Medication Guide App

Saw Palmetto

Scientific Name(s): Serenoa repens (Bartram) Small. Also referred to as Sabal serrulata (Michx.) Nicholson or Sabal serrulatum Schult. Family: Palmae (palms)

Common Name(s): Saw palmetto , sabal , American dwarf palm tree , cabbage palm , fan palm , scrub palm

Uses

Saw palmetto is used to treat symptoms of benign prostatic hyperplasia, including reduction of urinary frequency, increase of urinary flow, and decrease of nocturia. Saw palmetto may delay the need for prostate surgery. However, the mechanism of action is unknown.

Dosing

The crude saw palmetto berries are usually administered at 1 to 2 g/day; however, lipophilic extracts standardized to 85% to 95% fatty acids in soft native extract or 25% fatty acids in a dry extract are more common. Brand-name products include Permixon , Prostaserene , Prostagutt , Remigeron , Quanterra Prostate , and LG 166/S . Typical dosages of standardized extracts range from 100 to 400 mg given twice daily for benign prostatic hypertrophy.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

Increased anticoagulant effect of warfarin has been reported during concurrent ingestion of saw palmetto. However, there was a more likely alternative explanation for the interaction. Until more data are available, patients taking warfarin should consult their health care provider before taking saw palmetto or other alternative medicine products.

Adverse Reactions

Saw palmetto is generally well tolerated, with occasional reports of adverse GI effects. Because of well-documented antiandrogen and antiestrogenic activity, avoid taking with any hormone therapy, including oral contraceptive and hormone replacement therapy.

Toxicology

Research reveals little or no information regarding toxicology with the use of saw palmetto.

Botany

The saw palmetto is a low, scrubby palm that grows in the coastal plain of Florida and other southeastern states. Its fan-shaped leaves have sharp saw-toothed edges that give the plant its name. Dense clumps of saw palmetto can form an impenetrable thicket. The abundant 2 cm long berries are harvested in the fall and are dried for medicinal use. They also serve as a source of nutrition for deer, bears, and wild pigs. 1

History

Native tribes of Florida relied on saw palmetto berries for food; however, Europeans often found the taste of the berries objectionable. 1 While native medicinal use of saw palmetto is not recorded, it was introduced into Western medical practice in the 1870s and was a favorite of eclectic medical practitioners for prostate and other urologic conditions. Saw palmetto berries were officially included in the US Pharmacopeia in 1906 and 1916, and in the National Formulary from 1926 to 1950. While use in the United States declined after that time, saw palmetto has long been a staple phytomedicine in Europe. Interest in the plant has been rekindled, and saw palmetto is ranked among the top 10 herbal products in the United States, primarily for its activity in benign prostatic hyperplasia (BPH). 2

Chemistry

Saw palmetto berries contain large quantities of beta-sitosterol and other plant sterols, 3 as well as free and esterified fatty acids. 4 Most standardized commercial preparations are liposterolic extracts containing nonpolar constituents (eg, fatty acids and sterols) produced either by conventional hexane extraction or by supercritical carbon dioxide extraction. The fatty acid components have been quantitated by gas chromatography 5 and supercritical fluid chromatography, 6 while the alcohols and sterols have been analyzed by thin-layer chromatography and electrospray mass spectrometry of ferrocenyl derivatives. 7 An acidic polysaccharide with anti-inflammatory activity has been isolated from saw palmetto fruit. 8 , 9

Uses and Pharmacology

Benign prostatic hyperplasia

Saw palmetto's mechanism of action in suppressing the symptoms of BPH is poorly understood. Animal and human in vitro studies have led to several different hypotheses.

Animal data

The leading hypothesis involves the inhibition of testosterone 5-alpha reductase, an enzyme that converts testosterone to 5-alpha-dihydrotestosterone in the prostate. Hexane extracts of saw palmetto inhibited the enzyme from human foreskin fibroblasts, while they had no direct effect on androgen receptor binding. 10 Investigators found various saw palmetto extracts to be much weaker 5-alpha reductase inhibitors in vitro than the synthetic drug finasteride. 11 Similarly, in humans, serum levels of dihydrotestosterone (DHT) were reduced markedly by finasteride, but not by saw palmetto. 12

Further studies using both known 5-alpha reductase isozymes found that finasteride inhibited only type 1 reductase, while saw palmetto inhibited formation of all testosterone metabolites in cultured prostate epithelial cells and fibroblasts. 13 A different saw palmetto extract, IDS 89, dose dependently inhibited 5-alpha reductase in both the stroma and epithelium of human BPH tissue. This inhibition was related to the free fatty acids present in the extract. 14 A tracer study found that radiolabeled oleic acid in saw palmetto extract was taken up preferentially by rat prostate compared with other tissues. 15 Studies in a coculture model of human prostate epithelial cells and fibroblasts found that saw palmetto inhibited types 1 and 2 isoforms of 5-alpha reductase without altering the secretion of prostate-specific antigen. 16 Other work has shown that saw palmetto extract inhibits trophic as well as androgenic effects of prolactin in a rat model of prostatic hyperplasia. 17 Structure-activity studies of pure fatty acid inhibition of steroid 5-alpha reductase found gamma-linolenic acid was the most potent and specific inhibitor of the enzyme. 18 It is possible that the C18 monounsaturated fatty oleic acid in saw palmetto was partly responsible for the observed effects on 5-alpha reductase, though more extensive analysis of saw palmetto fatty acids is required.

There is less support for other hormonal mechanisms. One study found 5-alpha reductase inhibition and inhibition of DHT binding to androgen receptors, 19 and another study demonstrated inhibition of DHT and testosterone receptor binding. 20 Administration of saw palmetto extract over 30 days led to no changes in plasma levels of testosterone, follicle-stimulating hormone, or luteinizing hormone. 21 Hormonal pathways were invoked to explain reduced prostate weights in castrated rats treated with estradiol, testosterone, and saw palmetto extract as opposed to estradiol and testosterone alone. 22 In the human prostate cancer line LNCaP, saw palmetto induced a mixed proliferative/differentiative effect that was not seen in the nonhormone-responsive PC3 human prostate cancer cell line. 23 Treatment of patients for 3 months with saw palmetto preceding prostatectomy caused a reduction in DHT levels in BPH tissue, along with a corresponding rise in testosterone levels. A marked reduction in epidermal growth factor concentration was also observed in the periurethral region of the prostate. 24

Other observations of saw palmetto extracts include the following: a spasmolytic effect on rat uterus, suggested to be caused by effects on cyclic AMP and calcium mobilization 25 ; an inhibition of smooth muscle contraction in rat deferens and guinea pig ileum and bladder, postulated as alpha-adrenoreceptor antagonistic, 26 as found in other studies to be noncompetitive in nature 27 ; and interference with 5-lipoxygenase metabolites in neutrophils. 28 A few studies have suggested an increase in apoptosis with administration in mice and humans. 29 , 30

Clinical data

Although the mechanism of action of saw palmetto is not completely understood, clinical trials in BPH have shown convincing evidence of moderate efficacy. A 6-month, double-blind, head-to-head study versus finasteride in 1,098 men found equivalent efficacy and a superior adverse reaction profile for saw palmetto. 31 Likewise, a 3-year study of IDS 89 in 435 patients with BPH found clear advantage to placebo in reduction of BPH symptoms. 32 A 1-year study of 132 patients comparing 2 dose levels of saw palmetto demonstrated efficacy in symptom reduction, but little difference between dose levels. 33 One study observed Serona repens compared with placebo in 189 patients with a mild International Prostate Symptom Score (IPSS). Patients were observed for clinical progression into moderate or severe IPSS. After 24 months the Serona repens group had fewer patients with clinical progression of bladder outlet obstruction. 34 In contrast, a 1-year double-blind study of 225 men compared American Urological Association BPH Symptom Index in saw palmetto versus placebo-treated patients and found no difference between the 2 groups. 35 The general consensus has been that saw palmetto extracts reduce BPH symptoms without reducing prostate size, therefore delaying surgical intervention. 36 A meta-analysis that included a total of 18 clinical trials in BPH concluded that saw palmetto was better tolerated than finasteride and equivalent in efficacy. 37 A clinical trial in BPH of the saw palmetto constituent beta-sitosterol showed efficacy similar to that seen with saw palmetto itself. 38

Studies have compared the use of saw palmetto in combination with other products versus current prescription therapy. A randomized double-blind trial compared PRO 160/120 ( Prostagutt ), a fixed combination preparation of 160 mg sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 , per capsule versus tamsulosin in lower urinary tract symptoms. In the 140 subjects with moderate to severe IPSS, there was a decrease in IPSS total scores in both groups after 60 weeks. 39 Similar results were found in an earlier trial comparing PRO 160/120 with placebo. 40 An open-label extension of this trial observed patients for a total of 96 weeks. All patients received PRO 160/120 for the last 48 weeks. A decrease was found in IPSS total score and residual urine volume, along with an increase in peak and average urinary flow. 41 Another study had 3 arms comparing Serenoa repens 320 mg daily, tamsulosin 0.4 mg daily, and S. repens 320 mg plus tamsulosin 0.4 mg daily. After 6 months of therapy in the 60 study subjects, the groups were not statistically different in urinary flow rate and decrease in IPSS. 42

Dosage

The crude saw palmetto berries are usually administered at a dosage of 1 to 2 g/day; however, lipophilic extracts standardized to 85% to 95% fatty acids in soft native extract or 25% fatty acids in a dry extract are more common. Brand-name products include Permixon , Prostaserene , Prostagutt , Remigeron , Quanterra Prostate , and LG 166/S . Typical dosages of standardized extracts range from 100 to 400 mg given twice daily for benign prostatic hypertrophy to the most commonly used dosage in clinical trials of 160 mg twice daily or 320 mg daily. 21 , 25 , 38 , 43 , 44 , 45

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking; however, antiandrogenic activity suggests that saw palmetto should not be used in pregnancy.

Interactions

Two men stabilized on warfarin experienced an increase in the international normalized ratio (INR) after taking an herbal combination containing cucurbita, saw palmetto, and vitamin E. 46 In both patients, the INR returned to previous values when the herbal product was discontinued. Although neither cucurbita nor saw palmetto can be ruled out as the cause of the increase in INR, it is more likely that vitamin E interfered with vitamin K-dependent clotting factors, adding to the anticoagulant effects of warfarin.

Adverse Reactions

Saw palmetto products are generally well tolerated, with occasional reports of adverse GI effects.

Because of well-documented antiandrogen and antiestrogenic activity, avoid taking with any hormone therapy, including oral contraceptive and hormone replacement therapy.

A study assessing the affects of several herbal medications including saw palmetto on platelet function in adult volunteers found no effect of saw palmetto on platelets after 2 weeks at the recommended dose. 47 However, there has been 1 case report linking saw palmetto to intraoperative hemorrhage. 48 A 53-year-old white man with normal preoperative prothrombin time and activated partial thromboplastin time underwent surgical resection of meningioma. Surgery was terminated early after administration of 4 liters of crystalloid fluids, 4r units of packed red blood cells, 3 units of pooled platelets, and 3 units of fresh frozen plasma. After surgery, the patient had an elevated bleeding time, which normalized over the next 5 days. No other medication use or events were reported that could be linked to the elevated bleeding time; saw palmetto dose, duration of therapy, or manufacturer were not reported in the case report.

Two case reports link saw palmetto to intraoperative floppy-iris syndrome, which is also associated with multiple alpha 1 -adrenergic antagonist. This condition can cause complications during cataract surgery. 49

Toxicology

Research reveals little or no information regarding toxicology with the use of saw palmetto.

Bibliography

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3. Elghamry M, Hänsel R. Activity and isolated phytoestrogen of shrub palmetto fruits ( Serenoa repens Small), a new estrogenic plant. Experientia . 1969;25(8):828-829.
4. Shimada H, Tyler VE, McLaughlin JL. Biologically active acylglycerides from the berries of saw-palmetto ( Serenoa repens ). J Nat Prod . 1997;60(4):417-418.
5. De Swaef S, et al. Simultaneous quantitation of lauric acid and ethyl laureate in Sabal serrulata by capillary gas chromatography and derivatisation with trimethyl sulphoniumhydroxide. J Chromatogr . 1996;719:479.
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12. Strauch G, Perles P, Vergult G, et al. Comparison of finasteride ( Proscar ) and Serenoa repens ( Permixon ) in the inhibition of 5-alpha reductase in healthy male volunteers. Eur Urol . 1994;26(3):247-252.
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15. Chevalier G, Benard P, Cousse H, Bengone T. Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of Serenoa repens ( Permixon ) supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol. Eur J Drug Metab Pharmacokinet . 1997;22(1):73-83.
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17. Van Coppenolle F, Le Bourhis X, Carpentier F, et al. Pharmacological effects of the liposterolic extract of Serenoa repens ( Permixon ) on rat prostate hyperplasia induced by hyperprolactinemia: Comparison with finasteride. Prostate . 2000;43(1):49-58.
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21. Casarosa C, Cosci di Coscio M, Fratta M. Lack of effects of a lyposterolic extract of Serenoa repens on plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone. Clin Ther . 1988;10(5):585-588.
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24. Di Silverio F, Monti S, Sciarra A, et al. Effects of long-term treatment with Serenoa repens ( Permixon ) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate . 1998;37(4):77-83.
25. Gutiérrez M, Hidalgo A, Cantabrana B. Spasmolytic activity of a lipidic extract from Sabal serrulata fruits. Further study of the mechanisms underlying this activity. Planta Med . 1996;62(6):507-511.
26. Odenthal K. Phytotherapy of benign prostatic hyperplasia (BPH) with Cucurbita , Hypoxis , Pygeum , Urtica and Sabal serrulata ( Serenoa repens ). Phytother Res . 1996;10:S141.
27. Goepel M, Hecker U, Krege S, Rübben H, Michel MC. Saw palmetto extracts potently and noncompetitively inhibit human alpha1-adrenoceptors in vitro. Prostate . 1999;38(3):208-215.
28. Paubert-Braquet M, Mencia Huerta JM, Cousse H, Braquet P. Effect of the lipidic lipidosterolic extract of Serenoa repens ( Permixon ) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils. Prostaglandins Leukot Essent Fatty Acids . 1997;57(3):299-304.
29. Wadsworth TL, Worstell TR, Greenberg NM, Roselli CE. Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mourse prostate model (TRAMP). Prostate . 2007;67(6):661-673.
30. Vela-navarrete R, Escribano-burgos M, Farré AL, García-Cardoso J, Manzarbeitia F, Carrasco C. Serenoa repens treatment modifies BAX/BCL-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia. J Urol . 2005;173(2):507-510.
31. Bach D, et al. Long-term drug treatment of benign prostatic hyperplasia. Results of a prospective 3-year multicenter study using Sabal extract IDS 89. Phytomedicine . 1996;3:105.
32. Braeckman J, Bruhwyler J, Vanderkerckhove K, Geczy J. Efficacy and safety of the extract of Serenoa repens in the treatment of benign prostatic hyperplasia: Therapeutic equivalence between twice and once daily dosage forms. Phytother Res . 1997;11:558.
33. Marandola P, et al. Main phytoderivatives in the management of benign prostatic hyperplasia. Fitoterapia . 1997;68:195.
34. Djavan B, Fong YK, Chaudry A, et al. Progression delay in men with mild symptoms of bladder outlet obstruction: a comparative study of phytotherapy and watchful waiting. World J Urol . 2005;23(4):253-256.
35. Bent S, Kane C, Shinohara K, et al. Saw Palmetto for benign prostatic hyperplasia. N Eng J Med . 2006;354(6):557-566.
36. Wilt T, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA . 1998;280(18):1604-1609.
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38. Braeckman J, Bruhwyler J, Vanderkerckhove K, Geczy J. Efficacy and safety of the extract of Serenoa repens in the treatment of benign prostatic hyperplasia: therapeutic equivalence between twice and once daily dosage forms. Phytother Res . 1997;11:558-563.
39. Engelmann U, Walther C, Bondarenko B, Funk P, Schläfke S. Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. Arzneimittelforschung . 2006;56(3):222-229.
40. Lopatkin N, Sivkov A, Walther C, et al. Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms, a placebo-controlled, double-blind, multicenter trial. World J Urol . 2005;23(2):139-146.
41. Lopatkin N, Sivkov, Schläfke S, Funk P, Medvedev A, Engelmann U. Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms—long-term follow-up of a placebo-controlled, double-blind, multicenter trial. Int Urol Nephrol . 2007:39(4):1137-1146.
42. Hizli F, Uygur MC. A prospective study of the efficacy of Serenoa repens , tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia. Int Urol Nephrol . 2007;39(3):879-886.
43. Gerber GS, Zagaja GP, Bales GT, Chodak GW, Contreras BA. Saw palmetto ( Serenoa repens ) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology . 1998;51:1003-1007.
44. Marks LS, Partin AV, Epstein JI, et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol . 2000;163(5):1451-1456.
45. Redecker W. Sabal extract W 1473 in benign prostatic hyperplasia. Extracta Urol . 1998;21:24-26.
46. Yue QY, Jansson K. Herbal drug curbicin and anticoagulant effect with and without warfarin: possibly related to the vitamin E component. J Am Geriatr Soc . 2001;49(6):838.
47. Beckert BW, Concannon MJ, Henry SL, Smith DS, Puckett CL. The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature. Plast Reconstr Surg . 2007;120(7):2044-2050.
48. Cheema P, El-Mefty O, Jazieh AR. Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a case report and review of literature. J Intern Med . 2001:250(2):167-169.
49. Yeu E, Grostern R. Saw palmetto and intraoperative floppy-iris syndrome. J Cataract Refract Surg . 2007;33(5):927-928.

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