By Len Monheit
This past week saw the publication of another blow to the herbal sector as the New England Journal of Medicine published a study (http://content.nejm.org/cgi/content/short/354/6/557) on 225 men with moderate to severe benign prostatic hyperplasia (BPH) who received either 160mg of saw palmetto or placebo for one year. The researchers concluded that there was no difference in symptom changes between the group taking saw palmetto and those receiving placebo, contradicting previous research. The results were measured as symptom changes including maximal urinary flow rate, prostate size, PSA levels and quality of life, with no significant difference observed in any measurement, nor according to the release issued by study supporter, Kaiser Permanente (http://www.npicenter.com/anm/templates/newsATemp.aspx?articleid=14844&zoneid=28), the results also showed no difference when subgroups of patients with different levels of symptom severity or different prostate sizes were examined.
Media pick up on this story has been quite predictable, implying that yet another herb has been found wanting when a ‘properly’ designed and managed trial has examined the efficacy of an herbal product. The more kind of the treatments observe things like “Saw palmetto questioned as prostate treatment” and “Men who take the popular herbal remedy saw palmetto for their enlarged prostate may be needlessly shrinking their wallets, according to the most comprehensive study yet of the herb.” (Reuters)
Various groups within the industry were quick to respond with the American Botanical Council (ABC), Council for Responsible Nutrition (CRN), National Nutritional Foods Association (NNFA) and American Herbal Products Association (AHPA) all issuing releases, and product testing company Consumerlab.com also provided input into the issue.
ABC observed that the results of the new clinical trial might confuse the public, especially men with prostate problems. They described the study as well designed, and believed it employed a high quality extract, but noted that men in this trial experienced moderate to severe symptoms of BPH, although most of the previous controlled trials showing positive results and efficacy for saw palmetto were conducted on men with mild to moderate symptoms of BPH. In examining serious adverse events, ABC observed that there were twice as many serious adverse events in the placebo group as in the saw palmetto group, suggesting other serious health issues might have been present in the population. ABC presented a list of references including monographs from the German government, the World Health Organization and Canada's Natural Health Products Directorate.
CRN emphasized how puzzling there results were – in light of previous clinical studies, and also noted the study’s population. Specifically, Andrew Shao, Ph.D., CRN vice president said, “While this trial is an important piece of research, it should by no means close the book on saw palmetto research. Science is an evolutionary process, so it is inappropriate to simply discount the benefits previously found.”
NNFA, in a release entitled “Dietary Supplement Industry Claims Saw Palmetto Study Misleading” pointed out what it called a number of flaws in the study, including the substantial existing body of clinical studies, some with larger patient populations, which support efficacy for mild to moderate symptoms. Issue which NNFA pointed out was the lack of a positive control (such as a pharmaceutical intervention), as well as the lack of evidence of effective chemical and biological standardization of the test materials used in the study. NNFA also raised the possibility that the placebo was not determined to be inactive as well as the fact that only one hormonal marker associated with BPH was measured.
AHPA’s release focused on the fact that the current study needs to be considered in the totality of clinical research on saw palmetto, including specifically 2002 meta-analysis of 21 previous studies ((Wilt T, Ishani A, MacDonald R. Serenoa repens for benign prostatic hyperplasia. The Cochrane Database of Systematic Reviews 2002;(3):CD001423)) which concluded that the evidence ““suggests that Serenoa repens provides mild to moderate improvement in urinary symptoms and flow measures [and] produced similar improvement in urinary symptoms and flow compared to finasteride [a drug often prescribed for BPH] and is associated with fewer adverse treatment events.” AHPA also points out that since there was no difference in apparent risk of serious adverse events between treatment and placebo groups, the study does support the safety of saw palmetto.
Interestingly, the Kaiser Permanente release directly challenged previous studies, asserting that placebos might not have been adequately formulated to blind participants, claiming that the placebo might not have duplicated the strong taste and smell of the herb, influencing the results. Kaiser also commented on small previous study size and duration.
Consumerlab.com also contributed to the dialogue, using its recently released prostate products review as an example. They noted that the investigators did not confirm that the product they used contained proper amounts of the specific fatty acids and sterols expected in saw palmetto. The investigators confirmed total fatty acids and sterols but not the expected 13 specific fatty acids and sterols contained in the full chemical profile. As it turns out, this very issue was the cause of one product failing the recent Consumerlab.com testing – it was found to contain the right total fatty acids, but had olive oil in it instead.
This current dialogue points out several issues, some of which are noted in the various industry releases. Science is an evolving frontier and new information continuously appears and must be evaluated in its appropriate context. The sum total of evidence (pro and con) must be weighed. Consistent end points must be used for data to be pooled or summed or for a comparison to be made between results. A perfectly characterized and qualified product must be used in research. (Otherwise however will we duplicate it) How often have we heard the claim that the characterization of a research material is too cumbersome or ourselves tried to use the argument or implication that because one special standardized extract works in a study, then all ginseng, ginkgo or other extracts are effective. (piggybacking on other’s science) Ironic isn’t it?
The reality of it is that we can’t have it both ways, choosing arguments from each side to support our beliefs. Any study has its limitations and context, any report of the study has its inherent bias. And media messaging is something that industry certainly can’t control.
Where do we stand?
- There is another study on saw palmetto on record, adding to the body of science.
- The importance of condition and population groups has been raised again (as it was in the case of St. John’s wort a few years ago).
- Industry has acknowledged the study and critiqued it – exactly as others have been observed to do with industry research
- Be careful what you wish for – we’ve asked for more science on herbs to be supported and with more science certainly comes neutral, negative or simply unexpected results. We’ll have to get used to that as industry continues to grow.
On the flip side, this result and its pickup certainly doesn’t do any good to the sector and confidence in product efficacy. Some can make an argument though that, since safety was assured, even in the current study, the core consumers currently using the product will continue to do so. The missed opportunity is for conversion of fence-sitters or non-believers in herbal or supplement approaches, those seeking solid evidence to support a move to these products. In market terms, this means no new growth, but probably no sharp fall off either. Time will tell.
The fact that the industry groups responded as they did is encouraging. The outcome of the entire experience hopefully is “more research required”.