Saw Palmetto

• How It Works

  Saw palmetto was shown in some studies to help relieve the symptoms of benign prostatic hypertrophy (BPH), but it has not been shown to prevent or treat prostate cancer.

  Studies in the laboratory show that saw palmetto works by countering effects of male sex hormones such as testosterone and DHT. It appears to reduce levels of these hormones in body tissues like the prostate. Other studies have noted that saw palmetto reduces the conversion of testosterone to DHT, its more potent form. Saw palmetto berry extracts also reduce inflammation and swelling by preventing the formation of compounds that cause these reactions.

  In a laboratory study, saw palmetto extract was found to slow the growth of normal prostate cells and increase their sensitivity to radiation, while not affecting prostate cancer cells. Since this may increase the risk of complications, patients should consult with a physician before using saw palmetto supplements during radiation therapy.

• Purported Uses
  • To treat benign prostatic hypertrophy (BPH)
    Several clinical trials and meta-analyses have shown that saw palmetto improves urinary tract symptoms associated with BPH.
  • To treat prostate cancer
    Saw palmetto shows anti-inflammatory and anti-androgen properties in laboratory studies and reduces the levels of DHT in the prostate in clinical trials. However, it is not an effective treatment for prostate cancer.
  • To promote urination
    One study suggests an increase in urine flow, with an herbal combination formula including saw palmetto in addition to drug therapy.
  • As an anti-inflammatory
    Various studies suggest anti-inflammatory effects.
• Do Not Take If
  • You are taking warfarin or other blood thinners: Saw palmetto may increase the risk of bruising and bleeding.
  • You are taking antiplatelets such as clopidogrel: Saw palmetto may increase the effects of these drugs.
  • You are taking nonsteroidal anti-inflammatory drugs (NSAIDs): Saw palmetto may increase the side effects of these drugs.
  • You are taking drugs that are substrates of UGT (uridine 5’-diphospho-glucuronosyltransferase): Saw palmetto may increase the risk of side effects of these drugs.
  • You are taking drugs that are substrates of cytochrome P450: Saw palmetto may increase the risk of side effects of these drugs.
• Side Effects

  Common: Gastrointestinal upset, diarrhea, fatigue, headache, decreased libido and rhinitis
  Most effects are reported as mild and similar to effects with placebo.

  Case reports

  • Potentially fatal blood accumulation around the heart: In a 76-year-old man taking a blood thinner for irregular heart rhythm who had also been taking saw palmetto. Although this condition appeared related to the use of his medication, saw palmetto may have contributed to this drug’s increased activity.
  • Severe bleeding during surgery
  • Blood in the urine and impaired blood clotting
  • Severe inflammation of the pancreas
  • Severe liver damage
  • Hot flashes and first menstrual cycle: Two cases in children who were treated with saw palmetto for hair disorders.
• Scientific Name

  Serenoa repens

• Clinical Summary

  Saw palmetto is a dwarf palm that grows in the coastal lands of North America, West Indies, and Mediterranean countries. The fruits are a rich source of fatty acids and phytosterols and have been used to promote urination, reduce inflammation, and for treatment of conditions such as benign prostatic hyperplasia (BPH).

  Various heterogeneous extracts of saw palmetto are available, but many basic research and clinical trials used a hexanic extract of S. repens, which has anti-inflammatory, anti-androgenic, and antiproliferative activity ^(36) (37). Whereas some data indicate that various saw palmetto extracts improve lower urinary tract symptoms (LUTS) in patients with BPH ^{(2) (3) (4) (5) (15) (17) (18) (26)}, conflicting data suggest no such effects ^{(6) (14) (19) (28) (38)}. In another large study, a saw palmetto extract did not affect serum prostate specific antigen (PSA) more than placebo even at high doses ⁽³⁰⁾. Pretreatment with saw palmetto reduced intra- and postoperative complications in patients who underwent transurethral resection of the prostate and open prostatectomy ⁽²²⁾. A saw palmetto extract was found to inhibit growth of normal prostate cells and increase their sensitivity to radiation in vitro, but did not affect malignant prostate cancer cells ⁽²⁰⁾. A large epidemiologic study did not find associations with the use of saw palmetto and reduced risk of prostate cancer ⁽²⁷⁾.

  In an exploratory study, a hexanic extract of S. repens demonstrated anti-inflammatory effects in patients with BPH-related LUTS, ⁽³⁹⁾. In an open-label study, saw palmetto extract plus tamsulosin was found to be more effective than tamsulosin-only to reduce storage symptoms in BPH patients ⁽⁴⁰⁾.

  Multi-phytotherapy approaches have also been investigated. One study suggests saw palmetto may benefit patients with chronic bacterial prostatitis when coadministered with nettle, curcumin, and quercitin ⁽¹⁶⁾. Along with selenium and lycopene, saw palmetto exerted anti-inflammatory effects ⁽³¹⁾. In addition, patients with LUTS had greater improvement in International Prostate Symptom Scores (IPSS) and increased urine flow with this combination therapy in addition to tamsulosin therapy than with either single therapy ⁽⁴¹⁾.

  Due to the increased risk of normal tissue complications, patients should consult with a physician before using saw palmetto supplements during radiation therapy. There is an ongoing study to determine the effects of saw palmetto on symptom management during radiation therapy ⁽³²⁾.

• Purported Uses
  • Benign prostatic hypertrophy (BPH)
  • Inflammation
  • Promote urination
  • Prostate cancer
• Mechanism of Action

  Studies with a liposterolic extract of saw palmetto berries showed that it reduced tissue uptake of both testosterone and dihydrotestosterone (DHT) by more than 40%, suggesting antiandrogenic activity ⁽⁷⁾. Further, the extract inhibited binding of DHT to its receptor ⁽⁸⁾ and blocked conversion of testosterone to DHT by inhibiting 5-alpha-reductase activity ⁽⁹⁾. The berries also inhibit cyclooxygenase and 5-lipoxygenase pathways, thereby preventing the biosynthesis of inflammation-producing prostaglandins and leukotrienes ⁽¹⁰⁾. Other possible mechanisms attributed to benefits in BPH include the blocking of estrogen receptor activity in the prostate as well as bladder muscle antispasmodic and anti-inflammatory activities ⁽⁴²⁾. Possible mechanisms by which saw palmetto could cause hot flashes and vasomotor symptoms especially in children include its antiestrogenic activity influencing physiological endocrine activity and increased availability of sex hormone-binding globulin ^(35) (43).

  Studies of a hexanic extract of S. repens suggests it decreases prostaglandin and leukotriene production to inhibit the arachidonic acid cascade and decreases B lymphocyte infiltrates and interleukin (IL)-1b and tumor necrosis factor (TNF)-a levels to adjust inflammatory status and gene expression ⁽³⁶⁾. In animal models of prostate hyperplasia, it demonstrated a global anti-inflammatory effect on hyperplastic prostates with lobe-specific anti-androgenic effects ⁽⁴⁴⁾. In human prostate and vascular cells in an inflammatory environment, it also decreases monocyte chemotactic protein-1 production and vascular cell adhesion molecule-1 expression ⁽³⁷⁾. In human prostate carcinoma cells, inhibitory effects on cell growth were attributed to downregulation of inflammatory-related genes and activation of nuclear factor-kappa B pathway ⁽⁴⁵⁾.

  A chalcanonol glycoside from the seeds of saw palmetto as well as sterolic derivatives have demonstrated antiproliferative effects ⁽⁴⁶⁾.

• Adverse Reactions

  Common: Gastrointestinal disturbances, diarrhea, fatigue, headache, decreased libido, rhinitis ^(47) (48)
  Most effects are reported as mild and similar to effects with placebo ⁽⁴⁷⁾.

  Case reports

  • Hemopericardium: In a 76-year-old man receiving rivaroxaban who had also been taking saw palmetto. Although the development of hemopericardium appeared related to the use of rivaroxaban, saw palmetto may have contributed to the increase in rivaroxaban activity ⁽⁴⁹⁾.
  • Intraoperative hemorrhage, anticoagulant effects and prolonged bleeding time: In a 53-year-old white male during surgical resection of a tumor, despite negative results for a workup for bleeding disorders and no preoperative use of anti-inflammatory medications. Further inquiry led to disclosed use of saw palmetto for BPH. Prolonged bleeding time normalized a few days after the patient stopped taking this supplement ⁽¹¹⁾.
  • Hematuria and coagulopathy: In a 79-year-old man taking multiple medications along with long-term use of saw palmetto, the dosage of which he had recently increased to relieve BPH symptoms ⁽²¹⁾. Urinary symptoms and coagulation parameters improved with the discontinuation of saw palmetto.
  • Acute pancreatitis: In a 65-year-old man following use of saw palmetto for 1 week before onset of symptoms. His condition improved after treatment and avoiding saw palmetto ⁽²³⁾.
  • Severe liver damage: In a 58-year-old man following consumption of saw palmetto to alleviate BPH symptoms ⁽²⁴⁾.
  • Hot flashes and subsequent menarche: In an 11-year-old girl after treatment for a type of alopecia with a food supplement for 2 months that contained saw palmetto ⁽³⁵⁾; and in a 10-year-old girl using a food supplement that contained saw palmetto extract to treat hirsutism. Symptoms abated when the supplement was discontinued and reappeared with a supplement “re-challenge”. Menarche also commenced about 4 months post-supplement ⁽⁴³⁾.
• Herb-Drug Interactions
  • Anticoagulants, antiplatelets: Saw palmetto may have additive anticoagulant effects ^{(11) (21) (49)}.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): Saw palmetto may have increase the risk of side effects with these drugs ⁽²¹⁾.
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Saw palmetto inhibits UGT enzymes in vitro and can increase the side effects of drugs metabolized by them ⁽²⁵⁾.
  • CYP 450 substrates: Saw palmetto inhibits cytochrome P450 3A4, 2D6, and 2C9 and may interfere with the actions of drugs metabolized by these enzymes ⁽²⁹⁾.
• Herb Lab Interactions
  • May prolong bleeding time ⁽¹¹⁾
• References

  1. Feifer AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease. J Urol 2002;168:150-4.

  2. Fagelman E, Lowe FC. Herbal medications in the treatment of benign prostatic hyperplasia (BPH). Urol Clin N Am 2002;29:23-9.

  3. Gerber G, et al. Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology. 1998 Jun;51(6):1003-7.

  4. Boyle P, Robertson C, Lowe F, et al. Meta-analysis of clinical trials of permixon (saw palmetto) in the treatment of symptomatic benign prostatic hyperplasia. Urology 2000;55:533-9.

  5. Wilt TJ, Ishani A, Start G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998;280:1604-9.

  6. Bent S, et al. Saw palmetto for benign prostatic hyperplasia. N Engl J Med 2006;354(6): 557-566.

  7. El-Sheikh MM, Dakkak MR, and Saddique A. The effect of Permixon on androgen receptors. Acta Obstet Gynecol Scand. 1988;67(5):397-9.

  8. Carilla E, Briley M, Fauran F, et al. Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate.J Steroid Biochem 1984;20(1):521-3.

  9. Bayne CW, Donnelly F, Ross M, Habib FK. Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH. Prostate 1999;40(4):232-41.

  10. Goldmann WH, Sharma AL, Currier SJ, et al. Saw palmetto berry extract inhibits cell growth and Cox-2 expression in prostatic cancer cells. Cell Biol Int 2001;25:1117-24.

  11. Cheema P, El-Mefty O, Jazieh AR, et al. Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a case report and review of literature. J Intern Med. 2001 Aug;250(2):167-9.

  12. Newall C, Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.

  13. Chevalier G, et al. Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of serenoa repens supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol. Eur J Drug Metab Pharmacokinet 1997;22:73-83.

  14. Avins AL, Bent S, Staccone S, et al. A detailed safety assessment of a saw palmetto extract.Complement Ther Med. 2008 Jun;16(3):147-54.

  15. Shi R, Xie Q, Gang X, et al. Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shanghai, China. J Urol. 2008 Feb;179(2):610-5.

  16. Cai T, Mazzoli S, Bechi A, et al. Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents. 2009 Jun;33(6):549-53.

  17. Lopatkin N, Sivkov A, Schläfke S, et al. 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):1137-46.

  18. 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):879-86.

  19. Tacklind J, MacDonald R, Rutks I, Wilt TJ. Serenoa repens for benign prostatic hyperplasia. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD001423. DOI: 10.1002/14651858.CD001423.pub2.

  20. Hasan Y, Schoenherr D, Martinez AA, et al. Prostate-specific natural health products (dietary supplements) radiosensitize normal prostate cells. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):896-904.

  21. Villanueva S, González J. Coagulopathy induced by saw palmetto: a case report. Bol Asoc Med P R. 2009 Jul-Sep;101(3):48-50.

  22. Anceschi R, Bisi M, Ghidini N, Ferrari G, Ferrari P. Serenoa repens (Permixon) reduces intra- and postoperative complications of surgical treatments of benign prostatic hyperplasia. Minerva Urol Nefrol. 2010 Sep;62(3):219-23.

  23. Wargo KA, Allman E, Ibrahim F. A possible case of saw palmetto-induced pancreatitis. South Med J. 2010 Jul;103(7):683-5.

  24. Lapi F, Gallo E, Giocaliere E, et al. Acute liver damage due to Serenoa repens: a case report. Br J Clin Pharmacol. 2010 May;69(5):558-60.

  25. Mohamed ME, Frye RF. Inhibitory Effects of Commonly Used Herbal Extracts on UGT1A4, 1A6, and 1A9 Enzyme Activities. Drug Metab Dispos. 2011 Jun 1. [Epub ahead of print]

  26. Sinescu I, Geavlete P, Multescu R, et al. Long-term efficacy of Serenoa repens treatment in patients with mild and moderate symptomatic benign prostatic hyperplasia. Urol Int. 2011;86(3):284-9. Epub 2011 Feb 8.

  27. Brasky TM, Kristal AR, Navarro SL, et al. Specialty supplements and prostate cancer risk in the VITamins and Lifestyle (VITAL) cohort. Nutr Cancer. 2011 May;63(4):573-82.

  28. Barry MJ, Meleth S, Lee JY, et al. Effect of Increasing Doses of Saw Palmetto Extract on Lower Urinary Tract Symptoms. A Randomized Trial. JAMA. 2011;306(12):1344-1351.

  29. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9 . J Altern Complement Med. 2005 Jun;11(3):433-9.

  30. Andriole GL, McCullum-Hill C, Sandhu GS, et al. The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial. J Urol. 2013 Feb;189(2):486-92.

  31. Morgia G, Cimino S, Favilla V, et al. Effects of Serenoa repens, selenium and lycopene (Profluss®) on chronic inflammation associated with benign prostatic hyperplasia: results of “FLOG” (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study. Int Braz J Urol. 2013 Mar-Apr;39(2):214-21.

  32. Saw Palmetto: Symptom Management for Men During Radiation Therapy. http://clinicaltrials.gov/ct2/show/NCT01585246. Accessed December 19, 2013.

  33. Little DP, Jeanson ML. DNA barcode authentication of saw palmetto herbal dietary supplements. Sci Rep. 2013 Dec 17;3:3518.

  34. Plosker GL, Brogden RN. Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia.Drugs Aging. 1996 Nov;9(5):379-95.

  35. Miroddi M, Carnì A, Mannucci C, et al. Hot flashes in a young girl: a wake-up call concerning Serenoa repens use in children. Pediatrics. 2012 Nov;130(5):e1374-6.

  36. Ficarra V, Rossanese M, Zazzara M, et al. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Curr Urol Rep. Dec 2014;15(12):463.

  37. Latil A, Libon C, Templier M, et al. Hexanic lipidosterolic extract of Serenoa repens inhibits the expression of two key inflammatory mediators, MCP-1/CCL2 and VCAM-1, in vitro. BJU Int. Sep 2012;110(6 Pt B):E301-307.

  38. MacDonald R, Tacklind JW, Rutks I, et al. Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review. BJU Int. Jun 2012;109(12):1756-1761.

  39. Latil A, Petrissans MT, Rouquet J, et al. Effects of hexanic extract of Serenoa repens (permixon((R)) 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Prostate. Dec 2015;75(16):1857-1867.

  40. Ryu YW, Lim SW, Kim JH, et al. Comparison of tamsulosin plus Serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia in Korean men: 1-year randomized open label study. Urol Int. 2015;94(2):187-193.

  41. Morgia G, Russo GI, Voce S, et al. Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial). Prostate. Nov 2014;74(15):1471-1480.

  42. Pagano E, Laudato M, Griffo M, et al. Phytotherapy of benign prostatic hyperplasia. A minireview. Phytother Res. Jul 2014;28(7):949-955.

  43. Morabito P, Miroddi M, Giovinazzo S, et al. Serenoa repens as an Endocrine Disruptor in a 10-Year-Old Young Girl: A New Case Report. Pharmacology. 2015;96(1-2):41-43.

  44. Bernichtein S, Pigat N, Camparo P, et al. Anti-inflammatory properties of Lipidosterolic extract of Serenoa repens (Permixon(R)) in a mouse model of prostate hyperplasia. Prostate. May 2015;75(7):706-722.

  45. Silvestri I, Cattarino S, Agliano A, et al. Effect of Serenoa repens (Permixon(R)) on the expression of inflammation-related genes: analysis in primary cell cultures of human prostate carcinoma. J Inflamm (Lond). 2013;10:11.

  46. Abdel Bar FM. New chalcanonol glycoside from the seeds of saw palmetto: antiproliferative and antioxidant effects. Nat Prod Res. 2015;29(10):926-932.

  47. Agbabiaka TB, Pittler MH, Wider B, et al. Serenoa repens (saw palmetto): a systematic review of adverse events. Drug Saf. 2009;32(8):637-647.

  48. Al-Shukri SH, Deschaseaux P, Kuzmin IV, et al. Early urodynamic effects of the lipido-sterolic extract of Serenoa repens (Permixon(R)) in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. Nov 2000;3(3):195-199.

  49. Shivamurthy P, Brar N, Therrien ML. Isolated hemopericardium associated with rivaroxaban: first case report. Pharmacotherapy. Sep 2014;34(9):e169-172.