Saw Palmetto: A Dietary Supplement

Megan EricksonSummer 2006

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.

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

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

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

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

Benign Prostatic Hyperplasia (BPH)

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

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

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

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_SymptomScore.html

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

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)

Most Recent Study: Results

Most Recent Study: Results

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

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

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

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

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

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

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

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

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.