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

I found info stating vitamin D reduces folate production maybe you have low vitamin D like so many others in here? Have you had them checked?

Cant find the source again, atleast not now.

As previously stated, I am currently working together with a clinic in order to design a demethylation therapy. I am currently serving as a guinea pig and am glad to report that I am very satisfied with the results so far. Since my last run, I have been able to quit the antidepressants and am generally feeling much better than only a few weeks ago. It’s really amazing.

HOWEVER: In our case there seems to be no free lunch. Demethylation plays a critical role in the regulation of gene expression levels, genomic imprinting and error correction mechanisms during DNA replication (proof reading). Google terms in bold if so inclined. Without going into too much detail, global demethylation can cause inappropriate levels of gene expression, activation of genes which are normally supposed to be silent and cause mutations. Any of these can lead to disease and potentially even be lethal in the long run. On the other hand, maybe all will go well and we could be cured.

So here is a nice problem to think about: Supposing this therapy can bring you back to “normal” again, would you be willing to risk your long term health and possibly even death in your attempt to recover? This might very well be the choice that we could be faced with. I would be interested to hear your thoughts on this question.

         [b][Size=4]YES[/size][/b]

If this is the cure then it is the only chance I will have of leading a normal life… I now know that falling in love with a woman is more important than anything.

I think your attempt to find a cure is truly inspiring and I can see an honorary PhD for you it this works. I only hope that it does.

Answer to question: yes, we’re fucked already, some of us to an intolerable degree.

Awor, has it improved your overall physical health? I know it’s still early days.

Awor,

I am an accutane sufferer very interested in your work/experience with demethylation. After lurking for a few months, it seems apparent that you are one of the few here approaching this problem from a rigorous, scientific perspective. I also believe I can be of some help to you, and vice versa. One of my professors has done a lot of pioneering work in this area, and I have been in contact with him regarding these issues. If you would be so inclined, could you allow me to send PMs? I really do think we could be of great help to each other.

Physical changes (positive or negative) take longer to manifest than mental ones, so yes, it’s still early days. However, I can say that I have improved across all symptom areas (mental, physical, sexual):

  • Mental: increased clarity, reduced depression, more emotions, generally more feeling of well being, somewhat more aggressive, dumped all AD medication
  • Physical: fuller penis, less muscle cramps, feel a little stronger
  • Sexual: consistent, stronger nocturnal and morning erections. More libido. Slightly better sensitivity, improvement of ED

Bottom line is that I am feeling a little more like a living human being again.

Having said this, THIS IS NOT A RECOVERY THREAD. I am NOT proclaiming victory and I am not sure yet if this will work in the long run. All I am saying is that initial signs are positive and that I have hope of being on the right track. But it will take more time until we have objective results. If I can establish that this works for myself, the next step will be to establish reproducibility with other affected men. That will be the real test because if it’s not 100% reproducible, we haven’t reached the core problem. Btw, I am monitoring key suspect hormonal values such as Adiol-G, Vitamin D, FT3, FT4, RT3, etc. as I believe that hormonal abnormalities are a result of the problem and not the root cause.

awor - This is probably a stupid question, but I’ll ask it anyways. What do you think of the otc procaine pills that are available on the internet? Here is a link to one such site:
betterlife.com/prod_home_page.asp?prod_id=2531&source=googlebase
They claim it is a anti-aging drug (Gerovital) that was developed in the 50’s. Also I have read where the body can go through “methylation waves” where the gene methylation can get better and then get worse over time. Maybe this can explain how some people get temporarily better. Do you have theory how some people do get better on their own?

Procaine by a delivery method other than IV will not work for our purpose. The reason for this is the extremely short half life of only about 40-80 seconds.

As to why some people get better on their own: That’s a good question. For one, enzymes exist which demethylate. JHDM2A for example, demethylates promoter regions of genes which express AR regulatory elements. Secondly, it is also possible to loose small amounts of methylation during a cell replication cycles if enzymes responsible for methylation are not sufficiently active (DNMT1, DNMT2 for example). To be frank, the exact function of epigenetic processes such as methylation is still relatively poorly understood. There is still much that needs to be discovered.

This is simply HUGE!!! This is the first time that a promising treatment is designed from a theoretical point of view first, and successfully applied in practice later. All other successful “treatments” or protocols in the recovery stories sound like random trials that have worked for some men, but don’t work on others. On the other hand, this procaine treatment is a direct consequence of awor’s theory, and therefore awor’s current success can be probably replicated to other sufferers.

awor, from a theoretical point of view, do you think that the demethylation induced by procaine is permanent? In other words, if you stopped the treatment, would its benefits ween off?
Sorry if my question sounds stupid, but the demethylation concept is something really hard to grasp.

Also, have you noticed any side effects? If I understood correctly, you said that this treatment might demethylate other functional areas, possibly causing serious problems.

Maybe someone should forward a link to this thread to Dr. Jacobs? I think he might be the best chance we have of any of the docs trying it. And, yes… I’d try this too. I’m not living like this for the next 30-40 yrs. I’d cap myself first.

Your question is right on target on not stupid at all. Many cancer forms have been linked with methylation of certain genes (for example tumor suppressor genes). Hence, much research is currently going on to find out how to demethylate those genes. One of the problems with such therapies has been that the demethylated genes have been shown to remethylate after a while (around 20-30 days). This is particularly true if the underlying mechanism, which caused the methylation in the first place, is still active. In our case, according to “my” theory, it is AR hypersensitivity, induced by androgen ablation, which lead to an overexpression of the AR signal after the return of DHT and hence caused a strong negative autoregulatory response, which silences the AR signal. Quite a mouth full, I know :wink:. For reasons which are too complex to explain in a short post, I believe that persistent AR hypersensitivity is the driving force behind our syndrome and is persistent because some regulatory gene got methylated.

So to get to the point and answer your question, I further believe that we must rapidly bring down AR hypersensitivity in order to improve our chances of not getting remethylation. How to achieve this in a hopefully safe way currently is the center of my attention.

Up to now I have noticed no side effects, but I am still in a dosage range which is pretty harmless. The problem is that once I would notice side effects, it would probably already be too late because I would have over-demethylated.

I have directly contacted him about this and he is in possession of the full theory paper. He has promised to study it and get back into touch with me.

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[Size=4]Whatever happens awor is the first person in the history of the world to try anything like this.[/size]

awor, how will you know that you have had sufficient demethylation therapy?
I only ask because you are reporting positive results in a low dosage range, it is logical to assume you are already being effected to a large degree.

No offence but are you certain that you are not experiencing a placebo effect?

Is it your plan to stop the therapy to see if things continue to improve? Men with hypogonadism dont report a resolution of all symptoms as soon as they are put on TRT.

Also, do you believe this theory can explain everyone’s problems? Even those like Mew who experienced terrible side effects while using Fin?

Well I hope the above isnt true. Hopefully our bodies (or AR) are now used to our hormone levels but something is methylated which prevents correct gene expression.

Thanks

awor - Any idea how long the de-methylation will take? It took some people years (including me) to screw themselves up this bad on fin, so I’m guessing it could take years to undo the damage.

How you doing awor?

I’m curious to see if you continue to improve!

It looks like genistein could be a potential, along with the already discussed high doses of egcg

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829855/

Maybe a supplement to stay away from: SAMe

http://en.wikipedia.org/wiki/S-Adenosyl_methionine

http://www.biopsychiatry.com/sameart.html

“And without SAMe, there could be no methylation as we know it. Though various molecules can pass methyl groups to their neighbors, SAMe is the most active of all methyl donors. Our bodies make SAMe from methionine, an amino acid found in protein-rich foods, then continually recycle it. Once a SAMe molecule loses its methyl group, it breaks down to form homocysteine. Homocysteine is extremely toxic if it builds up within cells. But with the help of several B vitamins (B6, B12 and folic acid), our bodies convert homocysteine into glutathione, a valuable antioxidant, or “remethylate” it back into methionine.”

ncbi.nlm.nih.gov/pubmed/12204?dopt=AbstractPlus

I will also be starting this treatment @ 1 cc of Procaine injected sub q daily. Will let you know how it goes. I spoke to Dr. Shippen today and he said one of the doctors in Europe has had some success with this treatment. (maybe he was talking about Awor?) I want to get some clarifications on the risks first, but should be starting this very soon.

How goes treatment for you Awor? Still seeing steady improvement?

It is risky as far as I believe so you must be in hospital. You have to have i.v. procaine according to awor. I’ve tried to contact awor but he hasn’t responded of late. He said he had to stop it temporarily as he was coming of an antidepressant which could be antagonistic to his therapy. But he will start back on it soon.

Let us know how you get on.

Does anyone other than Awor (he’s been out for a bit fighting the good fight) have a solid understanding of his demethylation theory? I would really like to contact Dr. Denise O’Keefe (upmc.com/Services/Urology/Experts/ResearchFaculty/Pages/Denise-S-OKeefe.aspx), but don’t really have a full grasp on this theory.

Awor - how have you been?