Alternative Medications to Prevent Prostate Cancer

Many patients come to urology clinic asking about alternative medications for the prevention of prostate cancer.  Some are interested in taking a pill because other men in their families have prostate cancer and they are concerned they might be next in-line with the diagnosis.  Some men are already on alternative medications and wondering if they will actually work.  Here we review the scientific data regarding the most common supplements on the market for the prevention of prostate cancer.

Selenium and Vitamin E

Identification: Selenium - trace element and nutrient; Vitamin E - fat-soluble vitamin.  The best evidence regarding alternative medications for the prevention of prostate cancer exists for Selenium and Vitamin E.
Potential mechanism: anti-tumorigenic and antioxidant, possible effects on angiogenesis, cellular proliferation and apoptosis [1]
Preclinic evidence: numerous laboratory and epidemiologic studies indicate selenium and Vitamin E may prevent development or progression of prostate cancer [2-9]
Clinical evidence: do not prevent prostate cancer, Vit E may increase risk of prostate cancer

• SELECT (Selenium and Vitamin E Cancer Prevention) Trial, included over 35,000 men randomized to receive supplements alone or in combination was closed early due to an increased risk of prostate cancer in the men taking Vitamin E.  In fact, starting 3 years after enrollment and at a median follow-up of 7 years, men taking Vitamin E were 17% more likely to be diagnosed with prostate cancer.  [10]
• Another randomized, controlled trial of selenium for the prevention of prostate cancer in men at high-risk for disease failed to show any benefit for the prevention of prostate cancer. [11]

Curcumin

Identification: derived from turmeric

Potential Mechanism: anti-inflammtory, antiproliferative

Preclinical evidence: 

• suppresses growth of androgen-dependent prostate cancer cell line LNCaP and androgen-independent DU145 [12]
• inhibits VEGF and angiogenesis in vivo [13]
• anti-inflammatory mediators are downregulated by curcumin [14]
• curcumin can improve the effect of chemotherapy in prostate cancer cell lines [15]

Clinical evidence: None

Green Tea

Identification: used for centuries in Eastern culture and medicine, one of the most widely consumed beverages in the world, contains many compounds, most prominent is epigallocatachin-3-gallate

Potential Mechanism: apoptosis, cell-cycle arrest through anti-oxidant effects and androgen receptor effects

Preclinical Evidence: 40% reduction in tumor development and reduction in metastatic spread of cancer with coincident 70% improvement in survival in TRAMP mouse-model of prostate cancer [16]

Clinical Evidence: Mixed data showing both modest benefits and no benefit 

• In a double-blind, placebo-controlled trial in 60 men with HGPIN (high-grade prostatic intraepithelial neoplasia) at high-risk for prostate cancer, only 1 man in the group getting Green Tea developed cancer while 9 in the placebo group developed cancer [17]
• Phase II clinical trial given after prostate biopsy demonstrating cancer and before radical prostatectomy demonstrated a decrease in serum PSA and other growth factors.  [18]
• Another Phase II trial of men with advanced prostate cancer failed to demonstrate a significant decrease in PSA while a number of patients complained of significant toxicities. [19]

PC-SPES

Identification: herbal mixture of chrysanthemum, isatis, liquorice and others [20]

Potential Mechanism: enhanced effects of multiple antioxidant components

Preclinical Evidence: activity in androgen-dependent and independent cell lines [21-24]

Clinical Evidence: Harmful medication, withdrawn from the market.  PC-SPES was withdrawn from the market in 2002 due to contamination with prescription medications including warfarin and diethylstilbestrol leading to a number of significant side effects including gynecomastia, erectile dysfunction, loss of libido and blood clots (both deep venous thromboses and pulmonary emboli). [25]

Pomegranate Extract

Identification: active ingredients in the naturally occurring juice are polyphenol punicalagins and ellagic acid

Potential Mechanism: potent antioxidant, stronger than Green Tea or red wine

Preclinical Evidence: 

• inhibits nuclear factor kappa-B (NF-kB) in prostate cancer cell lines [26]
• 12% in cell proliferation and 17% increase in apoptosis in prostate cancer cell lines [27]

Clinical Evidence: Increased PSA doubling time in men with advanced cancer.  No data for prostate cancer prevention.  In a phase II clinical trial in men with rising PSA levels after surgery or radiation therapy, daily pomegranate juice increased the PSA doubling time from 15 months to 54 months.[27]

Resveratrol

Identification: compound found in the skin of grapes

Potential Mechanism: inhibits prostate cancer cell growth

Preclinical Evidence: regulates androgen receptor gene transcription, expression and degradation through a variety of mechanisms [28-31]

Clinical Evidence: None

Silbinin

Identification: natural phenol from milk thistle plant

Potential Mechanism: decreased angiogenesis, proliferation and increased apoptosis

Preclinical Evidence: decreases incidence of tumors, size of tumors and progression of tumors in TRAMP mouse model [32-33]

Clinical Evidence: None

Zyflamend

Identification: herbal blend of extracts from rosemary, turmeric, ginger, holy basil, green tea and others

Potential Mechanism: cell growth suppression and apoptosis through COX-inhibition [34]

Preclinical Evidence: inhibits androgen-dependent and independent tumor growth in mouse models [35]

Clinical Evidence: Early phase data may indicate a benefit in men at higher than normal risk to develop prostate cancer.  Phase I clinical trial in men with HGPIN at risk for developing prostate cancer demonstrated a 50% reduction in PSA levels in 50% of the men taking the medication with a lower than expected rate of progression to prostate cancer [36]

Summary

There is much pre-clinical data that alternative medications and supplements may affect the ability of prostate cancer cells to grow and flourish.  However, there is little evidence that any supplement will prevent or alter the course of prostate cancer in humans.  In fact, a number of studies have demonstrated significant detriments to taking supplements specifically for prostate cancer.  

Alluding to the fact that they are often health conscious and more likely to undergo screening, Dr. Patrick Walsh often says, 

"Men who take more than one supplement are more likely to be diagnosed with prostate cancer."  

In fact, the data may show that supra-physiologic levels of alternative medications, even if naturally occurring or based on organic compounds, may be harmful.  

For more details, two great resources for this entry and your reading are:

Klempner SJ, Bubley G.Complementary and alternative medicines in prostate cancer: from bench to bedside?  Oncologist. 2012;17(6):830-7. doi: 10.1634/theoncologist.2012-0094. Epub 2012 May 22.

Philippou Y, Hadjipavlou M, Khan S, Rane A.Complementary and alternative medicine (CAM) in prostate and bladder cancer.  BJU Int. 2013 Dec;112(8):1073-9. doi: 10.1111/bju.12062.

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