Kathy E. Acquistapace, DC, NHP, CNC
The media recently reported upon a new study on saw palmetto that showed inconsistent conclusions to those already found in the existing body of scientific literature. The trial, published the week of February 5, 2006 in the New England Journal of Medicine, tested the effectiveness of saw palmetto in relieving symptoms of benign prostatic hyperplasia. The National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Complementary and Alternative Medicine funded the study.
In the double-blind trial, conducted at the University of California at San Francisco, 225 men (112 in the saw palmetto group; 113 in the placebo group) 49 years of age or older with moderate to severe BPH were randomly assigned to groups who took a leading saw palmetto extract (160 mg twice per day, the normal dose shown effective in over 21 clinical trials) or a matching placebo capsule. The patients made 8 study visits over a one-year period to assess changes in the AUASI scores (the American Urological Association Symptom Inventory, the primary outcome of the trial), maximal urine flow, post-void residual urine volume, prostate size, and other health-related outcomes. On average, participants in both the saw palmetto and the placebo groups improved over the one-year duration of the trial, but there were no significant differences in the rates of improvement overall between the two groups as measured by the AUASI.1
At first glance, it would seem that saw palmetto is completely ineffective—until one analyzes the group of patients studied. According to Dr. Michael T. Murray, N.D., “All this new study of saw palmetto extract tells us is that it is important to use it early in the disease process. It tells us nothing new as detailed double-blind studies have clearly shown that roughly 90 percent of men with mild to moderate BPH experience improvement in symptoms during the first four to six weeks after starting saw palmetto extract (320 mg per day of the liposterolic extract). The key is to start saw palmetto as soon as symptoms of BPH appear. If a man waits until his prostate has enlarged so severely that it results in significant obstruction of the bladder, saw palmetto is simply not likely to work. But, if he starts it early enough it may actually works as effectively as popular prescription drugs without the side effects.” 2
"The results from this study are particularly puzzling," said Andrew Shao, Ph.D., vice president, Council for Responsible Nutrition (CRN), "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. 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."
Dr. Shao called the trial "well-designed and well implemented" but, like Dr. Murray, noted that the disappointing conclusions may have resulted from an inappropriate study population. The study examined men with moderate-to-severe symptoms of benign prostatic hyperplasia (scores between 8-35 according to the AUASI), when most of the literature cites positive results among men with mild-to-moderate symptoms. "It may be," said Dr. Shao, "that exclusion of those patients with mild symptoms from the study may have reduced the ability to detect the benefits we've seen in other trials. Future trials need to explore in more detail the response of those with both mild and moderate symptoms."3
“Our primary concern with this trial is the relatively advanced condition of the prostate problems in many of the men who were tested,” agreed Mark Blumenthal, Founder and Executive Director of the American Botanical Council. “Most of the official international monographs that recognize the benefits of saw palmetto do so for stage 1 and 2 of BPH, i.e., the mild to moderate range of BPH symptoms. These include monographs from the German government and the World Health Organization.”
Blumenthal added, “The results of this trial need to be seen in the perspective of the preponderance of the existing evidence, including at least 21 controlled trials showing positive outcomes with saw palmetto preparations.”
What’s more, in the new trial reported in NEJM, which used a high quality saw palmetto extract, there was a 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. In this trial, minor adverse effects in the saw palmetto and placebo groups were nearly equal (saw palmetto, 39; placebo, 34) — evidence of the safety of saw palmetto. 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 moderate-to-severe BPH symptoms.3
About Saw Palmetto
Saw palmetto (Serenoa repens) preparations are made from the fruit of a small palm tree, native to Florida, which was a former staple food of Seminole Indians. Saw palmetto berries were widely used by eclectic physicians of the late 19th and early 20th centuries for a variety of indications, including treating the male reproductive system.
Extracts of saw palmetto berry are used extensively throughout the world for the relief of BPH. Saw palmetto extracts are widely used in Europe and in the past decade in the United States as a natural way to help maintain normal prostate and urinary function, particularly by treating the symptoms of BPH in men with mild to moderate cases of BPH. Both the French and German governments approve lipo-philic extracts of saw palmetto berries for this purpose. Saw palmetto reduces prostate hypertrophy by blocking the conversion of testosterone to dihydrotestosterone (DHT) by inhibiting 5-alpha reductase and by preventing the binding of DHT to androgen receptor cell sites. These actions increase DHT breakdown and excretion. Saw palmetto also interferes with the actions of inflammatory substances that contribute to prostate inflammation and reduces the pro-hypertrophic effects of estrogen and progesterone on the prostate.
Clinical Trials
Positive results with saw palmetto have been confirmed in numerous open as well as double-blind, placebo-controlled clinical trials. All of these studies demonstrated statistically significant improvements in BPH symptoms, which included increased volume and rate of urine flow, alleviation of pain and night time urination, and reduced number of voidings per day. Overall, these studies showed a consistent benefit of saw palmetto extract, with virtually no side effects of any consequence. A striking characteristic of these studies is that most subjects experienced relief within days of beginning the therapy, with benefits continuing to improve over time — in many cases, as much as one year of continuing improvement! Most studies however, were terminated after 30, 60 or 90 days.4
A meta-analysis (statistical analysis of a group of studies) of 18 clinical trials published in the Journal of the American Medical Association and another on 21 clinical trials carried out on over 3,000 men as reviewed by the Cochrane Collaboration have confirmed the safety and efficacy of saw palmetto extract preparations in treating symptoms of BPH, usually of stage 1 and 2. The latest meta-analysis concludes that the clinical literature supports the use of saw palmetto preparations in treating symptoms of BPH in stages 1 and 2, and that saw palmetto preparations have shown efficacy and greater safety when compared to conventional pharmaceutical drugs.5-6
The safety and efficacy of saw palmetto preparations have gained international recognition by various governments and professional health groups. Saw palmetto has been approved by the German government’s respected Commission E and the Canadian government’s Natural Health Products Directorate. It is also recognized by leading scientists and physicians in Western Europe through a positive monograph by the European Scientific Cooperative on Phytotherapy (ESCOP), which acknowledges its efficacy for symptomatic treatment of micturition (urinary) disorders in mild to moderate BPH. The World Health Organization also recognizes the efficacy of saw palmetto for treating lower urinary tract symptoms secondary to BPH stages I and 2. Additional recent reviews of the medical and scientific literature have concluded that saw palmetto extract preparations are safe and effective for treating symptoms of BPH.7-10
In one recent study, it was found that saw palmetto treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelial cells.11
In another 6-month randomized trial, researchers studied the underlying mechanism of how saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia. At baseline, the two groups were similar in age (65 versus 64 years), and symptoms (International Prostate Symptom Score 18 versus 17). Comparing prostatic tissue of 20 men consuming SPHB and 20 men consuming a placebo, scientists found that SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect was found.12
Conclusion
The NEJM article cited a 2002 survey showing that about 2.5 million men were estimated to have been using saw palmetto preparations. Clearly, there is a large body of prior research that supports the widespread use of this botanical. The vast majority of the research demonstrates that saw palmetto works well when used appropriately and doesn’t seem to cause any dangerous side effects.
References
1. Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, et al. Saw Palmetto for Benign Prostatic Hyperplasia. New Engl J Med. Feb 9, 2006;354(6):557-566.
2. Murray M. Natural Facts Newsletter. Feb 15, 2006.
3. Staff, et al. New Study on Saw Palmetto Demonstrates Puzzling Results—Findings Inconsistent with Benefits Demonstrated by Other Studies. PR Newswire. Feb 9, 2006.
4. Dean W. Benign Prostatic Hypertrophy. Vitamin Research News. August 2005.
5. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 1998;280(18):1604–1609.
6. Wilt T, Ishani A, Mac Donald R. Serenoa repens for benign prostatic hyperplasia. The Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD001423. DOI: 10.1002/14651858.CD001423.
7. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs -Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communication; 1998.
8. Health Canada Natural Health Products Directorate. Monograph – Saw Palmetto May 1, 2004. Accessed Feb. 6, 2006.
9. ESCOP. Serenoae Repentis Fructus (Sabal Fructus). In: ESCOP Monographs: The scientific foundation for herbal medicinal products. New York: Thieme Publishers; 2003:477-486.
10. . WHO. Fructus Serenoae Repentis. World Health Organization Monographs on Selected Medicinal Plants, Vol.2. Geneva: World Health Organization; 2002:285-299.
11. Wadsworth T, Carroll J, Mallinson R, Roberts, C, Roselli C. Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-jun n-terminal kinase phosphorylation in human prostate epithelial cells. Endocrinology. 2004;145(7):3205-3214.
12. Chavez, ML and Chavez, PI. Saw Palmetto. Hospital Pharmacy. 2001 Jun; 33(11):1335-1361.
