A selected Summary
Research Data on
the Efficacy of Prostate Health Cocktail

EPIGALLOCATECHIN: Green Tea Extract

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Study

Prostate Carcinoma and Green Tea: (-) Epigallocatechin-3-Gallate Inhibits Inflammation-Triggered MMP-2 Activation and Invasion in Murine Tramp Model
Luigi Sartor, Elga Pezzato, Massimo Dona, Isabllea Dell’Aica, Fiorella Calabresse, Monica Morini, Adriana Albini and Spiridione Garbisa International Journal on Cancer: 112, 823-829 (2204)

Findings

In vitro and in vivo findings show that green tea abolishes tumor growth containment triggered by inflammatory cell recruitment and suggest that an acute inflammatory involvement of PCa could be efficaciously prevented by green tea consumption.

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Study

According to a news release from the American Association for Cancer Research in April, 2005, a team of Italian researchers from the University of Parma and University of Modena and Reggio Emilia led by Vaverio Bettuzzi, PhD, found that:

Findings

• Green tea catechins are safe for use in humans
• EGCG targets prostate cancer cells specifically for death, without damaging benign controls
• Among subject volunteers with high-grade prostatic intraepithelial neplasia (pre-malignant lesions that presage prostate cancer within one year in nearly one-third of cases) who received a year’s oral administration of green tea catechins (GTCs), only one man in a group of 32 developed the disease as opposed to nine out of 30 in a control. 

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Study

Green tea constituent epigallocatechin-3-gallate slectivity inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells
Tajamul Hussain, Sanjay Gupta, Vaqar M. Adhami and Hasan Mukhtar International Journal on Cancer: 113, 660-669 (2005)

Findings

• Data shows that infusion of green tea polyphenols inhibits tumor progression in a mouse model of prostate cancer that recapitulates human disease
• demonstrates that EGCGH inhibits cell growth and induces apoptosis in prostate cancer cell lines
• shows synergistic efficacy of combining green tea components with the NSAID sulindac.

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LYCOPENE:  A  nonprovitamin A carotenoid; the red pigment of tomatoes; known as a  potent antioxidant

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Study

Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate
Angelika Herzog, Ulrich Siler, Volker Spitzer, Nicole Seifert, Athanasios Denelavas, Petra Buchwald Hunziker, Willi Hunziker, Regina Goralczyk and Karin Wertz
The FASEB Journal express article 10.1096/fj.04-1905fje. Published online November 15, 2004

Findings

Researchers supplemented young rats with lycopene for up to 8 weeks, measured the uptake into individual prostate lobes and analyzed lycopene-induced gene regulations in dorsal and lateral lobes after 8 weeks of supplementation.

The data show for the first time that lycopene reduced local prostate androgen signaling, IGF-I expression and basal inflammatory signals in normal prostate tissue. 

In other words, lycopene reduces testosterone’s stimulatory effect on PC and also reduces the effect of the prostate cancer cells’ own growth factors.

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Study

Lycopene Inhibits the Growth of Human Androgen-Independent Prostate Cancer Cells In Vitro and in BALB/c Nude Mice
Lili Tang, Taiyi Jin, Xiangbin Zeng and Jia-Sheng Wang
American Society of Nutritional Sciences.  0022-3166/05

Findings

Data show that lycopene inhibited the growth of all three prostate cancer cell lines: androgen-independent prostate DU145 and PC-3 as well as androgen-dependent prostate LNCaP. 

The inhibition depended on the concentration of lycopene used and the duration of the treatment.  Supports epidemiologic findings that lycopene is an effective chemopreventive agent for human prostate cancer.  

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Study

Tomato Phyochemicals and Prostate Cancer Risk
Jessica K. Campbell, Kirstie Canen-Adams, Brian L. Lindshield, Thomas W.M. Boileau, Steven K. Clinton, John W. Redman, Jr.
American Society of Nutritional Sciences.  0022-3166/04

Findings

Investigators conclude that a majority of prospective and case-control epidemiological studies support the hypothesis that diets rich in tomatoes and tomato products are associated with a reduced risk of prostate cancer.

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Study

Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells
ES Hwang, PE Bowen
National Library of Medicine, J Med Food. 2004 Fall; 7(3):284-9

Findings

In vitro research finds that lycopene at 1 microM inhibited cell growth by 31%, compared with its placebo formulation after a 48-hour incubation. Lycopene at 5micorM increased the number of cells in the G(2)/M phase of the cell death cycle from 13% to 28% and decreased S-phase cells from 45% to 29% while no shifts in cell cycle were detected in placebo-treated groups.  Apoptosis was observed at the 5 microM lycopene formulation at the late stages during the 24- and 48-hour treatments.

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Study

Lycopene: A novel drug in hormone refractory metastatic prostate cancer (HRPC)
MS Ansari, NP Gupta
National Library of Medicine,Urol Oncol. 2004 Sep-Oct;22(5):425-20

Findings

Data show that lycopene therapy appears to be effective and safe in the treatment of HRPC.  It not only takes care of the rising PSA but also improves the ECOG performance status, bone pain and LUTS.

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Study

Lycopene: modes of action to promote prostate health
K Wertz, U Siler, R Goralczyk
National Library of Medicine,Arch Biochem
Biophys. 2004 Oct 1;430(1):127-34

Findings

Investigators conclude that epidemiological evidence strongly suggests lycopene consumption contributes to prostate cancer risk reduction.  In addition, lycopene reduces local androgen signaling in the prostate, suggesting efficacy in prevention of benign prostate hyperplasia.

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Study

Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model
U Siler, L Barella, V Spitzer, J Schnorr, M Lein, R Goralczyk, K Wertz
National Library of Medicine, FASEB J. 2004 June;18(9):1019-21.
Epub 2004 April 14

Findings

Data show that both lycopene and vitamin E contribute to the reduction of prostate cancer by interfering with internal autocrine or paracrine loops of sex steroid hormone and growth factor activation/synthesis and signaling in the prostate – in other words, by reducing the proliferation and development of prostate cancer cells.

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SAW PALMETTO: An herb taken from the partially dried ripe fruit of the American dwarf palm tree.

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Study

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with urinary tract symptoms
GS Gerber, D Kuznetsov, BC Johnson, JD Burstein
National Library of Medicine,Urology. 2001 Dec;58(6):960-4; discussion 964-5

Findings

Data show that saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo.

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Study

Saw Palmetto for Prostate Disorders
Andrea E. Gordon, MD and Allen F. Shaughnessy, Pharm.D
American Family Physician, Vol.67/No.6, March 15, 2003

Findings

Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia (BPH). A meta-analysis reviewed the results of 21 trials with duration of four to 48 weeks, comparing saw palmetto with placebo or other drugs for its effect on symptoms such as urine stream, post-void dribbling, overflow incontinence, urinary retention, urine flow rate, changes in prostate size and residual volume.  The analysis found that:

• saw palmetto is an effective treatment for the symptoms of BHP;
• saw palmetto appears to be as effective as finasteride, and is better tolerated and less expensive;
• although here has been some concern that saw palmetto could mask prostate cancer by lowering prostate-specific antigen (PSA) levels, a andomized study of more than 1,000 patients did not demonstrate this effect.  The same study showed that finasteride decrease PSA levels by 41%;
• clinical studies have used a dosage of 160-320 mg once daily.  As with most herbal medications, the recommended dosage may vary because of the lack of standardization of such products in the United States;
• teas are not effective because they do not contain the volatile oils; and
• the primary side effect occurring in humans is gastrointestinal distress, which is mild and can be minimized by taking saw palmetto with food.

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Study

Effects of a Saw Palmetto Herbal Blend in Men with Symptomatic Benign Prostatic Hyperplasia
Leonard S. Marks, Alan W. Partin, Jonathan I. Epstein, Varro E. Tyler,
Inpakala Simon, Maria L. Macairan, Theresa L. Chan, Frederick J.
Dorey, Joel B. Garris, Robert W. Veltri, Paul Bryan C. Santos, Kerry A.
Stonebrook and Jean B. deKernion
The Journal of Urology, Vol. 163, 1451-1456, May 2000

Findings

A randomized, placebo controlled trial of 44 men ages 45 to 80 found that saw palmetto herbal blend for symptomatic BPH resulted in the contraction of prostatic epithelial tissues, apparently via a non-hormonal mechanism. Serum PSA was unchanged.  The effect on symptom score and urinary flow was mild but statistically significant in large studies.  Thus, saw palmetto herbal blend appears to be a reasonable alternative for men with early, uncomplicated, mild to moderate prostatism.  No major side effects were observed.  

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Study

Saw palmetto berry extract inhibits cell growth of Cox-2 expression in prostatic cancer cells
WH Goldmann, AL Sharma, SJ Currier, PD Johnston, A Rana and CP
Sharma
National Library of Medicine, Cell Biol Int. 2001;25(11):1117-24

Findings

Saw palmetto was examined as neat oil using a set of prostatic cell lines: 267B-1, BRFF-41T and CNCaP.  Investigators found reduced cellular growth of all three cell lines.  They speculate this may be related to decreased expression of Cox-2 and may be due to changes observed in the expression of Bcl-2.  Since Cox-2 expression is associated with an increased incidence of prostate cancer, and since saw palmetto decreases its expression, it should be studied further for its use against BPH and in prostate cancer chemoprevention.

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Study

Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression
FK Habib, M Ross, CK Ho, V Lyons, K Chapman
National Library of Medicine, Int J Cancer. 2005 Marc 20;114(2):190-4

Findings

In vitro study confirms the therapeutic advantage of serenoa repens (saw palmetto) over 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent, and will permit the continuous use of PSA measurements as a useful biomarker of prostate cancer screening and evaluating tumor progression. 

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GENISTEIN: An isoflavone or plant estrogen;soybeans are concentrated sources of isoflavones

Studies in laboratories have shown that genistein has a strong inhibitory ability in a number of prostate cancer cell lines.  Genistein has been shown to reduce the growth of cancer cells, whether androgen-dependent or –independent. 

The exact system by which genistein works is not fully understood.  There is the belief that it blocks several key cellular pathways in cancer cells. 

Much of the interest in soy stems from the fact that Asian men (who have diets high in soy) have a lower rate or death from prostate cancer than American men. 

There are limited human data available for evaluating the link between soy foods and prostate cancer.  Studies of mice and rats fed high soy diets show good outcomes in retarding tumor growth. 

Finally, it is also though that genistein intake reduces prostatitis, inflammation of the prostate gland.

Study

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Randomized, Double-Blind, Placebo-Controlled Crossover Study in Men with Prostate Cancer and Rising PSA: Effectiveness of a Dietary Supplement
Fritz H. Schroder, Monique J. Roobol, Egbert R. Boeve, Renee de
Mutsert, Sonja D. Zuijdgeest-van Leeuwen, I. Kerstein, Mark F.
Wildhagen, Ardy van Helvoort

Findings

This study took 49 patients with a history of prostate cancer and rising PSA levels after radical prostatectomy or radiotherapy and randomized them for a dietary supplement or placebo. 

The supplement consisted of soy, isoflavones, lycopene, silymarin and antioxidenants as main ingredients.  Treatment periods of 10 weeks were separated by a 4-week washout period. 

The data show that the soy-based dietary supplement significantly delayed PSA progression after potentially curative treatment.

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Study

Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer
FS Dalais, A Meliala, N Wattanapenpaiboon, M Frydenberg, DA Suter,
WK Thomson, ML Wahlqvist
European Urology-1000, Accepted 18 August 2005, 10 pages

Findings

This study of 29 men (who were diagnosed with prostate cancer and scheduled to undergo a radical prostatectomy) randomized them into three groups: soy (high phytoestrogen), soy and linseed (high phytoestrogen), or wheat (low phytoestrogen). 

The data indicate that a daily diet containing four slices of a bread rich in HT soy grits favorably influences the PSA level and the free/total PSA ratio in patients with prostate cancer and supports epidemiologic studies claiming that male populations who consume high phytoestrogen diets have a reduced risk of prostate cancer development and progression.

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Study

The specific role of isoflavones in reducing prostate cancer risk
NB Kumar, A Cantor, K Allen, D Riccardi, K Besterman-Dahan, J
 Seigne, M Helal, R Salup, J Pow-Sang
National Library of Medicine, Prostate. 2004 May 1;59(2):141-7

Findings

A total of 76 prostate cancer patients with a Gleason score of 6 or below, between ages 50 and 80, were admitted and supplemented with soy isoflavones or placebo for a 12 week period; and changes in PSA and steroid hormones were analyzed at baseline and post intervention. 

The data suggest that supplementing early stage prostate cancer patients with soy isoflavones, even in a study of short duration, altered surrogate markers of proliferation such as serum PSA and free testosterone in a larger number of subjects in the isoflavone supplemented group than the group receiving placebo.

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Study

Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model
Gilda G Hillman, Yu Wang, Omer Kucuk, Mingxin Che, Daniel R.
Doerge, Mark Yudelev, Michael C. Joiner, Brian Marples, Jeffrey D
Forman, Fazlul H Sarkar
American Association for Cancer Research, Molecular Cancer
 Therapeutics, 2004;3:1271-1279

Findings

In this animal study, established prostate tumors were pretreated with a p.o. genistein for 2 days followed by tumor irradiation.  One day after radiation, genistein was resumed and given every other day for 4 weeks. 

The data show that genistein combined with prostate tumor irradiation led to a greater control of the growth of the primary tumor and metastasis to lymph nodes than genistein or radiation alone, resulting in greater survival.

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SELENIUM: A trace mineral found primarily in plant foods that have been grown in soil with high selenium content

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Study

Intake of Selenium in the Prevention of Prostate Cancer: a Systematic Review and Meta-analysis
M Etminan, JM Fitzgerald, M Gleave, K Chambers
National Library of Medicine, Cancer Causes Control. 2005 Nov;16(9):1125-31

Results

The results of this systematic review of the literature suggest that selenium intake may reduce the risk of prostate cancer.

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Study

Redox modulation of human prostate carcinoma cells by selenite increases radiation-induced cell killing.
B Husbeck, DM Peehl, SJ Knox
National Library of Medicine, Free Radic. Biol Med. 2005 Jan 1;38(1):50-7

Findings

Data show that (a) selenite inhibits cell growth and induces apoptosis in androgen-dependent LAPC-4 prostate cancer cells; and (b) both LAPC-4 and androgen-independent DU 145 cells pretreated with selenite have increased sensitivity to gamma-irradiation as measured by clonogenic survival assays.

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Study

A prospective study of plasma selenium levels and prostate cancer risk
H Li, MJ Stampfer, EL Giovannucci, JS Morris, WC Willett, JM Gaziano,
J Ma
National Library of Medicine, J Natl Cancer Inst. 2004 May
5;96(9):645-7

Findings

This study examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the 1982 Physicians’ Health Study. 

Using plasma samples obtained in 1982 from healthy men enrolled in the study, investigators conducted a nested case-control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. 

The data show an inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggesting that higher levels of selenium may slow prostate cancer tumor progression. 

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Study

Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling.
Y Dong, SO Lee, H Zhang, J Marshall, AC Gao, C Ip
National Library of Medicine, Cancer Res. 2004 Jan 1;64(1):19-22

Findings

Data show that selenium significantly down-regulates the expression of prostate-specific antigen (PSA) transcript and protein within hours in the androgen-responsive LNCaP cells. 

In view of the fact that PSA is a well-accepted prognostic indicator of prostate cancer, this study implies that a selenium intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of the disease.

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Study

Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study
PA van der Brandt, MP Zeegers, P Bode, RA Goldbohm
National Library of Medicine, Cancer Epidemiol Biomarkers Prev. 2003
Sep;12(9):866-71

Findings

The association between prostate cancer and baseline toenail selenium level was evaluated in this Netherlands Cohort Study, conducted among 58,279 men, ages 55-69 years at entry. 

In multivariate survival analysis, an inverse association between toenail selenium level and prostate cancer risk was observed. 

These results confirm the hypothesis that higher selenium intake may reduce prostate cancer risk.

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Study

Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial
LC Clark, B Dalkin, A Krongrad, GF Combs, Jr, BW Turnbull, EH Slate,
R Witherington, JH Herlong, E Janosko, D Carpenter, C Borosso,
S Falk, J Rounder
National Library of Medicine, Br J Rol. 1998 May;81(5):730-4

Findings

A total of 974 men with a history of either basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 microg of selenium or a placebo. 

Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years.  The data show that selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence.

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Study

Antioxidants block prostate cancer in lady transgenic mice
V Venkateswaran, NE Fleshner, LM Sugar, LH Klotz
National Library of Medicine, Cancer Res. 2004 Aug 15;64(16):5891-6

Findings

Male 12T-10 Lady transgenic mice received vitamin E, selenium and lycopene in their diet.  This treatment resulted in a 4-fold reduction in the incidence of prostate cancer compared with untreated animals.  These observations provide support for the chemopreventive effect of these micronutrients.

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Study

Changes in serum proteomic patterns by pre-surgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer
J Kim, P Sun, YW Lam, P Troncoso, AL Sabichi, RJ Babaian, LL Pisters,
CA Pettaway, CG Wood, SM Lippman, TJ McDonnell, R Lieberman,
C Logothetis, SM Ho
National Library of Medicine, Cancer Epidemiol Biomarkers Prev. 2005
Jul;14(7):1697-702

Findings

A total of 48 patients with clinically localized prostate cancer were randomized to take selenium, vitamin E, both, or a placebo for 3 to 6 weeks before prostatectomy. 

Eliminating an outlying value and performing post hoc analysis (using Fisher’s least significant difference method) showed that effects in the group treated with the combination were significantly different from those in the other groups. 

In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.

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Study

Vitamin D May Lower Prostate Cancer Risk: Sunlight, Diet, Supplements Can Boost Vitamin D Levels
Haojie Li, MD, PhD, Lead Researcher, Fellow, Brigham and Women’s
Hospital and Harvard University School of Public Health
WebMD Medical Health, Brigham and Women’s Hospital and Harvard
University School of Public Health,Feb 18, 2005

Findings

The study involved 1,029 men with prostate cancer and more than 1,300 healthy men.  The men’s blood was analyzed, looking for several factors including levels of vitamin D. 

The data show that men with the highest levels of vitamin D had significantly lower overall risk of prostate cancer, including aggressive prostate cancer. 

Also, men who have a specific receptor that helps vitamin D work for greater protection—if they had high levels of vitamin D in their blood—had a 55% lower risk of prostate cancer. 

Therefore, the researchers conclude that vitamin D plays a role in reducing the risk of prostate cancer and its aggressiveness.

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Study

Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trail.
F Meyer, P Galan, P Douville, I Bairati, P Kegle, S Bertrais, C Estaquio,
S Hercberg
National Library of Medicine, Int J Cancet. 2005 Aug 20;116(2):182-6

Findings

The trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years.

Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of the follow-up from 3,616 men. 

Among those with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements.  These findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.

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Study

Vitamin E and prostate cancer: is vitamin E succinate a superior chemopreventive agent?
A Basu, V Imrhan
National Library of Medicine, Nutr Rec. 2005 Jul;63(7):247-51

Findings

Data from this study in transgenic mice show a synergistic inhibitory effect of dietary vitamin E succinate, selenium and lycopene on prostate cancer incidence.

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Study

Effects of long-term alpha-tocopheral supplementation on serum hormones in older men
TJ Hartman, JF Dorgan, K Woodson, J Virtamo, JA Tangrea, OP
Heinonen, PR Taylor, MJ Barrett, D Albanes
National Library of Medicine, Prostate. 2001 Jan 1;46(1):33-8

Findings

Sex hormones are thought to be involved in the etiology of prostate cancer.  This study examined whether long-term supplementation with alpha-tocopherol modified serum hormone levels. 

All participants were cancer free, consumed > 90% of the study capsules and had both baseline and follow-up blood available for analysis. 

The data found that compared to men who received a placebo, significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentration was found among men who received alpha-tocopherol after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking and fasting time. 

These results suggest that long-term alpha-tocopherol supplementation decreases serum androgen concentrations, and could be one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha-tocopherol treatment groups of the previous ATBC Study.