Foods/Supplements-Vitamins: Green Tea - Human Studies

[pjoshea13]

Having undermined the appeal of green tea in yesterday's post:

"Foods/Supplements-Vitamins: Green Tea, etc, & Pollutants"

I'll present the scant human-study evidence for green tea as being protective against PCa.

The epidemiological studies are concerned with PCa incidence, rather than potential benefit following diagnosis. I could find nothing on survival (or the dose that might be required).

Interest in green tea was initially due to low PCa rates in Asian populations having a high green tea intake. Yet [2] (Japan) & [5] (Singapore) report no protective effect. [4] (Japan) found a reduced risk only for advanced PCa, not local disease. The remaining Asian study [3] (China) reported an 86% reduction in risk when comparing extreme quartiles of intake, which makes it something of an outlier.

The persistance of interest in green tea may be due to the biological effects of EGCG in cell studies. It's not clear whether green tea itself is a realistic source for the EGCG needed to fight existing PCa. A pharmacological dose might be required, but studies are lacking.

Studies - oldest first:

[1] (2006 - Italy)

This seems like a useful intervention study. High-grade PIN [HG-PIN] is thought to be a precursor of PCa. For many who have a negative initial biopsy but are later diagnosed with cancer, the Gleason score will perhaps be 3+4. i.e. lesser Gleason scores & HG-PIN often escape detection using normal sampling. It's unfortunate, since, while earlier detection would likely add to over-treatment, it could also act as a warning to make lifestyle changes to avoid progression.

In this study, the probability of HG-PIN becoming PCa within 12 months was 30%: 9 of 30 controls were subsequently diagnosed. In contrast, only one of 30 men who received 600 mg of green tea catechins, was later diagnosed with PCa within 12 months. In addition, 6 of the 9 cases in the placebo arm were found at the 6-month biopsy, while the solitary cancer in the treatment arm was found at 12 months.

"Content was as follows: EGC, 5.5%; EC, 12.24%; EGCG (epigallocatechin-3-gallate), 51.8%; ECG, 6.12%; total GTCs, 75.7%" {i.e. 310.8 mg EGCG daily}

The Life Extension product [7] is standardized to 98% polyphenols. 45% of the 725 mg capsule (326.25 mg) is EGCG. Not only is this equivalent to 7 cups of tea, but with 98% being polyphenols, I'm assuming that heavy metals have not made it to the capsule. It would be interesting to know the fluoride content, which has been described as "low". Anyway, 1 LEF cap is equivalent to the Italian dose.

[2] (2006 - Japan)

"In a prospective study of 19, 561 Japanese men, green-tea intake was not associated with a lower risk of prostate cancer (110 cases), the multivariate hazard ratio for men drinking ≥5 cups compared with <1 cup per day being 0.85 ..."

[3] (2007 - China)

"a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls."

"Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14 ...) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors."

[4] (2008 - Japan - Japan Public Health Center-based Prospective Study [JPHC])

"49,920 men aged 40-69 years who completed a questionnaire that included their green tea consumption"

"404 men were newly diagnosed with prostate cancer, of whom 114 had advanced cases, 271 were localized, and 19 were of an undetermined stage. Green tea was not associated with localized prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer. The multivariate relative risk was 0.52 ... for men drinking 5 or more cups/day compared with less than 1 cup/day "

[5] (2012 - Singapore)

"Tea consumption data for 27,293 men were collected at baseline (between 1993 and 1998) using a validated food frequency questionnaire. After an average of 11.2 years of follow-up, 298 men had developed prostate cancer."

"There was no association between daily green tea intake and prostate cancer risk, compared with no green tea intake [hazard ratio (HR) = 1.08 ...]."

"For black tea, a statistically significant positive association and trend were observed for daily intake compared with no black tea intake (HR = 1.41 ..."

[6] Polyphenon E (PolyE), a proprietary mixture of green tea catechins.

[6a] (2009 - U.S.)

"Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (−)-epigallocatechin-3-gallate (EGCG) ..."

"We report here that men diagnosed with prostate cancer who take 1.3 g daily of green tea catechins (800 mg EGCG) show a significant reduction in serum HGF, VEGF, IGF-I, IGFBP-3, and PSA with a median dosing period of 34.5 days. Liver function tests revealed no abnormalities, suggesting that this dose of tea polyphenols is safe when administered for a few months."

{In men with an intact prostate, a drop in PSA cannot be attributed directly to PSA produced by PCa cells. EGCG inhibits NF-kB, thereby reducing inflammation. Thus, PSA due to BPH should fall.}

[6b] (2012 - U.S.)

"Randomized, Double-Blind, Placebo-Controlled Trial of Polyphenon E in Prostate Cancer Patients before Prostatectomy: Evaluation of Potential Chemopreventive Activities" Dose: 800 mg epigallocatechin gallate.

"The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease."

[6c] (2015 - U.S.) {Compare result with [1]}

"97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP)" Dose: 400 mg EGCG per day,

"The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo)"

"Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP."

-Patrick

[1] cancerres.aacrjournals.org/...

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

[3] apjcn.nhri.org.tw/server/AP...

[4] aje.oxfordjournals.org/cont...

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

[6a] cancerpreventionresearch.aa...

[6b] cancerpreventionresearch.aa...

[6c] ncbi.nlm.nih.gov/pubmed/258...

[7] lifeextension.com/Vitamins-...

[CERICWIN]

What a well-researched and presented post about green tea. You are quite a scholar.

I'd just like to add simply that I've enjoyed green tea for more than 30 years. I found it soothing to the spirit when I drink it hot, and somewhat helpful with an upset stomach when drunk cold, or at room temperature.

But I don't believe that there is any one thing, dietary or in a supplement, that will in and of itself prevent prostate cancer. Perhaps there is a combination of diet and supplements that can help to inhibit prostate cancer's start or growth, but so far nothing definite has been proven to my knowledge.

There is so much quackery on the internet about different substances supposedly curing prostate cancer, but I haven't seen anything to substantiate such claims. I only wish that one of them would prove to be beneficial.

CERICWIN

[BigRich]

"... it could also act as a warning to make lifestyle changes to avoid progression." Beside Avodart and testosterone replacement every 90 days; what lifestyle changes have you made to avoid progression?

Rich

[pjoshea13 in reply to BigRich]

Rich,

My prescriptions are all PCa-related. (1) Simvastatin, (2) Metformin, (3) Arimidex, (4) Avodart, (5) Testosterone & now (6) Nitroglycerin.

3 months on T is a lifestyle change. Triglycerides plummet to the HDL-C level; fat:muscle ratio improves; VLDL drops, etc. None of this can happen purely with diet & exercise while T is low.

I have a ton of supplements that I am weary of taking.

My wife has been very ill for a year, & this has affected my diet, since she has no appetite. I'm the cook & I can't bring myself to prepare a meal that she will not eat. & I'm not interested in the few things she will eat. Basically, I skip a lot of meals.

I'm hoping that we can get back to normal by year-end. I used to enjoy cooking. I don't like take-out food, or anything that I don't make from scratch. But what I cooked before her illness was what I was cooking before my diagnosis, so that wasn't a change.

-Patrick

[BigRich]

Patrick,

My wife too can only eat certain foods. I too, am the cook. I understand why you are taking: drugs 1,2,4 and 5. But, why Arimidex and Nitroglycerin for PCa. Please provide the PubMed links you consulted before you utilized testosterone replacment in your peotocol.

Rich

[pjoshea13 in reply to BigRich]

Rich,

There are two reasons for men to use Arimidex:

(i) when estradiol [E2] is above the 20-30 pg/mL range

(ii) when using testosterone [T] supplements. PCa cells often have elevated levels of aromatase. Dr. Myers denies that E2 has any bearing on PCa, but (from June):

"prostate tissue ... expresses enzymes essential for local oestrogen metabolism, including aromatase (CYP19A1) and 3β- and 17β-hydroxysteroid dehydrogenases. Increased expression of these enzymes in malignant prostate tissue compared with normal prostate indicates that oestrogen synthesis is favoured in malignancy and thus may influence tumour progression."

PCa cells have a fundamental change in the estrogen receptor [ER] area. The anti-proliferative ERbeta disappears & the pro-growth ERalpha emerges. Not only are significant levels of ERalpha present in aggressive cells, but the cells make aromatase, to convert T to E2. Blood levels of E2 can't tell one about what is happening in the cells.

Arimidex is an aromatase inhibitor.

Why use T? Morgentaler's "Saturation" model [2] states that PCa has all the access to T that it could possibly want, at T levels that are below the hypogonadal cutoff. Dr Myers agrees - in the off-phase of IADT, PSA rises as T recovers in his patients, but there is no excess effect as T rises above 350 ng/dL. (Morgentaler says that AR saturation occurs at somewhere in the low 200's.)

i.e. both would say that T=650 or 950 is no less safe than T=350.

My feeling is that, when IADT is safe, there is benefit in being T-dominant versus E2-dominant.

(My distrust of E2 goes back 12 years.)

-Patrick

[1] erc.endocrinology-journals....

[2] ncbi.nlm.nih.gov/pubmed/168...

[BigRich in reply to pjoshea13]

I like how you think, outside the box. I take 150 mg. Casodex which lowers my PSA and increases my testosterone. This maybe a rhetorical question: why do you take Nitroglycerin?

[pjoshea13 in reply to BigRich]

Rich,

This study is the reason:

ncbi.nlm.nih.gov/pubmed/194...

With hypoxia, the cancer becomes very hard to control. The nitro dilates the blood vessels - more oxygen to tumors.

In the study, PSA doubling time increased dramatically.

The only side effect was that my head felt as though I had drunk 5 cups of coffee. That eased off after a few days. I don't have any side-effects now.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

Thank you, I understand the science. I hope, you may have many years, for I enjoy reading your posts. I find them highly informative. I will include you in my prayers.

God Bless,

Rich