding ding!!!  The first paper outlines all the very bad insulin resistance related stuff not covered in the second.  Slam dunk! 

Not so fast.  It's buried a bit in the initial paper, and all the talk of fat oxidation and metabolic rates is distracting.  For sure if your metabolism is slower you should gain more weight -- the glucose group ate 8.4% more while the fructose group only 7.4% more, a statistically insignificant amount that wouldn't have countered the REE changes anyway.  So what went on here?  Did the fructose drinkers gain more weight?  Surprisingly NO.  Again, the difference is not significant, but glucosers gained 1.8%  body weight vs. 1.4%  for fructose group.  They also gained more body fat, 3.2% vs. 2.8%.    However what fat was gained, was disproportionately put on the middle by the fructose consumers.  

Changes in Total Body Weight                                                              Abdominal Fat Changes

Now, this looks super crappy for the fructose folks, so yeah, don't go out and exchange 1/4 of your dietary intake for fructose-only sweetened beverages.  And if for some reason you're hell-bent on consuming 1/4 of your daily caloric intake as SSB's, be careful to scale back your other calories so you're not overeating and gaining weight!!  It's not good for your general risk profile or metabolic health.  

That said ... these folks were Frick and Guac from our experiment to a degree.  They consumed other carbs along side their prescribed sugary drinks.  Only Frick and Guak are envisioned to be calorie restricted.  So what do you think happens then?  I'm guessing nothing really.  At calorie balance, the fructose is likely just refilling glycogen.  No IR to speak of, but even with the IR in the Havel studies, this did NOT produce greater fat gain overall.  

So TWICHOO X.0 is out the window too.  Is NuSI planning to study this in the future?   Fund longer, better controlled (from an intake/compliance standpoint) studies, perhaps by Havel's relatively local group?  We'll see.  

There are more thoughtless experiments from Taubes post to tackle, and perhaps a few of the comments, both hilarious and saddening as this level of confusion only remains at this point because of the deliberate deception of a science writer who fancies himself a visionary.

Oh ... and to avoid abdominal obesity and it's concurrent metabolic woes, if you're going to overeat, perhaps choose an insulin-stimulating food.  

Now, assuming this did happen, or at least could happen, it would lead us to some other interesting observations as well. For instance, if A puts on this fat above the waist, it will increase his heart disease risk. The more fat he gains, the greater his risk of diabetes. In fact, depending on the size of the effect, he might become diabetic over the course of the study. His brother might not. A’s cancer risk goes up, as well, with his adiposity. So does his risk of getting Alzheimer’s. All without consuming a single calorie more than his twin brother did. In fact, if we run the experiment long enough, the brothers might die of different diseases and one might out live the other by a significant amount

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