Page 1155 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 64 Dietary Supplements & Herbal Medications 1141

SAW PALMETTO (SERENOA REPENS OR associated with a few rare case reports of pancreatitis, liver dam-
SABAL SERRULATA) age, and increased bleeding risk, but due to confounding factors,
causality remains uncertain. In comparison to tamsulosin and
Chemistry finasteride, saw palmetto was claimed to be less likely to affect
sexual function (eg, ejaculation).
The active constituents in saw palmetto berries are not well
defined. Phytosterols (eg, β-sitosterol), aliphatic alcohols, poly- Drug Interactions, Precautions, & Dosage
prenic compounds, and flavonoids are all present. Marketed
preparations are dried lipophilic extracts that are generally No drug-drug interactions have been reported for saw palmetto.
standardized to contain 85–95% fatty acids and sterols. Because saw palmetto has no effect on the PSA marker, it will
not interfere with prostate cancer screening using this test.
Pharmacologic Effects Recommended dosage of a standardized dried extract (containing
85–95% fatty acids and sterols) is 160 mg orally twice daily. The
Saw palmetto is most often promoted for the treatment of benign lack of positive results as noted in the review of randomized con-
prostatic hyperplasia (BPH). Enzymatic conversion of testosterone trolled studies cited above indicates that the use of saw palmetto
to dihydrotestosterone (DHT) by 5α-reductase is inhibited by in prostate disease cannot be recommended.
saw palmetto in vitro. Specifically, saw palmetto shows a noncom-
petitive inhibition of isoforms I and II of this enzyme, thereby
reducing DHT production. In vitro, saw palmetto also inhibits ■ PURIFIED NUTRITIONAL
the binding of DHT to androgen receptors. Additional effects
observed in vitro include inhibition of prostatic growth factors, SUPPLEMENTS
blockade of α adrenoceptors, and inhibition of inflammatory
1
mediators produced by the 5-lipoxygenase pathway. COENZYME Q10
The clinical pharmacology of saw palmetto in humans is not
well defined. One week of treatment in healthy volunteers failed Coenzyme Q10, also known as CoQ, CoQ10, and ubiquinone, is
to influence 5α-reductase activity, DHT concentration, or testos- found in the mitochondria of many organs, including the heart,
terone concentration. Six months of treatment in patients with kidney, liver, and skeletal muscle. After ingestion, the reduced
BPH also failed to affect prostate-specific antigen (PSA) levels, form of coenzyme Q10, ubiquinol, predominates in the systemic
a marker that is typically reduced by enzymatic inhibition of circulation. Coenzyme Q10 is a potent antioxidant and has been
5α-reductase. In contrast, other researchers have reported a reduc- heavily promoted for this reason. It may have a role in maintain-
tion in epidermal growth factor, DHT levels, and antagonist activ- ing healthy muscle function, although the clinical significance of
ity at the nuclear estrogen receptor in the prostate after 3 months this effect is unknown. Reduced serum levels have been reported
of treatment with saw palmetto in patients with BPH. Recent in Parkinson’s disease.
reports suggest that daily saw palmetto, as compared to daily tam-
sulosin (see Chapter 10), has greater anti-inflammatory activity on Clinical Uses
infiltrating prostatic cells in men with BPH-related lower urinary 1. Hypertension—In clinical trials, small but significant reduc-
tract symptoms at 3 months. The anti-inflammatory effects on tions in systolic and diastolic blood pressure were reported after
infiltrating prostatic cells may serve as a link between hormonal 8–10 weeks of coenzyme Q10 supplementation. The exact
changes and the remodeling process promoted by growth factors. mechanism is unknown but might be related to the antioxidant
The anti-inflammatory effects of saw palmetto also raise questions and vasodilating properties of coenzyme Q10. In three random-
as to the value of early initiation of BPH therapy as well as the ized, placebo-controlled trials, coenzyme Q10 was reported
value of early combination therapy with 5α-reductase inhibitors to significantly lower systolic and diastolic blood pressure by
(see Chapter 40).
11 mm Hg and 7 mm Hg, respectively, compared with no change
in the placebo groups. However, an exaggerated treatment effect
Clinical Trials may have occurred as adequate randomization, blinding, and
The most recent review involved 32 randomized controlled trials concealment of allocation have been questioned for these studies.
in 5666 men with symptoms consistent with BPH. Seventeen tri- Whether coenzyme Q10 can be used to lower blood pressure
als compared saw palmetto monotherapy with placebo and found remains unclear.
no significant improvement in most urologic symptoms (eg,
international prostate symptom scores, peak flow, prostate size). 2. Heart failure—Low endogenous coenzyme Q10 levels have
been associated with worse heart failure outcomes, but this associa-
Adverse Effects tion is likely because low levels are a marker for more advanced heart
failure, rather than a predictor of disease. Despite these findings,
Adverse effects are reported with an incidence of 1–3%. The coenzyme Q10 is often advocated to improve heart muscle function
most common include abdominal pain, nausea, diarrhea, fatigue, in patients with heart failure. According to the most recent meta-
headache, decreased libido, and rhinitis. Saw palmetto has been analysis, coenzyme Q10 was shown to improve ejection fraction