1. Saw Palmetto: A Dietary Supplement Megan Erickson Summer 2006

2. Learning Objectives Identify what is thought to be the active ingredients. Name the most common use for saw palmetto. Describe the two main mechanisms in which saw palmetto is thought to work. Identify the conclusion of the most recent study performed with saw palmetto vs. a placebo for treating BPH. Describe why saw palmetto is thought to be safe.

3. Saw Palmetto Also called: Serenoa repens, Sabal serrulata Origin: Ripe fruit of the plant Grown in Southern United States Taken as liquid extract, tablet, capsule, infusion, or tea Extract most effective, tea least effective

4. Saw Palmetto Active ingredient: Not fully known, but thought to be fatty acids and sterols, which are in highest concentration in extract form USP suggests 70-95% fatty acids and.2-.5% sterols Appropriate dose: 320 mg extract/day One of 8 herbs in PC-SPES (PC=prostate cancer, SPES=hope) Used in Europe much more than U.S. U.S.: 1.1% of population or 2.5 million use saw palmetto Germany: used in 90% of BPH treatment Italy: used 5x more often

5. Reported Uses Used for its effects on the hormones testosterone and dihydrotestosterone (DHT) Most common: benign prostatic hyperplasia (BPH), prostate cancer, other urinary tract problems One study found 11.8% of men with prostate cancer used saw palmetto, second highest use after vitamin E Less common: chronic pelvic pain, bladder disorders, low libido, low sperm production, hair loss, hormone imbalances, bronchitis, cancer, diabetes, migraines, as an aphrodisiac, to build muscle, and increase breast size

6. Benign Prostatic Hyperplasia (BPH) Prevelance: 6.5 million Caucasian men ages 50-79 Enlarged prostate due to increasing number of cells and inflammation which pushes against the urethra Signs/symptoms: hesitancy, frequency, and urgency of urination, decreased force of stream, incomplete emptying of bladder, incontinence, nocturia

7. Benign Prostatic Hyperplasia (BPH)

8. Mechanism of Action: 5-alpha reductase inhibitor 5-alpha reductase inhibitor converts testosterone to DHT DHT causes an increase in cell proliferation of the prostate, thus enlarging the gland Less conversion to DHT means less blood DHT and a decrease in cell proliferation Other drugs: finasteride and dutasteride

9. Mechanism of Action: alpha- andrenergic-receptor antagonist Blocks DHT from binding to andrenergic receptors on prostate Less DHT enters the prostate causing less cell proliferation Other drugs: terazosin and doxazosin

10. Mechanism of Action Other claims: Has less adverse side effects than the prescription medications which include sexual dysfunction and decreasing prostate-specific antigen (PSA) Decreases inflammation: May decrease number of mast cells (involved with inflammation) May inhibit cyclooxygenase and lipoxygenase

11. Symptom Scoring Methods American Urological Association Symptom Index (AUASI) and International Prostate Symptom Score (IPSS) Questionnaires used in many studies Composed of seven frequency questions Scores symptoms 0-35 http://godot.urol.uic.edu/~web/ASIS.html http://www.usrf.org/questionnaires/AUA_S ymptomScore.htmlhttp://www.usrf.org/questionnaires/AUA_S ymptomScore.html

12. Most Recent Study Bent S, Kane C, Shinohara K, Neuhaus J, et al. Saw palmetto for benign prostatic hyperplasia. The New England Journal of Medicine. 2006;354:557-568. Randomized, double-blind, placebo trial Subjects: 225 men over 49 years of age Moderate-severe symptoms according to American Urological Association Symptom Index (AUASI) Design: Study lasted 12 months Subjects took 160 mg twice daily Measured AUASI score, quality of life, prostate size, residual volume after voiding, PSA, creatinine, testosterone, and general health

13. Most Recent Study: Results Significant decrease in AUASI scores for both groups 0.68 for saw palmetto 0.72 for placebo No significant difference between groups for: AUASI scores peak urinary flow rate prostate size residual volume after voiding quality of life serum PSA, creatinine, and testosterone levels adverse events (26 total, 8 saw palmetto group, 18 placebo)

14. Most Recent Study: Results

16. Most Recent Study: Conclusions Clinically meaningful change in AUASI score should be at least 3 points, but this study showed a change of less than 1 point Results did not significantly differ between men that started out with higher or lower AUASI scores Saw palmetto is not an effective treatment for BPH

17. Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate. 1996;29:231-240. Randomized double-blind trial Subjects: 1,098 men over 50 years of age Included only men with IPSS over 6, large prostate, urinary flow problems Design: Study lasted 6 months Subjects took 160 mg saw palmetto twice daily or finasterde Measured IPSS score, peak and mean urinary flow rates, quality of life, sexual function, prostate volume, residual volume after voiding, and PSA

18. Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate. 1996;29:231-240. Results: 951 subjects completed the study IPSS score: P: -37%, F: -39% Quality of life: P: -38%, F: -41% Sexual function: P: -6%, F: +9% Peak urinary flow rate: P: 25%, F: 30% Mean urinary flow: P: 15%, F: 20% Prostate volume: P: -6%, F: -18% PSA: P: 3%, F: -41% All were statistically significant changes from baseline except sexual function and PSA of saw palmetto group Saw palmetto and finasteride differed significantly in serum PSA, sexual function, and prostate size

19. Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate. 1996;29:231-240. Conclusions: Both treatments are equally effective in treating BPH There was no placebo given to determine if the results are due to placebo effect Adverse events included hypertension, decreased libido, abdominal pain, and impotence in both groups

20. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA. 1998;280:1604-1609. Systematic review and meta-analysis Subjects: 18 studies included 2,939 men Design: Had to be longer than 30 days, average 9 weeks Measured IPSS score, peak and mean urinary flow rates, prostate volume, residual volume after voiding, and nocturia

21. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA. 1998;280:1604-1609. Results: Compared to finasteride, saw palmetto was just as good at relieving symptoms and associated with less sexual dysfunction Compared to placebo, saw palmetto improved Urinary tract symptoms: 28% Nocturia: 25% Peak urine flow: 24% Mean urine flow: 28% Residual volume: 43% Adverse events were mild and comparable with placebo Most common were sexual dysfunction and gastrointestinal irritations

22. Other Studies BPH: Non-blind study found effective in reducing the IPSS, quality of life, and maximum flow rate (2000) Double blind study found only significant result was contracted prostatic epithelium tissues (2000) Saw palmetto vs. finasteride: both lowered levels of DHT, but finasteride had a larger effect (2001) Mechanism of Action: Does not occupy adrenoreceptors in vivo Decreases number of mast cells No effect on cytochrome P450 system

23. Safety Studies showed no significant adverse effects Side effects include constipation, decreased libido, headache, nausea, diarrhea, and gastrointestinal irritation Did not effect cytochrome P450 system so drug interactions not a problem Integrity may be a problem: Found as much as 141% more and 97% less of supplement than reported (6 tested) Fatty acid content 80.7-40.7% in 14 brands

24. Conclusions Saw palmetto is safe Many studies found effectiveness when not blinded, not using a placebo, and performed in Europe where commonly prescribed Studies blinded, using a placebo, and most recent study did not find effectiveness The jury is still out? More comprehensive studies needed.