Below is a summary of information originally posted by Poshea. I thought it deserved its own discussion chain.
Basically as I understand him, he is saying that methylation causes a number of epigenetic changes to critical tumor suppressor genes. And that eating rice and wheat (which are fortified with Vitamin B12 and Folate in the US) can exacerbate the problem.
But Genistein can actually reverse the methylation. Perhaps a way to suppress the speed of mutation.
(Patrick, if I am getting anything wrong, please correct me)
If anyone has anything to contribute to this subject, or has any additional questions, please contribute and/or post.
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"RB1 is a tumor suppressor gene. Seems that it is not too uncommon for it to be silenced along with PTEN & P53 in treatment-resistant cells.
The silencing is usually due to methylation. This is an epigenetic change & is reversible in theory. There have been threads on methylation. PCa cells tend to want to be hypermethylated. Depriving them of unlimited methyl is difficult in the U.S. & countries that followed the FDA lead of fortifying grains with folic acid. Folate is the primary methyl donor.
Men with low vitamin B12 are at an "advantage", since B12 is an essential cofactor in the recycling of homocysteine that leads to SAM (SAMe), which carries methyl to cells that want it.
High doses of genistein may demethylate cells. For a while, it looked like Disulfiram (anti-alcohol drug) might be useful [1] [2], but results were disappointing."
-Patrick
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"Dietary soy does not deliver enough genistein & is thought to promote PCa & BCa growth. Genistein has a biphasic effect in the lab. Pharmaceutical levels are required to inhibit PCa growth.
Which is why I only use the LEF product. If you find a product with more, please let the group know.
We ordered a Kilo of 99% genistein from Alibaba. We have not used it yet, it is part of our "backup plan". Originally read about it here: cancertreatmentsresearch.co...
I'm running to work so I don't have time to look for it now, but I recall a study where most prostate cancer responded favorably to genisein, but a small percentage had learned to use it to its advantage, so monitor PSA closely. Of course it has actions beyond androgen receptor influence too.
This topic does warrant further discussion. Patrick indicated that people who are deficient in B12 may have an advantage. Metformin (which I take) causes a deficiency in B12. I wonder whether this side effect may be a contributing factor to its ability to increase OS. Cheers, Phil
The connection was catalyzed by Patrick’s comment. I have been taking B12 as well to avoid this side effect of metformin. I have been monitoring B12 levels in the blood and adjusting the dosage of the supplement to keep the B12 in the low end of the range. I may have to reconsider this. Cheers, Phil
You don't want to be too deficient in B12 -- brain health will suffer. Those of us who take acid reducers for GERD have to be careful. Acid is required to convert meat protein to B12. Darned if we do, darned if we don't situation regarding B12 levels?
Great post, Cesanon. Lots of possible threads, here. I will put in my two cents and provide a broader context for the biological role of DNA methylation. It isn't simply a negative indicator of gene repression (as in the RB1).
Currently, the process is only vaguely understood, but all cellular biologists would agree that the process seems critical to cell differentiation generally. This paper is a only a bit dense, I liked it a lot: nature.com/scitable/topicpa...
As Patrick relates, there is indication of hypermethylation with PCa, but HYPOmethylation is also important and seems to be related to metastatic PCa: ncbi.nlm.nih.gov/pmc/articl...
In the above article, the so-called "LINE-1" (a protein encoder) is hypomethylated in mPCa. Interestingly, LINE-1 hypomethylation has been indicated in...simply put....fatter people. See: ncbi.nlm.nih.gov/pmc/articl...
This seems to indicate that mPCa controls methylation - both hyper and hypo - by selectively suppressing the body's normal genetic controls and tipping the balance to cellular systems like body fat that support its growth. Scary.
Yikes. I just thought of an analogy. PCa becomes hypermethylated to promote its cellular stability while promoting hypomethylation in other cell types to destabilize theirs. It's a terrorist war - stable cancer "terrorist cells" (pun unintended) that promote a greater social unrest and instability.
I take 2000 mg of metformin a day. When my B-12 got below 400 (first time in 3-4 years) doc prescribed sublingual B-12 . I had been taking it daily, but when B-12 reading went from 750 to 980, I backed off to every other day. When my B-12 got below 400, I noticed black and blue marks on the legs (which can be a sign of deficiency). Within 3-4 days it went away. Miraculous
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