Mechanisms Behind Ketogenic Diet's Anti-autoimmune Properties?

[Waynish]

I haven't seen very convincing explanations for why so many people who suffer from so-called autoimmune conditions like rheumatoid arthritis get better benefits from ketogenic diets than anything else. Sure, we could accuse those (like millions) of people of not trying enough things. We could say "autoimmune" doesn't exist (because it isn't part of Ray Peat's work), and end the discussion there. But I'm looking for some deeper explanations of mechanisms whereby eating very low carbohydrate diets reduce inflammation and autoimmune conditions systemically. Also, the explanations must be deeper than "the carbs were feeding pathogens in the stomach/small intestine" because antibiotics don't cure these conditions.

 

[Diokine]

I think chronically elevated insulin, or transient periods of hyperinsulinemia, might represent a failure in the feedback mechanisms involving the cholinergic system. Insulin secretion is a complicated process, and cholinergic activity has been shown to be essential. I think that in general, excessive insulin will reduce the sensitivity of the cholinergic system, which precedes autonomic and especially parasympathetic dysfunction, which is highly indicated in something like rheumatoid arthritis. So a reduction in levels of insulin can restore sensitivity to a system which is grossly fatigued due mainly to lack of proper thyroid activity and vitamin D.

 

[ilikecats]

Cortisol

 

[ilikecats]

Also removing bread (gluten) from the diet has a very profound anti inflammatory effect for most people.

 

[SB4]

I think high fat gets too bad a rep on here. Yes some people get worse on it, they may be doing it wrong, it may not suit there illness, etc. But lots of people do better on it aswell.

It could be through improving metabolism. Eating foods (keto) with a high FADH2/NAD ratio will cause your fat cells to stop taking in as much food and signal to your body that there is a lot of excess energy.

It could be through deuterium. Fats are D depleted compared to carbs. Less D = faster TCA and faster ATPase / cytochromes.

It could be through removing irritants, immune triggers, in diets and having a relatively simple to absorb diet.

 

[opiath]

Ultimately for a lot of people inflammation is the result of a slow metabolism.
The limiting factor for many is their ability to exhale carbon dioxide.
Why is this so?
Carbon dioxide generated by the cells becomes carbonic acid and like any acid it lowers the PH level of the body.
In order to maintain the PH level optimal the body simply reduces the metabolism rate so less carbon oxide is generated.
Metabolism is kept exactly at the level at which carbon dioxide is able to leave the body.

Why do you think millions of people get addicted to smoking cigarattes?
What does nicotine do? It bind to acetylcholine receptors and thus increases the stimulatory action on the ANS which results in faster ventilation.
Faster ventilation -> more CO2 exhaled -> metabolism goes up.

Why am I talking about this?

Unless there is a deficiency of something, ventilation ability is not that easily changed.
It depends on a lot of factors: genetics, organs state, environment, hormones, stress, exercise.
What can be changed though is the dietary macros.

Just compare the structures of sugar and fat.
Their molecular structures determines their respiratory quotient.
Respiratory quotient - Wikipedia

What this means is that fat generates less CO2 per energy produced.
For people that are limited by their CO2 exhalation, fats allow for a higher metabolic rate.

 

[ecstatichamster]

Ray has said he believes there is more CO2 creation with glucose rather than fat burning, and this accounts for the benefits of glucose for energy.

I think the benefits of keto diets are in the ketones. Ketones seem to be a good energy source. High cortisol also suppresses immunity.

 

[Steven Bussinger]

Cortisol

High cortisol also suppresses immunity.

There may be something to this. Perhaps the cortisol is like a steroidal drug given to quell inflammation (ie immune actions).

 

[ecstatichamster]

There may be something to this. Perhaps the cortisol is like a steroidal drug given to quell inflammation (ie immune actions).

that is its function.

 

[Waynish]

Ray has said he believes there is more CO2 creation with glucose rather than fat burning, and this accounts for the benefits of glucose for energy.

I think the benefits of keto diets are in the ketones. Ketones seem to be a good energy source. High cortisol also suppresses immunity.

This would be easy to test. Just get one of the many people who get rheumatoid arthritis, for example, to vanish when they stop carbs and get them to go back on carbs with exogenous ketones. I bet they would not have a similar experience.

 

[Mito]

Ultimately for a lot of people inflammation is the result of a slow metabolism.
The limiting factor for many is their ability to exhale carbon dioxide.
Why is this so?
Carbon dioxide generated by the cells becomes carbonic acid and like any acid it lowers the PH level of the body.
In order to maintain the PH level optimal the body simply reduces the metabolism rate so less carbon oxide is generated.
Metabolism is kept exactly at the level at which carbon dioxide is able to leave the body.

Why do you think millions of people get addicted to smoking cigarattes?
What does nicotine do? It bind to acetylcholine receptors and thus increases the stimulatory action on the ANS which results in faster ventilation.
Faster ventilation -> more CO2 exhaled -> metabolism goes up.

Why am I talking about this?

Unless there is a deficiency of something, ventilation ability is not that easily changed.
It depends on a lot of factors: genetics, organs state, environment, hormones, stress, exercise.
What can be changed though is the dietary macros.

Just compare the structures of sugar and fat.
Their molecular structures determines their respiratory quotient.
Respiratory quotient - Wikipedia

What this means is that fat generates less CO2 per energy produced.
For people that are limited by their CO2 exhalation, fats allow for a higher metabolic rate.

What about renal compensation?

 

[opiath]

What about renal compensation?

Yes, kidneys have a very important function in this.
But their role is not to excrete the carbon dioxide.
At best they lose few grams of bicarbonate per day which is insignificant compared to the 2-3 pounds ot carbon dioxide that
your lungs exhale.

The job of the kidneys when ventilation is limited is to increase the buffering which allows for a higher metabolic rate but
the compensation only goes so far.
The more bicarbonate increases the more pressure there is on the kidneys as an organ and you become very sensitive to changes
in ventilation.
Kidneys take days to recalibrate bicarbonate while ventilation can change in less than a few seconds due to stress or exercise.

 

[B-styles]

I haven't seen very convincing explanations for why so many people who suffer from so-called autoimmune conditions like rheumatoid arthritis get better benefits from ketogenic diets than anything else. Sure, we could accuse those (like millions) of people of not trying enough things. We could say "autoimmune" doesn't exist (because it isn't part of Ray Peat's work), and end the discussion there. But I'm looking for some deeper explanations of mechanisms whereby eating very low carbohydrate diets reduce inflammation and autoimmune conditions systemically. Also, the explanations must be deeper than "the carbs were feeding pathogens in the stomach/small intestine" because antibiotics don't cure these conditions.

Plants (carbs) have irritants in them which when people remove think it was the 'sugar' feeding pathogens when really it was the irritants continuing to inflame the gut. Fats (healthy) are also ANTI-inflammatory and have a soothing effect on gut. Removing the offender(s) and eating the RIGHT carbs and PREPARING them properly is the real solution.

 

[Steven Bussinger]

The immune system is charged with maintaining the physical structure and integrity of an organism. Inflammation is almost always co-incident with "auto-immunity". The inflammation is created by the immune system as part of its tissue remodeling process. The tissue remodeling is what is perceived as "the body attacking itself".

There is a thing called "sterile inflammation" where no infection or foreign bodies are involved. This is a problematic fact for the auto-immunity theory.

Inflammation seems to occur as part of a domino chain effect; each inflammatory signaling molecule involves yet more inflammatory signaling molecules until the healing issue is resolved. In a sufficiently healthy individual (like a healthy child), the inflammatory process is very short, and may not even be necessary. Think of the inflammation that occurs from a sprained ankle or cut.

Ketogenic diets have anti-inflammatory effects. So does omega 3. The immune system is knocked down and no longer attempts inflammatory action to rebuild tissue.

Some of this is discussed in this episode:

 

[Mito]

Ketogenic diets have anti-inflammatory effects. So does omega 3. The immune system is knocked down and no longer attempts inflammatory action to rebuild tissue.

So in people with autoimmune diseases, the immune cells begin remodeling damaged tissue causing inflammation, but there is no signal (off switch) to stop the remodeling process and inflammation? The keto diet, omega 3, prednisone provide the signal (off switch)?

 

[LLight]

Ketones are supposedly HDAC inhibitors:

Ketone bodies as signaling metabolites

HDACi have the potential to increase antimicrobial peptides production:

Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections

Some people think that autoimmune diseases are caused by pathogenic organisms which have colonised the body, especially intracellular for immune cells. Their theory is that the peptides production is downregulated because of them.