Saw Palmetto Supplement Use and Prostate Cancer Risk Raven M. Bonnar-Pizzorno, Alyson J. Littman, Mark Kestin, and Emily White Abstract: Saw palmetto is an herb used to treat the symp- toms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50–76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto–containing multivitamins over the previous 10 yr in addition to other information on supplement intake, med- ical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the west- ern Washington Surveillance, Epidemiology, and End Re- sults cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw pal- metto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer develop- ment [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74–1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw pal- metto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk. Introduction Prostate cancer is the most common non-skin cancer and has the second highest cancer death rate in men (1). Age, family history of prostate cancer, and race are the only well-established risk factors for the disease. Identifying modifiable risk factors could help decrease the incidence and mortality rates of prostate cancer. Saw palmetto’s use in the treatment of benign prostatic hyperplasia (BPH) (2,3) and its purported mechanism of ac- tion have prompted researchers to consider its possible effi- cacy in decreasing the risk of prostate cancer. Saw palmetto supplements are derived from the berries of the plant Serenoa repens, which is native to the South Atlantic coast of the United States and other areas. About 2% of American men use saw palmetto supplements (4). Popular saw palmetto supplements are available as encapsulated, powdered berries in doses of 900 mg or above or as a lipid and sterol extract in doses of about 160 mg (5). Although BPH is not considered a precursor for prostate cancer pathologically, 83% of prostate cancers occur in men with BPH (6), and both conditions respond to anti-androgen treatment and share common risk factors (7). Saw palmetto is thought to treat BPH by inhibiting the 5-α-reductase enzyme (8–17), which irreversibly converts testosterone to the more potent androgen dihydrotestosterone (DHT), although con- flicting evidence exists (18–20). The Prostate Cancer Preven- tion Trial found that treatment with finasteride, a strong 5-α-reductase inhibitor also used to treat BPH, decreased the risk of developing prostate cancer (21). In vitro studies have described other mechanisms of action for saw palmetto, such as inhibiting DHT from binding to androgen receptors (22,23), diminishing estrogen (24), and decreasing inflam- mation (25–27). These associations have prompted scientists to investigate whether saw palmetto is active against prostate tumors in in vitro studies. Saw palmetto lipidosterolic extract appears to inhibit the growth of LNCaP (27–31), PC-3 (29,31), 267B-1 (27), and BRFF-41T (27) cancerous human prostatic cell lines in vitro when used in physiologically plausible doses (32). This extract has been found to inhibit cancerous prostate cell growth through several different mechanisms, including apoptosis (27,30), necrosis (30), and growth inhibition (27–29). Saw palmetto also appears to tar- get prostate tissue. Active compounds in saw palmetto ex- tract, when taken orally, accumulate in the prostate gland preferentially over other organs in rats (33), although no studies have examined saw palmettos activity against pros- tate cancer in rodent models. The only human studies involving saw palmetto and pros- tate cancer have been on the use of saw palmetto for treat- ment of prostate cancer, including clinical studies of the saw palmetto–containing formula PC-SPES (34–36), and two case reports of aggressive prostate cancer treated with a com- bination of saw palmetto and other supplements in the ab- sence of conventional treatment (37,38). PC-SPES includes eight herbs and was withdrawn from the market in 2002 due to contamination with synthetic estrogens (39), thus limiting our ability to speculate on the role saw palmetto may play rel- NUTRITION AND CANCER, 55(1), 21–27 Copyright © 2006, Lawrence Erlbaum Associates, Inc. R. Bonnar-Pizzorno and M. Kestin are affiliated with the School of Nutrition and Exercise Science, Bastyr University, Kenmore, WA 98028–4966. A. Littman and E. White are affiliated with the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA.