Serenoa repens (Saw Palmetto)

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Chapter 122 Serenoa repens (Saw Palmetto)

Serenoa repens (family: Arecaceae)

Common names: saw palmetto, palmetto scrub, Sabal serrulata

image Chemical Composition

Saw palmetto berries contain about 1.5% of a fruity-smelling oil containing saturated and unsaturated fatty acids and sterols.1 About 63% of this oil is composed of free fatty acids, including capric, caprylic, caproic, lauric, palmitic, and oleic acids. The remaining portion is composed of ethyl esters of these fatty acids and sterols, including beta-sitosterol and its glucoside. The lipid-soluble compounds are thought to be the major pharmacologic components. Other components of the berries are proanthocyanidins, carotenes, lipase, tannins, and sugars.

The purified fat-soluble extract, the most researched medicinal product, contains 85% to 95% fatty acids and sterols. It is made up predominantly of a complex mixture of saturated and unsaturated free fatty acids, their methyl- and ethyl-esters (approximately 7%), long-chain alcohols in free and esterified forms, and various free and esterified sterol derivatives.

image History and Folk Use

The American Indians, and later eclectic and naturopathic physicians, used saw palmetto berries in the treatment of genitourinary tract disturbances and as a tonic to support the body nutritionally.2,3 This substance was strongly recommended as a remedy for symptoms of benign prostatic hyperplasia as early as 1919.4 It was used in men to increase the function of the testicles and relieve irritation in mucous membranes, particularly those of the genitourinary tract and prostate. Saw palmetto has been used in women with disorders of the mammary glands; long-term use was reputed to cause the breasts to enlarge slowly.2 Many herbalists have regarded saw palmetto as an aphrodisiac.1

image Pharmacology

A standardized liposterolic (fat-soluble), saw palmetto berry extract has demonstrated numerous pharmacologic effects relating to its primary clinical application in the treatment of benign prostatic hyperplasia (BPH), a common disorder of the prostate gland. Saw palmetto extract affects BPH through multiple mechanisms, including inhibition of the intraprostatic conversion of testosterone to DHT and of its intracellular binding and transport, antiestrogenic, and receptor site–binding effects.57

Estrogen may contribute to BPH because it inhibits the hydroxylation and subsequent elimination of DHT. Serenoa appears to inhibit the activity of estrogen in the prostate. For example, in a double-blind study of 35 men with BPH, 18 were given the saw palmetto extract at 160 mg twice daily and 17 were given placebo.5 At the end of the 90-day study, the men receiving the saw palmetto extract had significantly lower cytosol and receptor values for estrogen and progesterone than the placebo group. The results imply that at least part of the efficacy of the saw palmetto extract is due to its antiestrogenic effect.

There was no change in the number of cytosol androgen receptors, but the number of nuclear androgen receptors was significantly lower in the saw palmetto group (60% of the placebo group tested positive for the nuclear receptor, compared with 10% of the saw palmetto group). These results indicate that the saw palmetto extract probably competitively blocks the translocation of the cytosol androgen receptor to the nucleus.

Preliminary analysis of the extract demonstrates that separate fractions are responsible for the antiandrogenic and antiestrogenic effects. Researchers in this study said, “It cannot be excluded, however, that the primary effect is antiestrogenic and that the inactivation of androgen receptors and progesterone receptors and of the 5-α-reductase activity is secondary to the estrogen receptor blockade.”7

Serenoa standardized extracts do not affect systemic levels of androgens, follicle-stimulating hormone, or luteinizing hormone in men with BPH.8 This may help explain the relatively low incidence of adverse effects of this substance in clinical trials. These findings do not, however, rule out localized effects of saw palmetto on androgen or estrogen effects in other tissues of the body.

Various locally produced growth factors also play a role in the pathogenesis of BPH, and liposterolic extracts of Serenoa block the ability of one of them, basic fibroblast growth factor, to induce prostatic hyperplasia in vitro.9 High prolactin levels may also stimulate prostate hyperplasia; Serenoa extracts interfere with this process in rats but the drug finasteride does not.10

Saw palmetto extracts exert antispasmodic effects on smooth muscle. Rat smooth muscle was originally shown to be inhibited by two Serenoa extracts owing to inhibition of calcium ion influx.11 A later study found that Serenoa extract but not pumpkin seed extract, stinging nettle root extract, or β-sitosterol consistently inhibited human α1-adrenergic receptors in vitro.12 Whether this effect is relevant clinically is still unknown.

The standardized extract has demonstrated antiedematous effects, and the polysaccharide components have been shown to have immunostimulatory effects.13,14 Serenoa extract and myristoleic acid induced apoptosis and necrosis in an androgen-sensitive human prostate cancer cell line in vitro.15

image Clinical Applications

The primary clinical application of saw palmetto berries (specifically the fat-soluble extract) is in the treatment of men with BPH. There is also preliminary evidence that saw palmetto may also help counter male-pattern baldness. On the basis of its pharmacology, this extract may also be of benefit in conditions of androgen excess in women, such as hirsutism and polycystic ovary disease.

Benign Prostatic Hyperplasia

The major symptoms of BPH (increased urinary frequency, nighttime awakening to empty the bladder, and reduced force and caliber of urination; see Chapter 152), have been shown to be significantly improved by saw palmetto extract in more than a dozen double-blind placebo-controlled clinical trials (summarized in Table 122-1).1629 At least three meta-analyses have combined data from these and other trials and concluded that, despite some limitations in trial design, Serenoa extracts have been shown to reduce symptoms of BPH and increase urine flow in comparison with placebo without affecting prostate volume.3033 One of these analyses also concluded that Serenoa

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