In Good Calories Bad Calories, Gary Taubes wrote the somewhat shockingly definitive summary paragraph below (I've separated out the numbered statements for clarity):
By the mid-1960s, four facts had been established beyond reasonable doubt:(1) carbohydrates are singularly responsible for prompting insulin secretion;(2) insulin is singularly responsible for inducing fat accumulation;(3) dietary carbohydrates are required for excess fat accumulation; and(4) both Type 2 diabetics and the obese have abnormally elevated levels of circulating insulin and a “greatly exaggerated” insulin response to carbohydrates in the diet, ... (Kindle Locations 8010-8014)
I had addressed this in one of my early posts here at the Asylum (here, dated 6/28/10), but some parts of it need expanding and updating. My original responses will be bold/small/gray font.
Carbs Singularly Stimulate Insulin
We know this isn't true, protein elicits an insulin response. Furthermore fats have been shown to at least amplify insulin responses by, for example, stimulating GLP-1.
It is interesting looking back how one commenter wanted to argue the meaning of "singularly". Nobody can be absolutely certain if Taubes knew about protein stimulating insulin, but there is no mention of this obvious "confounder" to his various hypotheses in GCBC that I am aware of. Feel free to provide me a citation.
There are citations too numerous to include here that counter this "fact", but here are two that should have at least been considered in what Taubes describes as his 3 PhD thesis equivalent, five year research effort: Insulin Index of Foods, Holt 1997 and Effect of Protein Ingestion on Glucose and Insulin Responses to Oral Glucose, Nuttall et.al. 1984. Some have claimed that concurrent glucagon release stimulated by protein is a factor here, but this was not discussed in GCBC other than glucagon being listed as acting on adipose tissue circa 1965 understanding. Glucagon's direct action on fat tissue metabolism is an unsettled matter, but current consensus seems to be little if any.
I would add that roughly half of the total 24 hour insulin secretion on a "standard" diet is basal secretion.
Insulin Singularly Induces Fat Accumulation
Insulin is key regulator in the Fatty Acid/Triglyceride cycle, but when you think about it, aside from moving glucose into the fat cells, it is not heavily involved in policing the entry door. This appears to be ASP which itself can stimulate glucose uptake. Insulin does have an indirect role in this as it has been shown to increase ASP activity approximately 2-fold, but this is a much lower response than to chylomicrons (dietary fat). Fat accumulation (net flow in) occurs each and every time fat is ingested. Whether or not it stays accumulated depends on energy requirements. Eat too much, gain fat mass. Simple. Taubes acknowledges the continual nature of the FFA/trig cycle then goes on to make absolute statements of how the fat is "trapped" in the fat cells. How can as much as 60% of mobilized fat get re-esterified to triglycerides in a continuous cycle be explained?? If you eat too much fat it will stay in the fat cells, and if it is mobilized, elevated NEFA/FFA are NOT a good thing!
As it appears my stalkers have initiated a disinformation campaign regarding this topic, I will be setting the scientific record straight when time permits later this month. In GCBC, Taubes writes:
With the invention by Rosalyn Yalow and Solomon Berson of their radioimmunoassay to measure insulin levels, it quickly became clear that insulin was what Yalow and Berson called “the principal regulator of fat metabolism.” Insulin stimulates the transport of glucose into the fat cells, thereby effectively controlling the production of glycerol phosphate, the fixing of free fatty acids as triglycerides, and all that follows. The one fundamental requirement to increase the flow of fatty acids out of adipose tissue— to increase lipolysis— and so decrease the amount of fat in our fat tissue, is to lower the concentration of insulin in the bloodstream. In other words, the release of fatty acids from the fat cells and their diffusion into the circulation require “only the negative stimulus of insulin deficiency,” as Yalow and Berson wrote. By the same token, the one necessary requirement to shut down the release of fat from the fat cells and increase fat accumulation is the presence of insulin. When insulin is secreted, or the level of insulin in the circulation is abnormally elevated, fat accumulates in the fat tissue. When insulin levels are low, fat escapes from the fat tissue, and the fat deposits shrink. (Kindle Locations 7916-7925)
Right after this Taubes presents the 1965 understanding of adipocyte hormonal control. In a table he lists 8 hormones that work to get fatty acids out of adipocytes. What of these? I realize that acylating stimulating protein, ASP, was not yet known in 1965, but it had been studied quite a bit by the time of GCBC. I addressed this more specifically beginning in September of 2011 with The Full Physiological Regulation of Fat Tissue ~ Part I of ? That post contains excerpts from Keith Frayn's Metabolic Regulation, 3rd Ed 2010, the most important of which is:
The complement story is interesting. Some years ago adipocytes were found to express in large quantities a protein that was called (for want of a better name) adipsin. Later, adipsin was found to be identical to factor D, a component of the so-called alternative complement pathway. Now we know that adipocytes produce several factors involved in this pathway and that these may interact, somewhere outside the fat cell, to produce a fragment known as acylation stimulating protein (ASP). ASP is a potent stimulator of fatty acid esterification in adipocytes. Thus, adipocytes seem to act locally to regulate their own fat storage. (Kindle Locations 3437-3441)
The role of ASP and how it works is discussed in several posts here on my blog, but I'll direct you towards two important ones: Fat Tissue Regulation: Part IV ~ How Acylation Stimulating Protein Works and Fat Accumulation: Taubes v. Frayn ~ ASP in vivo in humans. The first link demonstrates how ASP directly stimulates the enzyme that goes by the acronym DAGAT, a key enzyme in the esterification (creation of triglycerides from fatty acids) process. In doing so, ASP enhances FA uptake into adipocytes directly. The second link was done in living breathing humans and clearly demonstrated that ASP is the primary hormone involved in the uptake of chylomicron (dietary) triglycerides/fatty acids. The same study discussed there also demonstrated that insulin's most prominent effect was to reduce circulating NEFA by suppressing lipolysis. Insulin also seems to stimulate RE-esterification within the adipocyte but I have yet to find confirmation that it does this like ASP by upregulating DAGAT or other enzyme specifically. Please, if you know of this evidence I would be interested in this!
So anyway, I don't believe insulin or ASP is functioning to regulate fat mass, said belief (discussing insulin only) I outlined here: What Does Insulin Regulate Anyway?. There is a hormone charged with regulating fat mass, that would be leptin. There is only one mention of this hormone in GCBC vis a vis weight regulation.
So, I'm going to move on for now, but it is important to keep in mind that much of what was written in posts circa 2010 was written in the environment where the predominant "Gary tells us" meme in the community was that you can't store fat without carbs, and by inference, insulin. Thus at the time the mere existence of ASP presented a problem for TWICHOO and clearly this hormone plays a role in "fixing" fat in our fat tissue. The concept of not being able to store fat without carbs was tied in with the whole glycerol-3-phosphate aka alpha glycerol phosphate story that seemed to Taubes to be that "secret" to it all that nobody put together before. So ...
Carbs are Required to Accumulate Fat
Patently false. Since Fred Hahn is advocating dietary experiments over at weightology at the moment, I've got one for him and Gary. Drink 5000 cals of olive oil a day and protein to meet needs for a few weeks. Report back on your fat mass.
The G3P story is old but not forgotten. Gary Taubes had probably intended to highlight it in WWGF rather than leave it out. But the pesky discovery of his knowledge of glyceroneogenesis by a very obscure blogger prompted Taubes to take to the LLVLC airwaves to address unnamed bloggers who were bringing up the subject. We later learn that scientists like Drs. Kevin Hall and Carson Chow (GT felt it important to repeatedly remind his readers/listeners that these two were *young*) had been challenging him on this for months, but he doggedly hung onto this aspect of TWICHOO including it nervously in his lectures. In that first interview with Jimmy, Taubes, after lots of hemming and hawing and throat clearing, admitted that it looked like the G3P story was not correct after all. He didn't correct the record fully, but more tellingly he (I'll be generous with my wording here) misspoke and stated that all the fuss was not over something he wrote in GCBC but just stated in the lectures -- that something being that you needed carbs to store fat. A concept skeptics and non-believers were shouted down with routinely back when I first began blogging. This is simply not true, however, because he did say it in GCBC:
Just a few more details are necessary to understand why we get fat. The first is that the amount of glycerol phosphate available to the fat cells to accumulate fat— to bind the fatty acids together into triglycerides and lock them into the adipose tissue— also depends directly on the carbohydrates in the diet. Dietary glucose is the primary source of glycerol phosphate. The more carbohydrates consumed, the more glycerol phosphate available, and so the more fat can accumulate. For this reason alone, it may be impossible to store excess body fat without at least some carbohydrates in the diet and without the ongoing metabolism of these dietary carbohydrates to provide glucose and the necessary glycerol phosphate. (Kindle Locations 7974-7979)
Had Gary Taubes read his own seminal reference on this topic, Newsholme & Start (from which his early lecture slides were obtained), this would have never made the book. Because (see: GCBC Reference Check ~ Part III of ? ~ Is glycerol phosphate rate-limiting?):
"there is no evidence that the concentration of glycerol phosphate is limiting for the process of esterification."
Insulin does play a role in glucose transport into fat cells and stimulates G3P production in the postprandial state for the purpose of facilitating triglyceride formation. I would stress that this is good and desired for metabolic health because it is important to efficiently clear fats from circulation! But this is only part of the picture, and that is really what is wrong with Taubes' hypotheses. And lastly:
The Obese and T2s are Hyperinsulinemic - Basal and Postprandial
True, but they also have elevated NEFA's!
That short response back then was in reference to the whole notion that this hyperinsulinemia is somehow trapping and accumulating fatty acids in the fat cells. In the book, the four facts are preceded by a discussion of "internal starvation". Yet this abundance of "free" fatty acids in and of itself counters TWICHOO. But for today let's address the insulin levels.
First the obese. Where basal hyperinsulinemia is concerned while many obese are hyperinsulinemic, not all are. I blogged on a study Lustig was involved in a little while ago: Hyperinsulinemia, Insulin-Suppressive Drugs & Obesity (and Lustig). That study, involved giving octreotide to obese patients but there was some pre-screening for postprandial insulin hypersecretion -- only 28% of the initial obese candidates made that cut. In normal weight individuals, even rather extreme postprandial hypersecreters had normal basal insulin levels. Hopefully I can come back and flesh out a few more links here, but the bottom line is that basal insulin and postprandial spikes (you know, the ones that are trapping your fat in your cells and causing your "hyperinsulinemia") are not necessarily related.
Which brings me to the diabetics that generally have elevated basal insulin levels but as disease progresses definitively lack the appropriate postprandial insulin spike and later even total response. This dysfunction is essentially a compensatory insulin secretion to attempt to compensate for the hyperglycemia resulting from early insufficiency of insulin secretion. Does the hyperinsulinemia prevent weight loss? You would think so if it were the cause of the weight gain ... er ... fat accumulation. But it appears not.
In conclusion, then, the "facts" put forth in GCBC were not facts at all. If they were ever, circa 1960's, newer information (most if not all predating GCBC) has demonstrated them inaccurate.
That's all for now. I will expand on some other points when time frees up.