jnmaciuch
Senior Member (Voting Rights)
I linked it earlier in the thread, it looks like the original version did not include this thread's author (and did not include reference to ME/CFS)
Preprint Spironolactone for ME/CFS in a Patient Homozygous for rs5522 (I180V): A Case Report, 2026, Donnellan et al
- Thread starter forestglip
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jnmaciuch
Senior Member (Voting Rights)
Sorry to hear you've been experiencing that. We all want people with ME/CFS to get effective treatments too. On this forum we go through papers in-depth, which is why we are interested in the details. We'd be very interested to know the raw data and your process for determining that you had the Ile180Val mutation
Utsikt
Senior Member (Voting Rights)
The only reference to ME/CFS is in relation to the case report from this thread.
There is a claim about how «hyperactivity mediated by brain rs5522» «contributes to ME/CFS», but no evidence is provided in the paper.
leokitten
Senior Member (Voting Rights)
Sorry but the end there is not correct, 23andme TT = AA on the forward strand
I’m not sure who prevailed in the genetic discussion or whether it was resolved.
Regardless of mechanism, a well documented n=1 case history of symptom improvement is always welcome.
If the there is an improvement in the more common genotype that means that it is possible spiro might work for more patients.
Regardless of mechanism, a well documented n=1 case history of symptom improvement is always welcome.
If the there is an improvement in the more common genotype that means that it is possible spiro might work for more patients.
Venicequeenf
Established Member (Voting Rights)
As I have taken spironolactone in the past, I will try to get a new prescription and try it, if I succeed to get it
And it helped you in the past? With which symptoms and about how much improvement?
Venicequeenf
Established Member (Voting Rights)
I have taken it many years for a completely different reason (PCO Syndrome) so I cannot say it. But I was already in the early years of ME / POTS, but undiagnosed, probably mild at that time as I was still able to work
Venicequeenf
Established Member (Voting Rights)
I have the prescription now! Will try it soon.
Any news from the peer reviewing?
Any news from the peer reviewing?
jnmaciuch
Senior Member (Voting Rights)
Sorry, didn’t see this till now. Probably good to make note in the public thread, in case the preprint leads others to start seeking the drug or paying for genetic testing.
The author mentioned TT genotype twice now, so seems likely it is TT and not the genotype causing the mutation mentioned in the case study. AI seems to give the wrong information about that gene, probably getting mixed up by the reference genome—might explain the confusion in this case study if the analysis was done by AI instead of someone with genetics training. Unless the raw data for the gene can be produced and more than one month of improvement can be shown, maybe best to take with a hefty grain of salt?
Spironolactone is prescribed for a lot of things—acne, treatment resistant blood pressure, hormone replacement therapy, etc. If it was a magic bullet, seems unlikely that we wouldn’t have heard before.
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Spiro brought up by Cort here (EBV)
Old Drug Points to a New Way to Knock the Epstein-Barr Virus Down - Health Rising
An old drug called spironolactone opens the door to a new generation of more effective Epstein-Barr virus drugs that could help with chronic fatigue syndrome, long COVID and other diseases.
www.healthrising.org
ChronicallyOverIt
Senior Member (Voting Rights)
Quite a few women in my local group have taken it for hair loss which was a totally separate conversation. They didn’t note or talk about any improvement other than hair
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Art Vandelay
Senior Member (Voting Rights)
Venicequeenf
Established Member (Voting Rights)
Tried it, unfortunately did nothing for me
DonnellanP
Established Member
The mechanism paper has been published. The cause of chronic fatigue syndrome is now known.
https://authors.elsevier.com/c/1mt6x,99wrFyt
Due to the uniqueness of how genetic testing companies report strand data, impacted individuals would have TT listed under rs5522 on 23 and me, ancestry or sequencing.com. This codes for valine instead of isoleucine in the cells. It causes MR receptors to be over reactive and steal cortisol. When the body robbed of the cortisol it needs to run basic bodily functions, symptoms of CFS arise. Why wasn't this detected earlier? Medicine tests cortisol using blood, but that does not tell you what is happening in the cells.
Think of it as looking at a highway (blood) and thinking there are a lot of trucks out there so the stations that need aid must be getting what they need. This doesn't tell you that at the aid stations, the much needed aid (cortisol) is being stolen away by the MR receptor. Just as if the aid was taken out back and never got to where it was truly needed. Blood tests= highway testing. Not accurate for people with the genotype.
https://authors.elsevier.com/c/1mt6x,99wrFyt
Due to the uniqueness of how genetic testing companies report strand data, impacted individuals would have TT listed under rs5522 on 23 and me, ancestry or sequencing.com. This codes for valine instead of isoleucine in the cells. It causes MR receptors to be over reactive and steal cortisol. When the body robbed of the cortisol it needs to run basic bodily functions, symptoms of CFS arise. Why wasn't this detected earlier? Medicine tests cortisol using blood, but that does not tell you what is happening in the cells.
Think of it as looking at a highway (blood) and thinking there are a lot of trucks out there so the stations that need aid must be getting what they need. This doesn't tell you that at the aid stations, the much needed aid (cortisol) is being stolen away by the MR receptor. Just as if the aid was taken out back and never got to where it was truly needed. Blood tests= highway testing. Not accurate for people with the genotype.
Could you please copy the specific information in the sequencing results which says TT is present at this location, and the documentation from the sequencing company that this interpretation is based on?
I don't know why any sequencing company would report a T in this location for someone with the minor allele, as the minor variant is either C or G depending on strand.
Jonathan Edwards
Senior Member (Voting Rights)
That does not make sense to me. If cortisol levels are normal the body is not robbed of anything surely? Especially if the body is made of cells that pick up cortisol even more than usual and there is a normal amount available outside the cells.
jnmaciuch
Senior Member (Voting Rights)
The speculation is based on a theory of preferential capture since both the MR and GR bind cortisol. But in post #22 I already explained why it doesn't really apply here. [Edit: There was one preprint showing an increased transcriptional response downstream of cortisol binding to the MR with that valine substitution, but no evidence that this is due to increased binding affinity.] It all seems like AI reasoning rather than...reasoning
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leokitten
Senior Member (Voting Rights)
I think this is getting the cart way before the horse. Like cart miles in front
DonnellanP
Established Member
Here is the published mechanism paper. https://authors.elsevier.com/c/1mt6x,99wrFyt
Look up rs5522 in your 23andMe raw data. Or ancestry. Or sequencing. If it says T/T, you’re homozygous for the hyperactive variant (Val/Val)
Look up rs5522 in your 23andMe raw data. Or ancestry. Or sequencing. If it says T/T, you’re homozygous for the hyperactive variant (Val/Val)