Sunday, January 31, 2021

Hall and CICO part 3

Okay, this is the image I missed on my first read through the results/methods of Hall's latest offering:

I have to apologise for failing to pick this up possibly because I would never read the discussion or conclusion of a Hall paper. My interest in what Hall thinks is distinctly limited. The image shows a delay in the onset of fat mass loss with LC which then proceeds at a remarkably similar rate to the fat loss in the LF group.

But clearly, the changes in fat mass under LC trend upwards (ns) initially before trending downwards, (also ns) compared to fat mass at initiation of the diet.

As David Ludwig has pointed out, appetite suppression on LC can be delayed and shows most reliably from 2 weeks onwards. This might well be related to the rising levels of ketone bodies providing enhanced energy availability as ketosis develops using the concept outlined here:

This brings to mind a very short term study from some time ago looking at ketogenic diets based around saturated vs polyunsaturated fats.

Differential Metabolic Effects of Saturated Versus Polyunsaturated Fats in Ketogenic Diets

Both diets were individualised to be weight maintaining, so we can say nothing about spontaneous food intake (ie appetite, ie weight/fat mass changes). The main point of interest is the very right hand end of Figure 1:

which shows calculated insulin sensitivity. Under high PUFA intake insulin sensitivity, after an overnight fast, is clearly enhanced.

We have no information about the FFA levels so assessing the "blood energy content" is impossible for either diet. However we can look at the relative changes in glucose vs beta hydroxybutyrate (BHB). They look to be reciprocal, but this is simply an artefact of percentage change.

Glucose drops by 10% from normal fasting levels in the PUFA group, measured as 79.2mg/dl, a sizeable number. Ketones in the PUFA group rise by 10% over the same period. But this is 10% of 1.34mg/dl, a vanishingly small amount, physiologically. There is no ability for this modest rise in BHB to offset the fall in glucose. The energy content of ketone bodies and glucose are approximately equal, per gram. Free fatty acids would be the unknown confounder.

That study looked at high (10% energy) vs very high (42% energy) from PUFA intakes, both under modest ketogenic conditions.

Hall's study looked at a mildly ketogenic diet with around 15% of energy from linoleic acid, a pathologically high intake, in comparison to a carbohydrate based diet deriving around 3% of calories from linoleic acid, ie a physiological linoleic acid intake. 

Linoleic acid at 3% of calories, ie very low, will have no blunting effect on the ability to limit caloric ingress in to adipocytes ("loss") in the peak-absorptive period (so will not generate the need to eat more food to offset this loss in to adipocytes) and will not facilitate pathological insulin sensitivity to allow hypoglycaemia in the post-absorptive period (with subsequent hunger).

I think we can sum Hall's study up in the words of the abstract section:

"One participant withdrew due to hypoglycemia during the low-carbohydrate diet."

translated as

"One participant withdrew due to hypoglycemia during the high-polyunsaturated fatty acid diet."

The other participants had to (spontaneously) eat more to successfully avoid these problems during the first week. 

The effect diminished through the second week of the study as ketones rose further to compensate for the hypoglycaemic effect of excess PUFA.



cavenewt said...

Here's a somewhat tangential question that's bothered me for a long time about crossover trials.

You have a "slightly chunky" group of young Americans who have no doubt spent their life eating the SAD: High carb, high fat with, no doubt, high PUFA.

Then you suddenly switch them to Hall's low fat (thereby low PUFA), high carb diet. This for two weeks, which in dietary/metabolic terms is a fairly short period of time.

Then boom, you suddenly switch them to the essentially opposite diet: high fat, high PUFA, low carb, again for two weeks.

Half the test subjects go in the opposite direction. Talk about yo-yo dieting!

At the risk of anthropomorphizing metabolic systems, these repeated sudden shocks could send one's system reeling in confusion. And it makes me wonder how useful, in a real-life context, any information such a test yielded could be.

I understand the rationale for crossover trials; I've just always felt that the downsides aren't usually addressed, or even acknowledged.

Peter said...

cave, I sort of doubt it. I think the mitochondria are making acute decisions, probably in milli/micro or even nano second timescales about what they should or shouldn't do to enhance survival. One electron at a time.


cavenewt said...

Peter—right, I understand they react quickly. But then why does keto adaptation take a couple of weeks?

You have lingering effects from a certain type of diet: stuffed adipocytes, mitochondrial density, malformed subcellular membranes (maybe I'm grasping here), or whatever. That could affect how you react to a certain diet change compared to other people. I'm thinking about a more macro scale than individual mitochondria.

Peter said...

Ah, I guess so. If you have lived on glucose for decades then suddenly need "n" times as many mitochondria to deal with lipid oxidation that's going to mangle the LC period but is just more of the same but slightly increased so during the low fat period. Yes, quite possible... Like the athletic performance should be assessed after 3 weeks rather than 3 months of keto if you want LC to fail.



Passthecream said...

Thanks Peter. As I found when I was seiving through the details of the earlier Hall papers and comparing them to similar papers from other groups it takes dogged determination to work through all the numbers, graphs, rationalisations etc. I admire your efforts, and Tucker's for gritting your teeth, girding your loins and sorting through it all.

At this point though I'm feeling the need of some explanatory noodles and a timing diagram!!

(Ha, my spellcheck rendered determination as detonation. Perhaps more apt?)

Carl Crawford said...

Interesting that this morning’s email also had this post discussing ramifications of PUFA metabolism:

Gyan said...

I wonder about the Croissant diet which is definitely not low-carb but apparently leads to weight loss in many people. So, it is not necessary to produce ketones--the high ROS provided by long chain saturated fats may be enough.
Curiously, some people report weight gain from following this diet.

Passthecream said...

I think the croissant diet was a bit tongue in cheek really. How many croissants per day? Per week? Nice to indulge if you can find well-made croissants but anything like that would be fattening for me.

Peter said...

Yes Carl, Brad is thinking nicely along ROS lines...

Gyan and Pass, I think there is a lot to be considered in this area. Once you move from theoretical to practical anomalies are bound to come up. Lots of sources of variation. I recall Mike Eades blogging years ago about the LC advice in Protein Power and how it could end up as being interpreted IRL, not always identical! But people are going to consider their n=1 experiences and these will no doubt be illuminating for themselves.


Passthecream said...

Peter, there us one feature if my n=1 which continually puzzles me. I have lost a lot of weight in the last 15 years approx 30 kilos and kept it off, except I am still heavier than I would like to be and I still gain weight very easily if I dont take care. I avoid pufa even mufa as much as possible, my lipid intake is mostly of the saturated variety. Must be plenty of insulin capacity still.

However it makes sense to me that if you have a high fat diet it makes you more sensitive to any carb intake at all and the losing of weight, once you get away from the rapid water loss phase, is all about getting fat from within rather than consuming it, perhaps the proportions given by the optimal diet are useful here???

Malcolm said...

I guess once you're fully keto, carbs will spike your glucose and therefore insulin quite hard, perhaps not too surprising if that provokes weight gain? But if you have access to fat-burning it should come off again easily enough? Maybe there are other things that can encourage more fat-burning, coffee / walking / thyroid / fasting??
I think it comes down to calories in the end, I think Brad ate not very much in his initial trial so not surprising he lost weight. The question is do people feel full enough while eating less? I've been trying to mostly eat beef / lamb / veg / dark chocolate since new year with a little rice or banana here and there and green tea / coffee to drink, and it took me a while to realise that I struggle to eat enough calories! (I was feeling the cold a lot, but I thought that was the weather.) If I stick to this list and go from 2 to 3 meals a day, then I'm just full and have to cut down the meal size. Generally I eat 2 meals a day and I can eat 800-1000 calories at each meal (big meals :) and I'm good and roughly weight stable. (Currently aiming at roughly 150g fat and 150g carbs+protein = 1950 calories, mostly I just try to balance all my carbs and protein with fat.) But if I was smaller / older / female then I guess 1800/2000 calories might be far too many ...

(Peter: if and when you find out any more about insulin / igf-1 and health, particularly with reference to higher protein intakes on low carb / keto diets, that would be interesting to hear about ... but obv no problem if your interest is elsewhere just now ...)

Passthecream said...

Malcolm, apart from the idea of an insulin spike from carbs stopping fat burning from stores and sending excess carbs into storage, a spike in ketones can stall fat burning too. I experienced a strong case of the 'munchies' once - reactive hypoglycaemia, from consuming some purified coconut oil ie MCT which tend to go straight to ketone production. I wonder if the MCTs in butter can also have an appetite stimulating effect like that???

Bill said...

I don't know. In most of the ad lib studies, the spontaneous reduction in appetite & food intake "kicks in" in the beginning. Doesn't take weeks/months. Maybe it's more sustainable on those longer timescales for some people, but doesn't seem like a great rebuttal against this study imo.

Peter said...


I’m interested in better explanations that Protons. Obviously PUFA are a rabbit hole I’m waaay down, I never asked to go there. Do you have ideas which might give better insight?


tadas said...

How plausible would it be to think that both, high fat and high carb diets in real life help to lose weight due to the low fraction of animal protein in net calories, and subsequently low methionine? In rodent feeding studies and some small human diet trials restricted methionine diets show profound methabolic effects.

Peter said...

tadas, for me personally keeping protein below 1g/kg on LC was always difficult. On carnivore it's gone up to more like 2g/kg. I dropped a couple of kg going from LC to carnivore despite increased methionine... I wouldn't suggest methionine, or -SH moieties in general, are unimportant, but the rat work doesn't seem to transfer directly to myself. And I like rat studies.


tadas said...

Thanks for the answer. Have been reading your blog (some other nutrition authors as well, fireinthebottle among them), and now commented for the first time.

Regarding the exclusively croissant (butter and flour) diet the low protein comes in mind. There will be approximately 40 g of protein and less than 2 g of methionine+cysteine in ~2000cal. But also there will be no more than 3% calories from PUFA's.

Peter said...

Mechanistically its interesting that some amino acids generate ETF as part of their catabolism (BCAAs do I think) as part of the process, which is normally reused by that same process but could conceivably be diverted to generate ROS. But my main reason to reduce protein over the years was to reduce signalling through the GH/IGF1 pathway. I relax more about protein nowadays as maintaining insulin low enough for ketosis reduces the hepatic generation of IGF1 under the influence of GH...