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A Novel Human Lawsuit Undermines The Carbohydrate-Insulin Hypothesis Of Obesity, Again

The carbohydrate-insulin hypothesis of obesity states that carbohydrates (particularly refined carbohydrates as well as sugar) are the primary travail of obesity due to their powerfulness to increment circulating insulin, as well as that the solution to obesity is to bound saccharide intake.  Numerous studies receive got tested this hypothesis, to a greater extent than or less directly, inward animals as well as humans.  Despite the fact that many of these studies undermine the hypothesis, it remains extremely popular, both inward the pop media as well as to a lesser extent amid researchers.  A novel human trial yesteryear Kevin Hall's inquiry squad at the the U.S. of A. National Institutes of Health offers real rigid evidence that the carbohydrate-insulin hypothesis of obesity is incorrect.  At the same time, it offers surprising as well as provocative results that challenge prevailing ideas well-nigh diet as well as weight loss.


Despite taking a serious battering over the concluding few years*, the carbohydrate-insulin hypothesis of obesity remains pop inward the populace sphere, as well as to a lesser extent, amid researchers.  Public advocates such as Gary Taubes, as well as researchers such as David Ludwig as well as Robert Lustig, receive got vehemently argued that obesity has niggling to exercise amongst calories.  Rather, it's a status inward which the torso is primed for hunger as well as obese storage due to a hormonal disorder-- as well as the culpable hormone is insulin.  

Insulin is an attractive machinery because of its powerfulness to deport upon blood levels of refined saccharify as well as fat, as well as obese flux in/out of obese cells.  According to 1 pop iteration of the carbohydrate-insulin hypothesis, high levels of insulin cut blood refined saccharify as well as obese inward the bloodstream, as well as also trap obese within obese cells, leading to hunger as well as obese gain.  Since nosotros know that carbohydrates are specially expert at elevating insulin levels, as well as obese people tend to receive got high levels of insulin, it all seems to add together upward pretty well.  Adding to the attractiveness of the hypothesis, nether free-living conditions, overweight people tend to lose to a greater extent than weight when they follow a moderate low-carbohydrate diet than when they follow a moderate low-fat diet.

These facts led to the evolution as well as meteoric rising of the modern carbohydrate-insulin hypothesis of obesity, consummate amongst ardent claims that saccharide as well as insulin are the only relevant causes of obesity.  I can't explicate this meliorate than Kevin Hall as well as colleagues did inward the introduction of their newspaper (1):
Weight loss diets frequently recommend targeted restriction of either carbohydrates or fat. While low-fat diets were pop inward the latter purpose of the 20th century, saccharide restriction has regained popularity inward recent years, amongst proponents claiming that the resulting decreased insulin secretion causes elevated release of gratis obese acids from adipose tissue, increased obese oxidation as well as liberate energy expenditure, as well as greater torso obese loss than restriction of dietary obese (Ludwig as well as Friedman, 2014, Taubes, 2007, Taubes, 2011, Westman et al., 2007). One influential writer concluded that “any diet that succeeds does therefore because the dieter restricts fattening carbohydrates …Those who lose obese on a diet exercise therefore because of what they are non eating—the fattening carbohydrates” (Taubes, 2011). In other words, torso obese loss requires reduction of insulinogenic carbohydrates. This extraordinary claim was based on the observation that fifty-fifty diets targeting obese reduction typically also cut refined carbohydrates. Since the primary regulator of adipose tissue obese storage is insulin, as well as a reduction inward refined carbohydrates reduces insulin, saccharide reduction lonely may receive got been responsible for the loss of torso fat—even amongst a low-fat diet.
This hypothesis may live on a fleck extreme, but it's a expert hypothesis inward the sense that it makes testable predictions.  For example, it predicts that specifically dropping saccharide from the diet should travail to a greater extent than obese loss than specifically dropping the same number of obese calories from the diet, if everything else is held constant.  Surprisingly, no report has e'er direct tested this!  Many studies receive got compared low-carbohydrate to low-fat weight loss diets nether equal-calorie conditions, but all of them changed the intake of multiple macronutrients from baseline values, rather than manipulating only unmarried macronutrients.

Influenza A virus subtype H5N1 novel report yesteryear Hall's grouping direct tests this prediction, making it 1 of the most pertinent tests of the carbohydrate-insulin hypothesis of obesity e'er conducted.  Onward!

The study

Hall's squad started amongst a grouping of xix manful somebody as well as woman somebody obese volunteers without overt disease.  Volunteers were randomly assigned to 1 of ii groups:
  1. Controlled baseline diet for five days, followed yesteryear six days of 30% calorie restriction.  Calorie intake was reduced yesteryear reducing saccharide intake ONLY.
  2. Controlled baseline diet for five days, followed yesteryear six days of 30% calorie restriction.  Calorie intake was reduced yesteryear reducing obese intake ONLY.
All diet phases were strictly controlled nether metabolic ward conditions.  The baseline stage was used to decide each volunteer's calorie needs.  After completing 1 diet stage (e.g., low-carbohydrate), each volunteer went habitation for 2-4 weeks, therefore completed the other diet stage (e.g., low-fat).  This is called a crossover report design, as well as it's extremely robust because each somebody is compared to himself, which reduces measuring variability.  In other words, this report compares Bob eating a low-carbohydrate diet to Bob eating a low-fat diet.

It's worth noting that refined saccharify intake was the same betwixt the baseline as well as low-fat periods.  Any observed effects cannot live on attributed to reduced refined saccharify intake.

At several points during the experiment, Hall's squad took a broad diversity of metabolic measurements, including metabolic charge per unit of measurement as well as obese oxidation.  To exercise this, they measured the breath telephone substitution of carbon dioxide as well as oxygen that dot how many calories a somebody is burning, as well as whether those calories are coming from saccharide or fat.  By subtracting the amount of obese a somebody is burning from the amount of obese they're eating, researchers tin calculate how much obese a somebody is losing (or gaining)**.  They also measured torso weight, as well as direct measured torso composition using DXA, a gold-standard method. 

They also measured blood insulin levels, urine C-peptide levels, as well as several other hormones.  C-peptide is a poly peptide that's co-released amongst insulin but has a longer half-life inward circulation than insulin.  It ends upward inward the urine, as well as it's commonly used as a marking of overall insulin secretion over the course of report of the day.

I desire to banking concern annotation that this study's methods were downright obsessive.  The overall report blueprint as well as diets were extremely tightly controlled, as well as the researchers took a large number of measurements using gold-standard methods.  Even though the report was short, it must receive got required a huge assay as well as toll a lot of money.  The study's rigor is reflected inward the fact that it was published inward Cell Metabolism, a high-quality journal.


As expected, the low-carbohydrate diet led to a 22 per centum reduction inward overall insulin secretion, as measured yesteryear urine C-peptide.  In contrast, the low-fat diet had no impact on insulin levels.

Also as expected, the low-carbohydrate diet caused greater weight loss than the low-fat diet.  The low-carbohydrate diet also led to a higher charge per unit of measurement of obese burning.  Yet this did non quite brand upward for the fact that the low-carbohydrate diet contained to a greater extent than obese than the low-fat diet.

Metabolic measures indicated that the low-carbohydrate diet caused a 245 gram (0.5 lbs) loss of torso obese over the 6-day diet period, field the low-fat diet led to a 463 gram (1 lb) loss of torso obese over the same period.  Total liberate energy expenditure decreased significantly inward the low-carbohydrate group, but non inward the low-fat grouping (-98 vs. -50 kcal/d).

DXA analysis showed that both groups lost fat, but the changes were also little as well as the variability also large to discovery a pregnant deviation betwixt groups.   


First, let's brand sense of the results.  Body weight loss was higher on the low-carbohydrate diet, yet torso fat loss was higher on the low-fat diet.  This mightiness appear hard to imagine, but inward fact it's non as weird as it mightiness seem, because low-carbohydrate diets travail a rapid loss of H2O weight from liver as well as musculus tissue.  This is 1 of the reasons why they're therefore popular-- they deliver big, immediate weight loss results.

Yet obesity is a status of excess torso fat, non excess H2O weight.  What matters is losing fat.  In this study, the low-fat diet caused twice as much obese loss as the low-carbohydrate diet over the 6-day period.  

The study's championship is provocative: "Calorie for Calorie, Dietary Fat Restriction Results inward More Body Fat Loss than Carbohydrate Restriction inward People amongst Obesity".  And that is indeed the case-- over a 6-day period.  Yet surprisingly, using their evidence-based mathematical model of human metabolism, Hall's squad predicts that the low-fat diet would move along to outpace the low-carbohydrate diet out to six months.  I don't pretend to empathise the mathematical underpinnings of the model, but I volition banking concern annotation that previous sense shows that it's pretty darn expert at predicting the metabolic as well as torso weight outcomes of human diet studies.

How exercise nosotros reconcile this amongst previous inquiry suggesting that over longer periods of time, diet composition stops existence real of import for weight loss as well as only calories matter?  And how is the deviation inward obese loss they observed possible, since calorie intake was the same on both diets?  I believe purpose of the explanation may live on relatively straightforward: macronutrient extremes outcome inward metabolic inefficiency (just to live on clear, this is a hypothesis that I believe explains the evidence, but it remains to live on tested directly).  By default, the torso uses a liberal mix of saccharide as well as fat, as well as a fleck of poly peptide to fuel its daily activities.  When y'all bound 1 of those to an extreme, y'all accept the torso exterior its normal operating parameters, as well as metabolism becomes less efficient.  In other words, your torso requires to a greater extent than liberate energy to perform the same tasks.  

In the electrical flow study, calories were subtracted alone from dietary saccharide or fat, but because of the composition of the baseline diets, the low-fat diet ended upward amongst a much to a greater extent than extreme composition than the low-carbohydrate diet.  Here are pie charts showing the composition of each diet, including the baseline diet:

As y'all tin see, the low-fat diet was a spartan 8 per centum fat!  That is extremely low-- amid the lowest of whatever diet report I've e'er seen.  Meanwhile, the low-carbohydrate diet was a comfortable 29 per centum saccharide (although that represents a 60% reduction inward absolute saccharide intake vs. baseline).  This was necessitated yesteryear the report design, but it did Pb to a to a greater extent than extreme diet composition inward the low-fat group. 

My hypothesis well-nigh metabolic efficiency is supported yesteryear the fact that the low-fat diet didn't travail a reduction inward liberate energy expenditure, field the low-carbohydrate diet did.  In other words, the low-fat diet had a little "metabolic advantage", demonstrating that it was to a greater extent than inefficient.  Yet this metabolic wages isn't large plenty to work organization human relationship for the deviation inward obese loss, leaving most of it unexplained.  Assuming the obese majority information are correct, this suggests that the low-carbohydrate grouping may receive got led to a greater loss of calories from sources other than torso obese (e.g., glycogen and/or lean tissue), which they allude to inward the paper.

The "metabolic advantage" is unremarkably associated amongst low-carbohydrate/high-protein diets.  For example, inward a report yesteryear David Ludwig's group, a spartan 10 per centum carbohydrate, higher-protein diet led to a higher liberate energy expenditure next weight loss than a moderate low-fat diet (2).  Yet to a greater extent than moderate low-carbohydrate diets don't appear to yield a metabolic wages (3).  Again, an extreme diet composition seems to live on the key, non saccharide restriction per se.

It's interesting to banking concern annotation that diet advocates inward both the very-low-carbohydrate as well as very-low-fat camps claim a metabolic wages as well as superior obese loss.  If my hypothesis is correct, they're both right!  

Hall's grouping genuinely alludes to this hypothesis inward their paper.  According to their metabolic model, if the low-carbohydrate diet had been fifty-fifty lower inward saccharide (with a corresponding increment inward obese intake to keep calories), it would receive got matched the very-low-fat diet inward the obese loss department.  Their information advise that both macronutrient extremes are a fleck to a greater extent than effective for obese loss than existence inward the middle, fifty-fifty when calories are held constant.

Another explanation for the possible metabolic wages of typical low-carbohydrate diets is the higher poly peptide intake, which tin Pb to both short-term as well as long-term increases inward liberate energy expenditure, specially during as well as subsequently weight loss.  That wasn't a component inward Hall's study, but it could receive got been a component inward others.

These results direct refute the carbohydrate-insulin hypothesis of obesity (at to the lowest degree 1 if its most pop incarnations).  The low-carbohydrate diet caused a 22 per centum reduction inward insulin secretion, but only one-half the obese loss of the low-fat diet.  Under the atmospheric condition of this study, the human relationship of insulin levels to obese loss was the reverse of what the carbohydrate-insulin hypothesis predicts.  Let me move yesteryear the mic to Hall as well as colleagues:
We tin definitively spend upward the claim that saccharide restriction is required for torso obese loss.
Now, let's speak well-nigh what this report is, as well as what it isn't:
  • It is an investigation of the mechanisms of short-term weight loss, specifically the mechanistic importance of calories vs. diet composition.
  • It is a well-designed show of the carbohydrate-insulin hypothesis of obesity.
  • It isn't a show of which diet industrial plant best nether real-world conditions, or how unlike diets deport upon hunger, nutrient motivation, or nutrient intake.
We already receive got many other studies that show the real-world effectiveness of low-fat as well as low-carbohydrate diets.  These studies demo that neither diet is real effective as a stand-alone obese loss measure, but moderate low-carbohydrate diets tend to live on to a greater extent than effective than moderate low-fat diets, mayhap due to their greater powerfulness to command appetite.  We withal demand to a greater extent than information on the real-world effectiveness of very-low-fat diets, which may live on to a greater extent than effective than the moderate low-fat diets typically used as command groups inward low-carbohydrate diet studies.


This is a real sophisticated report that takes us several steps toward agreement the metabolic as well as liberate energy residuum effects of unlike diet compositions.  The results are surprising as well as provocative.

The results advise that over a 6-day period, specifically dropping obese from the diet leads to greater torso obese loss than specifically dropping saccharide from the diet, when calories are held constant.  Yet, the deviation inward obese loss may depend on the fact that the composition of the low-fat diet was much to a greater extent than extreme than that of the low-carbohydrate diet.  If both diets were every bit extreme, Hall's model predicts that obese loss would receive got been similar.  This hypothesis needs to live on taken ex silico to live on confirmed, hopefully inward a longer-duration diet trial.

Since dropping carbohydrates from the diet lowered insulin but slowed obese loss when compared to dropping dietary fat, this report falsifies 1 of the most pop incarnations of the carbohydrate-insulin hypothesis of obesity.  I promise regular readers of my weblog aren't also shocked.

* Which I volition modestly accept unopen to credit for.

** Their method also takes de novo lipogenesis into account.



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