There have really been very few meaningful, randomized, double-blind trials of any forms of supplement in the prevention of prostate cancer … and to date none of the trials that have been done have shown unarguably meaningful, positive results.
By contrast, another small, randomized trial can now be added to the list of studies showing negative results. This is a study by Gontero et al., published in The Prostate and focused on the effects of lycopene, selenium, and green tea catechins (GTCs) in men with multifocal, high-grade prostatic intraepithelial neoplasia (HG-PIN) and/or atypical small acinar proliferation (ASAP).
Between 2009 to 2014, this small trial enrolled just 60 patients into a Phase I protocol. These 60 men were initially treated with daily lycopene (35 mg), selenium (55 µg), and GTCs (600 mg) or a placebo for 6 months. In men whose plasma lycopene concentrations fell into the expected range (1.2 to 90 µg/l) and who had no side-effects of grade higher than Grade 1, the study proceeded to Phase II (n = 50).
The basic clinical results reported are as follows:
- At 6 months, 53 men underwent re-biopsy and 13/53 (25 percent) were diagnosed with prostate cancer.
- 10 patients with cancer came from the supplement-treated group.
- 3 patients with cancer came from the placebo-treated group.
- At 37 months, an additional three patients in the placebo group were found to have prostate cancer.
- There were no significant differences in the PSA levels of patients in the two groups.
Micro-RNA profiling data were also collected from a subset of patients. Whether the data from these eight patients are really of any clinical significance at all is questionable … but you can read the data in the abstract.
The authors conclude that:
Administration of high doses of lycopene, GTCs, and selenium in men harboring HG-PIN and/or ASAP was associated with a higher incidence of [prostate cancer] at re-biopsy and expression of microRNAs implicated in [prostate cancer] progression at molecular analysis. The use of these supplements should be avoided.
Now we need to recognize that this was a very small study, and that, because the men in the supplement arm of the study were receiving three different supplements, it is very hard to know exactly what supplement might have been having what effects in which individual patient.
On the other hand, it is equally clear that there was no evidence of benefit from the use of this combination of supplements. If anything, the use of this combination of supplements appeared to increase risk for diagnosis of prostate cancer within just 6 months.
The only thing that The “New” Prostate Cancer InfoLink thinks that we can conclude with certainty from this trial is that using this combination of supplements presents more risk than benefit when it comes to the prevention of prostate cancer. We already knew that selenium supplementation isn’t a good idea anyway (unless patients have low selenium levels). However, this trial does also confirm that the idea that using supplements to prevent prostate cancer is safe and effective may be a complete illusion. We could do with some more large trials to actually prove some hypotheses one way or the other — particularly in the case of lycopene and green tea extracts. But whether such trials will ever be carried out is harder to know. The costs are becoming exorbitant because of the size that such trials would need to be to prove anything with confidence.
Filed under: Diagnosis, Prevention, Risk | Tagged: green tea, GTCs, lycopene, Prevention, selenium |
THE "NEW" PROSTATE CANCER INFOLINK 
Discouraging but not surprising double-blind, randomized trial result for combined supplement
It would have been great to have a result favoring the use of this supplement combination, but that also would have been surprising based on the history that Sitemaster mentioned. Lycopene and selenium supplementation have been disappointing in previous studies. (I’ll argue for pomegranate supplementation, but I see a good basis for Sitemaster’s position.) It would have been nice to know the form of selenium used, as there are a number of forms and they have some significantly different effects (one being quite toxic, and another associated with apparent ineffectiveness in the SELECT trial, etc.), but that information is not available in the abstract.
Regarding the “don’t use” recommendation in the conclusion section of the abstract, that seems reasonable based on the lack of evidence of effectiveness, but the evidence of actual danger is shaky. The evidence is in this sentence: “… At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with prostate cancer (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. …” What the p-value of 0.053 means is that there was no statistically significant difference between the groups — based on the accepted convention of a cut-off of p = 0.05 or higher as favoring chance versus cause — at 6 months, meaning that the results may well have been due to chance; that interpretation was further emphasized by the 37-month follow-up that added three more men with prostate cancer in the placebo group, but none in the supplement group, for revised totals of 10 prostate cancer patients in the supplement group versus 6 in the control group out of only 53 patients total, a rather small overall group. On the other hand, the authors’ analysis of miRNA prompted their comments in the abstract to the effect that the supplement seemed to foster progression of prostate cancer. Detail in the abstract was not adequate to further address that.
I have been consuming green tea for more than 16 years, with at least eight bags-worth daily since my diagnosis in late 1999 (14 bags daily throughout that first year). I brew the tea with a few drops of lemon juice to prevent oxidation, and I have been taking one green tea extract pill for most of that time to hedge my bets. Since diagnosis I have been consuming about 16 ounces of V8 juice daily, which has a big tomato/lycopene component, plus other fairly frequent sources of dietary lycopene, but no pills for many years, since the first unfavorable evidence. I stopped taking selenium pills prior to radiation in 2013 and have not resumed. So far, for my challenging case (with an initial PSA of 113.6 and a fairly rapid PSA doubling time of 3 to 4 months), my IADT3 regimen for about 14 years plus TomoTherapy IMRT radiation in 2013, plus lifestyle tactics, have resulted in PSA levels that have not exceeded 0.02 since the adjuvant ADT run-out date after radiation, a period now extending for about a year. I believe but cannot prove that lifestyle tactics, including what I consume, especially foods, have helped me against prostate cancer.
Jim,
One has to look at a Phase I/II clinical trial as an elimination round. If no red flags are raised, then it may be worthwhile to go on to a full-scale Phase III clinical trial. The sample size used here was enough to show a statistically significant safety concern to taking the combination. I’m sure the researchers were hoping to show that the combination slowed down the cancer in men at risk. Not only did it not prevent it, it caused it to happen sooner! And, the researchers found a plausible biochemical mechanism for it. The fact that the control group got worse later may suggest that the combination hastened the cancer process — not something we want to do!
As for the components of combination, none of them have raised safety concerns before, other than selenium, which only had safety concerns when levels were already high, or when taken with vitamin E (and studies have shown no difference in biologic effects of selenomethionine and selenium from yeast). Even if it is not harmful on its own, it has been shown to be of no benefit to men at risk.
As for lycopene, a recent meta-analysis of all the studies done on it found there was no statistically significant benefit associated with consumption of raw tomatoes, cooked tomatoes, or lycopene.
As for green tea catechins, a similar randomized controlled trial of that alone (400 mg EGCG per day) found it “did not reduce the likelihood of PCa in men with baseline HGPIN or ASAP.”
So we have three components here that do no good, but individually probably do no harm either. Yet, when taken together, they hastened cancer development. I know men who take handfuls of these drugs, thinking that if they are labeled as supplements they must be safe. We would never take prescription drugs without first looking at drug interactions (at least I hope not!), yet we do just that with impunity when taking supplements. The biochemical progression of cancer is far too complex for us to risk taking untested combinations.
Hi Allen,
I have a somewhat different take on these studies, as reflected in my post above, but I try to help people see that supplements are not safe just because they are supplements, and that taking handfuls of these drugs is risky.