Saw Palmetto

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Serenoa repens (W. Bartram) Small (syn. Sabal serrulata [Michx.] Nutt. ex Schult. & Schult. f.; Serenoa serrulata (Michx.) G. Nichols.

[Fam. Arecaceae]

Overview

Saw palmetto is a small, low-growing, dwarf-palm tree, native to southeastern North America, particularly Florida. The berries were a staple food and medicine of the indigenous Floridians before the Europeans’ arrival (Duke, 1985; Vogel, 1970). Indigenous Americans prepared an aqueous infusion of the berries to treat stomachache and dysentery (Duke, 1985). They also used the fruit as a diuretic and sexual tonic (Duke, 1985). Since the mid-1990s, saw palmetto has been one of the ten top-selling herbs in the U.S. (Blumenthal et al., 1998; Blumenthal, 2001). Total sales in mainstream retail stores in 2000 in the U.S. were over $43 million, ranking saw palmetto sixth in total herb sales (Blumenthal, 2001). In Europe saw palmetto extract is the most commonly used phytotherapeutic agent for benign prostatic hyperplasia (BPH) (Di Silverio et al., 1993), and in Germany it is one of the most frequently prescribed botanical preparations (Blumenthal et al., 1998). Saw palmetto berry was commonly recommended for various prostatic conditions by healthcare professionals in the early part of the 20th century. It was an official drug, listed in the United States Pharmacopeia (USP) from 1906 to 1916 and in the National Formulary (NF) from 1926 to 1950 (Boyle, 1991) before its use as a therapeutic option for urinary tract disorders by the medical community declined in the U.S. (Tyler, 1994). In the 20th century, the United States Dispensatory, 23rd edition, included saw palmetto with an indication for treatment of enlargement of the prostate gland (Wood and Osol, 1943).

Description

Saw palmetto preparations consist of the berry (fruit) of Serenoa repens (W. Bartram) Small (syn. Sabal serrulata) [Fam. Arecaceae] or its extracts.

Primary Uses

Prostate

Benign prostatic hyperplasia (BPH) (Marks et al., 2001, 2000; Ziegler, 1998; Redecker, 1998; Di Silverio et al., 1998; Braeckman et al., 1997; Bach and Ebeling, 1996; Kondás et al., 1996; Carraro et al., 1996; Braeckman, 1994; Casarosa et al., 1988; Champault et al., 1984). The German Commission E approved the use of saw palmetto for mild to moderate BPH stages I and II (Blumenthal et al., 1998).

Dosage

Internal

Crude Preparations

Cut fruit and other equivalent galenical preparations: 1–2 g (Blumenthal et al., 1998).

Crude berries: 10 g twice daily (Pizzorno and Murray, 1999).

Fluid extract: 1:1 (g/ml), 1–2 ml twice daily; 1:2 (g/ml) 2–4 ml twice daily (Blumenthal et al., 2000).

Soft native extract: 10:1–14:1 (w/w), contains approximately 85–95% fatty acids, 160 mg twice daily (Blumenthal et al., 2000) or 320 mg once daily (Braeckman et al., 1997).

Dry normalized extract: 4:1 (w/w) contains approximately 25% fatty acids, 400 mg twice daily (Blumenthal et al., 2000).

Tea: Not effective because the lipophilic-active constituents are insoluble in water (Bratman and Kroll, 1999).

Note: Most clinical trials have been conducted with native extract.

Duration of Administration

Research suggests that, four to six weeks of treatment are needed for a therapeutic effect (Braeckman, 1994; Champault et al., 1984).

Chemistry

The main constituents of saw palmetto include carbohydrates (inert sugar, mannitol, high-molecular-weight polysaccharides with galactose, arabinose, and uronic acid), fixed oils (free fatty acids and their glycerides), steroids, flavonoids, resin, pigment, tannin, and volatile oil (Newall et al., 1996). The fruits and seeds are rich in triacylglycerol-containing oil (50% of the fatty acids contain 14 or less carbons) (Bruneton, 1999). The liposterolic fraction is the primary active component. A recent systematic review described the chemistry of saw palmetto fruit and related species at different dates of maturity, dosage forms and commercial products, and fruit samples from other species of palm in order to help control the quality of commercial products (Peng et al., 2002).

Pharmacological Actions

Human

Anti-estrogenic activity (Di Silverio et al., 1992); increases urinary flow rate (Redecker, 1998; Ziegler and Holscher, 1998; Braeckman et al., 1997); decreases residual urine (Redecker, 1998; Ziegler and Holscher, 1998; Braeckman et al., 1997); decreases painful urination (Champault et al., 1984); decreases nocturia (Boyle et al., 2000; Ziegler and Holscher, 1998; Vahlensieck et al., 1993a, 1993b); anti-inflammatory (Ziegler and Holscher, 1998); anti-exudative (Ziegler and Holscher, 1998).

Animal

Anti-androgenic in rats (Carilla et al., 1984); relaxes smooth muscle in rats (Gutierrez et al., 1996); anti-edemic (Stenger et al., 1982).

In vitro

Anti-inflammatory (Breu et al., 1992).

Mechanism of Action

Human

Lowers DHT levels in prostate tissue (Marks et al., 2001).

Animal

Suppresses prostatic epithelium through a nonhormonal mechanism (Epstein et al., 1999).

Reduces dihydrotestosterone (DHT) in prostate tissue, which has been implicated as a causative factor of BPH in vivo (Koch and Biber; 1994).

Competes with endogenous estrogen for receptor sites (Di Silverio et al., 1992).

Induces apoptosis and inhibits cell proliferation in prostate epithelium and stroma (Vacherot et al., 2000).

In vitro

The following mechanisms are based on results from in vitro studies using supraphysiologic dosages.

Inhibits action of 5a-reductase, which catalyzes the metabolism of testosterone to DHT (Bayne et al., 2000; Chavez and Chavez, 1998; Marks et al., 2000; Sultan et al., 1984), due to the free fatty acid content of the fruit’s lipophilic extracts (Niederprüm et al., 1994; Weisser et al., 1996).

Inhibits receptor binding of androgens (Chavez and Chavez, 1998; Sultan et al., 1984).

Inhibits noncompetitively human a1-adrenoreceptors in vitro (Goepel et al., 1999).

Inhibits both the cyclooxygenase and lipoxygenase pathways in vitro (Breu et al., 1992).

Inhibits growth factors in vitro (Plosker and Brogden, 1996).

Binds selectively to and increases apoptic index for prostate cells in vitro (Bayne et al., 2000).

Contraindications

Saw palmetto is not indicated for advanced BPH with severe urinary retention. It should not be used without first ruling out prostate cancer (Bratman and Kroll, 1999). For this reason, the German Commission E clarifies that saw palmetto relieves only the symptoms associated with BPH and recommends consulting a healthcare provider at regular intervals (Blumenthal et al., 1998).

Pregnancy and Lactation: No known restrictions (Blumenthal et al., 2000), although saw palmetto is seldom used by women. Due to potential hormonal activity, saw palmetto is not recommended for pregnant or lactating women, though this has not been confirmed by scientific studies (Blumenthal and Riggins, 1997; Newall et al., 1996; Elghamry and Hänsel, 1969).

Adverse Effects

Rare cases of gastrointestinal disturbance have been reported (Blumenthal et al., 1998). Ingestion on an empty stomach may cause nausea (Bruneton, 1999). Hypertension was reported in 3.1% of patients taking the saw palmetto extract Permixon^® (a proprietary form of saw palmetto) (Carraro et al., 1996), although hypertension is not a generally reported effect associated with the use of saw palmetto, either from clinical trials or case reports. The general safety profile of saw palmetto extracts has been shown to be better than finasteride (Wilt et al., 1998). Sexual dysfunction was less common with saw palmetto (p<0.001), and the herb has not been associated with erectile dysfunction, ejaculatory disturbance, or altered libido (Wilt et al., 1998). Gastrointestinal disturbances, urinary tract infections, ejaculation problems, and impotence were reported in 2% of patients taking saw palmetto in a clinical trial on 315 men with BPH stage II or III over three years (Brach and Ebeling, 1996). Other trials have noted mild GI upset in a small percentage (1.3%) of patients (Wilt et al., 1998).

Drug Interactions

There are no known interactions associated with saw palmetto (Brinker, 2001). Most clinical trials excluded men taking diuretics, alpha blockers, and anticoagulants; thus, the potential for drug-herb interactions cannot be dismissed, though none have been reported by patients or healthcare providers. A review of the literature does not reveal evidence of adverse drug interactions between saw palmetto and conventional drugs. In vitro, saw palmetto potentially inhibits the binding of a1-adrenoceptor antagonists (e.g., tamsulosin and prozacin) and calcium mobilization; the clinical relevance has not been confirmed (Brinker, 2001).

American Herbal Products Association (AHPA) Safety Rating

Class 1: Herbs that can be safely consumed when used appropriately. The editors note that rare cases of stomach problems have been recorded and that the German Commission E suggests regular consultation with a healthcare provider when using saw palmetto for treatment of enlarged prostate, based on the assumption that it treats only the symptoms without eliminating hypertrophic concern (McGuffin et al., 1997).

Regulatory Status

Canada: Approved active ingredient in over 45 licensed products including some Traditional Herbal Medicines (THMs). Natural Health Products (NHPs) and homeopathic medicines (Health Canada, 2002).

France: Authorized as a prescription drug reimbursable by the national health insurance (Chauvarie, 2001).

Germany: Dried fruit and other galenical preparations or lipophilic extracts are approved by the Commission E as non-prescription drugs (Blumenthal et al., 1998). Fresh ripe fruit for preparation of mother tincture and liquid dilutions are official in German Homeopathic Pharmacopoeia (GHP, 1993).

Belgium: Approved as a prescription adjuvant in BPH treatment.

Italy: Authorized as a registered drug only (Ris, 2001).

Sweden: Classified as Natural Remedy for self-medication requiring premarketing authorization. Two combination products, Curbicin^® with pumpkin seed (Curcubita pepo) and Prostakan^® with nettle root (Urtica dioica), are registered in the Medical Products Agency (MPA) “Authorised Natural Remedies” with the approved indication: “Traditionally used in case of micturition problems caused by benign prostatic hyperplasia, e.g. frequent need to urinate and nocturia. Prior to treatment other serious conditions should have been ruled out by doctor” (MPA, 2001). A product monograph for Curbicin^® and a document discussing the risk for an anticoagulation effect are included (MPA, 2000, 1999).

Switzerland: Herbal medicine with positive classification (List D) by the Interkantonale Konstrollstelle für Heilmittel (IKS) and corresponding sales Category D with sale limited to pharmacies and drugstores, without prescription (Morant and Rupanner, 2001; Ruppanner and Schaefer, 2000). Three saw palmetto monopreparation phytomedicines, six polypreparations (i.e., multi-ingredient products), and 12 saw palmetto homeopathic preparations are listed in the Swiss Codex 2000/01 (Ruppanner and Schaefer, 2000).           

U.K.: Herbal Medicine on the General Sale List, Table A (internal or external use), Schedule 1 (requires full Product License) (MCA, 2002).

U.S.: Dietary supplement (USC, 1994). In view of the levels of evidence in clinical trials of “moderate scientific quality” indicating that commercial extracts of saw palmetto are more effective than placebo to treat symptoms of BPH, the United States Pharmacopeia (USP) moved saw palmetto preparations from National Formulary (NF) status to inclusion into the USP. This is the first time this has been done for an herb formerly classed only as a dietary supplement. This USP status is designated only for articles that are either approved by the Food and Drug Administration and/or have a USP-accepted use (USP, 2002). The mother tincture 1:10 (w/v), 65% alcohol (v/v), of ripe fruit, is an OTC Class C drug official in Homeopathic Pharmacopoeia of the United States (HPUS, 1992).

Clinical Review

Nineteen studies are outlined in the following table, “Clinical Studies on Saw Palmetto,” including 7,210 participants. All but two (Gerber et al., 1998; Champault et al., 1984), demonstrated positive effects for BPH. Numerous studies concluded that saw palmetto improves symptoms of BPH including one randomized, single-blind, placebo controlled, parallel group multi-center study (R, SB, PC, PG, MC) (Braeckman et al., 1997), two open-label (OL), MC studies, (Braeckman, 1994; Ziegler and Holscher, 1998), an R, DB, controlled study (Carraro et al., 1996), a R, comparative study (Di Silverio et al., 1998), a prospective MC study (Bach and Ebeling, 1996), a R, PC study (Champault et al., 1984), and two observational studies (Vahlensieck et al., 1993a and 1993b). Two OL studies found positive results (Kondás et al., 1996; Redecker, 1998), but another OL study failed to find significant improvement in objective measures of bladder outlet obstruction (Gerber et al., 1998). Similarly, one DB, C study found no difference between saw palmetto and placebo (Reece et al., 1986). Several clinical trials (Carraro et al., 1996; Rhodes et al, 1993; Strauch et al., 1994) have shown that serum levels of testosterone, dihydrotestosterone, and prostate-specific-antigen (PSA) are not changed significantly. One PC study looked at hormone levels, finding no changes in testosterone, luteinizing hormone (LH), or follicle stimulating hormone (FSH) levels (Casarosa et al., 1988).

It is well-accepted that at least 30–50% of BPH patients report an improvement in their symptoms after treatment with placebo (Bruneton, 1999). This percentage is about the same after simple monitoring (Chapple, 1993). Two meta-analyses of 18 R, PC trials concluded that saw palmetto treatment for at least 30 days improves urologic symptoms and flow measures (Wilt et al., 1998, 2000). Adverse effects were mild and infrequent. The authors concluded that further research is needed using standardized preparations to determine saw palmetto’s long-term effectiveness and ability to prevent BPH complications. Another meta-analysis (Boyle et al., 2000) focused on 11 R clinical trials and two OL trials using saw palmetto extract on men with BPH. The analysis concluded that saw palmetto compared to placebo provided significant improvement in the peak urinary flow rate and a reduction in nocturia.

Some anecdotal reports state that saw palmetto can mask prostate cancer by lowering PSA levels. However, several large studies including a total of 1,256 patients did not show this effect (Carraro et al., 1996; Braeckman, 1994). Originally, it was thought that saw palmetto relieves the symptoms associated with an enlarged prostate without reducing the enlargement (Blumenthal et al., 1998). However, a recent study has detected shrinkage of the epithelial tissue in the transition zone of the gland (Marks et al., 2000; Marks and Tyler, 1999). Further studies are needed to confirm the finding.

A meta-analysis of recent PC trials included seven clinical studies (Boyle et al., 2000). All trials lasted three months, and indicated a decrease in nocturia frequency (0.5 times per night) and an increase in the peak rate of urinary flow rate by 1.5 ml/second over placebo. A six-month, R, DB, PC study (Carraro et al., 1996) comparing Permixon^® and finasteride (Proscar^®) included 951 patients with BPH, and showed an equally improved symptom score in both groups (37% with Permixon^® vs. 39% with finasteride), and equally improved peak urinary flow rates. One of the first U.S. trials (Gerber et al., 1998) reported symptomatic, but not urodynamic, improvement in 46 men treated for six months with a saw palmetto berry extract.

Five studies focused on a saw palmetto and nettle combination for BPH symptoms. One R, DB, PC study on the Nutralite^® product examined use of a saw palmetto, nettles, lemon bioflavonoid extract, and vitamin A combination, and found significant improvement in prostate epithelial contraction without adverse effects (Marks et al., 2000). The same combination produced a 32% reduction in dihydrotestosterone levels compared to baseline in six months in prostate tissue extracted via needle biopsy (Marks et al., 2001). Four well-designed studies on the fixed combination, PRO 160/120^®, ranging from 12 weeks to one year, found good efficacy and tolerance (Sökeland, 2000; Sökeland and Albrecht, 1997; Metzher et al., 1996; Schneider et al., 1995).

Branded Products*

IDS 89: Strathmann AG & Co. / Sellhpsweg 1 / 22459 / Hamburg / Germany / Tel: +49-401-55-9050 / Fax: +49-40-55-9051-00 / www.strathmann.de / Email: info@strathmann.de.

LG 166/S: Laboratori Guidotti S.p.A, Via Trieste 40 56126 Pisa, Italy / Tel: +39-05-05-0521-1 / Fax: +39-05-04-0250 / Email: a.viti@giofil.it / www.giofil.it. 160 mg liposterolic extract.

Nutrilite^® Saw Palmetto with Nettle Root: Nutrilite^® / 5600 Beach Blvd. / Buena Park, CA 90622 / U.S.A. / Tel: (714) 562-6200 / www.nutrilite.com. One tablet contains 106 mg saw palmetto lipoidal extract and 80 mg nettle root extract.

Permixon^®: Pierre Fabre Médicament / 45, Place Abel-Gance / 92654 Boulogne / France / Tel: +33-01-49-10-8000 / Fax: +33-01-49-10-9712 / www.dermaweb.com. Liposterolic hexane extract of saw palmetto berries, comprised of free (90%) and esterified (7%) fatty acids, sterols, polyprenic compounds, and flavonoids. This extract was the template for current liposterolic extracts manufactured using either ethanol or carbon dioxide extraction.

PRO 160/120^®: Dr. Willmar Schwabe Pharmaceuticals / International Division / Willmar Schwabe Str. 4 / D-76227, Karlsruhe / Germany / Tel: +49-721-4005 ext. 294 / www.schwabepharma.com / Email: melville-eaves@schwabe.de. Fixed combination of 160 mg of saw palmetto extract (WS 1473), 10–14.3:1, and 120 mg of stinging nettle root (Urtica dioica) dry extract (WS 1031), 8.3–12.5:1.

Prostagutt^® (a.k.a. WS 1473): Dr. Wilmar Schwabe Pharmaceuticals. Liposterolic extract made from alcohol extraction.

Prostagutt^® forte: Dr. Willmar Schwabe Pharmaceuticals. Fixed combination of 160 mg of saw palmetto extract (WS 1473), 10–14.3:1, and 120 mg of stinging nettle root (Urtica dioica) dry extract (WS 1031), 8.3–12.5:1.

Prostaserene^®: Therabel Research / Egide Van Ophemstraat 110 / 1180 / Bruxelles / Belgium / Tel: +32-02-370-4611 / Fax: +32-02-370-4690. Liposterolic extract of saw palmetto berries.

Solaray^® Saw Palmetto: Nutraceutical Corporation / 1400 Kearns Blvd / Park City, Utah 84060 / U.S.A. / Tel: 800-669-8877 / www.nutraceutical.com. Each 160-mg gelcap contains 85%-95% (approximately 136 mg) essential fatty acids and steroids.

Strogen forte^®: Strathmann AG & Co. The liposterolic extract is produced through carbon dioxide extraction. Sabal extract IDS 89 is a constituent of Strogen^® forte.

Strogen^® S: Strathmann AG & Co. Sabal extract IDS 89 is a constituent of Strogen^® S.

Talso^®: Sanofi Synthelabo GmbH / 174 avenue de France / 75013 Paris / France / Tel: +331 53 77 4000 / www.sanofi-synthelabo.fr.

*American equivalents, if any, are found in the Product Table beginning on page 398.

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