Home • AltMed Home • Search • Feedback

Pharmacology of Saw Palmetto

The scientific research on saw palmetto extract (SPE) has primarily been conducted in Europe, specifically Germany, where it is approved as an over the counter drug. The SPE that has been used in research and is an OTC in Germany is lipophilic extract, most commonly the aforementioned Permixon.  Such extracts are prepared from the dried and milled berries by the use of hexane, ethanol, and hypercritical carbon dioxide as other solvents. 

Once removed, the extract contains a mixture of free fatty acids (90%), esthers (7%), and small quantities of phytosterols, aliphatic alcohols, and various polyprenic compounds.

Although the active ingredient in SPE has not been identified, it is most commonly accepted to be in the lipophilic extract. According to this understanding, the active ingredients could not be found in teas or other water soluble forms. 

It can also be noted that the unsaponifiable fraction of SPE has also been linked to a reduction in prostate cell proliferation (Paubert-Braquet et. al., 1998).

Proposed Mechanism Of Action

The mechanism of action of SPE has not been clearly identified, but recent research has shed some light on the subject.

In a paper found in the February 1999 edition of the journal Prostate, saw palmetto was found to noncompetitively inhibit agonist binding to alpha1-adrenoceptors and prevent the formation of [3H]inositol. This suggests a mechanism of action similar to Tamsulosin.

Another paper in the May 2000 edition of the Journal of Urology noted that use of SPE led to epithelial contraction and possibly shrinkage of the gland. This suggests a mechanism similar to Finasteride and blockage of the 5-alpha reductase enzyme within the prostate. However, SPE does not effect PSA level, and this would suggest another mechanism in countering the effects of DHT.

Talpur et al. in Molecular and Cellular Biochemistry concluded that SPE decreases the rate of DHT formation and blocks the ability of DHT to bind to target cells, preventing the action of the hormone.

Additional proposed mechanisms of action include alteration in cholesterol metabolism and a decrease in available sex-hormone binding globulin. 

Furthermore, SPE  has been shown to reduce prostate inflammation and pain suggesting a potent anti-inflammatory action (Navarette et. al. 2002,  Vacherot et al, 1999,Ragab et al, 1988). This may be achieved through a dose-related blockade of cyclooxygenase and lipoxygenase pathways.  Furthermore, inhibition of prolactin and growth factor may be another protective effect of an enlarged prostate by saw palmetto.  The latest proposed mechanism of action  by Wadsworth et al. in 2004 is that SPE may inhibit specific components of the IGF-I signaling pathway and induce JNK activation, resulting in antiproliferative and proapoptotic effects on prostate epithelia due to IGF-I's importance in prostate growth and development.  Accumulating evidence suggests that dysregulation of the IGF-I system is involved in the pathogenesis of human BPH. 

Clinical Efficacy

The use of saw palmetto in the treatment of BPH has not been customary in the US. This is largely due to the fact that conclusive trials were unavailable to prove its effectiveness versus more conventional therapies. Recently, some studies have come to light which indicate that SPE does in fact offer symptomatic treatment of BPH.

In the May 2000 edition of the Journal Of Urology, Marks et al. report a randomized blinded placebo controlled trial in which SPE proved effective in alleviating patient's symptoms of BPH. However, this trial was unable to identify any measurable changes in urinary flow rates or other measures of genitourinary competence.  More recently, in vitro studies performed by Wadsworth et al. suggested that SPE inhibits growth of prostate cancer cell lines in culture, and therefore may possess chemopreventative potential.

Gerber and Fitzpatrick (2004) performed a review of clinical trials involving extracts of S. repens, focusing on the benefit/risk ratio in patients with BPH in the British Journal of Urology International.  The objective of the study was to critically review the clinical database on Permixon and on this basis make a more rational decision on the potential of this plant-derived pharmaceutical in the treatment of lower urinary tract symptoms.  Their results showed that SPE significantly reduces the symptoms of BPH, increases urinary flow, improves the quality of life, and is well tolerated.  Thus they concluded that analysis of the overall clinical database indicates SPE may be considered a viable first-line therapy for treating lower urinary tract symptoms.

Also in 2004, Gong and Gerber performed a review of clinical trials involving SPE for the American Journal of Chinese Medicine.  Their article review the effects of saw palmetto on BPH.  These authors also emphasized that most of the research reviewed was  based on Permixon, thus may not pertain to the other saw palmetto products available within the USA.  They concluded that recent evidence suggests that the use of SPE leads to subjective and objective improvement in urinary function.  Yet, what degree of this benefit is due to placebo effect is yet to be determined.  However, very few if any adverse effects have been noted with SPE, especially in regards to sexual function.  Their final comments stated that at present, men considering the use of SPE can be told that it is safe, will not mask the detection of prostate cancer, and may lead to a mild to moderate improvement in symptoms.      

Beckman and Mynderse (2005) authored an article for the Mayo Clinic Proceedings Journal to assist physicians in evaluation and medical management of BPH.  Their article concluded that although an exact mechanism of action has not been proved, SPE is considered safe and current evidence supports its effectiveness for BPH symptom improvement.  Their final comments included that evidence supports the use of saw palmetto for initial treatment of BPH in men who prefer herbal therapies.

Dosing 

Currently in Germany the effective dose is suggested to be 320 mg daily of SPE standardized to contain 85-95% of the liposterolic content.  Alternatively, a dosage of 160 mg twice daily can be employed.  Dosages as high as 480 mg were not found to be any more effective in a studies up to 6 months.

Kinetics

Studies on the kinetics of SPE are limited but one study using only 12 males with a mean age of 24 found that administration of 320 mg SPE the mean peak plasma concentration was 2.6 mg/l at 1.5 hrs, and the t1/2 was 19 hrs. Oral administration of 14C-labeled oleic and lauric acid supplemented SPE demonstrates that radioactivity is selectively concentrated in the prostate and not other target organs, thus displaying tissue specific accumulation.

Adverse Effects

Currently there are no known adverse effects of SPE. In one study gastrointestinal distress was reported with some participants but this decreased as the study progressed.  This can be minimized by taking saw palmetto with food.

Contraindications

There are no known contraindications except that due to its possible similarity to finasteride it should not be taken by patients using this medication. Also due to its possible hormonal effects SPE should not be taken by children and pregnant or lactating women.  Dosages as high as 2 grams per day for 6 months were well tolerated in experimental rats and dogs with no mutagenic or teratogenic effects. There are no known drug interactions to date.