The Carb-Sane Asylum

Related Post:   Insulin Doing Its Thang! And Still No Starving Cells .  It discusses another study by Keith Frayn that shows increased NEFA uptake into the muscle cells of men with hyperinsulinemia.  It may be worth a read for newer readers along with The Myth of Starving Cells. Original Content Published June 7, 2013: A couple of years ago I wrote:   The Myth of Starving Cells .  As the story goes --as related by science journalist Gary Taubes, to Low Carb Diet Doctor Mike Eades, to Fat Head Naughton -- insulin traps our fat in our fat cells, causing "internal starvation" as the rest of our cells go without, triggering hunger and overeating.   We overeat because we are getting fat, or some nonsense like that.   In the post, I discussed studies demonstrating the opposite is true.  In obesity, there is failure to properly suppress NEFA release from fat cells, NEFA are elevated in the fasted state, and irrespective of absolute concentration,...

A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women I don't know that this study is worth three posts -- grin -- but I decided to break it up anyway.  I blogged on the diet itself here , and the weight loss here .  This post will address the impact on ectopic fat.  So first, I want to mention the "misleading title" peeves.  Ectopic fat is defined in the abstract: Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause. Here's the relevant synopsis of the results: Liver triglyceride levels decreased by 49% whereas IMCL [intramyocellular lipid] levels in skeletal muscle were not significantly altered. Which apparently garnered the conclusion: A modified Palaeolithic-type diet has strong and tissue-specific effects on ectopic lipid deposition in postmenopau...

In comments yesterday, Wayne/ProudDaddy wondered whether triglycerides might be the bad guy instead of NEFA based on this study from Keith Frayn's research group: Adipose tissue fatty acid metabolism in insulin-resistant men . Aims/hypothesis   Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BMI 25–35 kg/m 2 ).

Lots of buzz over mitochondria of late.  So I thought I'd share this find: High-fat diets cause insulin resistance despite an increase in muscle mitochondria It has been hypothesized that insulin resistance is mediated by a deficiency of mitochondria in skeletal muscle. In keeping with this hypothesis, high-fat diets that cause insulin resistance have been reported to result in a decrease in muscle mitochondria.    In contrast, we found that feeding rats high-fat diets that cause muscle insulin resistance results in a concomitant gradual increase in muscle mitochondria.

Before some of the recent commotion around here, a blog post entitled Let's Play Concentration   caught the eye of Paul Jaminet over at Perfect Health.  His commentary then inspired me to write  Glucose and NEFA: From Dysfunctional Metabolism to Toxicity .   In the comments section Paul and I got into a discussion about free fatty acid (NEFA) clearance from circulation.  It seems that this is a subject of a lot of uncertainty.  Indeed when I first started looking into this stuff, way back when, I kept coming across statements like that insulin was required for fatty acids to be taken up by fat cells (three guesses where that traced to and the first two don't count ...).  My inner geek was prompted to look back into this.   This topic is of interest to me as my regular readers are well aware of my near-obsession with NEFA.  {grin}

This post started out as a comment in response to Paul Jaminet's mention of a post on this blog in his Around the Web   post yesterday.  It got rather long so I decided to move it here.  In the interest of more rapid publication, I'm not going to be doing a whole lot of referencing in my discussion here, but if you're interested in a particular statement please indicate so in the comments section and I'll try to track down the reference(s) I have in mind.  Paul writes: Every once in a while someone writes to ask me if they should fear a high-fat diet because of CarbSane’s writings on lipotoxicity. I reply that lipotoxicity only appears after metabolic syndrome has developed and, while it may drive the transition from obesity to diabetes, it is not a cause of obesity, and not a danger to people who don’t have metabolic syndrome. Also, the implications for diet are not obvious, since carb intake suppresses NEFA clearance from the blood and enhances glucotoxicity. The l...

The low carb theory on weight loss revolves on insulin's action on adipocytes.  Specifically, high insulin favors deposition (esterification to form triglycerides) in the fat cells and suppresses lipolysis (breakdown to free fatty acids).   This of course is true.  But the problem with this discussion is that it is incomplete.  You see, lipolysis has little to do with fat burning per se.  That is beta-oxidation occurring in the mitochondria in a series of cyclical reactions commonly called the Fatty Acid Spiral, FAS.  Free fatty acids are constantly delivered to the cells and being taken up.  Those that are not oxidized for energy are re-esterified and stored as triglycerides inside the cells (e.g. IMCL or IMCT).

On the heels of my last post discussing Tom Naughton's novel theory on obesity and blood glucose regulation, I'm reminded again of the whole "fatty acids are locked away in the fat cells" - what I'll call the Starving Cells  Myth - of obesity.  Dr. Eades is w eighing in on his blog on Taubes' Why We Get Fat and reiterates once again the fallacy that is the locked away fat.  Here's how he puts it: ... A non-obese person eats, uses the energy from the food and stores the rest. During the time between meals and during sleep, the non-obese person draws on the stored fat to provide energy. When the fat cell mass decreases to a certain critical point, the body signals the brain that the fat cells need a refill, so the brain initiates the hunger response. The non-obese person eats, uses some energy for immediate needs, fills the fat cells with the rest, uses the stored energy as needed, and then the cycle repeats. It doesn’t work that way in the obe...

J. Denis McGarry's Banting Lecture ~ 2001 Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes This post is fast fowarding to the final contribution to the field by JD McGarry.  I'll back track and be posting works in between in coming weeks.  According to this  tribute to McGarry , he was quite ill by this point, and indeed he was unable to deliver the lecture, but was present at its delivery.  It is unfortunate that Taubes has misrepresented McGarry's work, because as I read more and more about this man and from this man, he really was a scientist in the vein of bucking conventional wisdom ... something that should have perked Taubes' interest.

As many of my readers know, I've been challenged lately on my beliefs on NEFA.  So I thought I would summarize my thinking on this in a post rather than having several comments scattered amongst a few threads.   I'm not going to be referencing my post here at this time (it's too time consuming to do so at the moment).  If/when I have the opportunity to do so in the future, I'll do a bumped update.   These are my thoughts based on extensive research of the peer review literature on this topic, in almost all cases, considered review of full text articles including reading as many supporting citations in major reviews as possible.  Over the past year I have read at least a hundred such articles. Elevated non-esterified or free fatty acids (NEFA/FFA) are a symptom associated with insulin resistance, Metabolic Syndrome (aka Syndrome X) and Type II diabetes.  The overwhelming evidence in the literature points to elevated NEFA being more than just associated wit...

There's an interesting related conversation on this topic going on over at Paul Jaminet's site: Water Weight: Does It Change When Changing Diets? Does It Matter? For those not familiar with the Perfect Health diet, one component is to get ~400 cal in "safe starches" -- around 100g.  For those transitioning to their diet from a low carb diet, some have experienced a not-unexpected weight gain.  I've added some thoughts to the comments there and -- can't be sure and some is just a hunch -- but I think any weight bounce is probably more carb associated, predominantly glycogen repletion.  It may well be due to replenishing other "carb" molecules with their associated water as well.  My guess is that for the most part these changes show up on the scale more than in dimensions.  That was my experience during the almost 3 years of my "low carb cheating" plan.  I can't know for sure for the first year and a half or so of that, because I never...

This post may well make heads spin.  It sure did mine. A common claim in LC circles is that we "waste" excess fats through futile cycling.  Although this has not been demonstrated in any significant amount in humans except in massive fat overfeeding, it is still incorporated into books and blog posts by the likes of Dr. Mike Eades (futile cycling to "blow off" low carb excesses is stated as if fact in The 6 Week Cure). Inherent in these statements is the implication that this only happens for excess dietary fat when carbs are low ... insulin would be trapping the fats in the cells as the theories go.  Well ... Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity   (2004 Review Article,  PDF)

Reader Ryan emailed me this link a while back and I've been remiss in getting around to it.  Better late than never!  Thanks for the link Ryan! Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H 2 O 2 -emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H 2 O 2  emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves i...

Just some musings on carbohydrates and fats, but with a scientific basis so put it here. Personally I believe the obesity epidemic can be blamed primarily on two phenomena: 1.  The abundance of high calorie foods high in fats & carbs (I'll call them CF) in ever larger portions, and 2.  Liquid calories loaded with sugar and/or fat To prevent obesity my solution is simple:  Keep the fats and carbs separate.  If you're going to eat carbohydrate, eat it with lean protein and/or in whole form so you get sufficient fiber.  Go easy on the fat.  If you're going to eat fat, chances are it is attached to protein, forgo the carbs.  If you simply must eat CF foods, rely on portion control/calorie counting and not on satiety to determine how much you eat.  Keep the total caloric load low, perhaps in the 2-300 cal range, to keep the unnatural assault on your metabolism to a minimum.   My reasons for this are twofold: 1.  Our paleolithic ances...

Just a "bookmarking" post to share an interesting article. Minireview: Weapons of Lean Body Mass Destruction: The Role of Ectopic Lipids in the Metabolic Syndrome

In response to my recent post --  Can low carb cause central adiposity?  -- James Krieger posted a link to a recent study indicating I may well be on to something.  So I thought I would post this study separately (I don't have access to the full text on this one). Longitudinal adaptations to very low-carbohydrate weight-reduction diet in obese rats: body composition and glucose tolerance. Longitudinal effects of a very low-carbohydrate (VLC) and a calorie-matched high-carbohydrate (HC) weight reduction diet were compared in dietary obese Sprague-Dawley rats exhibiting impaired glucose tolerance and insulin resistance. Obese rats were divided into weight-matched groups:  (i) VLC rats consumed an energy-restricted 5% carbohydrate, 60% fat diet for 8 weeks, (ii) HC rats consumed an isocaloric 60% carbohydrate, 15% fat diet, and (iii) HF rats consumed a high-fat diet ad libitum. HC and VLC rats showed similar reductions in body fat and hepatic lipid at the midpoint of ...

Thanks to reader Cody for finding a study I had come across previously regarding IMCL/IMTG.  Actually the study linked to was an update, but there's a secondary lesson, I believe, to be had from the results.  Since this was a study in older folks, there's a sub-message here:  it's never too late! Study:   Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited We previously reported an “athlete’s paradox” in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin- resistant, older subjects. Twenty-five older (66.4 0.8 yr) obese (BMI 30.3 0.7 kg/m2) men (n 9...

High-fat diet, muscular lipotoxicity and insulin resistance A high dietary fat intake and low physical activity characterize the current Western lifestyle.  Dietary fatty acids do not stimulate their own oxidation and a surplus of fat is stored in white adipose tissue, liver, heart and muscle. In these organs intracellular lipids serve as a rapidly available energy source during, for example, physical activity. However, under conditions of elevated plasma fatty acid levels and high dietary fat intake, conditions implicated in the development of modern diseases such as obesity and type 2 diabetes mellitus, fat accumulation in liver and muscle (intramyocellular lipids; IMCL) is associated with the development of insulin resistance. Recent data suggest that IMCL are specifically harmful when combined with reduced mitochondrial function, both conditions that characterize type 2 diabetes. In the (pre)diabetic state reduced expression of the tra...