Use of Saw Palmetto Extract for Benign Prostatic Hyperplasia
Use of Saw Palmetto Extract for Benign Prostatic Hyperplasia
January 1998; Volume 1: 1-4
By E.P. Barrette, MD
Many older male patients suffering from benign prostatic hyperplasia/hypertrophy (BPH) are reluctant to start pharmacologic therapy because of what they have learned—mostly through popular media—about the commonly prescribed medications. Indeed, the potential for impotence, syncope, and other side effects intimidates patients. At the same time, these patients are likely to have read or heard about complementary options—extract of saw palmetto berries in particular. Judging from the popularity of saw palmetto products, your patients may already be self treating prostate difficulties with this readily available herbal remedy. While some studies have shown that saw palmetto might be effective for relieving BPH symptoms, clinicians must remember that this herbal preparation can also lower PSA levels and potentially mask prostate cancer.—The EditorHistory of Saw Palmetto
The saw palmetto, a small palm tree, is found along the coastal southeastern United States and the West Indies. It is also known as the American dwarf palm tree, palmetto scrub, sago palm, and Sabal serrulata botanical name). The plant was named after Sereno Watson (Serenoa repens family arecaceae), a nineteenth century Harvard botanist. In early winter, a blue-black fruit appears. The extract from this berry is the major component of most commercial herbal products marketed in Europe for BPH. Phytotherapy is extremely popular in Europe, accounting for more than 90% of prescribed drugs in Germany and 48.6% in Italy.
Folklore
Native Americans used the fruit of S. repens s food. Naturopathic practitioners adopted S. repens or genitourinary tract and prostate disorders.
Mechanism of Action
The purified lipid soluble extract of saw palmetto berry (SPBE) is felt to contain the active agents. It contains 85-95% fatty acids, long chain alcohols, and sterols (beta-sitosterol, stigmasterol, cycloartenol, lupeol, lupenone, methylcycloartenol). The esterified steroids, specifically beta-sitosterol, are the likely active component. Multiple mechanisms have been proposed, but uncertainty still remains. In vitro studies have shown inhibition of 5-alpha-reductase, though variable study design and use of high doses limit their generalizability. Clinical studies did not confirm inhibition of 5-alpha-reductase in men. While a control group treated with finasteride showed an increase in testosterone and decrease in dihydrotestosterone due to inhibition of 5-alpha-reductase, levels in SPBE-treated men did not change. SPBE did not change PSA levels in an open trial.
An alternative mechanism involves changes in steroid receptor levels. A double-blind study examined prostate tissue from 35 men treated with either SPBE or placebo for three months prior to prostatectomy for BPH. A significant decrease in nuclear estrogen receptors, nuclear progesterone receptors, and nuclear androgen receptors was seen in the men treated with SPBE.
Clinical Studies
Early double-blind, randomized, controlled trials (RCT) are limited due to their small sample size and short study duration of three months or less. Six of seven RCTs showed symptom improvement, while five of seven trials showed an increase in flow rate with SPBE. However, a lack of standardized symptom scores (e.g., American Urological Association symptom index)1 hinders interpretation.2 Most of these trials did not show improvement in the placebo arm, while large trials comparing alpha blockade or finasteride vs. placebo have consistently shown a large placebo response.3
Two recent studies have been more rigorous in design. A European multicenter, double-blind RCT compared Permixon (a hexane extract of saw palmetto available in Europe), 160 mg bid, with finasteride, 5 mg daily, in 1098 patients with BPH.4 At six months, both Permixon and finasteride decreased the International Prostate Symptom Score (37% and 39%, respectively; P = 0.17), improved quality of life (38% and 41%; P = 0.14), and increased peak urinary flow rates (25% and 30%; P = 0.035). Discontinuation was higher with Permixon than finasteride (16% vs 11%). The finasteride arm recorded a significant worsening in sexual function scores (8.6 to 9.3, maximum score 20; P < 0.001) compared with Permixon (8.4 to 7.9), although this may not be clinically significant.
Another German multicenter, double-blind RCT in 200 men with BPH followed the recommendations of the International Committee on the therapy of BPH (Second International Consultation, Paris 1993).5 This six-month study compared beta-sitosterol, 20 mg tid, vs. placebo. Harzol, the preparation used in the trial, contains a mixture of 10 mg beta-sitosterol, 0.1 mg beta-sitosterol-beta-D-glucosidase, and lesser amounts of stigmasterol, campesterol, and other sterols. End points matched those in trials of alpha blockers and 5-alpha-reductase inhibitors. Beta-sitosterol-treated patients had significant improvement in Modified Boyarsky score, International Prostate Symptom Score, peak flow, and residual volume. Though Harzol is derived from South African star grass (Hypoxis rooperi, its principal ingredient beta-sitosterol is the same as in saw palmetto.
Adverse Effects
Mild adverse effects have included headache, nausea, and dizziness. Carraro et al noted hypertension in 3.1% of patients receiving Permixon.4 Berges et al and Carraro et al monitored for changes in laboratory values and reported none.4-5 High doses of SPBE reportedly cause diarrhea. Long-term effects on lipids and bone density have not been studied.
Drug Interactions
No serious drug interactions have been reported, although trials have usually excluded men taking diuretics, alpha-blockers, and anticoagulants.
Formulation
Multiple companies promote saw palmetto. A month’s supply of 160 mg twice daily typically costs $10-15. Since many companies will combine saw palmetto berry extract with other ingredients (e.g., Pygeum africanum African plum, cucurbita pepo/pumpkin seed, zinc, etc.) comparison of efficacy and cost is difficult. Capsules containing much greater than 160 mg are available, though no clinical trials have used doses higher than 320 mg/d.
Dosage
Saw palmetto is usually taken 160 mg twice daily.
Conclusion
BPH is the most common benign tumor in men. By age 55, 25% of men complain of a decrease in the force of their urinary stream, and this rises to 50% by age 75. The natural history of BPH over five years is improvement in 40%, no change in symptoms in 45%, and deterioration in only 15%. Typical symptoms include weak stream, hesitancy in initiating urination, dribbling, sensation of not emptying completely, frequency, nocturia, and urgency. The clinical evaluation should rule out alternative diagnoses: urinary tract infection, bladder calculus, urethral stricture, neurogenic bladder, and bladder or prostate cancer. Symptom scoring with a validated instrument (e.g., American Urological Association symptom index) allows one to easily follow disease or treatment course. A clinical guideline developed by a multidisciplinary panel has recommended watchful waiting for men with mild BPH (AUA score 0-7). For men with moderate BPH (AUA score 8-19) shared decision-making is recommended, with watchful waiting, medical therapy, and surgery as options.
Medical therapy includes an alpha-reductase inhibitor, finasteride, or an alpha-blocker (terazosin, doxazosin, prazosin). Finasteride provides symptom improvement though benefit may be limited to men with larger prostates. Finasteride may require six months to effect improvement and may cause sexual dysfunction. Alpha blockade provides more rapid improvement, but dizziness, postural hypotension, and syncope may appear. A recent trial showed terazosin to be more beneficial than finasteride.
One well-controlled trial has shown Permixon to be as effective as finasteride. However, the trial was limited by the lack of a placebo arm. Another rigorous trial of beta-sitosterol demonstrated benefit over placebo. SPBE may provide symptomatic improvement in mild-to-moderate BPH and appears to be safe. However, no long-term (> 6 months) treatment trials have been reported. The only rigorous trials have studied commercial European products, which may be difficult to acquire in the United States.
References
1. Barry MJ, et al. The American Urological Association symptom index
for benign prostatic hyperplasia.
J Urol 992;148:1549.
. Lowe FC, et al. Phytotherapy in treatment of benign prostatic hyperplasia: A critical review. Urology 996;48:12.
. Hansen BJ, et al. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia. Scand J Urol Nephrol 996;30:373.
4. Carraro JC, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: A randomized international study of 1098 patients. Prostate 996;29:231.
5. Berges RR, et al. Randomized, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet 995;345:1529.
Dr. Barrette is Assistant Professor of Medicine, University of Washington Medical Center, Seattle.
January 1998; Volume 1: 1-4Subscribe Now for Access
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