Human Studies

Saw palmetto extract in a dose of 160 mg or placebo three times daily was administered to 35 elderly men, and prostatic tissue was collected (14). The investigators found that some component of the saw palmetto extract inhibits nuclear estrogen receptors in the prostates of patients with BPH patients.

Clinically, 160 mg of Permixon® twice daily was superior to placebo in a double-blind trial in 110 men with BPH (15). A statistically significant (p < 0.001) benefit compared to placebo was seen in nocturia, flow rate, postvoid residual, self-rating, physician rating, and dysuria. Compared with baseline, both placebo and saw palmetto were beneficial in improving nocturia (p < 0.001), but only saw palmetto improved flow rate and postvoid residual compared to baseline (p < 0.001). Headache was the only adverse effect. A doubleblind study (16) compared Proscar® (finasteride, a prescription 5a-reductase inhibitor), 5 mg daily, with Permixon, 160 mg twice daily for 6 months. Both finasteride and saw palmetto improved International Prostate Symptom Score (I-PSS) and quality of life compared to baseline, with no statistical difference between the two treatments. Finasteride improved peak urinary flow rate more than saw palmetto (p = 0.035), and residual volume was decreased more with finasteride than with saw palmetto (p = 0.017). Finasteride decreased prostate volume more than saw palmetto (p < 0.001), and only finasteride decreased PSA compared with baseline (p < 0.001). Although only one patient in each treatment group withdrew because of sexual problems, the finasteride patients experienced a statistically significant deterioration in the sexual function score compared with baseline (p < 0.01). Twice as many pa tients withdrew from the saw palmetto group because of side effects (28 vs 14), but there were no statistically significant differences noted between the two groups in regard to any adverse effect. Hypertension was the most common adverse effect, occurring in 3.1% of the saw palmetto patients and 2.2% of the finasteride patients. Other adverse effects included decreased libido, abdominal pain, impotence, back pain, diarrhea, flulike illness, urinary retention, headache, nausea, constipation, and dysuria. A drawback of this study is that no placebo group was included; more data on the efficacy of these two drugs compared to placebo are needed.

The findings of Carraro and colleagues discussed previously suggest that Permixon does not affect PSA. These results were confirmed by an in vitro study in which Permixon 10 ^g/mL (calculated plasma concentration achieved with therapeutic doses), did not interfere with secretion of PSA (17). These findings imply that PSA can continue to be used for prostate cancer screening in men taking saw palmetto.

Another randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of lower urinary tract symptoms also demonstrated its usefulness in these types of conditions (18). These investigators studied 85 men, randomized to receive either saw palmetto or placebo for 6 months. Effectiveness was monitored using the I-PSS, a sexual function questionnaire and urinary flow rate. Results of these studies demonstrated that the I-PSS symptom score decreased (i.e., improved) from 16.7 to 12.3 in those subjects receiving saw palmetto, whereas the symptom score decreased from 15.8 to 13.6 in the placebo group (p = 0.038). No significant difference was noted in the quality of life component of the I-PSS. Also, no differences were noted in either the sexual function questionnaire score or peak urinary flow rate between the saw palmetto and placebo groups. This study demonstrated that saw palmetto administration for 6 months resulted in an improvement in symptoms associated with BPH but not in sexual function or peak flow rate.

Several well-conducted studies of saw palmetto effect on BPH symptoms have been conducted using combination products that may have additional active ingredients. Marks and colleagues (19) evaluated the effectiveness of a saw palmetto herbal blend (saw palmetto, nettle root extract, pumpkin seed oil extract, lemon bioflavonoid extract, Vitamin A, and other minor ingredients) in subjects with symptomatic BPH. Using a double-blind, placebo-controlled trial design, 44 subjects were investigated (n = 21 in the saw palmetto herbal blend group and n = 23 in the placebo group) following treatment for 6 months. Prostate epithelial contraction was noted where percent epithelium decreased from 17.8% at baseline to 10.7% at 6 months in the saw palmetto herbal blend treatment group (p < 0.01). Saw palmetto treatment increased the percent of atrophic glands from 25% to 41% (p < 0.01). Neither treatment (saw palmetto or placebo) altered PSA or prostate volume. Another group of investigators studied the effect of saw palmetto herbal blend (same ingredients as previously mentioned) on nuclear measurements of DNA content in men with symptomatic BPH (20). Using nuclear morphometric descriptors (NMDs) (size, shape, DNA content, and textural features) of the nucleus of prostatic tissue, 6-month treatment of saw palmetto herbal blend was compared to placebo control. After 6 months, 25 of the 60 NMDs were significantly different in the saw palmetto treatment group, whereas none were changed in the placebo group. These investigators then used four of these 25 altered NMDs to develop a multivariate model that was proposed to be predictive of treatment effect. These investigators proposed that saw palmetto herbal blend treatment alters the DNA chromatin structure and organization of prostate epithelial cells. Using a different combination formula containing saw palmetto (saw palmetto, cernitin, ^-sitosterol, and Vitamin E), Preuss and colleagues conducted a 3-month randomized, placebo-controlled trial in 127 subjects of this formulation in the treatment of BPH symptoms (21). These investigators found that treatment with this saw palmetto-containing product results in a statistically significant decrease in nocturia severity (p < 0.001, daytime frequency (p < 0.04) and the American Urological Association symptom index was significantly improved (p < 0.001). No change in PSA measurements, maximal and average urinary flow rates, or residual volumes was noted. Furthermore, no adverse effects were noted in either group.

A number of studies evaluating the effects of saw palmetto on BPH and urinary symptoms have been conducted that lack placebo controls, comparing saw palmetto to another agent or looking at longitudinal effect. Kaplan and colleagues (22) conducted a 1-year prospective trial of saw palmetto vs finasteride for the treatment of category III prostatitis/chronic pelvic pain syndrome. Finasteride significantly decreased (~25%) the National Institutes of Health Chronic Prostatitis Symptom Index score, whereas saw palmetto had no effect on this measure. Finasteride also improved quality of life and pain measures but not urination. These authors concluded that saw palmetto resulted in no appreciable long-term improvement in category III prostatitis/ chronic pelvic pain syndrome. However, this study suffers from lack of placebo control. Al-Shukri et al. (23) studied the effects of Permixon on lower urinary tract symptoms caused by benign prostatic hyperplasia. These investigators administered Permixon 160 mg twice daily for 9 weeks and compared the results to a control group who received no treatment at all. Permixon treatment increased maximum flow rate by 6% (p < 0.001), decreased maximum detrusor pressure by 12.8% (p < 0.001) and reduced residual urine volume by 12.6% (p < 0.001). Furthermore, the I-PSS and the quality of life score improved (26.8 and 18.2%, respectively) in treated patients. Control subjects exhibited no change in any of these parameters. Again, this study lacks a placebo treatment group to assess any possible placebo effects. Treatment with Permixon of symptoms related to BPH has also been evaluated in a 2-year study of effect on symptoms, quality of life, and sexual function (24). These investigators studied 150 men receiving Permixon 160 mg twice daily for 2 years. The I-PSS score improved by 41% at the end of 2 years. Approximately one-half of the subjects had improvements in obstructive and irritative symptoms, and a 40% improvement in quality of life score was noted. Again, no control group and no placebo group were used and thus any placebo effect could not be discerned.

A meta-analysis (6) of randomized trials comparing saw palmetto to placebo or other therapy was recently published. The authors concluded that despite methodology problems, saw palmetto appears to improve urologic symptoms and urinary flow to an extent similar to that of finasteride, but with fewer adverse effects.

Interestingly, saw palmetto has also been studied in a randomized, doubleblind, placebo-controlled trial for the treatment of androgenetic alopecia (25). Subjects received either active formulation or placebo for an average of 5 months. In the 10 subjects studied, six of the subjects (60%) were determined to have significant improvement in hair growth as assessed by both the investigators and the subject.

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