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Dietary stearic acid induces mitochondrial fusion in humans. Relevance for ME/CFS?

Cipher

Administrator
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838
Dietary stearic acid regulates mitochondria in vivo in humans (2018)

Abstract

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.
 

Wishful

Senior Member
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Alberta
At one point in my ME fatty acids made my symptoms worse, unless I added some carnitine. I thought it was palmitic acid responsible, but I didn't have reasonably pure fatty acids to test, so it's possible that stearic was involved. The problem went away after a few months of carnitine supplementation.

Does stearic acid affect ME? Try some and see ... and report back here. :)
 

serg1942

Senior Member
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543
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Spain
This is a great article! Stearic acid is the main fat in animals, and it is great that it seems to improve mitochondria, as I am doing a full nose to tail carnivore diet. It actually fits with the great antiinflammatory potential of this diet... I guess saturated fats should be adviced for ME/CFS, while poly-unsaturated linoleic acid should be excluded.

Sergio
 

nerd

Senior Member
Messages
863
What's the current understanding of the dysfunction of carnitine in CFS/ME? Why is it usually too low? Is too much metabolized or is there insufficient synthesis? If there was too little/much oxidation of acylcarnitine in CFS/ME, it would have to be due to cell infusion issues or coenzyme A catalysation, wouldn't it? What's really going on with acylcarnitine in CFS/ME in particular and not just carnitine?
 

serg1942

Senior Member
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543
Location
Spain
Carnitine levels drop after eating stearic acid because it's been used more in burning fats. This is actually good because fat metabolism is much more efficient (2.6 times more than glucose) and also presents the anti-inflammatory advantages of ketosis.

S-
 

nerd

Senior Member
Messages
863
Carnitine levels drop after eating stearic acid because it's been used more in burning fats. This is actually good because fat metabolism is much more efficient (2.6 times more than glucose) and also presents the anti-inflammatory advantages of ketosis.

S-

I meant specific for CFS/ME. This study just shows a general phenomenon. I mean, if this was applicable for CFS/ME, why would stearic acid play such a great role?
 

serg1942

Senior Member
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543
Location
Spain
Well, a good explanation is that methylation is requiered to form L-carnitine, and in ME/CFS we have poor methylation, as shown by Rich Konynenburg years ago. Also, this is tied to the CDR state, where cells down-regulate methylation on purpose in order to prevent virus from steeling our cellular machinery to form viral RNA or DNA...
 

percyval577

nucleus caudatus et al
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Ik waak up
What's the current understanding of the dysfunction of carnitine in CFS/ME? Why is it usually too low? Is too much metabolized or is there insufficient synthesis? If there was too little/much oxidation of acylcarnitine in CFS/ME, it would have to be due to cell infusion issues or coenzyme A catalysation, wouldn't it? What's really going on with acylcarnitine in CFS/ME in particular and not just carnitine?
I cannot remember what Hornig et al in 2018 have found or others since then, but I think findings and possible theories are still on their way.

Already 2004 though Vermeulen and Scholte investigated a treatment for CFS with carnetine with some interesting (but non-lasting) results:
Exploratory Open Label, Randomized Study of Acetyl- and Propionylcarnetine in Chronic Fatique Syndrom
Link to the Journal // Link to researchgate


p. 276
Kuratsune et al. () Plioplys and Plioplys () reported a decrease in plasma acylcarnetine In CFS, but this was not confirmed by others (7-9). The first report on carnetine treatment in CFS was by Grau et al. () who found no effect. Plioplys and Plioplys () reported significant improvement of CFS symptoms after 2 months of 3 g daily orally administered L-carnetine.

p. 280
The effect of ALC on mental fatique and attention concentration was significant. The PLC group showed most improvement in general and physical fatique and slightly less in attention concentration. The ALC+PLC group improved very well on general fatique and also, but not significantly, on physical and mental fatique. ...

In the second observation period, 50% of patients deteriorated in th ALC and PLC groups. For most the relapse was hardly acceptable ... The improved patiens in th ALC + PLC group (37%) all deteriorated in the second observation period.
So, this resembles an observations also sometimes reported on the forum, when influences work for some time and then they stop.
 

nerd

Senior Member
Messages
863
Thanks!

In the second observation period, 50% of patients deteriorated in th ALC and PLC groups. For most the relapse was hardly acceptable ... The improved patiens in th ALC + PLC group (37%) all deteriorated in the second observation period.

I guess this was just another case of the confused assumption that a pathophysiologically-targeted treatment could fix the causal pathology. We still have to pace.
 

Hip

Senior Member
Messages
17,824
The stearic acid content of various meats is given in table 2 of this paper:

Beef 100 grams contains 507 mg of stearic acid
Lamb 100 grams contains 898 mg of stearic acid
Lamb 100 grams contains 278 mg of stearic acid

So one 8 oz portion (227 grams) of steak, for example, will contain about 1.2 grams of stearic acid. It will contain more if you leave the fat on (see below).



This paper says beef fat is 19% stearic acid. So the more meat fat you leave on and eat on your meat, the more stearic acid you get.

If we consider lean ground beef, this contains 8% fat, so that means 100 grams of this ground beef will contain 1.5 grams of stearic acid. A typical beef burger weighs around 100 grams.



If we want to try stearic acid as a supplement, note that magnesium stearate powder contains about 4% magnesium by weight, and about 96% stearate. So it is mostly just stearate.

Thus a dose of around 2 grams of magnesium stearate powder daily would give you nearly 2 grams of stearic acid, which is comparable to what you would obtain from daily meat in your diet.

You can buy magnesium stearate powder easily online; 1 kg costs around $20.



Magnesium stearate is commonly used in supplement tablets and capsules. Tablets contain around 1%. So a 500 mg tablet will contain 5 mg of magnesium stearate, which is a negligible source compared to meat.
 
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sb4

Senior Member
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United Kingdom
There is a blog where a guy has been heavily supplementing stearic acid for around a year for wieght loss / health. He has lost some weight but not a lot but says he feels healthier.

He has been doing this experiment thanks to peter @hyperlipid blog on why saturated fat and insulin resistance is good for health.

Essentially it boils down to saturated fats having more input at FADH in the mitochondria. More input at FADH (relative to NADH) means more reverse electron flow (REF) in the mitochondria. More REF means more ROS means the cell becomes insulin resistant faster (which is actually what you want to happen, temporarly). This leads to cells signalling they have more energy faster and satiety is triggered. I assume this signal for cells being full then leads to mitochondrial fusion as they have energy to spend. Not sure though

It gets more complicated though because cells can upregulate SCD1 (Stearoyl-CoA desaturase-1 ) which means your body can turn that stearic acid into a monounsaturated fat. Indeed he sells a supplement called Sterculia oil which is an unsaturated fat that causes your body to downregulate SCD1. I have tried this recently but even small doses give me diarhea.

Anyway Ive done a poor job of explaining it but if you are interested read peter @hyperlidips blog or the fire in a bottle blog.
 

Hip

Senior Member
Messages
17,824
This paper suggests stearic acid possibly increases insulin receptor signaling (improves insulin sensitivity).



I find it interesting that after I was hit with ME/CFS, I developed an increase desire for meat and fat. Previously I used to have a healthy balanced diet, eating some meat, but also having lots of vegetables on the plate.

Now I have gone off the taste of a lot of vegetables I previously liked, but love fatty meat. So I assume there must be something in the meat that I intuitively feel is doing me good. Maybe that thing is the stearic acid?
 

Cipher

Administrator
Messages
838
If we want to try stearic acid as a supplement, note that magnesium stearate powder contains about 4% magnesium by weight, and about 96% stearate. So it is mostly just stearate.

Thus a dose of around 2 grams of magnesium stearate powder daily would give you nearly 2 grams of stearic acid, which is comparable to what you would obtain from daily meat in your diet.

You can buy magnesium stearate powder easily online; 1 kg costs around $20.

Unfortunately, it seems like most stearic acid products and derivatives on the market are very impure, in many cases containing more palmitic acid than stearic acid! This includes magnesium stearate:

The fatty acids used as raw material are derived from edible fats and oils and consist mainly of stearic and palmitic acid. The final product contains 4.0-5.0% magnesium, on a dried basis, and the fatty acid fraction is composed of ≥90% stearic and palmitic acids, at least 40% of which are stearic acid.
source

Commercial stearic acid is often a mixture of stearic and palmitic acids, although purified stearic acid is available
source

Cocoa butter might be a better source, as it contains a similar percentage stearic acid (35%) but way less palmitic acid (26%) compared to magnesium stearate (50-60% ish). Or shea butter, which contains even less palmitic acid.

The stearic acid dose used in this study was much higher than what you can ingest via meat:

We then asked the subjects to drink a banana milk shake containing 24 g of C18:0, roughly equivalent to the amount of C18:0 present in 200 g of milk chocolate
 

Hip

Senior Member
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17,824
Unfortunately, it seems like most stearic acid products and derivatives on the market are very impure, in many cases containing more palmitic acid than stearic acid! This includes magnesium stearate:

That does not sound good; but well researched!

Looking at this magnesium stearate pharmaceutical grade product (1 kg for £7) that I came across, it does seem to contain potentially lots of palmitic acid. Here is the product label:

Magnesium stearate pharmaceutical grade.png


The label says:

Fatty acids (C16 + C18) = 90 - 100%
Fatty acids (C18) = 40 - 100%

Where:
C16 is palmitic acid
C18 is stearic acid

So the amount of C18 (stearic acid) in this product is not precisely given, they just give a range of 40 to 100%. So it could be as little 40%, with the rest made up by C16 (palmitic acid). Or it could be as much as 100%.

Not sure why they do not know the precise amount of stearic acid in their product.


Is the palmitic acid doing any harm though? Would it counter stearic acid's mitochondrial fusion? I see that high intakes of palmitic acid are linked cardiovascular disease. Though for a short-term test on the possible benefits of stearic acid for ME/CFS, that should not be an issue.



Cocoa butter might be a better source, as it contains a similar percentage stearic acid (35%) but way less palmitic acid (26%) compared to magnesium stearate (50-60% ish). Or shea butter, which contains even less palmitic acid.

Treating ME/CFS by eating lots of chocolate — now that's my kind of medicine!

Looks like you can buy 1 kg of cocoa butter for around £12, which is not expensive.
 

Hip

Senior Member
Messages
17,824
If I'm not mistaken @dreamydays has taken lots of stearic acid without much improvements (he is severe+)

That's interesting, I wonder what daily dose of stearic acid @dreamydays took?



It could be that promoting mitochondrial fusion only benefits ME/CFS patients with viruses that spread by inducing mitochondrial fission, like Coxsackie B virus. And Dr Prusty found HHV-6 induces mitochondrial fission (but I am not sure of HHV-6 spreads by mitochondrial fission).

This paper which you posted previously explains that coxsackievirus B induces mitochondrial fission in order to spread, and that by blocking mitophagy (the degradation of mitochondria), it resulted in a marked reduction in viral replication:
We now report that CVB-infected cells trigger DRP1-mediated fragmentation of mitochondria, which is a precursor to autophagic mitochondrial elimination (mitophagy).

However, rather than being degraded by lysosomes, mitochondrion-containing autophagosomes are released from the cell. We believe that CVB localizes to mitochondria, induces mitophagy, and subsequently disseminates from the cell in an autophagosome-bound mitochondrion-virus complex.

Suppressing the mitophagy pathway in HL-1 cardiomyocytes with either small interfering RNA (siRNA) or Mdivi-1 caused marked reduction in virus production.




Of course the mitochondrial division inhibitor mdivi-1 that you detail in this thread and which was used in the above study is almost certainly going to be more potent at preventing mitochondria fragmentation.
 
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gbells

Improved ME from 2 to 6
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Alexandria, VA USA
Of course the mitochondrial division inhibitor mdivi-1 that you detail in this thread and which was used in the above study is almost certainly going to be more potent at preventing mitochondria fragmentation.

Why would you want to prevent it if it slows the progression of virally infected cells? Not a good idea.
 

Hip

Senior Member
Messages
17,824
Why would you want to prevent it if it slows the progression of virally infected cells?

Coxsackievirus B induces mitochondrial fission (the fragmentation or division of mitochondria into smaller mitochondria) in order to propagate from cell to cell in autophagosomes, which I believe are a type of extracellular vesicle (but @Pyrrhus may know more about this). See the above paper.

So by promoting the opposite mechanism, mitochondrial fusion, possibly you may be able to inhibit the cellular release of autophagosomes containing coxsackievirus B.



This study says:
Mitochondria are dynamic organelles that undergo continual fusion and fission to maintain their morphology and functions

This paper says both mitochondrial fission and fusion have advantages and purposes:
Mitochondrial fusion is particularly important in respiratory active cells. It allows the spreading of metabolites, enzymes, and mitochondrial gene products throughout the entire mitochondrial compartment. This serves to optimize mitochondrial function and counteracts the accumulation of mitochondrial mutations during aging.

Fragmented mitochondria are frequently found in resting cells, and mitochondrial fission plays an important role in the removal of damaged organelles by autophagy. Thus, mitochondrial fusion and fission both contribute to maintenance of mitochondrial function and optimize bioenergetic capacity.

Oxidative stress seems to promote mitochondrial fission, which is detrimental, according to this study:
We conclude that mitochondrial oxidative stress mediated through Drp1 and Mfn2 causes an imbalance in mitochondrial fission-fusion, resulting in mitochondrial fragmentation, which contributes to mitochondrial and cell dysfunction.

So given ME/CFS involves oxidative stress which promote fission, as well as coxsackievirus B which promotes fission, shifting the fission/fusion balance towards fusion may have some benefits.
 

gbells

Improved ME from 2 to 6
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Location
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I think a better plan is to clear the infected cells with apoptosis and then use PQQ supplement and exercise to regenerate the mitochondria.