Reversing silenced AR signal with demethylating agents - A promising treatment option?


#481

Hi,

its realy not that simple. Text from your link.
"A person’s rate of methylation (high, medium or low) is synonymous with youth, middle age or old age. If there was any one single marker that best describes how fast you are growing old it is your rate of methylation. So, keep your methylation rates high."

methylation can be good or bad. A very high rate of methylation can switch off tumor supessor gens. which is bad. Today the most scientists belive, that people who get very old have a natural HYPOmethylation. Sadly the methylation is not the only way, how cells can regulate the gene expression. The Text is not realy true, there are also more markers. Typical “I want to sale stuff side”
like: eu.wiley.com/WileyCDA/WileyTitle/productCd-0470873906.html

en.wikipedia.org/wiki/Regulation_of_gene_expression

its not all that simple sadly… but in anyway, we can see that awor is totaly on the right track! Something has been switched off…now we need to find the switch and let the house rock again!


#482

If I had the money I would definitely be calling them and asking their opinion on this.

BTW, quick question for you guys. So according to that website that boston posted, methylation slows down the aging process. Could this be another hint that we are “over menthylating” considering some users here have talked about how they haven’t really aged or changed in appearance over the course of years? The mentylation process is over compensating, thus doing this?


#483

in my personal case, i feel i have aged terribly since using finasteride in both the way i feel and my appearance (i.e. wrinkles etc.)


#484

me too


#485

would “under methylating” speed up the aging process then? perhaps we are under-methylating then? or maybe some under or over…

second & lennon – how do you guys react to vit b12 ?


#486

I think it’s important to keep in mind the website is advertising that supplement so information contained may be accurate but should not be considered scientific evidence.


#487

bryce,

i have not yet experimented with vitamin b supps, but will consider it in the near future and alert if anything moderately interesting happens. take care and feel better.


#488

Bryce you wouldnt have a fucking clue. Why are you guys ruining this thread?


#489

May be they have no fucking clue, but they want to understand more, they want to understand what happens to us and I think its their god dam right.

People can try things, many people here try a lot of things, Would you write in a PCT treat the same? no. So i would say, we can try such things. Or we can sit back, do nothing and cry that we dont have a clue.

@Bryce54
Like I said, he body has a lot of mechanisem to regulate the gene expression. aging faster, doesnt mean nothig to us. the skin is aging faster, cause its loosing oil and collagen and many other things like the high stress levels and the not refreshing sleep and and and… Androgens keeps us young.

To the hyper or hypo methylation, I just can say, google please how it works and what it does. It can be good or bad.


#490

interesting. thanks for the info.

cool, let me know hot it goes. if you haven’t purchased it yet, a good B12 is the one that is in the form called methylcobalamin.


#491

Ok just an update on what i’ve been ding:

I take Sulphoraphane, Omega 3, Vitamin D, Niacin, doxycycline, a small dose of isocort and sometimes vitamin A and oligonol.

This regime takes away pretty much all my prostate pains. Sometimes i have a little in the morning before my next dose. At first it also seemed to improve sensitivity and strength of erections although since i’ve started working hard and am lacking much sleep these effects have weakened. My vision slightly improved on it too.

I still notice if i work out or sleep on occasion for a long time in some ways I get worse. I put this down to the increase in testosterone levels associated with these things.

I’m going to continue with this and try to do some aerobic exercise too. I may punctuate it with small doses of T3 at times too.


#492

Hey Guys,

I posted this over on my other thread but thought I’d post it here as well for consideration:

Hey guys, this is another interesting article I found on valproic acid (HDAC inhibitor) enhancing androgen responsiveness (albeit in vitro).

Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells.
ncbi.nlm.nih.gov/pubmed/21862211

Valproic acid, also known as Depakote is an HDAC inhibitor used for bipolar disorder. Normally it is associated with a decrease in libido when used constantly, however the exciting thing that this paper found, is that if you pre-treat an androgen resistant prostate cell line for 2 days, and then treat with androgen (DHT), it increased androgen responsiveness (as measured by growth) by 70-120%! Now this is a study done in cells, but since Depakote is an approved prescription drug, it should be really easy for someone to try this out. Does anyone have means of (legally) obtaining some Depakote?

I’ve included the specific paragraph of interest below:

"…We thus investigated the effect of HDAC inhibitor on androgen-responsive cell growth. Androgen-independent C-81 cells were treated with 1 mM VPA for 48 h followed by 10 nM DHT in a steroid-reduced condition. The usage of 10 nM DHT is to determine if VPA pre-treatment can increase the common androgen-responsiveness of cell growth. In the presence of DHT for 48 h, the growth of VPA-pretreated C-81 cells increased by about 70% (column #4 vs. #3, Fig. 3B, left panel, p < 0.01), compared with only about 35% increase of control cells without VPA pre-treatment (column #2 vs. #1, Fig. 3B, left panel). Western blot results validated that the cPAcP 50 kDa mature form protein was elevated by VPA treatment (lane #3 vs. #1, Fig. 3B, right panel), which was decreased by subsequent DHT-treatment (lane #4 vs. #3, Fig. 3B, right panel), inversely correlating with cell growth stimulation [20], [27] and [28]. In parallel, cellular PSA level was greatly elevated by DHT in VPA-pretreated cells, about 1.5-fold of that in control cells without VPA-pretreatment (lane #4 vs. #2, Fig. 3B, right panel). In those same cells, AR expression level was not significantly changed after a total of 5 days treatments including 2-day by VPA and 3-day by DHT.

Due to the clinical importance of androgen sensitivity of PCa cells, we investigated whether VPA treatment could similarly increase the degree of androgen responsiveness in other androgen-independent PCa cells, including LNCaP C4-2 and MDA PCa2b-AI cells. As shown in Fig. 3C for LNCaP C4-2 cells and Fig. 3D for MDA PCa2b-AI cells, DHT alone could increase the basal cell growth by approximately 10% (column #1 vs. #2). Interestingly, DHT could greatly increase the growth of VPA-pretreated cells by about 70% and 120%, respectively, (column #4 vs. #3, Fig. 3C and D, left panels). We subsequently validated DHT effect by semi-quantifying PSA levels in those treated cells. Interestingly, PSA basal level was elevated in VPA alone-treated MDA PCa2b-AI cells in the absence of DHT (lane #3 vs. lane #1, Fig. 3D, right panel). Importantly, cellular PSA level was greatly elevated by DHT in VPA-pretreated cells, approximately 4- and 9-fold of that in control cells without VPA-pretreatment, respectively (lane #4 vs. #2, Fig. 3C and D, right panels). It should also be noted that due to the low expression level of AR protein in these two PCa cell lines, comparing with LNCaP C-81 cells, a prolonged hybridization with primary Ab to AR with longer exposure time periods was required. In summary, VPA pre-treatment enhances DHT effect on the increments of cell growth and PSA expression, which indicates that HDAC inhibitors can enhance androgen responsiveness of PCa cells."

After writing this, I did a search and saw that Awor mentioned trying Valproic Acid at one point. I will reach out to him and see if he ever used it.

One important point that this article brings up is that HDAC like Valproic Acid may suppress androgen activity when on them, but have androgen response enhancing properties when getting off. Thus when testing these agents, in some cases the most effective way may be to pre-treat with the HDAC inhibitor, then treat with testosterone gel after to determine if response to androgen goes up


#493

please don’t derail the thread. leave it to the topic.


#494

Apologies, I should have clarified, but HDAC inhibitors are well understood to have broader effects on DNA demethylation, including Valproic acid:

Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes.
ncbi.nlm.nih.gov/pubmed/17012225

Valproic acid shows a potent antitumor effect with alteration of DNA methylation in neuroblastoma
ncbi.nlm.nih.gov/pubmed/22863973

Also, I believe this product was mentioned earlier on in this thread so wanted to pass on some relevant information


#495

spstriken, he is on topic. It’s a thread about “demehtylating agents”. I don’t see a problem with him contributing those citations to the discussion here.


#496

When guys with PFS try to supplement with testosterone, they have a brief recovery, and then relapse. The same seems to be try for people who take anti-estrogens such as tamoxifan. Some men reported feeling cured, and then their symptoms returned. To me it seems like boosting testosterone may cause a further down regulation of androgen response. When men are taking anti-estrogens, are they up regulating their response to estrogen?

Do we have a reverse effect going on here? Our androgenic response is getting silenced while estrogenic response is getting up-regulated?


#497

There would be a lot more people with this problem if this were the case. There are millions upon millions of heavy steroid users out there who report not nearly the same problems we have.

I hate to move the thread over to another separate issue but this is exactly why it may all play into a autoimmune issue. You get temp relief from testosterone because it takes (assbackwards) the immune system a little while to adjust to the heightened androgens and begins acting against them.

I’m no molecular biologist but I have read the Androgen Receptor (Awor’s theory) from front to back and it seems they could be interlinked somewhat. Not saying we have both issues going on but it could be possible we have antibodies against out 5-Alpha Reductase, DHT and or the androgen receptor itself.

We really have a lot of “hall-marks” of an autoimmune disease: Low vitamin D, various forms of inflammation, tissue changes related to inflammation…

Before the crash (if you experienced it) didn’t many people feel better as the finasteride got out of your system? I sure did… I felt 100%, for about 10 hours…

In fact both theories may actually be the same in a sense, if the bodies immune response to a huge spike in DHT was to down-regulate androgen metabolism; either by producing antibodies against androgens or acting on the androgen receptor itself…


#498

If we do in fact have an auto-immune condition towards androgens (antibodies against DHT, test, or 5ar) wouldn’t this have been found out by now? And if we do have such an auto-immune disease, we’re pretty screwed. Forget trying to be cured.

Early on, I too suspected autoimmune and when to two immunologists and neither of them found any indication of autoimmune disease. They didn’t have tests specifically for testosterone, dht, and 5ar though.


#499

Problem is drug induced autoimmune diseases are rare all together, and testing for autoimmune diseases isn’t easy. I think maybe only a few of us have seen immunologists, who by the way are not testing for androgen antibodies, the tests just are not simply out there for the general public. They do exist but are done typically in research institutions.

Screwed? Maybe, maybe not… there are some treatments for autoimmune diseases… while their effectiveness might be questionable long-term. Also this would be the “first ever” drug induced, androgen, autoimmune disease. Making it entirely different from every other autoimmune disease, so there might be some hope.

Anyway who knows might not even be that… I’m just putting pieces of the puzzle together:

Very Low Vitamin D: very common
Low 3-Adiol-G: Common
Low 5AR metabolites: Common
Fluctuating Testosterone levels: common
Tissue Inflammation: Very common (shrinkage, pelvic issues and such)
Vulnerable to infection/fungus: common; due to altered hormones
Altered adrenals/thyroid hormones: Common; body trying to regain balance as best it can


#500

Another thing though that points towards it not being autoimmune is the fact that some men (including me) start shedding hair again and have some androgen response returning. This wouldn’t happen if it was autoimmune. And the crash that happens after a period of feeling 100% could be the whole down regulation of our androgen system.