Vitamin D analogues with high VDR and low DBP affinity

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Hontas

Vitamin D analogues are proven to be protective against TGF-B mediated fibrosis( by inhibiting myofibroblast differentiation).However the side effects contain hypercalcemia and that could in itself cause calcifications on previous plaques. Now there is one topical cream named Calcipotriol(or Calcipotriene in US), it has really low DBP(Vitamin D binding protein) affinity but similar VDR(Vitamin D Receptor) affinity compared to Calcitriol(Metabolite of actual Vitamin D) . It is proven now that VDR actively suppresses Smad2/Smad3 pathway in TGF mediated fibrosis. It could even stop fibrosis related to dysregulation of TGF by other factors(such as WNT3a, canonical Wnt element, helping the SMAD2/SMAD3 pathway). It is really promising on paper. I have used it for a few days now on my penis shaft and i have mixed results honestly. The main thing is i see more reddening of the skin which happened to me while using Pentoxyfylline as well. I am sure hydrocortisone cream helped me but i am not sure about calcipotriol. I have read about Maxacalcitol as well and most of the Vitamin D analogues with high VDR and low DBP affinity are used against Hyperparathyroidism. I am going to check my blood Calcium levels while using it and i hope it stays relevantly low to not suppress the helpful part of the drug.

Main question is have you guys used Vitamin D analogues that are prescribed for hyperparathyroidism, and had luck with Peyronies?Also would it be feasible to use it with Verapamil topical to make sure calcium is blocked and only the positives of Calcipotriol remain on the tissue.

I think Verapamil+Calcipotriol could be a killer duo in treating this disease. If any of you know any doctors that can adjust the dose, or any one of you tried those before let me know.

I actually found one article regarding that after posting this. Verapamil completely normalized Calcium influx to tissues according to the article. I am definitely going to try both of these together now.

https://www.ncbi.nlm.nih.gov/pubmed/9256155

Bent Ding Dong

Sounds interesting. I have been applying a vitamin d plus vitamin k2 oil to the penis every night and it gives me better erections in the morning and the plaque feels softer. I would like to try Calcipotriol as well as Verapamil cream but don't know where to get either of them?
Age, 40's.

Had peyronie's for more than 10 years. Developed glans lump, then had poor erections and soft glans.

Made a lot of progress over the years with diet and avoidance of sugar and high carbs. Still have the lump but it's much smaller now.

Bent Ding Dong

There is an ointment called Daivobet which has Calcitriol in it as well as Betamethasone which is a stronger than hydrocortisone. I'd like to give that cream a go.
Age, 40's.

Had peyronie's for more than 10 years. Developed glans lump, then had poor erections and soft glans.

Made a lot of progress over the years with diet and avoidance of sugar and high carbs. Still have the lump but it's much smaller now.

Hontas

Don't use betamethasone on your penis. Even with hydrocortisone i am taking risks. I have minor skin reddening and thinning and i have to stop now to avoid systemic side effects. The amount of corticoids you can absorb from your penis is 40 times higher than other skin. Calcitriol is the Vitamin D metabolite that is normally produced in our cells and has a high calcaemic effect so i would avoid that if i were you. However i was unable to find any article regarding connective tissue calcium uptake on Vitamin D analogues vs Calcitriol. This one article is about muscle tissue and even though blood Ca levels were much lower with Calcipotriol the muscle Ca uptake was higher. We need to focus on Vitamin D analogues with a treatment preferency of secondary hyperparathyroidism i think. I need to learn more stuff about tissue Ca uptake and calcification in regards to VDR and DBP binding. From what i understand these analogues only change systemic Calcium metabolism and not the local one, if thats the case then calcipotriol is good. Definitely much much more promising under the conditions with verapamil due to both serum calcium and tissue calcium levels being low. Calcipotriol is probably a double edged sword in that regard, however verapamil or any calcium channel blocker could completely reverse that calcium influx and fix that issue.

Then we have ourselves a VERY potent TGF-B SMAD2/SMAD3 pathway inhibitor. As i said, on paper it looks absolutely perfect. I am getting my verapamil gel made from a pharmacy and i already have calcipotriol so i guess i will try this non invasive and promising treatment myself first.

Best way to understand how Vitamin D analogues work on calcification would be probably looking into Systemic Sclerosis(SSc) articles, since they share the same properties with Peyronie's in regards to tissue type and probably pathway as well.

Bent Ding Dong

OK so is Calcipotriol doing anything for you other than just making your skin red? Are there any improvements to bend or plaque size?
Age, 40's.

Had peyronie's for more than 10 years. Developed glans lump, then had poor erections and soft glans.

Made a lot of progress over the years with diet and avoidance of sugar and high carbs. Still have the lump but it's much smaller now.

Graggaxy

Replace this text with critical info about your case
such as age
first symptoms (deformity, Erectile Dysfunction)
official diagnosis
treatments tried
relationship status
Etc

projectpd

interesting. is it possible to say/guess how much more effective vit D analogues could be than using real vit D?
Age 57, Onset 2010, 2" shortening, shrinking and angulation of glans, weaker erections, 30 degree bend. Mild pain few months, but far from worst symptom. Tried many ideas, not just from here, but not consistently. Moderate improvement, maybe 40%

P1992

Quote from: Hontas on September 22, 2019, 11:46:45 AM
Don't use betamethasone on your penis. Even with hydrocortisone i am taking risks. I have minor skin reddening and thinning and i have to stop now to avoid systemic side effects. The amount of corticoids you can absorb from your penis is 40 times higher than other skin. Calcitriol is the Vitamin D metabolite that is normally produced in our cells and has a high calcaemic effect so i would avoid that if i were you. However i was unable to find any article regarding connective tissue calcium uptake on Vitamin D analogues vs Calcitriol. This one article is about muscle tissue and even though blood Ca levels were much lower with Calcipotriol the muscle Ca uptake was higher. We need to focus on Vitamin D analogues with a treatment preferency of secondary hyperparathyroidism i think. I need to learn more stuff about tissue Ca uptake and calcification in regards to VDR and DBP binding. From what i understand these analogues only change systemic Calcium metabolism and not the local one, if thats the case then calcipotriol is good. Definitely much much more promising under the conditions with verapamil due to both serum calcium and tissue calcium levels being low. Calcipotriol is probably a double edged sword in that regard, however verapamil or any calcium channel blocker could completely reverse that calcium influx and fix that issue.

Then we have ourselves a VERY potent TGF-B SMAD2/SMAD3 pathway inhibitor. As i said, on paper it looks absolutely perfect. I am getting my verapamil gel made from a pharmacy and i already have calcipotriol so i guess i will try this non invasive and promising treatment myself first.

Best way to understand how Vitamin D analogues work on calcification would be probably looking into Systemic Sclerosis(SSc) articles, since they share the same properties with Peyronie's in regards to tissue type and probably pathway as well.

Hontas,

Have you tested calcipotriol + verapamil? If so, what were the results? Could it be used for the chronic phase of peyronie's disease? Update us if possible. Did you get any information on the internet or with a doctor about what percentage these two assets should have in the ointment or cream? Thanks
54 years, self-induced peyronie
Upward curvature ~40º-50º, narrowing and retraction in flaccid and erect. Multiple plaques, loss of sensitivity, pain sometimes in a flaccid state and always on erection, axial instability and erectile dysfunction

Graggaxy

How likely is it that vitamin D caused my peyronies? I took it and developed a small kidney stone but my levels were only 54ng/nl when I developed the stone and calcium was in rage. Do you have to be hypercalcemic for months in order for it to facilitate the calcification of plaques?
Replace this text with critical info about your case
such as age
first symptoms (deformity, Erectile Dysfunction)
official diagnosis
treatments tried
relationship status
Etc

Olive

Quote from: Graggaxy on September 06, 2020, 10:57:45 AM
How likely is it that vitamin D caused my peyronies? I took it and developed a small kidney stone but my levels were only 54ng/nl when I developed the stone and calcium was in rage. Do you have to be hypercalcemic for months in order for it to facilitate the calcification of plaques?

Jeeez, chill out man, you're obsessed with this vitamin d thing. Vitamin d reduces calcification and improves arterial health. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188424

How can you expect anything positive to happen to you when you are just thinking dark thoughts and obsessing with this thing? You're like a black hole that emanates darkness.  
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Threadneedle

I'm hoping to revive this old thread.

I had some Calcipotriene ointment for treatment of psoriasis on my elbow.
I decided to try it on my penis, and after a few days there is some evidence of positive results.

First, the skin on my penis naround the site of the scarring/plaques is returning to its normal color.
One of the prominent features of my Peyronies Disease is the narrowing of the shaft and lightening of skin just below the glans.

The color at least appears to be returning to normal, hopefully because of enhanced blood flow.

Also, the plaques seem a bit smaller, but this may not be an accurate observation.

No change to BPFSL or BPEL, but it's just been a few days.  Girth has improved a few mm at the injury site, but as you can see from my sig, I'm trying a lot of things simultaneously.
 
55 y.o. with penile fracture in Dec'22 or Jan'23, palpable plaques, divot + shortening

Treatments:
PTX (Rx), Topical Diclofenac, ALCAR+ALA, Niagen + Pterostilbene, Arginine/Citrulline, Vit. K-2 as MK-7, CoQ10, VED