Reading Friedman's book on hormones and lowering DHT ... but he states that higher levels of DHT decrease Bcl-2 and the proteins that protect the prostate cancer cells from dying. DHT lowers Bcl-2 levels five times more than T (p176) and low Bcl-2 is a good thing, leading to more apoptosis.
Then he goes on to advocate a high T, low DHT protocol, and the control of T to estradiol with an aromatase inhibitor. I get the estradiol part, but the lowering DHT part is confusing. It seems if we want low Bcl-2, then we want high DHT.
It appears to me that a 5-alpha-reductase inhibitor (finasteride, duasteride) is recommended to decrease intracellular androgen receptor activity, as blocking local aromatase prevents cancer. The low DHT seems to be a consequence of trying to inhibit 5-AR. Is DHT just being used as a proxy for decreasing intracellular androgen activity or am I completely missing the entire lower DHT reason?
He also states (p269) that finasteride and duasteride increase cell death by having more pro-apoptotic proteins. Perhaps it is better to have lower DHT and more pro-apoptotic proteins than higher DHT and less Bcl-2 (anti-apoptitic). Hmmm.
Finally, an interesting (and also somewhat confusing) discussion (p268) of phytoestrogens and men who were on finasteride and had higher PSA rise. A "situation" where low DHT and high phytoestrogens together increase Bcl-2 to the point where it is protective of for cancer cells - only if there is a lot of ER-beta present (??) and high local levels of estradiol. Interesting.
This then begs for a discussion on the whole phytoestrogen thing - maybe some other time.
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It seems the Friedman is used as the playbook by numerous brothers on this site. Lowering DHT and using an aromatase inhibitor to manage estradiol levels. Pretty convincing, but not completely and some of the explanations and reasoning lack some validity in my non-scientific and humble opinion.
I really want to believe this guy (or anyone) who has a plausible hypothesis that might lead to better solutions, but it seems there are caveats and inconsistencies within and between so many studies that I am left scratching my head. I don't know if Friedman is right or wrong, but I don't want to bet my life on something that I don't understand and may even be harmful.
Good questions, we are just reading this now as well. My husband is considering a consult with Dr. Leibowitz at Compassionate Oncology in L.A. (Leibowitz is mostly retired apparently but a colleague of his runs it). We are also trying to find a doctor here in NYC or closer who uses this approach.
His appointment is tomorrow, will update afterwards. In the meantime, they gave us a three page list of patients who agreed that prospective patients could contact them. So far we have spoken to two on that list - with nearly identical stories, i.e. MPCa to the bones, 3-digit PSA. Now PSA less than 1 and scans show no mets.
That must be very encouraging to hear from others doing so well. You are being very diligent and deliberate in your approach and I feel you will do well. All the best.
We are heading to LA on Monday to meet with Dr. Eshaghian (Dr. Leibowitz' associate). There is a dr at Mount Sinai here in NYC who will administer the protocol after the first one - low dose taxotere starting on Wednesday, along with the rest of the treatment. Will let you know how it goes. We are very hopeful.
I'm also trying to unravel the T vs DHT and the positive/negative effects of phytoestrogens; i.e., isoflavons vs lignans. My read is that isoflavons (soy, et.al.) and not lignans (flax) are the villans in Pca?
Wish I had more clarity on that too. I get mixed messages from different people and publications. "Phytoestrogens" is a broad category. Lignans (flax), isoflavones (soy, nuts, other legumes), resveratrol, quercetin (flavonoid). Walnuts and sunflower seeds are high in phytoestrogens, yet recommended as "good" anti-cancer foods. I don't know how to parse through all these and which are good phytoestrogens or bad and how much is too much.
I think I will just eat broccoli and mushrooms from now on 😬
Thanks. Just trying to understand the simple stuff and reconcile some perceived ambiguities -- DHT vs. Bcl-2, PSA increasing with 5AR inhibitors and phytoestrogens (and which phytoestrogens and how much?). The Armidex to manage E2 vs. estrogen proponents who seem to be having some success.
What's up with the progesterone? How do you block that?
Agreed. It is convenient to attribute his 20-year remission to controlling DHT and E2 when perhaps he was cured by radiation. It could be the hormone control thing made all the difference, but maybe not - just an illusion of validity and availability heuristic. We have a tendency to see meaningful patterns in meaningless data, especially when we are desperate for some "truth". I know there are many men who follow the Myers' protocols and have done well, but I suspect there are others who did not do so well.
For me, I would like to have a reasonable plan/protocol that gives me a fighting chance and is not harmful. The Friedman hypothesis/Myers approach is intriguing. I get off ADT in March 2019 and hope to have a durable remission (don't we all?) without more ADT.
It is my understanding that Dr. Myers maintained one of the largest controlled databases available tracking various treatments and protocols. From what I have heard, his outcomes with his patients were not just random
Thanks. Dr. Myers was/is certainly way (!) more informed and capable of evaluating different protocols and supplements that I am. That is what gives this credence in my mind. Needless to say, I don't think he would be suggesting and prescribing a course of action unless he thought it was good or at least best available.
I totally agree. He was in a class of his own and I am no longer in a position to discuss the matter with him. Keep in mind, he did dialog options with his patients, so there might be options on the margins that are difficult for us on this board to discern.
Thanks. Interesting indeed about all the hormones. My wife has thyroid issues and her naturopath just ran all the different hormone tests that Friedman talks about to look at relative averages, etc... Fascinating how he looked at the "whole" picture. Don't know whether to laugh or cry, but her T is 4x higher than mine. I was 750+ before ADT and now 4 😳.
Regarding phytoestrogens, maybe I better limit my intake of sweet potato fries and hummus.
As a bodybuilder what do you do for protein? I generally try to stay away from soy protein, but I am not fond of whey protein either. That pretty much leaves fish, some meat, nuts, legumes (though now aware of the phytoestrogens in these) and other vegetable proteins like pea protein.
Egg whites. Rx bars are good. I love whey and it might even help against PCa. Vanilla whey is about the cleanest powder that I know of.
Nuts, brown rice and lentils. Same as I did in college Complete protein. Cheap then, sorta cheap now. In the last month I've averaged 205.6 grams of protein per day.
2. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys – PubMed pubmed.ncbi.nlm.nih.gov/194...
4. Investigation and comparison of the anti-tumor activities of lactoferrin, α-lactalbumin, and β-lactoglobulin in A549, HT29, HepG2, and MDA231-LM2 tumor models – ScienceDirect sciencedirect.com/science/a...
I am on Avodart protocol from Dr. Myers to reduce DHT. It unfortunately comes with ED. I do not if there is any other option to achieve the same result.
Thanks. I have been an athlete and gym rat my entire life. Never could bulk up much because my sports - soccer and lacrosse - involved a lot of running. 6'4" and a skinny 190 my last year in high school. Made it to 215 for college lacrosse. Now 200. I still work out a lot. As many have said it helps with the SEs of ADT. I lost a little muscle, but thankfully seem to be maintaining okay. Might try some of that protein powder to see if I can add a little.
Not on ADT. Will the Avena Sativa (I have read about it in the best) do anything to offset the impact the low DHT (below) has on me which evidently is leading to ED? My T runs in the 580 - 680 range month to month.
In the adult (full-grown) prostate of a healthy male, cell division & cell death occur in such a way that prostate size remains essentially the same. I admit that organ size homeostasis is something of a puzzle to me, but it seems to work well - until something goes out of whack.
While BCL-2 is an anti-apoptotic (i.e. cell survival) protein, it is a player in homeostasis, so I don't view it as being inherently bad, but it is up-regulated in aggressive PCa & that is bad.
In a 2017 paper [1], the authors state:
"Expert opinion: BCL-2 plays a pivotal role in the progression of {androgen-independent prostate cancer} than in {androgen-dependent prostate cancer} since androgen represses BCL-2. BCL-2 acts as a pro-survival molecule in association with androgen-related signaling in the progression of {androgen-dependent prostate cancer}, while BCL-2 upregulation, PTEN loss, PI3K/AKT phosphorylation and receptor tyrosine kinase (RTK) activation are primarily involved in {androgen-independent prostate cancer}."
In Ed's book, there is a tendency to refer to the important players as being good or bad. That's useful for cancer cells, but perhaps not when everything is in balance. He writes that in normal epithelial cells, there are "low levels of Bcl-2 and lots of AS3" (p.177). Goldilocks would say that the levels are 'just right'.
Hardly anything appears in the PCa literature for AS3, but this will perhaps explain it's role [2]:
"In the prostate gland of adult mammals, most epithelial cells are in a state of proliferative quiescence. Androgens regulate this effect by inducing cell cycle arrest in the G(0)/G(1) phase. Potential mediators of this androgen-induced proliferative shutoff were identified by means of subtracted cDNA libraries. The expression pattern of one of these sequences, AS3, strongly correlated with the expression of the androgen-induced proliferative shutoff both temporally and dosewise. The AS3 gene is located on chromosome 13 q12.3, in close proximity to the BRCA2 gene. The loss of chromosomal regions where AS3 alleles are located correlates with various human cancers, including prostate."
Ed further describes the youthful situation: "very little ER-alpha, but lots of ER-beta present in young men, which means that estradiol will decrease the level of Bcl-2."
ER-alpha tends to be confined to stromal cells, while ER-beta is found only in epithelial cells. Estradiol [E2] acting on ER-alpha may promote epithelial proliferation in a paracrine fashion, but E2 bound to ER-beta resists. When PCa develops, the cancer down-regulates protective ER-beta. Adding insult to injury, ER-alpha appears in place of lost ER-beta in cancerous epithelial cells.
In addition, the cells start to produce aromatase, which converts testosterone [T] to estradiol [E2]. & so we have a situation where PCa cells have rigged the ER-alpha:ER-beta ratio to favor proliferation, & started producing E2 to fuel that proliferation.
Although E2 is the prime mover at this point, proliferation requires activation of the androgen receptor [AR] & the participation of T/DHT. At low levels of T (which are often common in men with PCa), & a poor E2:T ratio, T takes a growth permissive role. With higher levels of T & no estrogen dominance, T might resume its classic growth regulatory role.
However, it is generally thought that the natural ligand for ER-beta is 3beta-adiol, which is a metabolite of DHT - & not estradiol. In the absence of ER-beta, DHT would be growth-permissive & 3beta-adiol would have no protective role. In normal cells, DHT has a small window to promote growth. The presence of DHT induces enzymes to clear DHT, while 3beta-adiol binding to ER-beta inhibits further growth. (All hormones have a control mechanism; either a feedback loop or a local response that limits exposure.)
So at a certain point, when ER-beta is no longer a player, DHT must be inhibited via Durasteride (or Finasteride) [5-ARi].
Also, aromatase should be inhibited via Arimidex. Not just to keep systemic E2 at ~20 pg/mL, but to counter high levels of aromatase in the PCa cells.
(This is in the context of someone not on ADT ... i.e. when Ed "goes on to advocate a high T, low DHT protocol, and the control of T to estradiol with an aromatase inhibitor")
***
Tall_Allen mentions that estrogen is useful in PCa. High doses can cause T production to basically cease. Growth requires AR & a certain amount of T. Estrogen is good in the same way that castration is good (LOL).
But estrogen is not a friend of the aging man. We would age more gracefully if we could maintain a youthful E2:T ratio. Why a ratio? Because as T falls with age, E2 tends to increase. Numerous non-PCa studies have found the ratio to be more meaningful than E2 or T.
***
Ed was a contributing member of a group set up by Sammy Bates that I joined maybe 13 years ago. Sammy was mad at the world - with some justification, I feel. Consequently most of the members remained silent. As a participant, I was beaten up a few times, although he was apologetic afterwards. Ultimately, frustrated by lurkers, he disbanded the group & set up a closed group with just the 6 or 7 regular contributors. We were not all on the same page but were in general agreement. Seems so long ago that some of the things in Ed's book were being discussed. Odd to feel nostalgic for those days.
Is the loss of AS3 alleles similar to p53 mutation? Not much information on this. I am beginning to focus on ways to get around the p53 thing. Luteolin, apigenin, metformin with 2DG, etc... Still in the fact-finding mode, but want to have the troops ready to go before I stop ADT.
Great information. Thank you! That helps me understand better. Way above my pay grade, but I'm learning.
BTW, I'm sure Patrick knows this, but for others, I was just reading the latest (Dec 2018) Life Extension magazine and there is a good discussion in there on DHT and 5-alpha reductase inhibitors. And if you really want to take up the rest of the afternoon, a couple pages and bibliography related to PCa research, supplementation, and diet.
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Complete protein. Cheap then, sorta cheap now. In the last month I've averaged 205.6 grams of protein per day.
Blood tests to monitor while on ADT..etc
INCONTINENCE, Leaking, Dripping, etc. 
Genistein for PCa hormonal control.
Update after tests,etc
