SMAD7 - Potential Cure?

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healthyconsumption

Hi all, anyone with scientific mind, please have a quick sift through.

I read another thread here that referenced an article that says PDE5 + Tamoxifen made some great progress.

That motivated me to look into the article and found that Tamoxifen is a SERMs (Selective Estrogen Receptor Modulators). Having researched into SERMs, I looked at one of the supplements in my cupboard, DIM.

DIM acts similar to SERMs like Tamoxifen, and it is widely available as a workout supplement. I found some promising articles about DIM that it upregulates SMAD7 (like Tamoxifen does). I would love to know if anyone else is using DIM and if they had any success or if not, and they have one sitting in their cupboards. If you're going to try something, please go slow and don't overdo it, endocrine system holds a delicate balance.

SMAD7 effects on Peyronie's plaque: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430956/#sec1-3title
DIM helping to reverse fibrosis SMAD7 / miR-21: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792002/#__sec22title
Tamoxifen effects on TGF-B1 and fibrosis: https://pubmed.ncbi.nlm.nih.gov/31455237/
Age: 40's
What: Approx 30 degree left from mid shaft, 45 degree clockwise torsion.
How: PE (June 2021)

Regimen:
⁍ Pentox 400mg (3 x daily)
⁍ Tadalafil 10mg (2 x daily)
⁍ Verdanafil 100mg (1 x 2 days)
⁍ Arginine/NAC/Vit-E/Ginger/Berries/Kelp

Lostandsad

I appreciate all the research you're doing and posting it on here, thank you.

"Inhibition of the TGF-β pathway by use of SMAD7 may be a viable therapeutic strategy for the treatment of Peyronies Disease."

"Our present study demonstrates that DIM down-regulated miR-21 expression in both HSC-T6 cells and primary HSCs, and further in vivo studies in mice revealed that DIM down-regulated miR-21 expression during induction of fibrosis. As a consequence, the anti-fibrotic Smad7 protein was maintained at high levels during liver fibrogenesis and exerted sustained antagonistic effects on the central TGF-β signalling cascade, resulting in a much lower profibrogenic gene expression."

Have you been taking DIM at all lately?
Looks like I'm going to buy some right now to give it a shot.

Also, can you fill out your signature line?
https://www.peyroniesforum.net/index.php/topic,10819.0.html
MIA - nothing works after 5 months
supplements and pharmaceuticals I've tried:
cialis, pentox, magnesium chloride, dim, turmeric, hyaluronic acid, vitamin k2, paba, l-arginine, l-citrulline. either get surgery (and possible ed), get implant, or pray

healthyconsumption

I haven't started taking it again yet. I only found this research last night. Thank you for appreciating the effort, likewise, thank you for sharing yours. I have done so many searches and noting down information. But that doesn't mean they're all correct, but I cross check with PubMed, Google Scholar, and a science web site wherever I can.

What I've noticed in the forum is that all the information is posted in different threads, referencing to various sources. But there doesn't seem to be a centrally shared repository for people to update and refer to.

I think we should start something.

I don't like the idea of having a signature.
Age: 40's
What: Approx 30 degree left from mid shaft, 45 degree clockwise torsion.
How: PE (June 2021)

Regimen:
⁍ Pentox 400mg (3 x daily)
⁍ Tadalafil 10mg (2 x daily)
⁍ Verdanafil 100mg (1 x 2 days)
⁍ Arginine/NAC/Vit-E/Ginger/Berries/Kelp

Juan

Quote from: healthyconsumption on September 14, 2021, 11:27:50 PM
What I've noticed in the forum is that all the information is posted in different threads, referencing to various sources. But there doesn't seem to be a centrally shared repository for people to update and refer to.

I agree with this.
39 yo. Onset Oct/20. 25º dorsal bend 1cm before glans + high erection angle.
Pentoxifiline 400x3. Tadalafil 2,5. Vit E, D3, K2. Zinc.Omega3. Ubiquinol. ALCAR.
Traction with PMP.

Zlobenia

Very interested in this, thank you. It's always nice to see some genuinely fresh things come up on this board.

It looks like it's worth a try although with caution because of the tendency of side-effects. From what I read with Healthline, it looks like greater than 200mg a day is more likely to come up with nasty adverse reactions, so I'd recommend looking at 200mg a day or perhaps a bit less.

I may very well try this out too and I'd love to hear anyone else's experience with this going forwards.
Began with pain May 2020: has changed position and form numerous times since then, healing, some not.

1 inch shortening, <1.5" loss of girth, 20degree curvature, twist.. Probably 70% of what it was before.

On supplements, had shockwave, VED

Lostandsad

Yeah be careful. I tried the 300mg DIM by Nutricost off of Amazon, and had the worst stomach ache and diarrhea. It was the only supplement I added, and had no change in diet. I don't feel like attempting to take it again for a while.  
MIA - nothing works after 5 months
supplements and pharmaceuticals I've tried:
cialis, pentox, magnesium chloride, dim, turmeric, hyaluronic acid, vitamin k2, paba, l-arginine, l-citrulline. either get surgery (and possible ed), get implant, or pray

Mikel7

Quote from: healthyconsumption on September 14, 2021, 11:27:50 PM


I don't like the idea of having a signature.
It's called rules of the forum and it helps all of us out into knowing how peyronies has affected you and what treatments, Dr's etc... you have sought out.  You will also get a better response from other forum members to your actual posts. You should not even be bothered about placing important info regarding your situation.
Lump 4/2020, age 62 , Dr Levine 6-26-20, Dors Curve 11/2020, Peyronies
Vit E400mg, COQ10, Heat Therapy, Penimaster, Pentox, Cialis, Restorex
SNHL 7/2020 - Stopped all Meds because ototoxicity  Heat/traction/VED are working. CPPS Diagnosis - Stable :)

Fix This

I believe he has filled in his details to be fair Mikel7. I don't think it's justifiable or acceptable for other users to use any opportunity to start being rude to someone. There's just no need for it , and it diverts the line of the thread from the topic itself. I would like to thank Healthyconsumption for posting this possible lead, and concentrate on that

This is an interesting topic. I will be looking at DIM after reading this. I was looking at Tamoxifen, but if DIM performs a very similar role I may consider trying this. As it appears to be available without prescription.

I can see right off the bat that DIM (Diindolylmethane) is found in vegetables such as Kale, Broccoli and Cauliflower. More research required

Lostandsad, maybe the 300mg a day was a bit too much ? The amount that you took may be confirmation of what Zlobenia
posted that over 200mg daily was likely to cause nasty adverse reactions



47 , penis trauma July 2018 leading to Peyronies. 30-40 degree dorsal curvature, narrowing after plaque. 

I'm attacking it though, and I will fix this!

VED, traction, DMSO, Ultrasound, Acupuncture, meds, herbs

Mikel7

Quote from: Fix This on October 11, 2021, 05:58:43 AM
I believe he has filled in his details to be fair Mikel7. I don't think it's justifiable or acceptable for other users to use any opportunity to start being rude to someone. There's just no need for it , and it diverts the line of the thread from the topic itself. I would like to thank Healthyconsumption for posting this possible lead, and concentrate on that


 I am sorry if I offended you - I was not being rude. I'm just trying to convey to someone that placing your information in your signature line will help other members to give an educated response to their questions.  There is about 20,000 members here and it takes a lot of time to search their history. Rules are for the benefit of everyone.

 Also I might add that I have taken DIM to be used in conjunction with my hormone therapy. It basically
helped my body to convert the E2 bad estrogen to a less dangerous metabolite for my body to quickly eliminate.  It did not help or make worse my peyronies at all.
Lump 4/2020, age 62 , Dr Levine 6-26-20, Dors Curve 11/2020, Peyronies
Vit E400mg, COQ10, Heat Therapy, Penimaster, Pentox, Cialis, Restorex
SNHL 7/2020 - Stopped all Meds because ototoxicity  Heat/traction/VED are working. CPPS Diagnosis - Stable :)

Fix This

Hi, that's OK, you weren't being rude to me. So no you didn't offend me, and you don't need to apologise to me

I understand that you may want to know about a member's summarised history.  We should be working together . I would also respect an individual if they didn't want to complete the signature for their own privacy. We're all here for the same reason, we shouldn't be arguing, and should concentrate on the substance of what the user is posting, rather than throwing rule books and appearing to be annoyed. And anyway, he did post a signature didn't he?

Back to the point,thanks for posting that you'd taken DIM previously. That is completely relevant to the post. Always good to read accounts by people, not just lab results . Did you take it for long? And were you taking PDE5 inhibitors at the same time ?

47 , penis trauma July 2018 leading to Peyronies. 30-40 degree dorsal curvature, narrowing after plaque. 

I'm attacking it though, and I will fix this!

VED, traction, DMSO, Ultrasound, Acupuncture, meds, herbs

Mikel7

I took DIM for about 5 months until my Dr suggested that I try to use Arimidex because I was a high estrogen converter.  I did use Cialis 2.5mg during that same time and it was helping me a lot with slowing down the peyronies and helping with healing.  Unfortunately though I had to come off of all meds due to SNHL last year.  It was a very very rare occurrence and I am still dealing with it.  I wish I could have continued with it.  The best advice is to give it a try at a low dose and see after a month or so just how it works for you.
Lump 4/2020, age 62 , Dr Levine 6-26-20, Dors Curve 11/2020, Peyronies
Vit E400mg, COQ10, Heat Therapy, Penimaster, Pentox, Cialis, Restorex
SNHL 7/2020 - Stopped all Meds because ototoxicity  Heat/traction/VED are working. CPPS Diagnosis - Stable :)

Fix This

Hi, I'm very sorry  about your SNHL. So you've had that to deal with aswell as the Peyronies. That's a lot

Very interesting that you found the DIM beneficial in helping or treating with the Peyronies. especially as it was combined with Cialis. Pretty much exactly what helathyconsumption was speculating about ? So were you taking DIM for the estrogen conversion issue ? Or was it for Peyronies ? Can I ask at what stage in the development of your peyronies you were taking it please ? I don't suppose you noticed a reduction in curavture or narrowing then ? More of a slowing of progression by the sounds of it ?

Thanks . Much appreciated
47 , penis trauma July 2018 leading to Peyronies. 30-40 degree dorsal curvature, narrowing after plaque. 

I'm attacking it though, and I will fix this!

VED, traction, DMSO, Ultrasound, Acupuncture, meds, herbs

Mikel7

I was in the acute stage of peyronies in March of 2020 and I did not have any curvature at that time. I was also taking the DIM along with low dose Cialis 2.5mg  and Pentoxi . I was having a lot of severe pain all the time, but when I started on the combo I was taking things kind of slowed down.  The pain went to about zero and my erections were much better.  So I know something was working.   Sadly though everything changed on the last day of July when my other nightmare began- sudden hearing loss with hyperacusis with severe migraines.  All of the specialists I have seen took me off of everything except my hormone shots.  After that the pain did return and I had a dorsal curve start in November of 2020.  I did continue with traction and heat therapy and later on got the OK from all of my specialists to add in the supplements, E,CoQ10, etc....
Lump 4/2020, age 62 , Dr Levine 6-26-20, Dors Curve 11/2020, Peyronies
Vit E400mg, COQ10, Heat Therapy, Penimaster, Pentox, Cialis, Restorex
SNHL 7/2020 - Stopped all Meds because ototoxicity  Heat/traction/VED are working. CPPS Diagnosis - Stable :)

Fix This

Ah right, so with regards to starting taking the DIM, your urologist prescribed or suggested this along with the Pentox and Cialis to treat the Peyronies pains at the time ?  On the basis that DIM is similar to Tamoxifen ?   Or was the DIM suggested to treat the estrogen issue seperately ? Sorry to ask so many questions. Just trying to gather info.

You didn't have curvature at the time, you had pain, did you have a car tissue/ plaques at this stage? And any narrowing ?  Was you peyronies from an injury or unknown cause ? Mine was from an injury. Wasn't able o get hold of pentox in the early stages despite trying.

Many thanks
47 , penis trauma July 2018 leading to Peyronies. 30-40 degree dorsal curvature, narrowing after plaque. 

I'm attacking it though, and I will fix this!

VED, traction, DMSO, Ultrasound, Acupuncture, meds, herbs

Mikel7

I was already on the DIM when the peyronies struck me. Then Dr Levine added in the Pentox and the Cialis. I did not have any narrowing or indentations.  I did have scar tissue and plaque that was forming towards the glans area. I was in a lot of pain though - about a 10. I could barely even walk at times. I also  did not have any injury that I can recall - everything just happened out of nowhere. I have always wondered if it could be related to my hormone issues, but that is just speculation on my part.  I think that DIM is very mild compared to Tamoxifen though.
Lump 4/2020, age 62 , Dr Levine 6-26-20, Dors Curve 11/2020, Peyronies
Vit E400mg, COQ10, Heat Therapy, Penimaster, Pentox, Cialis, Restorex
SNHL 7/2020 - Stopped all Meds because ototoxicity  Heat/traction/VED are working. CPPS Diagnosis - Stable :)

Fix This

I wonder whether the DIM would have been a factor in the Peyronies developing then ? I wouldn't have thought so, but just wondering as you were already taking it .

I would imagine it could be related indirectly to your hormone issue, as I have seen somewhere that low test is often found in men with Peyronies. But I'm not sure about that. Prob related to not having such strong erections and making the penis semi rigid and more likely to bend causing injury.

Anyway, thanks for the info. I think I will try the DIM and see if anything changes



47 , penis trauma July 2018 leading to Peyronies. 30-40 degree dorsal curvature, narrowing after plaque. 

I'm attacking it though, and I will fix this!

VED, traction, DMSO, Ultrasound, Acupuncture, meds, herbs

healthyconsumption

Quote from: Fix This on October 12, 2021, 06:32:15 PM
I wonder whether the DIM would have been a factor in the Peyronies developing then ? I wouldn't have thought so, but just wondering as you were already taking it .

I would imagine it could be related indirectly to your hormone issue, as I have seen somewhere that low test is often found in men with Peyronies. But I'm not sure about that. Prob related to not having such strong erections and making the penis semi rigid and more likely to bend causing injury.

Anyway, thanks for the info. I think I will try the DIM and see if anything changes

I wouldn't think it would. Here in Australia, a lot of men are taking it as their gym supplement. Along with ALCAR, arginine, protein powders, citruline, NAC, berries, oats, creatine, BCAA, EAA and a whole host of other stuff.

Stress reduces testosterone, and I think any man would be stressed when suddenly, his penis changed in a not so positive way.

Nevertheless, I think that testosterone is good for the penis health, from what I read. But they never conducted any trials so it's likely just a hypothesis.
Age: 40's
What: Approx 30 degree left from mid shaft, 45 degree clockwise torsion.
How: PE (June 2021)

Regimen:
⁍ Pentox 400mg (3 x daily)
⁍ Tadalafil 10mg (2 x daily)
⁍ Verdanafil 100mg (1 x 2 days)
⁍ Arginine/NAC/Vit-E/Ginger/Berries/Kelp

Bud luck

I keep reading products that are potential cure, but I feel like big pharmaceutical companies and some Doctors don't want the cure because they only look for their interests, if they can't make money of it then they would stop a product that can cure us. How is possible that nobody ever find a solution for our disease?
My first symptoms started early in 2019
I tried Traction device, Pentofixiline, Q10, TRT, L-Argenine, cialis
I have narrowing/dent/hinge on the left side of my shaft
My ED is getting worse
Had a PRP shot Aug 2021
I have a girlfriend
Age 46

healthyconsumption

Going off-topic a bit in this paragraph. I partly agree with the big pharma conspiracy stuff. Especially with the Covid19 and treatments that actually have been proven times and times and time again to save lives at a fraction of the cost, but are not implemented by various government around the world. They say it's misinformation, subjected to misuse, etc. I personally have an experience with an injury that 4 out of 6 surgeons wanted to rush me into a surgery, hack my spine open and do stuff to it. But (touch wood) things have improved (not Peyronies Disease) with diet, and lifestyle change and it's measurable on MRI scans.

I've been to general practitioners (doctors) who will get irritated, if you're more educated than an average patient. They will say oh so you consulted "Dr. Google"? I used to, but now I also fact check on latest medical journals, trials, published paper, and other currently reliable sources and check for redaction wherever possible. I'm not one of those "But Pinterest posts told me differently!" people.
Age: 40's
What: Approx 30 degree left from mid shaft, 45 degree clockwise torsion.
How: PE (June 2021)

Regimen:
⁍ Pentox 400mg (3 x daily)
⁍ Tadalafil 10mg (2 x daily)
⁍ Verdanafil 100mg (1 x 2 days)
⁍ Arginine/NAC/Vit-E/Ginger/Berries/Kelp