Saturday, January 23, 2021

Hall and CICO again

I have no free time at the moment so no real chance for blogging. Apologies for the undoubtedly multiple typos and grammatical errors in this hastily written post.

Raphi and I had a chat which is up on Youtube here

Peter & Raphael talk about fatty acids, mitochondria, the origins of life, covid, vaccines & keto

and I also picked this thread up on twitter, again via Raphi

https://twitter.com/DaveKeto/status/1352389424714113024

which sums up why I don't do twitter. To join this discussion would take weeks of careful thought and reference trail following. However this review (DO NOT download it from SciHub!!!!!! Or if you do, make a donation. I didn't say that) came out of it:

Free Fatty Acids and Insulin Secretion in Humans

which has a core, absolutely correct statement:

"In fact, they [FFAs] increase insulin precisely to the degree needed to compensate for the fatty acid–induced insulin resistance."

After that it's all about ROS and double bonds, a concept which Boden (who sounds a really interesting chap) lacked at the time. The basic CIM (Carbohydrate Insulin Model) of obesity is undoubtedly incomplete and, nowadays, is a straw man for people like Hall to use to facilitate career enhancement. As in


Note: There are buzz-words even in the title of this paper which make me uncomfortable!

As Raphi and I discussed, studies do not arrive out of the blue. Hall knew exactly how to set this latest CIM "destroying" study up. The rival camp (Ludwig's group are current torch bearers here) have pointed out that in short term studies that CICO applies quite well. In longer term studies (over two weeks, and yes, of course Hall knows this) low carb has a significant ameliorating effect on the fall in metabolic rate associated with caloric reduction/restriction. As in:

Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies

People may recall I've looked at Hall vs Ludwig in the past. Of the two camps I personally favour the one with the most honest approach to the data. My thanks to David Ludwig for updating me on this latest interchange within the on-going process.

Anyhoo, time to get the children's breakfasts and keep working on the house before the builder arrives on Monday, while working towards various deadlines off blog.

Peter

19 comments:

Captain Sunset said...

Brill. Take care.

karl said...

Twitter is where people parrot approved memes without thought.

If the PUFA => T2D continues to be confirmed - it would be interesting to put numbers on the cost of selling concentrated seed oils in terms of lives.

At the top level overview - if eating PUFA causes over-storage of lipids - less energy is available - creating hunger - overeating. Eating a low-carb diet compensates by putting insulin driven fat storage on hold - but I long for a study that looks at LA in adipose tissue after a low PUFA diet for - 6 months. I don't think we know all the details of how strong the bio-concentration effect of LA is if people lose weight. Lots of simple experiments - measure LA before and after weight loss. Measure LA over time on a carnivore diet - perhaps one with just fish - one with just beef..

On an aside - I've been looking at the content ratios of amino acids in different protein sources - Fish, dairy, beef.. I had assumed that these ratios would not vary so much - even between species of fish - wide variations.

Tucker Goodrich said...

Hall's paper says nothing about CICO, effectively.

It does have a huge confounder in the middle of it, which I've blogged about, but in reviewing the twitter debate between Taubes and Hall, I'll give this one to Hall.

Taubes is unable to critique it without adopting absurd positions (the LC diet failed because it was more palatable, thus becoming Guyenet) or that it wasn't blinded, this refuting his prior position:

"Diet trials are particularly troublesome, because it’s impossible to conduct them with placebos or a double-blind. Diets including copious meat, butter, and cream do not look or taste like diets without them." — Gary Taubes

Hall has managed to tie LCHF advocates into such an incoherent knot with this study, it's really quite a thing of beauty.

For me—and I would assume for you, Peter—the confounder quite nicely explain the whole thing.

There's no surprise, or controversy.

"Interesting Study: "Effect of a Plant-Based, Low-Fat Diet versus an Animal-Based, Ketogenic Diet on Ad Libitum Energy Intake""

Passthecream said...

Tucker, another thing that Hall was tricky about was the amount of salt in each diet arm. It is different from one to t'other. I posted detailed comparisons some time back, also to a very similar older paper by different authors, but irc Hall even mentioned the potential effect of it via modelling in one paper then adjusted the diets in the main one quoted to use this effect, without adequate explanation or justification. As recent personal experience has taught me, high salt is a problem on a high sucrose/fructose diet so if you exclude that you get a better result.


My impression is that his modelling techniques are quite useful, and he uses them in a targeted fashion ... ...

Gyan said...

Hopefully the insulin resistance induced by fatty acids extends to the pro-growth effects of insulin.

ctviggen said...

Not to mention that, like every other study Hall ever does with low carb, the low carb arm is less than 2 weeks long. That's not enough.

Personally, I think Kevin Hall is like the Harvard School of Crapidemiolgy -- I basically ignore them. They both set out to "prove" keto is wrong (Hall) or whatever they want to (Harvard).

cavenewt said...

I agree with ctviggen and Peter. Any time I see a test with such a short timeframe, I don't even pay attention to it.

valerie said...

@Tucker Goodrich, you say there is a huge confounder in the study. Your link seems to point a finger at water weight.

I think there is indeed a huge confounder, but it's not water weight. Water weight is easy to track and does not affect energy stores. The huge confounder is calorie density.

Kevin Hall has used this trick before and he somehow got away with it. Remember his study on processed vs unprocessed food? Huge difference in calorie density. He went so far as to claim (in the abstract, IIRC) that the diets were matched for calorie density. That was a lie, and nobody seemed to insist that it be corrected.

I don't have access to the full paper of Hall's current study, but from the abstract, we know that the gap in caloric intake between the two diets decreased quite a bit between the first and second week. That's what happens when you change the calorie density of your food: you can fool your stomach in the short term, but you body notices the change in diet and your appetite adjusts over time. That's well known, both in humans and in animals.

Yet one more reason why short-term diet studies are worthless.

karl said...

I should have made it clear above - to "look at LA" means to run the MRI to see the amount in adipose tissue - non invasive - should be cheap.

,.,.
I did look at the 'supplemental' information of the Hall study - not food I would eat - much to much highly-processed foods in both arms. The amount of PUFA is staggering. There is this thing in one of the meals - 'American Cheese' which is a food-like substance that I think has a bunch of plant oils in it - or can have..

Seems like a very heavy diet - huge amount of PUFA - for people sitting around in a hospital? Full of PUFA..

"admitted as inpatients" - sounds sedentary? No mention if they had access to a gym? They had some activity monitor - no graph in pre print? Mentions a table-3 that I can't find? Was everyone is a respiratory chamber 24-7?

Almost twice the sodium for ABLC? A bit of a confounding variable?

Which leads me to the Plant based folks having lower systolic - like they were tired on that diet? All that fiber. They took BP daily I only see an average - no change over time.
They don't list the max and min Blood glucose - I consider anything over 110 after a meal bad news - symptom of low muscle mass. IMO if the average PPBG on the plant based diet was over 110 this is a somewhat sick population.

So you have a bunch of people sitting in a hospital room with nothing to do but eat snacks? They were sitting for a month? I think details have been left out.

Tucker Goodrich said...

"Your link seems to point a finger at water weight."

No. Read the whole thing.

Tucker Goodrich said...

"Almost twice the sodium for ABLC? A bit of a confounding variable?"

I don't think so. Hall had Voles design the diet for a previous study, so the difference in salt may be a remnant of that, added salt is a recommendation of Volek's.

I don't see how salt would be a confounder in this study.

It certainly doesn't explain the difference in fat loss.

Passthecream said...

@Tucker

I'll follow up the details and which paper is what after work today but a while ago (2018?) I noted:

"Hall et al study in which the macro ratios actually were in Keto territory.
https://academic.oup.com/ajcn/article/104/2/324/4564649
In Table 1 there the (higher fat) diet has 5060g sodium versus 3060g in the baseline. Big diff. Most fats don't contain a lot of sodium(!) so this must have been mixed in with the carbs??? This gets more interesting if you look up Hall et al's modelling paper
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838532

It is complex but the explanatory detail for equation 3 says in part " I assumed that a 5000mg/day change in sodium intake would be balanced by a 1.7 litre change in ECE ...." (ECE is extra cellular fluid mass) and also "removing dietary carbohydrate doubles the sodium excretion rate compared to a low sodium diet" "

Then you can consider how intimately linked sodium is to various porters and antiporters particularly where exogenously or endogenously derived fructose levels are concerned versus kidney function.

I remember thinking that the only way you could get much sodium from fat intake is in the form of soap. Frothing at the mouth???

karl said...

@Tucker
If you look at hard science - real science - there really can be only one variable. Every conceivable precaution should to be in place to isolate the effects of the test variable. That is why I keep wondering why they aren't doing synthetic diet studies - vary one thing at a time.

You can look at papers like this - but now you have to ask are the results due to the difference in fat types, difference in Carbs, difference in amount and types of fiber, or difference in salt?

I wonder if the differences in systolic were due to the large difference in salt?

If this was an eat the amount you want diet - why not just put out some salt shakers?

People did some synthetic diet work back in the Apollo project days - one thing they learned is if you switch glucose out for sucrose - trigly spike... (sucrose is 1/2 glucose 1/2 fructose)

So in a paper like this - looking at FFA - did they control for the type of sugars in the carbs? Diets with more fructose containing sugars would matter.

This goes way back - Harold Higgens in 1916 noted that fructose more easily converted to fats. Winitz papers on synthetic diets are from - 1967-1970 - then it sort of ends..

The money that gets wasted on papers like this could be used on synthetic diets and we could actually learn things. Instead we are left trying to put together bits from here and there - looking for what might be usable information.

E-S said...

Looking at the curves, I see nothing surprising. Anyone who has experimented with LC diets knows the first week you see loss of the glycogen and a quick reduction in mass of the liver, most of it dehydration. And then you’re adapted and on a steady fat loss slope.
Tucker is right about sodium, it’s a red herring. You need more salt on LC especially rhe elderly. I have a salt-wasting genetic condition and getting enough sodium in is all the challenge I have with LC.

Passthecream said...

I think it's a whole bunch of short term tweaks including the salt which are assembled in such a way as to satisfy the goals of the experiment ie that the result possibly justifies the means where you might hope for the opposite approach if you wanted to learn something.

It's rubbish no matter which way you parse it, a total waste of effort.

karl said...

So you really believe that a low carb diet needs 65% more sodium?

BS

And actually, setting this up this way sort of hides the actual problem - accumulation of sodium by the high carb diet.

No, it isn't science if you have multiple variables based on someone's assumption pulled out of their air(sp?)..

"I assumed that a 5000mg/day change in sodium intake would be balanced by a 1.7 litre change in ECE ...." "removing dietary carbohydrate doubles the sodium excretion rate compared to a low sodium diet" "

I've been low carb for more than a decade - I don't eat such huge amounts of salt.

There is an adjustment when low-carb is started - once people start peeing normally - but the dietary need for an extra bit of salt has not been shown to be long term. If you start LC and feel a bit crummy - eat a bit of salt - but I don't buy that there is a continuing need for a long term 65% increase.. Consider evolution - where did cave men find such salty food?

The fluid retention associated with high carb diets is very likely much more complex than just sodium..

I had a text book that they used to use back in the 1960's - it was for a course that research scientist would take on the scientific method. (They don't bother with this these days). Too much of what passes for science is what Richard Feynman's cargo-cult science speech was about. There are two types of research observational (see what is out there in the world) which is followed by making up a narrative that might explain it - then test it with a 'controlled experiment' - "controlled" refers to controlling the variables - there is only supposed to be one.

There are multiple confounding variables - and specific details left out. Was the food served as portioned plates? (as is the norm in in-patient hospitals..) Quite different than if you spoon up your own plate. We know that even plate size can change food intake - if one source is denser than the other. Does ad-libitum mean you have to bother a nurse and ask for more? Or just take a extra spoonful? Big difference.

Compare this to what we know about LPL and HSL. Did they figure out LPL and HSL with experiments with multiple variables?

( LPL move fat in to fat cells. HSL moves fat out of fat cells. insulin is known to activate LPL in adipocytes - HSL is inhibited by insulin.)

Does this paper disprove what we know about LPL and HSL? ( I don't think so ).

The high carb people had higher insulin - all things being equal, it is hard to see why they are not storing more unless they are moving less, or eating less due to some uncontrolled variable. Like fiber, salt(makes food taste better), social ques, Fat types, sugar-types, base serving size, availability of exercise (high-carb diets have been claimed to make people lethargic - but if both groups are restrained?)

Tweak a handful of these variables and you can get the outcome that the grant committee wants.

In the end, moving and eating are both social and emotional variables - put people in a restrained environment and there can be effects that are not easily measurable. (Some things are unknowable)..

What is most telling is to look at what data they sort of left out..Plate size, serving spoon sizes, ease of availability.. details about movement - where would I go for my daily run? Weights to lift?

Passthecream said...

It's cryptically amusing to call salt a red herring in that red herrings are anchovies and they're usually pickled in lots of salt :))))))


I'm weak, not perfect eh, with a 65+ year set of programmed food choices which I mostly avoid but in my occasional carb-lust moments the thing that gives me a raging thirst is a Chinese takeaway meal. Lots of carby rice and plenty of soy and other salty inputs. Pizza comes a close second (maybe it's the anchovies???) inevitably followed by short term bloating and weight gain which then goes away. Less than 2 weeks would cover it, actually things oscillate a bit for a few days.

Peter said...

Hi all, builder has finished the floors, I got the ceilings painted in time for him to start them, walls are done too, serious deadline has been met and I've finished my two days of theatre lists.

I wrote a post last night about Hall's study which I hope clarifies Tucker's confounder. I feel some amazement at his self restraint in not pointing it out and gratitude to get a clear run at it myself.

It needs tidying but is on its way.

Off topic but in the UK all cause mortality is now somewhat higher than a bad flu winter, currently worse than 2015. It has probably peaked.

Oh, and our UK Lighthouse Labs are currently using 30 cycles to define a positive "case". That is almost a reasonable cycle threshold and will lower the number of positive test results generated. Hospitals were still running at 40 cycles last I saw but I'm assuming they will quietly drop their cycle threshold. This will markedly improve the apparent effectiveness of any vaccines we give.

Peter

Passthecream said...

Lot of trouble to go to for something which doesn't really matter. Interesting to read how they produced it via boiling and briquetage:


https://en.m.wikipedia.org/wiki/Cucuteni%E2%80%93Trypillia_culture

"The earliest known salt works in the world is at Poiana Slatinei, near the village of Lunca in Vânători-Neamț, Romania. It was first used in the early Neolithic, around 6050 BC, by the Starčevo culture, and later by the Cucuteni–Trypillia culture in the Pre-Cucuteni period."

"The provision of salt was a major logistical problem for the largest Cucuteni–Trypillia settlements. As they came to rely upon cereal foods over salty meat and fish, Neolithic cultures had to incorporate supplementary sources of salt into their diet. Similarly, domestic cattle need to be provided with extra sources of salt beyond their normal diet or their milk production is reduced. Cucuteni–Trypillia mega-sites, with a population of likely thousands of people and animals, are estimated to have required between 36,000 and 100,000 kg of salt per year. "