Menthol causes significant reduction in CVB-mediated mitochondrial fission

[Swim15]

I've only glanced through this study and put it on my 'in-depth' reading list for later.

Just glancing, it seems like menthol attenuated the mitochondrial fission that is characteristic in CFS.

I've only been researching CFS for about a month since my diagnosis but someone might be able to shed some better light. I know menthol is toxic to a degree so then, if the study results seem legitimate, it comes down to determining the concentrations necessary and toxicity.


Found the full PDF somewhat but can't link it so here is the abstract

https://pubmed.ncbi.nlm.nih.gov/32231022/

 

[Swim15]

Another link

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232514/

 

[Swim15]

At this point I have no idea how to go about trying this but I ordered some pure menthol to try.

seems like the perfect fit since it targets one of the primary issues in CFS. Gonna start low and if I tolerate it progress to dosing several times per day to see if it helps any symptoms

 

[gbells]

I wouldn't use methol. I get a nasty side effect of GERD provocation. I vape it occassionally but there are better treatments.

 

[Hip]

Just glancing, it seems like menthol attenuated the mitochondrial fission that is characteristic in CFS.

In this post it's explained that unfortunately there isn't remotest change of obtaining in vivo the high menthol concentrations used in the in vitro study on mitochondrial fission.

When you see an in vitro study, you always have to look at whether the concentrations used can be attained in vivo. Very often they cannot, because they usually use high concentrations in vitro, just to demonstrate the effect.

 

[Mary]

@Swim15 - What menthol product did you buy? I saw a Bulk Supplements Menthol crystals supplement, which clearly states not to ingest it, it's not for human consumption. I think the pure crystals can cause burns.

Peppermint oil is high in menthol and there are peppermint oil products which are safe to ingest so this might be an alternative.

 

[Hip]

I saw a Bulk Supplements Menthol crystals supplement, which clearly states not to ingest it, it's not for human consumption. I think the pure crystals can cause burns.

Yes, pure menthol crystals can cause 3rd degree chemical burns on skin and tissues. I believe this is because it is an irritant substance, but because it is water insoluble, it sticks to the skin and does not wash away.

However, I've taken menthol by first dissolving it in cooking oil, so that I get around 250 mg of menthol in each tablespoon of oil (which is about the same menthol dose you get in typical peppermint oil capsules). If considerably diluted in oil in this way, I think it is safe.

 

[Swim15]

In this post it's explained that unfortunately there isn't remotest change of obtaining in vivo the high menthol concentrations used in the in vitro study on mitochondrial fission.

When you see an in vitro study, you always have to look at whether the concentrations used can be attained in vivo. Very often they cannot, because they usually use high concentrations in vitro, just to demonstrate the effect.

That’s what I was wondering and couldn’t find anything on the pharmacokinetics. What page did you get the 4.5um number on of the study?

I’m not sure if any menthol would be protein bound - or at least haven’t found any info but otherwise the concentration needed could be less than the in vitro study.

Worth a shot I thought lol. Also there was a compound isolated in nutmeg that does the same thing with 30x the potency supposedly - haven’t dug into that much yet but that compound was synergistic with menthol so combining them both might have some positive effects

 

[Swim15]

Study on nutmeg here - much lower EC50 and mentions additive properties with menthol

https://pubs.acs.org/doi/full/10.1021/acsmedchemlett.7b00104?src=recsys#

 

[Hip]

What page did you get the 4.5um number on of the study?

In the pharmacokinetic study, in the results section on the first page, it says that they measured a peak blood menthol concentration, Cmax = 698.2 ng/ml, when subjects were given peppermint oil capsules containing 187 mg of menthol.

To convert concentrations expressed as ng/ml (nanograms per milliliter) to molar concentrations of μM (millionths of a mole per liter), you use the formula:

μM = ng/ml divided by the molecular weight​

So that formula gives you the figure of 4.5 μM (since menthol molecular weight = 156.27 g/mol).

I've looked at hundreds of these in vitro papers, so I am now used to doing the mathematics.

 

[Hip]

If you want to do a very quick ballpark calculation for the blood concentration achieved after orally ingesting a substance, what you do is assume 100% bioavailability and 0% plasma protein binding (the best possible scenario).

Then assume around 40 liters of fluids in the human body, which is 40,000 ml of fluids, that this substance will distribute in when you take it orally. So to get the amount of substance per ml in the blood, you just divide your oral dose by 40,000.

So for example, if you take say an oral dose of 100 mg = 100,000 μg of a substance, you are going to get a blood concentration of 100,000 / 40,000 = 2.5 μg/ml.

 

[Swim15]

^That is helpful! I should know those calculations but sadly haven’t really done them.

I need to read this not on mobile but this report says the EC50 is around 10uM


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512136/#!po=1.51515

 

[Swim15]

This is sort of related/unrelated but testosterone inhibits TRPM8.

I’m going to read through some more literature but that may have some impact on the male vs female role of CFS

 

[Hip]

I need to read this not on mobile but this report says the EC50 is around 10uM

That would relate to a specific substance within nutmeg, so you'd have to find some figures for its percentage content in nutmeg before you can begin to start nutmeg dose calculations.

And then because it is a novel substance, you probably will not find any data for bioavailability or plasma protein binding, which means you will not be able to make more accurate calculation of dosage.



Incidentally, I've found peppermint oil (or my home made oil dosing with 250 mg menthol) quite good for my IBS-D. Ii helps reduce the IBS diarrhea, and I think this is due to menthol's action on TRPM8. Though presumably in the bowel, the menthol will be more concentrated. After the menthol gets systemically absorbed, it's concentration I guess will be reduce, due to the larger volume of the body's fluids.

 

[Hip]

I should know those calculations but sadly haven’t really done them.

That quick ballpark calculation is actually my own invention; I've not seen anyone else use it; but to me it makes sense that it would provide a rough ballpark figure for blood concentration.


The more accepted and more accurate way of determining blood concentration is via a pharmacokinetic study, where a group of volunteers are given a specific dose of the substance, and the concentration in the blood is measured. Obviously this is much more precise than any calculation you can do.