By: Dan Sperling, MD

The use of supplements as a way to prevent prostate cancer (PCa) has been and continues to be researched. Over a decade ago, some of the popular vitamins, antioxidants and minerals included vitamin E, saw palmetto, lycopene, selenium, etc. However, six years ago use of selenium and vitamin E came into question because of disappointing results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Enrollment ran from 2001-2004, with roughly 35,000 participants who were followed over time. Initial results, published in 2008, showed no protective effect for either selenium or vitamin E. Subjects were told to stop taking the supplements, but continued to be followed. Worse news emerged with the 2011 announcement of longer term results: men taking vitamin E alone had a 17% greater risk of developing PCa as time went on; those taking selenium alone, or selenium and vitamin E, had a slightly greater chance of developing prostate cancer.[i]

Many of the clinical studies were based on supplement use by men without PCa, but what about men whose glands contain tissue changes suggestive of the disease? Two prostate conditions that are thought to be precancerous are

1. High grade prostatic intraepithelial hyperplasia (HG-PIN) [ii] – this refers to cell and tissue changes that are similar to prostate cancer but are not invasive, and
2. Atypical small acinar proliferation (ASAP)[iii] – this includes a several types of lesions, some of which mimic prostate cancer (PCa) and may show up on imaging as suspicious for cancer, but lack clear diagnostic features for PCa.

Both conditions are considered precursors and able to become cancerous.

A new study out of Italy by Gontero et al. [iv] raises serious concerns about men with either condition using dietary supplements that were once believed to have protective benefits against PCa. The authors refer to the idea of such protection from supplements as “chemoprevention.” Their research suggests that for men with HG-PIN or ASAP, the use of lycopene, selenium or green tea catechins (GTC) produces greater risk of developing PCa. Although the study population is relatively small (60 patients) it’s an very well designed study because of its duration (5 years) and because it was a double-blind, randomized study involving a control group for comparison of results.

The study was divided into two phases. For Phase I (the safety phase) the men assigned to the experimental group received daily lycopene 35 mg, selenium 55 µg and GTCs 600 mg; those in the control group received a daily placebo (harmless substance made to look like the supplements so the patients and doctors would not know which patient was receiving which). When Phase I produced no adverse effects (demonstrated safety) the study proceeded to Phase II, at which time the results for the two groups were unblinded.

At six months after beginning Phase II, 53 men had another biopsy. Thirteen of them (24.5%) were diagnosed with PCa; 10 had been using the supplements, while only 3 had been on the placebo. MicroRNA assessment of tissue samples from the re-biopies revealed that those who had been on supplements had a greater number of genomic changes in both normal and cancerous tissues. The authors concluded that “… high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis.”

Based on their work, Gontero and his colleagues suggest that lycopene, selenium and CTCs have the capacity to bring about what they call “chemopromotion” of PCa. Their summary recommendation is that men with HG-PIN or ASAP should avoid these three supplements.

[i] http://www.cancer.gov/types/prostate/research/select-trial-results-qa#1

[ii] Bostwick D, Liu L, Brawer M, Qian J. High-grade prostatic intraepithelial neoplasia. Rev Urol. 2004 Fall;6(4):171-179.

[iii] http://emedicine.medscape.com/article/447780-overview

[iv] Gontero P, Marra G, Soria F, Oderda M et al. A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or “chemopromotion”? Prostate. 2015 Aug 1;75(11):1177-86. doi: 10.1002/pros.22999.