Soy & PCa

[pjoshea13]

New study of isoflavones & PCa risk below [1].

Isoflavones form a subfamily of polyphenols with estrogenic properties. The most well-known phytoestrogen is genistein. Soybean products are a significant source of genistein in the diet.

Getting up to speed after a PCa diagnosis, we are likely to read that Asians have a much lower risk of PCa, and that is probably due to a traditional Asian diet, since adoption of a "Western diet" increases risk. So, many men consider incorporating soy products into the diet as a meat substitute.

Unfortunately, genistein has biphasic properties in PCa - & BCa too:

[2a] (2004 - U.K.)

This study came out when I was diagnosed. I had begun using LEFs Ultra Soy product, which delivers a massive amount of genistein, so I wasn't concerned.

"In vitro studies have shown that genistein exerts biphasic effects on cancer cell growth, stimulating growth at low concentrations (<10 microm) and inhibiting growth at high concentrations (>10 microm), which suggests that low phyto-oestrogen levels may stimulate cancer growth in vivo. Plasma phyto-oestrogen concentrations of >10 microm cannot be achieved by dietary intake and therefore the timing of exposure to phyto-oestrogens may be of the utmost importance in determining their chemopreventive effects."

In other words, best avoid physiological levels, but pharmaceutical levels may help.

[2b] (2004 - U.S.)

"Although genistein has many potentially therapeutic actions against cancer, its biphasic bioactivity (inhibitory at high concentrations and activating at low concentrations) requires caution in determining therapeutic doses of genistein alone or in combination with chemotherapy, radiation therapy, and/or immunotherapies."

[2c] (2006 - U.S.)

"Low concentrations of genistein (0-12.5 micromol/L) significantly increased cell proliferation and ERK1/2 activity (P<.01) in RWPE-1 cells, while higher concentrations (50 and 100 micromol/L) of genistein significantly inhibited cell proliferation and ERK1/2 activity (P<.001). A similar biphasic effect of genistein on MEK1 activity, an ERK1/2 kinase, was also observed."

[2d] (2009 - U.S.)

"Our results suggest the presence of a biphasic regulation of CaP growth and metastasis by genistein, warranting careful examination of the effects of genistein on hormone-dependent cancers in a chemotherapeutic setting."

"Considered a chemopreventive agent, the ability of genistein to modulate the progression of existing prostate cancer (CaP) is not clear. We show here that the consumption of genistein (250 mg/kg diet) by 12-week-old transgenic adenocarcinoma mouse prostate (TRAMP-FVB) mice harboring prostatic intraepithelial neoplasia lesions until 20 weeks of age induces an aggressive progression of CaP, as evidenced by a 16% increase in the number of well-differentiated and poorly differentiated prostates, coinciding with a 70% incidence of pelvic lymph node (LN) metastases as opposed to 0% and 10% in 0 and 1,000 mg/kg groups ..."

[2e] (2013 - U.S.)

"These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy."

...

& now we have a human study from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [PLCO]:

"Experimental studies have revealed that phytoestrogens may modulate the risk of certain sites of cancer due to their structural similarity to 17β-estradiol. The present study investigates whether intake of these compounds may influence prostate cancer risk in human populations. During a median follow up of 11.5 years, 2,598 cases of prostate cancer (including 287 advanced cases) have been identified among 27,004 men"

"After adjustment for confounders, an increased risk of advanced prostate cancer [HR ... for quintile (Q) 5 vs. Q1] was found for the dietary intake of total isoflavones [1.91 ...], genistein [1.51 ..., daidzein [1.80 ...) and glycitein [1.67 ...]"

"For example, HR ... for comparing the Q2, Q3, Q4 and Q5 with Q1 of daidzein intake was 1.45 ..., 1.65 ..., 1.73 ... and 1.80 .., respectively ..."

{Daidzein is found with genistein in soy, & in soy-based supplements. It is often disregarded, since it must be converted to equol by gut bacteria, & many of us are not 'equol producers'.}

"No statistically significant associations were observed between the intake of total isoflavones and individual phytoestrogens and non-advanced and total prostate cancer after adjustment for confounders."

...

I believe that genistein is a useful supplement at pharma-doses.

I stay clear of soy foods, but they would be safe if a very large supplemental soy extract were also used - IMO.

-Patrick

[1] onlinelibrary.wiley.com/doi...

[2a] ncbi.nlm.nih.gov/pubmed/150...

[2b] ncbi.nlm.nih.gov/pubmed/155...

[2c] ncbi.nlm.nih.gov/pubmed/161...

[2d] ncbi.nlm.nih.gov/pubmed/193...

[2e] ncbi.nlm.nih.gov/pubmed/241...

[cesanon]

Hmmm

So given that there is no practical way to determine, with any clinical certainty, what levels of this genistein you are maintaining through diet....

It is probably best just to stay away from soy? It would seem that way.

Even a strict dietary regime intent to push blood levels of genistein up high, how do you know if you are pushing it up high enough. And even if you are, how do you know if you may or may not be yoyoing?

Who knows. It might be somewhat knowable what would be an effective dietary regime, with some strict clinical trials. But what pharmaceutical company would pay for those.

Patrick, I have to admit that I didn't read the studies you mentioned. Are they specific enough, with proper controls and specifics, from which to construct a soybean diet that could reasonably be trusted to generate the intended effect while avoiding any unintended effects?

[pjoshea13 in reply to cesanon]

Personally, I stay away from soy products. I imagine that vegetarians/vegans who use soy in some form, will be disturbed by the new study. Some might continue to use it, but there are no human studies that show soy to be beneficial in advanced PCa, & we now have a study that suggests it can accelerate growth. In any case, soy is not an essential part of a vegetarian/vegan diet, so why risk it?

-Patrick

[softwaremom00]

How much is considered a large pharma dose ? it sounded like 250 mg/kg is too small. I am not sure how to convert 100 micromol/L into a dosage. Thanks so much!

[pjoshea13 in reply to softwaremom00]

The LEF Ultra Soy label says:

3,125 mg extract std. to 40% isoflavones (1250 mg) providing 15% genistein (468.75 mg), 14% daidzein (437.5 mg)

plus 250 mg Soynatto ... with unspecified amount.

That's for 5 caps.

Back in 2004, LEF recommended that dose be taken 4 times/day.

They backed off some years ago & eventually killed the product.

It was very much a cancer product. Only a crazy person would have otherwise used it.

-Patrick

[softwaremom00 in reply to pjoshea13]

thanks

[paulofaus]

Interesting thank Patrick. Dr Bob Leibowitz tells all his patients to stay away from Soy and soy products and credits that with some of his apparent success. On the other side of the coin however, Michael Milken, was diagnosed with advanced PCa at age 49 and is stick upright at age 71 and credits much of his success in staying alive and healthy to switching from a heavy meat diet to a diet of vegetarianism, but with lots of Soy products. It's impossible to know what to believe.

[pjoshea13 in reply to paulofaus]

Paul,

I have the Milken cookbook.

One thing I have learned is to be wary of what people say they do. It's what they leave out that is the problem. The estrogenic effect of physiological levels of genistein is irrelevant while on ADT, because growth-permissive T levels are also required. 20+ years ago, Milken was in a bad way. He had to be on ADT - very few options then. Giving credit to soy would be misleading.

The interesting thing about the junk bond king is that he was a junk food junkie. The recipes try to replicate his comfort food without meat. Drove my wife crazy making some of that stuff. Not long after my surgery, I discovered the biphasic nature of phytoestrogens & asked her to put the book away.

-Patrick

[paulofaus in reply to pjoshea13]

Interesting, thanks Patrick. So his success, going from being 'in a bad way' to being seemingly OK 20 years later is down to ADT?

[pjoshea13 in reply to paulofaus]

Paul,

"His urologist, Stuart (Skip) Holden, MD, put him on androgen-deprivation therapy, which involved taking two pills three times a day, plus a monthly injection to deprive cancer cells of the male hormones they need to multiply. This therapy reduced his PSA levels over the course of several months to zero. Milken also chose to undergo eight weeks of radiation therapy. Subsequent scans showed the swelling in his lymph nodes had disappeared." [1]

-Patrick

[1] lifeextension.com/Magazine/...

[BigRich]

Patrick,

I swore off soy products, after reading the PubMed articles you cited in a post of yours, about a year ago. I will continue to do same, as you say why take the risk. I will say: I sure miss my soy burgers, for I don't eat red meat.

Rich

[pjoshea13 in reply to BigRich]

Rich,

Even if it's just one a year, treat yourself to a proper burger. That's what I do. I coarsely grind a mix of beef cuts with sufficient fat. Salt & pepper as the only seasoning. 6 oz loosely packed into shape. So good that you don't really need toppings.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

Thank you for the thought. I think I will indulge.

Rich

[Hidden]

I thought I had read advice on this site advocating soy as something to combat ADT induced hot flashes. I used soy milk for a time for that reason. Now that I am on an ADT vacation, and after reading this, no more soy for me.

[Hazard]

Well I am really confused. I starting taking soy supplements based on Snuffy Myers recommended supplement list, and since I have switched to a vegan diet I use soy milk in my coffee (1 per day) and eat tofu or tempeh once or twice a week. Should I avoid soy?

I am coeliac as well, so my food options are diminishing rapidly. Soon I will be on a diet of fruit and vegetables only. Very healthy no doubt, but very boring as well.

I am on ADT since May this year and likely forever, so does this mitigate the risks of soy?

[pjoshea13 in reply to Hazard]

IMO, you are safe with soy while on ADT. -Patrick

[Hazard in reply to pjoshea13]

Thanks Patrick

[rococo]

I've been eating soy food supplements, isoflavonnes, soy isolate genistien recommended by urologist. No strict adherence to any of the above.Never had a hot flash and still hormone sensitive 18 yr surviver. I'll be 79 nov 22. Hppe it hasn't effected my cognition. Thinking going back to grass fed beef this time. Hope the body can still produce the digestive enzymes since I still eat fish. Cheers to all. Rocco

[wstein25]

Hello Patrick - Here's a link to a small study on the effects of an equol supplement on PSA. I have been on active surveillance since 2017, things seemed to be under control, but psa has risen more than I would like in the last 6 months or so. Curious as to your take on the idea of taking equol. I barely understand what these studies present, but the psa of those in the study on average were cut in half over a 6 month period. Thanks -B

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