Polyunsaturated Fats Block Glycolysis: The Main Pathway of Metabolism
Rosetta Stone: You Can't Burn Carbohydrates in the Presence of Seed Oilz
Polyunsaturated Fats Block Glycolysis
Oncologists know this, but don't seem to have considered if it might have relevance outside oncology.
If it's true, I think it's one of the most important facts in medicine.
Suppose it's true in general. Then immediately:
PUFAs cause mental illness : Ketosis fixes it
Polyunsaturated fats block glycolysis
Without glycolysis, you can't burn glucose. (To a first approximation, glucose is all carbohydrates!)
Without glucose, you have to burn fat.
Your brain can't burn fat.
So if there are polyunsaturated fats in your system your brain is suffocating.
That likely results in it not working right, which is to say, you have 'psychiatric issues'.
But your brain can burn ketones.
So if you go into ketosis, your brain will start working right.
Many such cases:
https://med.stanford.edu/news/all-news/2024/04/keto-diet-mental-illness.html
PUFAs have caused the 'Epidemic of Hypothyroidism'
Without glycolysis, you can't burn carbohydrates. But if there's lots of glucose around, neither can you switch over to fat-burning, because there's lots of glucose around.
So your metabolism is running slow. Neither carb-burning nor fat-burning work properly.
Your metabolism is running slow.
Your waking temperature drops, because your basal metabolic rate is low.
You suffer from all the symptoms of slow metabolism.
Many such cases:
https://stopthethyroidmadness.com/
A very very large number of people around the world are convinced they've got thyroid disorders despite the fact that there's nothing wrong with their thyroid gland, or with the mechanism that controls it.
Why do they think this? Because they've got all the symptoms.
https://stopthethyroidmadness.com/symptoms/
All the symptoms of slow metabolism.
And they're right! If you did a 1960s-type diagnosis by symptoms, almost everyone's a bit hypothyroid these days.
Every doctor in the world is sick to the back fuck of people who are Tired All The Time and are claiming that they have a thyroid problem.1
Modern hormone tests tell us it's not a thyroid problem. But lots of people have the syndrome. You probably have some of these symptoms.
Thyroid drugs may help. Over-driving the sluggish metabolism.
Ketosis may help. Short-circuiting the broken glucose metabolism and running on the back up system.
PUFAs Cause The Swamp
One of the most intriguing discoveries/intuitions/hand-wavy justifications of r/saturatedfat (https://www.reddit.com/r/SaturatedFat/) is that people seem to do well on a low-carb, high-fat diet, and well on high-carb, low-fat diet.
But not so well on a balanced diet. The balanced diet is known as the âmetabolic swampâ, unde negant rediire possunt.
That's just weird, right? We're omnivores. We should probably be eating a balanced diet! It certainly shouldn't be worse than either extreme.
Suppose you've got PUFAs in your system, enough to inhibit glycolysis. Your metabolism is not working too well.
If you eat a very lot of carbohydrates, then maybe the sheer pressure of glucose in your system will drive enough glucose through the inhibited pathway anyway.
Maybe having your whole body in carb-burning mode will mean you donât release fat from stores. The fat from stores has PUFAs in it! Thatâs why youâre ill in the first place. Without the PUFAs from your fat stores, glycolysis will not be so inhibited.
And your metabolism will work better.
If you eat no carbohydrates, then you'll switch over to ketosis, the emergency backup carb-deprivation state.
And your metabolism will work better.
If you eat a balanced diet, then you get the worst of both worlds. There's glucose around, so you're not making ketones, but you can't burn the glucose, so your metabolism is running slow and your brain is suffocating.
PUFAs cause Insulin Resistance, Diabetes, and Obesity
I am not at all sure how this might work! Which is a bit embarrassing for a blog which is all about an old man worrying about his weight.
But if ânot being able to burn or store carbs or fat properlyâ doesnât have implications for insulin resistance, glucose homeostasis and dysregulation of weight homeostasis, I am a fucking Dutchman.
Ketosis May Not Be Necessary
At least for the brain-fixing bit, what you need is ketones, not ketosis itself.
You can just buy ketones. It may be that nutritional ketosis is not necessary for the mental benefits of ketosis.
But Iâm a bit sceptical of this. The presence of glucose is probably inhibiting fat metabolism. So there might be some weird side-effects of living in the swamp whilst taking exogenous ketones.
So, Do PUFAs Really Block Glycolysis?
Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation:
https://www.jci.org/articles/view/25256 (https://doi.org/10.1172/JCI25256)
This is in liver, it seems to be a fact generally accepted in liver cells, but it actually looks more general.
Here we've got the same effect in HeLa and MCF7, so immortalised cervical and breast cancer cells:
Omega-3 polyunsaturated fatty acid promotes the inhibition of glycolytic enzymes and mTOR signaling by regulating the tumor suppressor LKB1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925660/
It's thought that this is a defence mechanism against cancer. And that makes sense. Cancers love glycolysis and burn a lot of glucose.
Turning off glycolysis will do a lot more harm to cancer cells than to the rest of your cells.
That also implies that itâs a general mechanism, rather than something liver-specific.
The remaining question is:
Why would PUFAs set off a cancer defence? But there doesn't have to be a good reason. It could just be an accidental effect, a misfire.
Your body was never supposed to have large quantities of polyunsaturated fats in it.
EDIT: PUFAs Cause Post-prandial Slump
u/loveofworkerbees on r/saturatedfat pointed out a prediction I had not made:
I mean this is anecdotally true for me. A year ago eating fruit would put me into a coma. Now 1 year almost no PUFA I get sustained energy from fruit alone. Itâs actually really fucking crazy. If itâs placebo effect whatever but itâs night and day for me.
Everyone knows that if you give kids sugar they go crazy with energy.
Obviously: âCrikey a load of excellent fuel has just turned up all at once, Oh God the thingâs over-revving. Throttle Back! Throttle Back!â
And everyone knows that eating a load of carbs makes you tired. In fact it was one of the first symptoms of my curse, way back in my thirties. Tired after lunch. But everyone gets tired after lunch, donât they? Glycaemic Load and all that.
Obviously: âCrikey a load of excellent fuel has just turned up all at once. Better switch over to carbohydrate metabolism. Oh noes, its not working properly (because, and I hate to labour the point, glycolysis is blocked). Oops no enneeeeerrrrrrrrrgggggggyyyyyyyyyyyyyyâĤâĤ
And so I make the following prediction. Children (and adults) who have eaten nice normal natural foods (and these days that doesnât even include breast milk, so PUFA-filled are we.) and who have few PUFAs in their systems will get excited on sugar, but not particularly react to starch.
And children (and adults) with masses of PUFA in their systems will slump after eating large quantities of carbs.
The effect might even be a good proxy for a fat biopsy. I predict a strong correlation here.
And it gives me hope, because u/loveofworkerbees has apparently fixed the problem in a year. Maybe there are ways to get the polyunsaturated poison out faster than we think.
Psychiatry is the last area of medicine that will sometimes use thyroid drugs with normal thyroid tests, because they know that it sometimes fixes Major Depression (a syndrome which looks a lot like a classical presentation of hypothyroidism to me).
No-one knows why it works. There is some story about âpotentiating the antidepressantsâ.