Foods/Supplements-Vitamins: Genistein - Advanced Prostate...

Advanced Prostate Cancer

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Foods/Supplements-Vitamins: Genistein

8 years ago•5 Replies

Genistein is a polyphenol. Family classification as follows: Polyphenol ---> Flavonoid ---> Isoflavonoid ---> Isoflavone. It is a phytoestrogen.

The primary source is soybeans, & so I would therefore not necessarily describe it as a natural dietary nutrient. Soybeans contain a good number of antinutrients, & the beans must go through complex processing steps to be 'fit' for human consumption. Some think that, with the flood of non-traditional products containing soy now found in U.S. supermarkets, consumers might be at risk.

Michael Milken, the junk bond king, emerged from prison in 1993, aged 46, to a diagnosis of PCa. PSA=24, Gleason score=9 (4+5? or 5+4?); lymph node involvement. It seems that there was no form of junkfood that he didn't crave, so he hired Beth Ginsberg, Culinary Institute of America (CIA) graduate, to recreate those delights using soy products. A cookbook emerged in 1998: "The Taste for Living Cookbook: Mike Milken's Favorite Recipes for Fighting Cancer", & I bought a copy in 2004, just after I was diagnosed. Milken had survived more than 10 years at that point. It seemed like a good idea & my wife was eager to cook anything that might have survival value. After a month, much to her relief, I asked her to stop using the recipes.

The first of over 500 PubMed hits for <prostate genistein> was published in 1993; there were almost 300 papers by the time I bought the book in 2004. Soy then almost seemed like a health food for men with PCa.

One theory, which I had no time for at all, was that the protection was due to the genistein content (a plant estrogen) lowering androgen levels.

In a paper published last month [1]:

"{Endocrine disruptors}, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease."

It is a little unnerving to see genistein in the same company as DES & BPA.

Also from last month [2]:

"Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by {endocrine disruptors} such as bisphenol A, genistein, diethylstilbestrol, p,p'-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons."

Soybeans not only contain phytoestrogens, but also these antinutrients: trypsin inhibitors, phytates, saponins, soyatoxin & goitrogens. By the end of 2004, I had given up on the idea of soy replacing animal protein in my diet. No more soy protein isolate smoothies for me.

Nevertheless, I became convinced that genistein might be useful against PCa - & at pharmaceutical doses, not at observed physiological levels, because of a possible biphasic effect:

[3] (2004) "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."

& [4] (2009) A mouse study:

"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 ..."

"A pharmacologic dose (50 micromol/L) decreased proliferation, invasion, and MMP-9 activity (>2.0-fold) ..."

There are enough papers to make me think that soy products are not useful against PCa, unless high-dose genistein supplements are used. I wouldn't risk it.

What is a pharmacological dose? The LEF product claims to have 468.75 mg genistein, which is about ten times what a traditional Japanese diet might provide.

lifeextension.com/Vitamins-...

[5] How does genistein work? (2006 - McCarty, U.S.)

The prostate contains two types of estrogen receptor. ERalpha is found in the stroma, whereas ERbeta if found in the epithelium, where PCa occurs. ERalpha tends to be pro-growth & ER-beta is thought to resist the actions of ERalpha. As PCa progresses, ERbeta levels drop & ERalpha emerges in PCa cells.

As a phytoestrogen, genistein is able to bind to estrogen receptors. However, it has a very high affinity for ERbeta & hardly any for ERalpha. With ERbeta, it acts as an agonist & triggers its protective effects.

The obvious question is whether genistein has any activity if PCa has suppressed ERbeta. I'll tackle that elsewhere.

[6] Japanese studies. There doesn't seem much point in looking at studies in populations that do not have significant genistein intakes, so most of my chosen studies are Japanese.

I have an issue with blood studies, in that serum genistein will rise & fall according to when the last meal was, & a significant amount of dietary genistein will be converted to metabolites that may be bioactive. But this is the best we have right now.

[6a] (2004 - Japan Collaborative Cohort (JACC) Study)

"Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified."

"The {PCa} odds ratio ... for the highest level to the lowest was 0.38 ... for genistein"

[6b] (2006 - Japan Public Health Center-Based Prospective Study Group

"43,509 Japanese men ages 45 to 74 years" "During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage."

"Intakes of genistein, daidzein, miso soup, and soy food were not associated with total prostate cancer. However, these four items decreased the risk of localized prostate cancer."

"In contrast, positive associations were seen between isoflavones and advanced prostate cancer." {This might be an example of a physiological dose promoting growth when PCa had already occurred.}

[6c] (2007 - Japan) Case-control study from the Ibaraki, Nara, and Hokkaido areas.

"Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category (≥89.9 mg/d) compared with the lowest category (<30.5 mg/d) of isoflavone intake was 0.42 ..."

[6d] (2008 - Japan Public Health Center-Based Prospective Study Group)

"A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified."

"Plasma genistein level tended to be inversely associated with the risk of total prostate cancer."

"OR in the highest group of plasma genistein ... compared with the lowest of 0.54"

"Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer."

[7] European Prospective Investigation into Cancer and Nutrition - EPIC

Seems odd to do this kind of study in Europe, where soy intake is low & variable across the different countries, but the authors note that "soy additives are now also found in an increasing range of processed foods"

[7a] (2009 - EPIC) "950 prostate cancer cases and 1042 matched control participants"

"Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 ..."

[7b] (2012 - EPIC)

"Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants."

"Plasma genistein concentrations were not associated with prostate cancer risk"

Go figure.

{"In the current study, we combined data from [7a] with 655 additional men who had been subsequently diagnosed with prostate cancer (up to 2006) and their 655 matched control participants (designated phase 2), whose samples were assayed in 2009."}

[8] (2015 - Shanghai, China)

"Between 2012 and 2013, 100 men over the age of 40 underwent prostate biopsy for PCa at Huashan Hospital ..."

"Among the 100 patients, 46 (46.0 %) were diagnosed with PCa. The median plasma genistein concentration of non-PCa patients (728.6 ng/ml) was significantly higher than that of PCa patients (513.0 ng/ml)"

"The age-adjusted odds ratio of PCa risk comparing plasma genistein level above median to that below median was 0.31"

[9] (2008 - U.S.) Phase II trial with 20 men having "rising PSA after prior local therapy".

"Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months."

"it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period"

However: "the slope of PSA after study entry was significantly higher than before study entry in 2 patients."

I am surprised that with such a tepid intervention there was a positive outcome, however weak.

[10] (2009 - U.S.)

"Participants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for two weeks (14 days) prior to surgery."

"The present study took advantage of access to human prostate tissue collected during routine prostatectomy procedures to examine and contrast tissue and serum concentrations of isoflavones that had been administered by dietary supplementation for at least two weeks prior to surgery. There was a ∼6-fold higher total isoflavone concentration in the tissue compared to serum levels sampled at the time of tissue harvesting. . Further examination of specific types of isoflavones indicated that the tissue vs. serum difference was smaller for genistein (4-fold) than for daidzein (10-fold)."

There is no question that prostatic cells can & do take up genistein. (note that this was merely a 2-week study)

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[2] ncbi.nlm.nih.gov/pubmed/274...

[3] ncbi.nlm.nih.gov/pubmed/150...

[4] ncbi.nlm.nih.gov/pubmed/193...

[5] ncbi.nlm.nih.gov/pubmed/165...

[6a] onlinelibrary.wiley.com/doi...

[6b] cebp.aacrjournals.org/conte...

[6c] jn.nutrition.org/content/13...

[6d] jco.ascopubs.org/content/26...

[7a] ncbi.nlm.nih.gov/pmc/articl...