You Plow A Serious Challenge To The 2012 Low-Carbohydrate Metabolic Wages Study
Warning: this post service volition endure a chip to a greater extent than wonkish than usual, because I demand to instruct detailed to brand my points. To read a summary, skip to the end.
In 2012, David Ludwig's grouping published an interesting RCT that suggested a substantial "metabolic advantage" resulting from a high-protein, very-low-carbohydrate diet (VLC) (2).
This finding has been used yesteryear Ludwig, Gary Taubes, in addition to others to back upwards the carbohydrate-insulin hypothesis of obesity, although at that topographic point is no show that the consequence was mediated yesteryear insulin, in addition to also no show that it was mediated yesteryear reduced saccharide rather than increased poly peptide (3).
Since I published that post, my confidence inwards the finding-- in addition to specially the mutual interpretation of it that reducing saccharide intake to a real depression score increases REE in addition to TEE-- has gradually been eroding. This is partially because other studies receive got by in addition to large reported that the carbohydrate:fat ratio of the diet has petty or no consequence on REE, TEE, or fatty storage (4, 5, 6, 7, 8, 9, 10).
My confidence score dropped fifty-fifty to a greater extent than this week, when I saw a critical comment Kevin Hall added to the study inwards PubMed Commons (11). Ludwig in addition to colleagues receive got since responded (12). Here's my perspective on the exchange, organized yesteryear topic:
Inconsistency betwixt reported unloose energy expenditure in addition to weight change
Hall pointed out that measured TEE was 200-500 kcal/day higher than reported unloose energy intake for all diets, alongside the largest gap inwards the VLC diet. In other words, 200-500 to a greater extent than kilocalories were going out than were going in. Over a four-week period, if the information are correct, the VLC diet should receive got caused merely over a kilogram of weight loss-- but it didn't-- the VLC diet grouping genuinely gained a small-scale amount of weight (0.5 kg). This internal inconsistency inwards the information may advise that 1 or to a greater extent than of their measures is incorrect, either torso weight (unlikely), unloose energy intake (likely, every bit explained below), and/or unloose energy expenditure (possible, every bit explained below).
Ludwig responded that torso weight is an unreliable mensurate of unloose energy residuum over brusque periods of time-- inwards other words, at that topographic point could receive got been differential changes inwards torso composition betwixt groups that masked a torso weight loss effect. I gain handgrip that small-scale changes inwards torso weight over brusque periods of fourth dimension aren't a real company mensurate of unloose energy balance, but what Ludwig is proposing hither is basically that the VLC grouping was gaining H2O weight and/or thin majority to offset fatty loss that was simultaneously occurring. This hypothesized water/lean mas gain would receive got to offset to a greater extent than than 1.5 kg of weight alter (just over 1 kg predicted from TEE, + 0.5 kg weight gain on VLC diet). Since nosotros know that VLC diets tend to reduce H2O weight, in addition to are unlikely to pack on 1.5+ kg of thin majority inwards a calendar month (particularly inwards the confront of a diet that does non encounter unloose energy needs), Ludwig's explanation is difficult to believe.
This brings us to what is likely the existent argue for the lack of alter inwards weight.
Incomplete diet adherence
When I showtime wrote close this study, I don't scream upwards I fully appreciated the likelihood that the volunteers would "cheat" in addition to eat exterior food. Ludwig's squad provided them alongside all study foods, but since it wasn't a metabolic ward study, volunteers had the mightiness to eat additional nutrient at home. I'll add together that these people had a rigid incentive to eat more, because they were maintaining a 10-15% reduced torso weight throughout the study. This agency they were hungry in addition to highly motivated to eat additional nutrient at home.
And they likely did. This may explicate the fact that the volunteers gained a chip of weight on all diets, despite the fact that their supposed unloose energy intake was hundreds of kilocalories lower than their unloose energy expenditure! Ludwig acknowledges this inwards his comment, proverb "it is probable that around non-study foods were consumed". He downplays it, but we're talking close 200-500+ kcal/day here, which is non insignificant.
I sympathise that this variety of study is challenging to do, in addition to the blueprint is sure a lot to a greater extent than rigorous than the type of diet study where y'all merely transportation people dwelling menage alongside diet advice in addition to allow them create their ain food. This type of study blueprint works good inwards a lot of contexts, but perchance it isn't the best suited for situations where your volunteers are weight-reduced in addition to receive got a rigid incentive to eat additional food.
Statistical weaknesses
The study declared REE every bit the primary outcome, in addition to it works life that the VLC diet had a significantly higher REE than the LF diet. The divergence was only 67 kcal/day, but this finding is robust because it was declared inwards advance every bit the primary outcome. I scream upwards nosotros tin transportation away endure fairly confident that, nether the weather tested, the VLC diet led to an increment inwards REE vs. the LF diet. However, the increment is small-scale plenty that it has petty clinical or practical significance.
But the large splash made yesteryear this study wasn't the 67 kcal/day increment inwards REE-- it was the 300 kcal/day increment inwards TEE! Although this finding got all the press, it rests on much less company ground, every bit pointed out yesteryear Hall. The argue is that it's 1 of many secondary outcomes (66 possible statistical tests performed on 22 measured variables, to endure exact), in addition to when y'all receive got in addition to thence many possible outcomes, y'all destination upwards alongside a high likelihood of a faux positive finding unless y'all usage specific statistical tools to right the problem. This is called the multiple comparisons problem in addition to it's real mutual inwards science. In fact, it's 1 of the leading causes of unreliable findings inwards the scientific literature.
As I said, the multiple comparisons work tin transportation away endure avoided yesteryear using the right statistical tools (essentially, raising the bar for statistical significance inwards proportion to the issue of statistical tests y'all perform), but inwards Ludwig's study, these tools were non sufficiently applied to give us confidence inwards the secondary outcomes. And that's non genuinely every bit bad every bit it sounds, but it does remove an additional layer of interpretation. Basically, if y'all don't adequately right for multiple comparisons, your finding is "exploratory"-- pregnant it's non a statistically robust finding, but it is suggestive in addition to tin transportation away endure used to guide farther research. Researchers gain this all the time, in addition to inwards my persuasion it's acceptable every bit long every bit it's clearly labeled every bit exploratory. But it also agency that y'all can't (or shouldn't) proclaim to Earth that a diet increases TEE yesteryear hundreds of kilocalories per day, because that outcome is non statistically robust.
So to summarize, we're left alongside a small-scale REE consequence that is statistically robust, in addition to a large TEE consequence that is statistically questionable. And every bit nosotros volition see, the REE consequence is probable explained yesteryear the higher poly peptide content of the VLC diet.
The confounding consequence of protein
The VLC diet was 30% poly peptide yesteryear calories, spell the other 2 diets were 20% protein. Since high-protein diets are known to increment unloose energy expenditure, this may furnish a plausible explanation for the observed increment inwards REE on the VLC diet.
In Ludwig's reply to Hall's critique, Ludwig states that the higher poly peptide content of the VLC diet can't explicate the higher REE: "A poly peptide divergence of this magnitude can’t explicate differences inwards REE inwards the fasting state, long later the thermic effects of nutrient receive got dissipated". But inwards fact, other RCTs demonstrate that it can explicate the increment inwards REE.
In 2013, the enquiry grouping of Margriet Westerterp-Plantenga at Maastricht University-- 1 of the leading researchers inwards this area-- published a study that examined the effects of high-protein vs. normal-protein diets on REE later weight loss (13). It's worth noting that poly peptide was increased at the expense of fat, non carbohydrate.
Following a weight loss of close seven kg inwards both groups, the normal-protein grouping experienced a reduction of REE, but the high-protein grouping didn't. The between-group divergence inwards REE during weight maintenance? 81 kcal/day. This is very similar to the 67 kcal/day that Ludwig reported, except that it was produced yesteryear increasing poly peptide alone, non a combination of high poly peptide in addition to real depression saccharide every bit inwards Ludwig's study. In my view, high poly peptide intake likely explains the elevated REE inwards the VLC diet group.
Summary
The 2012 study yesteryear David Ludwig's grouping reported that inwards subjects maintaining weight loss, a high-protein, very-low-carbohydrate diet increased resting unloose energy expenditure yesteryear a small-scale amount (67 kcal/day), in addition to total unloose energy expenditure yesteryear a large amount ( 300 kcal/day), relative to a normal-protein, low-fat diet. Superficially, this seems to back upwards the thought of a substantial "metabolic advantage" for very-low-carbohydrate diets. However, at that topographic point are reasons to endure skeptical of around of the findings, which Kevin Hall seat out inwards a comment on NIH Commons. Here's a summary of my electrical flow views:
In 2012, David Ludwig's grouping published an interesting RCT that suggested a substantial "metabolic advantage" resulting from a high-protein, very-low-carbohydrate diet (VLC) (2).
This finding has been used yesteryear Ludwig, Gary Taubes, in addition to others to back upwards the carbohydrate-insulin hypothesis of obesity, although at that topographic point is no show that the consequence was mediated yesteryear insulin, in addition to also no show that it was mediated yesteryear reduced saccharide rather than increased poly peptide (3).
Baca Juga
Since I published that post, my confidence inwards the finding-- in addition to specially the mutual interpretation of it that reducing saccharide intake to a real depression score increases REE in addition to TEE-- has gradually been eroding. This is partially because other studies receive got by in addition to large reported that the carbohydrate:fat ratio of the diet has petty or no consequence on REE, TEE, or fatty storage (4, 5, 6, 7, 8, 9, 10).
My confidence score dropped fifty-fifty to a greater extent than this week, when I saw a critical comment Kevin Hall added to the study inwards PubMed Commons (11). Ludwig in addition to colleagues receive got since responded (12). Here's my perspective on the exchange, organized yesteryear topic:
Hall pointed out that measured TEE was 200-500 kcal/day higher than reported unloose energy intake for all diets, alongside the largest gap inwards the VLC diet. In other words, 200-500 to a greater extent than kilocalories were going out than were going in. Over a four-week period, if the information are correct, the VLC diet should receive got caused merely over a kilogram of weight loss-- but it didn't-- the VLC diet grouping genuinely gained a small-scale amount of weight (0.5 kg). This internal inconsistency inwards the information may advise that 1 or to a greater extent than of their measures is incorrect, either torso weight (unlikely), unloose energy intake (likely, every bit explained below), and/or unloose energy expenditure (possible, every bit explained below).
Ludwig responded that torso weight is an unreliable mensurate of unloose energy residuum over brusque periods of time-- inwards other words, at that topographic point could receive got been differential changes inwards torso composition betwixt groups that masked a torso weight loss effect. I gain handgrip that small-scale changes inwards torso weight over brusque periods of fourth dimension aren't a real company mensurate of unloose energy balance, but what Ludwig is proposing hither is basically that the VLC grouping was gaining H2O weight and/or thin majority to offset fatty loss that was simultaneously occurring. This hypothesized water/lean mas gain would receive got to offset to a greater extent than than 1.5 kg of weight alter (just over 1 kg predicted from TEE, + 0.5 kg weight gain on VLC diet). Since nosotros know that VLC diets tend to reduce H2O weight, in addition to are unlikely to pack on 1.5+ kg of thin majority inwards a calendar month (particularly inwards the confront of a diet that does non encounter unloose energy needs), Ludwig's explanation is difficult to believe.
This brings us to what is likely the existent argue for the lack of alter inwards weight.
Incomplete diet adherence
When I showtime wrote close this study, I don't scream upwards I fully appreciated the likelihood that the volunteers would "cheat" in addition to eat exterior food. Ludwig's squad provided them alongside all study foods, but since it wasn't a metabolic ward study, volunteers had the mightiness to eat additional nutrient at home. I'll add together that these people had a rigid incentive to eat more, because they were maintaining a 10-15% reduced torso weight throughout the study. This agency they were hungry in addition to highly motivated to eat additional nutrient at home.
And they likely did. This may explicate the fact that the volunteers gained a chip of weight on all diets, despite the fact that their supposed unloose energy intake was hundreds of kilocalories lower than their unloose energy expenditure! Ludwig acknowledges this inwards his comment, proverb "it is probable that around non-study foods were consumed". He downplays it, but we're talking close 200-500+ kcal/day here, which is non insignificant.
I sympathise that this variety of study is challenging to do, in addition to the blueprint is sure a lot to a greater extent than rigorous than the type of diet study where y'all merely transportation people dwelling menage alongside diet advice in addition to allow them create their ain food. This type of study blueprint works good inwards a lot of contexts, but perchance it isn't the best suited for situations where your volunteers are weight-reduced in addition to receive got a rigid incentive to eat additional food.
Statistical weaknesses
The study declared REE every bit the primary outcome, in addition to it works life that the VLC diet had a significantly higher REE than the LF diet. The divergence was only 67 kcal/day, but this finding is robust because it was declared inwards advance every bit the primary outcome. I scream upwards nosotros tin transportation away endure fairly confident that, nether the weather tested, the VLC diet led to an increment inwards REE vs. the LF diet. However, the increment is small-scale plenty that it has petty clinical or practical significance.
But the large splash made yesteryear this study wasn't the 67 kcal/day increment inwards REE-- it was the 300 kcal/day increment inwards TEE! Although this finding got all the press, it rests on much less company ground, every bit pointed out yesteryear Hall. The argue is that it's 1 of many secondary outcomes (66 possible statistical tests performed on 22 measured variables, to endure exact), in addition to when y'all receive got in addition to thence many possible outcomes, y'all destination upwards alongside a high likelihood of a faux positive finding unless y'all usage specific statistical tools to right the problem. This is called the multiple comparisons problem in addition to it's real mutual inwards science. In fact, it's 1 of the leading causes of unreliable findings inwards the scientific literature.
As I said, the multiple comparisons work tin transportation away endure avoided yesteryear using the right statistical tools (essentially, raising the bar for statistical significance inwards proportion to the issue of statistical tests y'all perform), but inwards Ludwig's study, these tools were non sufficiently applied to give us confidence inwards the secondary outcomes. And that's non genuinely every bit bad every bit it sounds, but it does remove an additional layer of interpretation. Basically, if y'all don't adequately right for multiple comparisons, your finding is "exploratory"-- pregnant it's non a statistically robust finding, but it is suggestive in addition to tin transportation away endure used to guide farther research. Researchers gain this all the time, in addition to inwards my persuasion it's acceptable every bit long every bit it's clearly labeled every bit exploratory. But it also agency that y'all can't (or shouldn't) proclaim to Earth that a diet increases TEE yesteryear hundreds of kilocalories per day, because that outcome is non statistically robust.
So to summarize, we're left alongside a small-scale REE consequence that is statistically robust, in addition to a large TEE consequence that is statistically questionable. And every bit nosotros volition see, the REE consequence is probable explained yesteryear the higher poly peptide content of the VLC diet.
The confounding consequence of protein
The VLC diet was 30% poly peptide yesteryear calories, spell the other 2 diets were 20% protein. Since high-protein diets are known to increment unloose energy expenditure, this may furnish a plausible explanation for the observed increment inwards REE on the VLC diet.
In Ludwig's reply to Hall's critique, Ludwig states that the higher poly peptide content of the VLC diet can't explicate the higher REE: "A poly peptide divergence of this magnitude can’t explicate differences inwards REE inwards the fasting state, long later the thermic effects of nutrient receive got dissipated". But inwards fact, other RCTs demonstrate that it can explicate the increment inwards REE.
In 2013, the enquiry grouping of Margriet Westerterp-Plantenga at Maastricht University-- 1 of the leading researchers inwards this area-- published a study that examined the effects of high-protein vs. normal-protein diets on REE later weight loss (13). It's worth noting that poly peptide was increased at the expense of fat, non carbohydrate.
Following a weight loss of close seven kg inwards both groups, the normal-protein grouping experienced a reduction of REE, but the high-protein grouping didn't. The between-group divergence inwards REE during weight maintenance? 81 kcal/day. This is very similar to the 67 kcal/day that Ludwig reported, except that it was produced yesteryear increasing poly peptide alone, non a combination of high poly peptide in addition to real depression saccharide every bit inwards Ludwig's study. In my view, high poly peptide intake likely explains the elevated REE inwards the VLC diet group.
Summary
The 2012 study yesteryear David Ludwig's grouping reported that inwards subjects maintaining weight loss, a high-protein, very-low-carbohydrate diet increased resting unloose energy expenditure yesteryear a small-scale amount (67 kcal/day), in addition to total unloose energy expenditure yesteryear a large amount ( 300 kcal/day), relative to a normal-protein, low-fat diet. Superficially, this seems to back upwards the thought of a substantial "metabolic advantage" for very-low-carbohydrate diets. However, at that topographic point are reasons to endure skeptical of around of the findings, which Kevin Hall seat out inwards a comment on NIH Commons. Here's a summary of my electrical flow views:
- There was likely important dietary non-compliance, alongside volunteers eating extra nutrient at dwelling menage inwards add-on to what they were supplied yesteryear the lab. This likely explains at to the lowest degree purpose of why they didn't lose weight, despite the fact that they should receive got lost weight according to the reported unloose energy intake in addition to expenditure figures.
- The finding that resting unloose energy expenditure was elevated on the VLC diet is statistically robust. However, the increment is small-scale plenty that it has petty clinical or practical significance.
- The increment inwards resting unloose energy expenditure tin transportation away endure explained yesteryear the higher poly peptide content of the VLC diet, in addition to it likely had petty to gain alongside the fact that the VLC diet was depression inwards carbohydrate.
- The finding that total unloose energy expenditure was elevated yesteryear 300 kcal/day on the VLC diet is non statistically robust, in addition to it's also difficult to reconcile alongside the results of other studies.
For me, here's the bottom line. Aspects of the study all the same stand upwards every bit reliable, but the findings gain non back upwards the determination that reducing saccharide intake yields a metabolic advantage. My best interpretation is that the study is consistent alongside other findings suggesting that high-protein diets yield a small-scale metabolic advantage, but that calorie intake is all the same the fundamental determinant of fatty majority changes.
