The New England Journal of Medicine (NEJM) recently released the results of a clinical trial conducted on saw palmetto (Serenoa repens), concluding that it is ineffective for problems associated with benign prostatic hyperplasia (BPH). This study (Bent S. et al. Saw palmetto for benign prostatic hyperplasia. NEJM 354(6):557-566) was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Complementary and Alternative Medicine. According to many of the dietary supplement trade associations, these recent findings are inconsistent with benefits demonstrated by other studies.

Saw palmetto—the third highest-selling herbal dietary supplement in the U.S.—is used by over two million American men for the treatment of mild to moderate symptoms associated with BPH and is commonly recommended as an alternative to drugs. BPH is a non-cancerous swelling of the prostate gland in older men, resulting in various symptoms associated with interruption of normal urinary flow.

The double-blind trial published in NEJM randomly assigned 225 men over the age of 49 years who had moderate-to-severe
symptoms of BPH to one year of treatment with saw palmetto extract (160 mg twice daily) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values and the rates of reported adverse effects.

The results of the trial suggested there were no significant differences between the saw palmetto and placebo groups in the change in AUASI scores, maximum urinary flow rate, prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen (PSA) levels. Therefore, the study concluded that the saw palmetto was no more effective than placebo in treating symptoms of BPH.

Various industry groups quickly responded to these findings. They claim that the results of this trial are misleading due to improper controls and other issues. The main flaw many cited was the fact that the study examined men with moderate-to-severe symptoms of BPH, while a majority of previous trials showed positive results and efficacy for saw palmetto among men with mild-to-moderate symptoms.

“Since the study raised the bar from mild-to-moderate symptoms to moderate-to-severe, the researchers should have also had a third arm in the trial testing a higher dosage to see if there was a dose-response relationship at that level,” said Mark Blumenthal, founder and executive director of American Botanical Council (ABC), Austin, TX.

Andrew Shao, PhD, vice president, Scientific & Regulatory Affairs, Council for Responsible Nutrition (CRN), Washington, D.C. also found the result from this study particularly puzzling. “Science is an evolutionary process. Given that more than 20 studies have shown promising findings for saw palmetto in alleviating symptoms commonly associated with prostate problems, such as frequent urination, a low stream of urination, and a feeling of heaviness in the prostate, it is inappropriate to simply discount the benefits previously found.”

Indeed, a recent meta-analysis of 18 clinical trials published in the
Journal of the American Medical Association and another on 21 clinical trials carried out on over 3000 men as reviewed by the Cochrane Collaboration have confirmed the safety and efficacy of saw palmetto extract in treating symptoms of BPH, usually of stage 1 and 2 (the mild-to-moderate range of BPH symptoms). The latest meta-analysis also concludes that saw palmetto preparations have shown efficacy and greater safety when compared to conventional pharmaceutical drugs.

ABC pointed out another anomaly of the trial—the significantly higher adverse effect profile in the placebo group. Saw palmetto preparations are known to be safe and very well tolerated, producing few adverse effects. However, there were almost twice as many serious adverse effects in the placebo group (11) as in the saw palmetto group (6), suggesting that the patient population may have had other serious illnesses, possibly interfering in the attempt to treat the BPH symptoms.

Daniel Fabricant, vice president of science and quality assurance, National Nutritional Foods Association (NNFA), Washington, D.C., cited the lack of a positive control, like a conventional pharmaceutical intervention, in the study design as contributing to the questionable outcomes of the study. “If CAM (complementary and alternative medicine) therapies are going to be evaluated with the accepted scientific yard stick, then the accepted tool must be used, which is a randomized, placebo- and positive-controlled clinical trial,” Mr. Fabricant said.

NNFA also faulted the study’s measurement of only one hormonal marker associated with BPH. “The scientific explanations behind BPH are diverse and evolving,” Mr. Fabricant said. “For instance, research indicates that estrogen may lead to abnormal cell proliferation in the prostate. Also, genetic variations in steroid receptor expression in individuals, as well as the ratios of other hormones such as DHT, to estrogens are factors that may all play a role in the occurrence of BPH. The authors only provide testosterone as a sole hormonal marker related to BPH, which, in light of current research on BPH, does not present an adequate scientific window to view the whole scene.”

ConsumerLab.com, White Plains, NY, noted that the investigators in the study did not confirm the product they used contained proper amounts of the specific fatty acids and sterols expected in saw palmetto. A deficit in these compounds, the company said, could potentially reduce the potency of the product. The investigators in this trial only evaluated the total (combined) amounts of the compounds, not the specific fatty acids and sterols.

According to a letter sent to the editor of NEJM from Tod Cooperman, MD, president, and William Obermeyer, PhD, vice president for research, ConsumerLab.com: “The results of the study by Bent et al would be more meaningful had the test material been shown to match the full chemical profile of authentic saw palmetto. This should be done in all studies of botanicals, but often is not.”