Wednesday, December 12, 2018

A post not about Walter Kempner

I've had this paper on my hard drive for a while. It's been sitting somewhere near the front of the back of my mind but was doing nothing to really grab my interest.

Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice

I've got a draft of a post from mid summer this year which I wrote simply because I like the attitude of the authors. They say things like:

"Excess carbohydrate intake causes obesity in humans".

That's the first line of the abstract. You know, it's that "nailing your colours to the mast" sort of a statement. Even though I do think life is a little more complex than that.

Anyway, I like these folks who are looking at the slimming effect of sucrose in BL6 mice. That's correct, sucrose is a slimming drug/food in mice, under the correct circumstances. People too. The data in the 2017 paper is an extension of the work they did in 2012, written up in this paper:

Ingestion of a moderate high‐sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon‐like peptide‐1 secretion

I don't intend to go through either paper in detail, it's just that the 2012 paper has some rather special macro ratios that caught my eye.

This is what they did to the mice in that original paper:

"After adaptation for 2 weeks, they [the mice] were divided into three groups and fed a normal chow diet (NC), a high‐starch diet (ST) supplemented with 38.5% corn starch or a SUC containing 38.5% sucrose; the latter two diets were prepared by the addition of corn starch or sucrose, respectively, to CE‐2 (Table 1)"

Essentially they are diluting chow with starch or sucrose. Here is Table 1 for the diet compositions, note my red rectangle:











With group sizes of n=4 and five weeks on the diet very little of anything reached statistical or biological significance. The 2017 study used a slightly modified version of the diet to keep a low fat percentage identical across the diets but still had 38.5% of calories from sucrose, was run for 15 weeks and had group sizes of n=8-10. Results were statistically significant all over the place and suggest that the sucrose diet is decidedly good for metabolic health and gives a slim phenotype on ad lib consumption. Just so long as fat calories are very, very low. This looks very much like what Denise Minger described as carbosis, based in part around Walter Kempner's very effective, very unpleasant, ultra low fat, high sucrose medical diet. The Rice Diet is very real.




This post is not about any of the above.




Now, watch carefully. I'm going to sneak in some more macros










If you wanted a "reduced" fat diet which induces carbosis in human beings I recon the red text is pretty well it. I particularly enjoyed that exactly 7.7% of calories came from fat in each diet, this could almost be deliberate. If you combine what is almost certainly a very effective spontaneous weight loss diet with a 30% calorie restriction I suspect you might be on to a winner when comparing it against a reduced carbohydrate diet. Of course to really nail it you would have to compare it to an absolutely non ketogenic diet, say one supplying a total of 140g/d of carbohydrate. Does carbosis beat a middling carbohydrate mixed diet? You bet.

Oh, the scribbled-in red numbers came from Table 2 of this paper.

Most people in respectable CICO based mainstream nutrition have never heard of carbosis, Walter Kempner, the Rice Diet and have probably never heard of Denise Minger.

But Kevin Hall has. My respect for his knowledge-base and ingenuity is vast. Such a pity it's wasted on constructing props for his bizarre pet theories of weight control.

While the 7.7% of calories as fat in both studies is something which amuses me greatly, I do have to admit it may just be an hysterical accident.

At least I'm up front about my rather pronounced personal biases and rather peculiar sense of humour.

Peter

Tuesday, December 04, 2018

An exchange of half bricks

I would guess that everyone is aware of the study by Ebbeling et al, Ludwig's group, looking at the metabolic effect of low carbohydrate diets on total energy expenditure (TEE, all graphs show kcal/d) in the aftermath of weight loss on a conventional diet.

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

I'd like to summarise their data using numbers taken from Tables 2 and 3 which, with a little arithmetic, allows me to produce this graph of TEE at various time points. These are as follows: when the subjects walk off the street (Pre on the graph), after a period of semi-starvation on a conventional diet (Start) and then during weight stability on a high, medium or low carbohydrate diet (End). The plot looks like this:


















In the study they compared the change from the Start TEE to the End TEE, ie they used these data points:


















They took the absolute changes from Start to End thus and got a resultant p of less than 0.05


















This, obviously, is completely unacceptable. Well, it is if you are Kevin Hall. So now we have this

No Significant Effect of Dietary Carbohydrate versus Fat on the Reduction in Total Energy Expenditure During Maintenance of Lost Weight

What Ludwig's group did wrong (amongst the many other things pointed out by Hall and Guo) is that they used the wrong data points.

Recall the original graph:


















According to Hall: If you want to ask about the effect of low carbohydrate diets on the depression in TEE produced by conventional semi-starvation you should NOT compare the semi-starved TEE (as in Start) to the TEE on a high, medium or low carbohydrate diet (End). You should instead use the TEE expenditure at randomisation (Pre on the graph). Like this:


















Using Pre as your anchor point you can draw the same data thus:


















Which obviously gives us p greater than 0.05 and all of the benefits of low carbohydrate diets are lost. Phew. Happy Hall. But why should anyone use the Pre values as an anchor point?

Now, no one is an unbiased researcher. Hall is, surprisingly, no exception. Hence the current exchange of half bricks in the BMJ.

As I see it the Ebbeling paper looks at the effect of LC eating on the damage done to TEE by conventional dieting.

What Hall wants the analysis to do instead is to look at the overall effect of damage done to TEE by conventional semi-starvation combined with partial rescue during weight-stable LC eating vs the combined damage done by conventional semi-starvation followed by maintained damage done by HC weight-stable eating. As he writes:

"However, the final analysis plan was modified to make the diet comparisons with the TEE measurements collected in the immediate post-weight loss period rather than at the pre-weight loss baseline"

To me Hall is stating that Ebbeling et al almost did make the "Hall" mistake of using the "Pre" TTE as anchor point but corrected this at the 11th hour, still before blinding was unmasked. What puzzles me is how Ebbeling could have ever even considered using the "pre weight loss baseline" as the anchor point in the original study design.

The massive benefit to Hall of including the conventional semi-starvation active weight loss period along with the intervention weight stability period is to dilute the remedial biological effect of LC eating out of statistical significance.

The core information which the study provides is about the remedial effect of LC eating on correcting the damage done by a conventional semi-starvation period. That effect only happens between "Start" and "End", which is when carbohydrate restriction is applied.

That's one of the MASSIVE problems with carbohydrate restricted eating. It only provides benefit when you don't eat carbohydrate!

Including data from "Pre" right through to "End" dilutes the clearly demonstrable biological effect of carbohydrate restriction on reduced TEE post conventional dieting.

So what doe the title and text of Hall's rebuttal tell us? Either about Hall or about TEE? Don't over think it!

I would also declare that my own biases are a conflict of interest but if you need me to say that then you have probably arrived here by accident, you know where the back button is.

However I would say that I am ambivalent about the importance of the TEE changes, though I suspect they do happen. What really matters to me is what happened in Aberdeen over a decade ago.

Peter