Posted by: colinhockings
A BBC article on a study (PubMed) by a group, led by Dr. James Cardelli at the Louisiana State University Health Sciences Center, reports that green tea extracts slow the progression of prostate cancer. It has also been reported on by Reuters and (briefly) in the Daily Mail, as well as various blogs such as Attorney-at-Law and BloggingStocks and a health information network that seems to focus on alternative medicine called HealthNews.
The study itself is not perfect. They took 26 patients with stage I, II or II prostate cancer who were scheduled for radical prostatectomy (removing the prostate) and gave them a high dose of polyphenon (a green tea extract marketed by Polyphenon Pharma) until the day before the operation. As the most important outcome (survival) is hard to measure, especially in a single-armed (i.e. one group) trial like this, they measured serum biomarkers (signalling molecules in the serum) that seem to correlate with prostate cancer progression: HGF, VEGF, PSA and the IGF-1/IGFBP-3 ratio before taking the pills and before surgery. They mention the small sample size and lack of a control group but don’t, to my mind, make these limitations clear when they discuss their results. There’s nothing wrong with it, as a purely preliminary trial, but it is very poor evidence. The American Association for Cancer Research (AACR, the body that published the study) press-release has a very important statement about this which was left out of all the reports I’ve seen on this study:
William G. Nelson, V., M.D., Ph.D., professor of oncology, urology and pharmacology at the Johns Hopkins Kimmel Cancer Center, believes the reduced serum biomarkers of prostate cancer may be attributable to some sort of benefit relating to green tea components.
“Unfortunately, this trial was not a randomized trial, which would have been needed to be more sure that the observed changes were truly attributable to the green tea components and not to some other lifestyle change (better diet, taking vitamins, etc.) men undertook in preparation for surgery,” added Nelson, who is also a senior editor for Cancer Prevention Research. However, “this trial is provocative enough to consider a more substantial randomized trial.”
This is the most sensible thing I’ve read about the study, clearly summing up the fact that while there may be an effect, this trial doesn’t show it at all convincingly. It also occurs to me that the samples from before and after treatment were all run on the same ELISA, i.e. the sample from before the treatment was stored at -80°C for between 12 and 214 days longer than the second sample. This may not be a problem, but I didn’t notice any acknowledgement that the researchers considered it. This is why we need control groups! With more participants and a control group you could say ‘well…they might have changed their lifestyles and some parts of the serum may be destroyed by cold and Mercury may have entered Vesuvius, but the treatment group still shows a benefit”. Clearly, such a preliminary trial is not worthy for publishing on its own, so the researchers also tested the safety of such high doses by measuring the liver function (verdict: safe) of the 26 patients and an in vitro study of fibroblast cells treated with EGCG (epigallocatechin gallate, the most common catechin in polyphenon).
Regarding the BBC article itself, I noticed three errors that are quite revealing:
- It claims that polyphenon is a compound, which it is not. It is a complex extract from green tea leaves. This is the difference between buying a stack of bricks from the manufacturer and bulldozing a house – a compound is quite pure, while a complex mixture has many unknown components. While not necessarily important to the story, this mistake somewhat undermines my confidence in the scientific literacy of the author.
- The location of the study was given as Philadelphia – the address of each researcher (all in Louisiana) is given on the first page of the study. Where could this mistake have come from?
- The age range was given as 41-72, but the original paper seems to think it was 41-68.
The age-range of 41-72 also appeared on the Polyphenon Pharma blurb about the trial, published a few days later. The source of the discrepancy: the press-release from the AACR. The 41-72 age range was presumably a typo – if they knew the original article to be incorrect they would presumably correct it: it hasn’t even been published on paper yet.
Imagine my surprise when I re-read the first paragraph of the press-release:
PHILADELPHIA – According to results of a study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, men with prostate cancer who consumed the active compounds in green tea demonstrated a significant reduction in serum markers predictive of prostate cancer progression.
So THIS is where the ‘Philadelphia-based researchers’ comes from – the press-release was written in Philadelphia. And, if we look closer, the first paragraph might also be the source of my other gripe: the ‘compound called Polyphenon E’. I may be wrong, but it seems to me that the author of the BBC article simply read the press release and regurgitated it, without ever taking the time to read the original paper. To be fair, though, I maintain my faith in the BBC News service to some degree because this lax effort was clearly not sufficient. The author got a statement from the head of the Prostate Cancer Charity – a modicum of journalistic investigation was performed, even if it began and ended with a call to the most relevant charity.
The Reuters article is a little better: it has the correct location and age range, and has some extra statements from the lead researcher, James Cardelli. There is nothing to indicate that the author read the original paper, but at least there were no glaring errors. In addition, it finishes with the observation that it ‘was a small trial and bigger studies would be needed to confirm the results’. The only thing I take exception to is the claim that the patients took the pills for ‘about a month’ – while the median duration was 34.5 days, the maximum was 214 days (although that was a special case – the next longest duration was 73 days) and the minimum was 12 days. I guess I may just be hard to please.
In conclusion: while I think it would be good to keep an eye on green tea as a potential supplement to cancer treatments in the future, this study is not the shining beacon that proves it. For a more balanced appraisal of the evidence then you’ll find in the media, I recommend searching PubMed for metastudies and literature reviews. As I expected, they mostly seem to say that while the pre-clinical (on cells in culture and in model organisms) research looks compelling, there haven’t been enough large, good-quality trials to show anything particularly significant in humans.
P.S. If you are a cancer patient and the sketchy evidence on the benefits of green tea make you decide to drink lots of it, first consider: a) green tea has caffeine – some studies of green tea showed a lot of side effects that were presumably due to the caffeine, and b) EGCG may interact with some cancer drugs, especially Velcade (bortezomib) so consult with your doctor. In general, it is a very bad idea to attempt to treat yourself with the preliminary results of trials of unlicenced treatments. They are unlicensed because their effectiveness, and more importantly their safety, isn’t known.
McLarty, J., Bigelow, R., Smith, M., Elmajian, D., Ankem, M., & Cardelli, J. (2009). Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In v Cancer Prevention Research DOI: 10.1158/1940-6207.CAPR-08-0167