New guy, 25yo, in a extremely relatable medical branch of the field

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Hello everyone,
new here, just turned 25, first symptoms appeared 8-9 months ago and i was diagnosed with Peyronies Disease 3 months ago (our healthcare is trash).
Not gonna post a sad story because that's not why i'm here for, so let's continue...

It started as painful palpable smaller-than-pea sized lump on one side, and since then it developed bilaterally, with lumps on both sides now, and a 2-3cm long plaque. Everything is localized pretty high up the shaft, just under the corona of glans. That means the penis is not curved but rather straight, while the head is leaning upwards and to the left (hard to decide an angle, depends on how hard i am, and harder results in a more straight look, but let's say 15 degrees?). I've seen the reduction of 2cm in length (17.5 -> 15.5) and local girth (just beneath the crown)
Judging by the occasional pain and the fact that inflammation is present, it's still not transitioned into the chronic phase, so i'm looking to limit the progression as much as i can.
Less then a month ago i realized i can't pretend the problem doesn't exist and started acting on it.

I'm finishing my masters degree in clinical chemistry, and translating to American terms, i have a bachelor's in pharmacy/medical biochemistry/toxicology, with a good knowledge of immunology as well.
Why's this important? Because i read countless scientific papers on Peyronies Disease, learned about all the conventional and unconventional treatments and most importantly analyzed my situation - and i think i can help the community with it.

An urologist didn't know what to do with me and told me to take 5mg tadalafil every other day (even though i didn't have ED, just not so strong glans blood pump, shaft is rock solid) which did nothing for me, just improved my sexual endurance a bit.
Since, as i said, our healthcare is trash and i can only dream about intralesional verapamil or god forbid xiaflex, I am currently experimenting with numerous things:

  • rigorous strength and endurance exercise with protein supplementation,
  • natural testosterone boosters from food,
  • arginine, fish oil, vitamin E and D, CoQ 10, Mg-citrate, multivitamin, occasional Zn/Se tablet and
  • paracetamol (acetaminophen)

and the progress seems to be astonishing. I am currently on a program to take 1,5-2,0g paracetamol/day (with all the other supplements) for a week or two (haven't decided yet) and will report during or after my experiment, but so far my glans is much harder (almost pre-Peyronies Disease hard), my erections are much more harder and frequent, there seems to be some reduction on the narrowness and i can actually feel some blood going around the plaque, which i couldn't.

I'm developing a patophysiological mechanism and explanation theory based on countless pages of literature, all the while analyzing myself as a case study.
When i'm done, i will make another topic here. Until then, give me recommendations what to include in my report, which details you want, etc. I'll probably include some pictures as well  ;D
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Hey man! Welcome aboard... You say your healthcare system is trash. Are you really located in Serbia?


Quote from: pfract on April 22, 2020, 02:28:11 PM
You say your healthcare system is trash. Are you really located in Serbia?
Yes I am, we have universal healthcare but when it comes to some complicated stuff you either need to go to a private hospital (expensive) or you need to bribe/have a connection to set up a meeting with a great specialist. If you just go the regular route you won't get much, especially when it comes to tricky conditions such as Peyronies Disease. They didn't even ultrasound it to assess the damage, they just squeezed it.
I had an appointment a month ago but this pandemic BS had our dictator of a president lock us down so i couldn't go, and i wanted to do something about it.
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Hey iam24yo

It's hard dealing with it for sure. I am European too, but living in North America right now. You seem to be very pro active in dealing with this and that is very good. Have you read the survival guide? there is great info in directing you in what to do.

Please stick around with us!


How does acetaminophen help?   I haven't seen any research on that.
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PxD 2 yrs 9/16.  Failed all treatment. 9/11/18: excision, grafting & implant Dr Karpman MtnView Ca, AMS CX 18cm + 3-1cm RTEs.
Pump failed.  2/11/20 Dr Karpman installed Titan 22cm +1cm RTE.


Quote from: surfcobra on April 23, 2020, 10:59:05 PM
How does acetaminophen help?   I haven't seen any research on that.
Quote from: TonySa on April 24, 2020, 12:00:27 AM
For pain?
I decided to experiment with acetaminophen after my analysis of what could be the cause in my case.

So here's my case

My whole life i've been struggling with extreme DOMS (deep onset muscle soreness) which usually occurs when people overtrain their muscles and manifests as a dull stretching pain 5-10 days after exercising. Mine were 10 days long in my teen years, no matter in which shape i was. Also, athletic progress and progress in the gym was much slower than that of my peers (it's not like i'm not physically developed, it's just that progressing past my baseline is much harder than it is for the others)
Now my DOMS last up to 21 days, which is something requiring medical attention, but since healthcare here is trash and i'm pretty knowledgeable in the field, i decided to study what the hell is going on.

So basically i started from my lifestyle:
- extremely stressful childhood, followed by poor hygiene and diet
- totally sedentary today, i barely even walk during the day, mostly on the computer, couch or in bed
- destroyed sleeping patters, i've been struggling with both insomnia and narcolepsia
- drinking energy drinks without following it with physical activity (important, will discus later)
- occasional weekend binge drinking
- occasional modafinil usage (for studying)
- intermittent fasting (various degrees)
And my underlying health conditions:
- DOMS after a mild exercise, as i mentioned
- i've been a pretty damn fat child, lost weight in puberty by exercising hard but still got an excess chub of fat (important)
- seborrheic dermatitis i got when i entered puberty
- recent tinnitus in left ear
- costochondritis that's coming and going, but has been around for more than a year now

Every single thing mentioned has one thing in common - chronic elevation of baseline cortisol levels. And we all know that chronic "stress" (this word gets thrown out way too ofter, i'd rather use the term "distress") causes a ton of chronic inflammatory illnesses.
After countless hours of reading i found a link between cortisol and inflammation that would explain everything that's happening to me.

Prepare, it gets a bit technical now... (i'm writing this from my notes, i haven't made a proper case study yet)
Keep in mind that my disease is still in the acute phase, so i'm looking at the disease from that angle, not sure this text will be applicable to people in chronic phase!
Every potential possible treatment i have concluded could be helpful will be bolded

As i was researching DOMS i stumbled upon this research where long story short they found out that DOMS in mice is caused by delayed/prolonged elevation of proinflammatory cytokines (TNF alpha and IL-1 beta) which synthesis is initiated by the NF-kB and MIF (Macrophage migration Inhibition Factor), and i quote "macrophage migration inhibitory factor (MIF), high mobility group protein 1 (HMGB1) and transcription factor NF-κB, all of which are involved in the persistence of the inflammatory response, often associated with severe and progressive fibrosis".
One more interesting thing this research has concluded is the ability of IGF-1 (in genetically modified mice that express it locally in muscles) to totally stop this inflammation and encourage regeneration indicating that intralesional IGF-1, growth hormone stimulation or injections, or even intralesional insulin could be helpful in stopping and reversing effects of Peyronies Disease. That also correlates with why L-arginine supplemets work for some, because other than providing NO and improving circulation, arginine is essential for brain in order to secrete growth hormone.

Now we'll focus on MIF, as it seems to be the key for maladaptive immunity and harmful chronic inflammation. MIF is secreted from the pituitary gland as a response to stress (found in a granules either alone or with ACTH or TSH). Since ACTH is the hormone that stimulates the adrenal glands to make and secrete cortisol, that means that elevated cortisol will correlate with elevated MIF - and chronic elevation of cortisol above baseline will result with the same elevation in MIF.
So glucocorticoids (including cortisol) are known immunosupressants which will lead you to conclude they decrease inflammation, but in this case cortisol acts more as a immunomodulator - shutting down one part of the immune system, and activating other indirectly via MIF, resulting in this unhealthy state.
As this research explains it, MIF activates ERK1/2 and attenuates cortisol's inhibition of cPLA2, while also inhibiting the synthesis of I-kB (NF-kB antagonist) meaning the activity of NF-kB rises and so do TNF alpha, IL-1 beta and a host of other proinflammatory cytokines.
They also found that cortisol causes delayed peak of MIF in muscles, associated with catabolism and atrophy.
In summary, MIF slows down cell growth and regeneration and perpetuates chronic harmful inflammation.
So naturally, everything that neutralizes MIF will be helpful for Peyronies Disease, first and foremost lowering cortisol (so sorting out your lifestyle), then physical activity, and then supplements. So far i've found these potential substances of help: acetaminophen/NAPQI, taxifoline, benzyl isothiocyanate.
- Acetaminophen and it's toxic metabolite NAPQI, while not so good at reducing inflammation as NSAIDs, are really good at inhibiting MIF, taken in regular doses (~2g, but <4g/day). NAPQI is infamous for it's liver damaging effects in paracetamol overdoses, but in smaller doses the metabolite gets neutralized enough not to damage liver but is still present enough to inhibit MIF (you should still be careful and monitor side-effects though)
- Dihydroquercetin (taxifolin) had been evaluated by different studies as the small-molecule regulator of signalling cascades as promising anti-inflammatory agent with biological targets such as COX-2, and related pro-inflammatory mediators (cytokines and chemokines, interleukins [ILs], tumour necrosis factor [TNF]-alpha, migration inhibition factor [MIF], interferon [IFN]-γ and matrix metalloproteinases [MMPs]) implicated in uncontrolled, destructive inflammatory reaction. Diftydroquercetin (taxifolin) was effective with relevant biological targets that include nuclear transcription factor (NF-κB), p38 mitogen-activated protein kinases (MAPK) and Janus protein tyrosine kinases and signal transducers and activators of transcription (JAK/STAT) signalling pathways has received growing attention
- Benzyl-isothiocyanates - haven't yet compiled info on it, but initial look at it seemed promising
Note: inhibiting MIF means nothing if your lifestyle and health conditions promote elevation of cortisol - sort out your lifestyle first!. Seriously, i can't stress this enough - get enough physical exercise. I wasn't having ED and it still improved my erections!

So that's it. Keep this wall of text in the context of my original post. Also keep in mind that i'm trying multiple things at once, so if it works i wouldn't be able to pinpoint why exactly, i'm just trying to achieve synergistic effect.
Update: i have opted to take 1,0-2,0g/day of acetaminophen for the first week
This text is just food for thought, i do not take any responsibility if you do something stupid to yourself. I am allowed to experiment on myself and am pretty confident in my knowledge, but i need to put this disclamer.

I'm making a diary of progress and will report back here when i have sufficient details to make a conclusion, or when something important happens.
If you have any questions or suggestions, fire at me  :)
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Wow, what a thorough explanation to an elementary question.   But i get it.  Inflammation reduction is key and your knowledge base indicates that acetaminophen in the indicated doses helps accomplish that.  Thank you.  
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