Saw Palmetto (Serenoa Repens Orsabal Serrulata)

SAW PALMETTO (SERENOA REPENS ORSABAL SERRULATA)

Chemistry

The active constituents in saw palmetto berries are not well defined. Phytosterols (eg, β-sitosterol), aliphatic alcohols, poly-prenic compounds, and flavonoids are all present. Marketed preparations are dried lipophilic extracts that are generally stan-dardized to contain 85–95% fatty acids and sterols.

Pharmacologic Effects

Saw palmetto is most often promoted for the treatment of benign prostatic hyperplasia (BPH). Enzymatic conversion of testoster-one to dihydrotestosterone (DHT) by 5α-reductase is inhibited by saw palmetto in vitro. Specifically, saw palmetto shows a non-competitive inhibition of both isoforms (I and II) of this enzyme, thereby reducing DHT production. In vitro, saw palmetto also inhibits the binding of DHT to androgen receptors. Additional effects that have been observed in vitro include inhibition of prostatic growth factors, blockade of α₁ adrenoceptors, and inhi-bition of inflammatory mediators produced by the 5-lipoxygenase pathway.

The clinical pharmacology of saw palmetto in humans is not well defined. One week of treatment in healthy volunteers failed to influence 5α-reductase activity, DHT concentration, or testos-terone concentration. Six months of treatment in patients with BPH also failed to affect prostate-specific antigen (PSA) levels, a marker that is typically reduced by enzymatic inhibition of 5α-reductase. In contrast, other researchers have reported a reduc-tion in epidermal growth factor, DHT levels, and antagonist activ-ity at the nuclear estrogen receptor in the prostate after 3 months of treatment with saw palmetto in patients with BPH.

Clinical Trials

The most recent review involved 30 randomized controlled trials in men with symptoms consistent with BPH. Fourteen trials used saw palmetto monotherapy compared to placebo and found no significant improvement in most urologic symptoms (eg, interna-tional prostate symptom scores, peak flow, prostate size). Although nocturia was significantly improved with saw palmetto compared to placebo, when studies were limited to those of higher quality and larger sample size, this significance was lost. In contrast, saw palmetto, 320 mg/d, was shown to have comparable efficacy to 5 mg/d of finasteride (a prescription 5α-reductase inhibitor) and 0.4 mg/d of tamsulosin (a prescription α blocker) in one random-ized, double-blind, clinical trial each, lasting 6 months and 1 year, respectively. These two trials lacked placebo controls.

Adverse Effects

Adverse effects are reported with an incidence of 1–3%. The most common include abdominal pain, nausea, diarrhea, fatigue, head-ache, decreased libido, and rhinitis. Saw palmetto has been associ-ated with a few rare case reports of pancreatitis, liver damage, and increased bleeding risk, but due to confounding factors, causality remains inconclusive. In comparison to tamsulosin and finas-teride, saw palmetto was claimed to be less likely to affect sexual function (eg, ejaculation).

Drug Interactions, Precautions, & Dosing

No drug-drug interactions have been reported for saw palmetto. Because saw palmetto has no effect on the PSA marker, it will not interfere with prostate cancer screening using this test. Recommended dosing of a standardized dried extract (containing 85–95% fatty acids and sterols) is 160 mg orally twice daily. Patients should be instructed that it may take 4–6 weeks for onset of clinical effects.