Protein Restriction Paradox
Isoleucine Anyone?
I have huge respect for the folks of reddit's r/saturatedfat.
One thing I've always liked about them is that despite the fact that they all think that polyunsaturated fats are deeply suspicious, there are very few reports of magic weight-loss effects from getting rid of them.
Everybody thinks that PUFAs are probably the cause of the obesity epidemic, but nobody seems to think that giving them up actually helps much immediately with obesity.
And that's a good thing.
Because if it was true that giving up PUFAs led immediately and clearly to weight loss, then we'd already know.
I've seen people claiming all sorts of effects from giving up the PUFAs, most often actually reports that they've stopped getting sunburn.
I've never burnt easily, so I can't really comment on that.
And I've seen lots of people claim that they were really quite unwell, and improved after cutting out PUFA.
And I've seen lots of people who suffered from uncontrollable weight gain claiming that they stopped gaining weight.
And I've seen people who've done it for a long time claiming that eventually their weight normalized.
But I don't remember anyone ever claiming that it caused a period of rapid weight loss by itself.
For sure this matches my experiences.
Particularly admirable is Brad Marshall, the resident biochemist, and one of the first people to suggest that PUFAs were the root of all evil.
He's always coming up with interesting biochemical mechanisms and schemes involving supplements and foods (which he sells) to fix the metabolic difficulties that he thinks are caused by PUFAs.
But he's always been quite open that none of it actually works. He's overweight, he's been overweight for a long time, and he's stayed overweight whatever he's tried. He's in the early stages of diabetes.
He could easily 'starve himself thin', to give credibility to his ideas, to increase his sales. But he never has. He wants to fix the damage to his metabolism and hopes to just go back to a normal weight when it's fixed.
That strikes me as the behaviour of a fundamentally honest man.
Originally he mostly wrote his stuff down, and it was clear and readable, but nowadays he only seems to make interminable youtube videos, which for some reason I can't extract any useful information from. My problem, not his.
Recently, he's completely changed his tune and started talking about BCAAs (Branched Chain Amino Acids, a particular component of protein). He thinks they should be avoided.
And suddenly, apparently, it's working. He's says he’s lost a fuckton of weight really quickly and fixed his pre-diabetes.
I trust Brad. Just because I don't know what he's talking about doesn't mean that he doesn't know what he's talking about.
And other people on r/saturatedfat are reporting that BCAA restriction is working for them too.
And that actually includes me and my friend u/exfatloss, who've been claiming effortless weight loss for a while now, because ex150 is a protein restricted diet, and BCAAs are in protein.
It's as a result of that, and of my own experiences where twice in the last six months protein seems to have put my own otherwise inexorable weight loss into reverse, that I've added an epicycle to my own much less gears-level ideas about what might be going on.
And recently, u/exfatloss, who's thought that protein might be involved ever since his low-protein diet ex150 started to show magic weight loss effects, has written this excellent article:
Where he goes over a number of clever, careful, recent studies from The Lamming Laboratory for the Molecular Physiology of Aging
https://lamminglab.medicine.wisc.edu/
Which seem to show that not only does protein restriction directly fix all sorts of 'metabolic dysfunction' markers (in mice), but it also seems to directly cause weight loss.
And it does it by causing mice to eat more.
Calories Out goes up. Calories In goes up to match. But not quite as much.
Because maybe the metabolism is fixed, and maybe the fat-homeostat starts working properly, and so the mice don't eat quite enough to make up for the increase because they notice that they are carrying too much stored energy, and so their weight normalizes.
This sort of effect is exactly what I've been expecting to happen from a no-PUFA diet this last year.
In fact it is what seems to have been happening to me for the last six months of my no-PUFA diet, except for the two periods where I ate an awful lot of protein.
And even better, they seem to have shown that it's not just protein, it's the specific amino acid isoleucine, which is one of the BCAAs that Brad has been going on about.
I take these Lamming people rather more seriously than I usually take medical researchers. They seem to have found something interesting and they're hammering on it in a manner that I very much approve of, trying to find out what the levers are, how the gears work, almost exactly like medical researchers never seem to do.
So is it isoleucine?
Is that the cause of all the horror?
The possibility must be admitted.
I say no.
For the same reason that I've never believed that saturated fat is bad for predators.
For the same reason that I've never believed that salt is bad for animals.
Two reasons in fact:
First:
That's a crap design for an animal.
If it's true in mice and it's true in humans then it's probably true in all mammals.
All it takes is an oversupply of protein and the animal is screwed.
No way.
Consider water. It's essential. It's ubiquitous, and it can also be deadly. Just drinking excessive water can kill you. Or you can drown in it.
But you can leave animals alone near water and they'll be fine.
It's really hard to drink enough water to hurt yourself. It's most uncomfortable and it was historically used as a method of torture.
The experience of inhaling water is so aversive that it's been used very successfully in modern times as a method of torture. By all the acknowledged experts in the field.
Of course protein can be bad for animals. A falling block of it could kill an animal, e.g.
But if protein in plausible amounts in animals' diets could fuck up their metabolisms, there would be mechanisms to prevent that.
These are ancient systems. To a first approximation they are fully debugged in the normal conditions they have encountered over deep time.
Excess protein in the diet in the amounts animals will naturally eat if they're left alone with unlimited supplies of protein cannot be bad for animals.
Take it to the bank. I will die on this hill.
Although I reserve the right not to die on this hill should it seem after careful consideration to be an inappropriate hill on which to die.
I have been catastrophically wrong about things before. It always feels like this. Absolute certainty combined with a certain nagging doubt about how the big picture fits together.
Second:
The Victorians after about 1850, the time of the last real hunger in Europe, were the richest people in the world. About ten times richer than anyone had ever been before. The wildest dreams of animals fulfilled. All the food they wanted, of whatever type.
If overeating protein could have made them obese and diabetic etc. etc. then it would have. But it didn't.
Since then we've only got richer. No real obesity or metabolic dysfunction anywhere outside America until comparatively recently.
So what can be going on?
If you want to kill yourself without pain or terror, you need something new.
Stand near a cliff edge and think seriously about jumping, you'll wet yourself with fear. Maybe you can force yourself over. A lot of people can’t even go near the edge.
Inhale carbon monoxide and you'll die without even noticing, full of useless broken red blood cells.
It's not that your red blood cells are themselves bad for you in isolation. It's that their interaction with a novel substance that your ancestors never encountered is bad for you, and evolution hasn't had time to get that bug out.
If isoleucine is a problem, then it's a problem because it's interacting with some novel substance.
Some modern poison is at the root of all this. That's what I've always thought. That's what I still think.
But what?
u/exfatloss points out that the mice in the Lamming Lab experiments are all eating high-PUFA diets. Very suggestive.
I am allowed to carry on believing that the problem is PUFAs.
No
Mice live wild in Northern Europe. Mice eat cold things. Earthworms. Seeds, grains, nuts. All these things contain PUFAs.
Even the combination of PUFAs and isoleucine can't be bad for mice. Darwin would have noticed. The bug would have been fixed.
The programmer is an idiot, but the test suite is comprehensive, and management is very focused on fixing bugs.
A Paradox, Then
My reasoning is faulty, or one of the things that I believe is wrong. I wonder which one it is?
Registering a prediction about the potential error: "can't be bad for mice" doesn't necessarily mean "can't reduce mouse metabolism and fatten them up." It'd be good for mice to be fatter with low metabolisms during the winter. I think Brad has suggested before that PUFA-heavy foods are relatively more abundant in the fall/winter and less in the spring, so "getting fat from this" could be exactly what they're genetically programmed for.
A detail i haven’t seen you go into: other types of protein. We didn’t used to eat straight up muscle meat. Traditional food contains glycine and collagen in much higher amounts. Same for a predator in the wild; they wouldn’t eat just muscle meat