Polyunsaturated Fats Will Suffocate You And Drive You Mad: Ketosis Will Fix That

A Bold Claim, Made With "No Evidence"

So for a while now, I have been saying that in ketosis I feel really energised and alert. Consulting my notes, in:

https://theheartattackdiet.substack.com/p/ex150ish-stable-state-ketosis-wow

As well as a lot of stuff that now seems pretty significant about running on two different fuels and being able to run out of the brain fuel independently, I wrote:

Is this decade of tiredness I've had because my usual glucose-burning metabolism is broken, but the emergency-back up system [ketosis] is still working fine?

I've decided that I should chase this thought, and so I've got interested in metabolism, and in particular, in what might sod up glucose metabolism whilst leaving fatty acid and ketone metabolism working. And as part of this hunt, I've read a couple of books about the Krebs cycle¹ that are aimed at five-year olds.

And of course, these days I believe in my heart that polyunsaturated fats are the root of all evil.

So in particular, I am googling around for relations between polyunsaturated fats and various bits of the Krebs cycle.

And look what you find if you google for 'glycolysis and PUFA'

https://www.jci.org/articles/view/25256

Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation.

This paper is not trying to show that PUFAs suppress glycolysis.

It is taking "PUFAs suppress glycolysis" as an established fact, and trying to elucidate the biochemistry behind that.

The very first line of the abstract is:

Dietary polyunsaturated fatty acids (PUFAs) are potent inhibitors of hepatic glycolysis and lipogenesis.

How interesting! This is known, as the Dothraki girls so wisely say.

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Let us cavalierly ignore the word 'hepatic' in that sentence. What is true for liver cells clearly must be true for all cells, no philosopher however pedantic could quibble.²³

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What eez thees 'glycolysis'?

You only need a bit of Greek to read that word as 'sugar splitting'

It is the bit of metabolism where you split the simple sugar glucose into pyruvate. It is itself beastly complicated, but all we need to know about it is that it's the pyruvate that gets fed into the Krebs cycle.

The Krebs cycle. The fundamental metabolic cycle that enables us to react oxygen with fuel to make energy.

PUFAs are potent inhibitors of glycolysis

Big if true, right?

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What would happen to a man, then, if he were unwise enough to consume large quantities of polyunsaturated fats?

If glycolysis were to be inhibited, potently?

He would suffocate.

Unable to split glucose to feed into respiration, because glycolysis is blocked, he would be unable to turn fuel into energy.

His foreground metabolism, the usual pathway, the central chemical process of life, would be disabled.

Luckily, glucose is not the only thing which can be metabolised.

It's absolutely the best thing which can be metabolised. The body's preferred fuel.

In the absence of glucose, fats can be burnt.

But not in the brain.

Brain cells cannot burn fats directly.

If you're short of glucose, then you can turn fats into ketones, which the brain can use (this is ketosis).

But if you've got plenty of glucose, you won't be doing that. You don’t make ketones if there’s glucose around. And your brain will be fucked. No ketones, plenty of glucose, but glycolysis is blocked. Your brain will, deprived of fuel, quite literally suffocate.

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So what would happen to a man who ate a little tiny bit of polyunsaturated fat, then?

Not enough to stop glycolysis, just enough to fuck it up a bit?

But who also ate a fair bit of carbohydrate, or a fair bit of protein? Both of which can be used to make glucose.

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Well, his metabolism would not work so well. There'd be plenty of glucose around for burning, but polyunsaturated fats are potent inhibitors of glycolysis, and without glycolysis, you can't burn glucose.

Instead of running on glucose, its preferred fuel, his metabolism would run by burning fats.

That's probably OK. Ketards don't seem to die. It might not be ideal.

But what about his brain?

Well, there's plenty of glucose around, remember, so there won't be any ketones.

His brain will be well supplied with glucose, but it won't be able to burn it, because glycolysis is blocked.

And there aren't any ketones.

So his brain will suffocate. Maybe he won’t die, if glycolysis is only a bit blocked, but maybe his brain won’t work so well.

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What happens to such a man if he cuts carbohydrates and protein out of his diet?

His glucose levels will fall. Not very quickly, because glycolysis is blocked. But they will fall. Presumably some glucose is getting burned, unless he's carelessly eaten so many polyunsaturated fats that he can't do it at all.

And when they fall sufficiently far, his system will notice that there is not much glucose around, and switch over to the backup metabolic pathway, and start producing ketones.

Ketones, the brain can burn.

It will stop suffocating and start working properly, at least to a first approximation. It would probably prefer glucose, all things considered, but ketones will do.…

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Get it? If you eat PUFAs. Or if you have PUFAs stored in your system that get released into your system even when you are not actually eating PUFAs, then glycolysis is blocked, mostly you are running on fat, and your brain is suffocating.

If you go into ketosis, if you eat a ketogenic diet, then your brain will stop suffocating and start working properly.

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Note, dear readers, the awe-inspiring lack of smugness with which I notice that ketosis seems to fix a vast array of 'psychiatric illnesses'.

Those of us who are a bit funny in the head seem to do well on ketogenic diets.

Bipolar disorder, Schizophrenia, Epilepsy, Depression, plenty more. I even found a report of Anorexia Nervosa fixed by ketosis.

How very intriguing?! A weight loss diet that fixes the insane desire to starve that affects young women who are funny in the head because of pictures in magazines or capitalism or the unceasing malevolence of the patriarchy or whatever....

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For that matter, I can think of some cases that I sort of know personally in a sort of vague way over the internet.

My friend u/exfatloss suffers from non-24 hour sleep disorder, which magically goes away on ketosis.

Carnivore guru Amber O'Hearn became a carnivore guru because the carnivore diet fixed her crushing mental problems.

And of course I myself have noted a certain mental clarity and energy on ketosis that I remember from my earlier life as a healthy young man, back in the days when I fried everything in beef dripping because it tasted better.

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But careful, ketards!

You might feel better on a keto diet, should you be in a state where glycolysis is blocked. On a keto diet you don't need glycolysis to be working.

But the reason that glycolysis is blocked might be because of the polyunsaturated poison circulating in your blood, stored in your fat cells.

If your keto diet involves eating plenty of polyunsaturated fats, you're maybe making the problem worse.

By all means live on fat. Humans can live on fat, many such cases, looks like an evolved mechanism to deal with carbohydrate shortages, but do make sure it's proper fat. The sort of fat that apex predators eat.

Not, for instance, the sort of fat that is a potent inhibitor of glycolysis.

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What else might go wrong, if glycolysis is blocked?

Everything to do with glucose!

Suppose you’ve got glucose in abundance. But you can't burn it, because glycolysis is blocked.

And you can't turn it into fat, because glycolysis is blocked. If you can't turn glucose into pyruvate, you can't feed it into the Krebs cycle, and you can't turn it into fat either.

Glucose, glucose, everywhere, and not a drop to drink. And you can't even save it for later.

That's type-2 diabetes isn't it? High glucose, high insulin, screaming at all your cells to take some of the glucose and do something, anything with it.

But they can't do that. Because glycolysis is blocked.

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I think it might be important, if PUFAs are indeed a potent inhibitor of glycolysis.

Big if true, as they say.

Further research is needed.

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EDIT: u/exfatloss made some great clarifying comments below and on the r/saturatedfat subreddit, which I endorse completely.

1. For the avoidance of doubt, I have not gone mental and started trusting the medical literature. This is biochemistry. Biochemistry is a proper science. You can tell, because it doesn’t have the word “science” in the name.

Before anyone embarrasses themselves, Computer Science is not a science, and this is accepted by all computer scientists.

The only known exceptions are “Earth Sciences” and “Materials Science”, which in some more scaly quarters are polite euphemisms for Geology and for what grew out of Metallurgy. I think they must have got confused somehow. Either that or no-one could remember the Greek word for materials. Generation of vipers….

2. Amazingly it turns out there *are* such people.

I’ve only managed to find one other paper

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925660/

using non-liver cells (HeLa and MCF7, so breast and cervical cancer cells?), and they seem to think that the glycolysis prevention is part of an anti-cancer defence. Cancers love glycolysis so if you think cells are going out of control shutting down glycolysis makes perfect sense. That does imply that it’s a general mechanism rather than liver specific.

Of course what I really need to know is whether ‘PUFAs block glycolysis’ is true of brain cells. Science seems silent on this question.

Which is, like, mildly terrifying. How can you believe ‘PUFAs block glycolysis’ and ‘PUFAs are good for you’ with the same brain?

3. To forestall another possible pesky objection from the sorts of people who can actually think straight, https://www.jci.org/articles/view/25256 seems kind of adamant that it’s only PUFAs, not MUFAs or SFAs, so it’s not just that you’re stopping glucose metabolism while you deal with the fats. Which would be really odd anyway….