Acupuncture has a potential role in multiple areas of urology—for example, hot flash reduction from androgen-deprivation treatment (ADT) [3], overactive bladder [4], monosymptomatic nocturnal enuresis [5], stress, and other forms of incontinence [6]—so it should not be surprising that acupuncture may have some role in alleviating BPH/LUTS [7]. Acupuncture can be delivered traditionally with needle insertion in a specific anatomical area or be primarily auricular or given as electroacupuncture. However, there are not enough data to recommend acupuncture for BPH/LUTS, and some small past studies suggest no clinical efficacy with this procedure [8]. Yet, theoretically by reducing blood pressure in some patients temporarily and other forms of sympathetic activity or insomnia in some clinical trials [9–11], it appears that some men could benefit by using acupuncture for adjuvant treatment of BPH/LUTS. Again this is based on theoretical benefits and no overt positive data. Patients should be careful about the out-of-pocket costs of any alternative medicine such as acupuncture, and in most clinical trials treatments are given just once or twice every 1–2 weeks and not daily.

Phytosterols are found in a variety of plants and plant oils [12]. Phytosterols are similar in structure to cholesterol, except for minor structural differences. They are not synthesized in humans and minimally absorbed, excreted more rapidly from the liver compared to cholesterol, and not found in high concentrations in human tissues. The main phytosterols found in diet are sitosterol, stigmasterol, and campesterol. Beta-sitosterol is arguably the phytosterol found in largest quantity in the diet. Phytosterols block the uptake of exogenous cholesterol from dietary and bile sources in the intestinal tract. LDL cholesterol is reduced by phytosterols, and HDL and triglycerides are not impacted. The blockage of cholesterol absorption may produce a relative cholesterol pool reduction that is followed by upregulation of cholesterol synthesis and LDL receptors, which can increase LDL removal. This is somewhat similar to how some healthy dietary fats found in many healthy foods, such as almonds or pistachios, may also reduce LDL and improve some specific urologic outcomes [13, 14].

An ample quantity of (over 40) clinical trials utilizing phytosterols themselves have been conducted that have ranged from 1 to 12 months in duration [12, 15, 16]. Plant sterols added to foods such as yogurt, margarine, orange juice, mayonnaise, olive oil, and milk have been shown to reduce LDL by approximately 10–15 % (mean of 10–11 %) when approximately 2,000 mg or more per day is ingested. And, 1,600–3,000 mg of plant sterol supplemental or tablet consumption can also reduce LDL by approximately 4–15 %. Plant sterols may also reduce the absorption of some fat-soluble vitamins, so there has been some debate as to whether multivitamin consumption should occur with the use of these products, and I agree that this should also be encouraged.

It is interesting that the primary mechanism of action of these sterols via cholesterol uptake reduction and a minor anti-inflammatory mechanism suggests, in my opinion, that they are weaker or less potent mimics of the drug ezetimibe (Zetia, Merck & Co., West Trenton, NJ), which can reduce LDL by approximately 20 % with a 10-mg dose [17, 18]. Laboratory research suggests ezetimibe favorably impacts prostate tissue and reduces BPH [19]. Ezetimibe is also commonly added to statin therapy or other lipid-lowering agents to achieve synergistic impacts and more favorably reduce LDL [17, 18]. Thus, it should not be surprising that beta-sitosterol by itself or with other lipid-lowering medications could reduce BPH progression and LUTS. For example, despite some data to suggest no impact of statins on established BPH over a short period of time [20, 21], other epidemiologic and past laboratory studies suggest potentially favorable impacts on BPH prevention and progression with cholesterol-lowering prescribed medications [22–25].

There are two critical and similar reviews that were published in 1999 that have allowed beta-sitosterol supplements to become a potential option for BPH [26, 27]. It is interesting that since this time period no other definitive clinical trials (positive or negative) have been published.

The first systematic review by Wilt et al. appeared in BJU International and identified studies from 1966 to 1998 [26]. A total of four clinical trials that included 519 men met the inclusion criteria [28–31]. All four were randomized, double-blind, placebo-controlled trials that included men with mild to moderate symptomatic BPH, and the intervention was given from 4 to 26 weeks. Beta-sitosterol significantly improved symptom scores and flow measures compared to placebo. For the two studies using IPSS scores, there was a −4.9 point difference (35 % urinary symptom score improvement), a 31 % improvement in quality-of-life score (one study), and the weighted mean difference for peak urinary flow rate and residual volume was 3.91 mL/s (45 % improvement) and −28.62 ml (24 % improvement) when all four studies were included. Beta-sitosterol had no impact on prostate size. It is interesting that a past animal study found that purified beta-sitosterol can inhibit 5-alpha reductase [32], but the inhibitory activity was dramatically lower compared to what has been observed with the drug finasteride, for example, in laboratory studies.

One of the four studies utilized in the meta-analyses utilized a unique form of beta-sitosterol known as “B-sitosterol-B-D-glucoside” (WA184), but this form did not improve urinary flow measures [28] compared to the positive benefits observed with higher doses (20 or 65 mg TID or 60–195 total per day) of beta-sitosterol within a mixture of phytosterols used in the other three effective clinical trials [29–31]. Overall, there were no differences in withdrawal rates in the beta-sitosterol (7.8 %) compared to the placebo groups (8.0 %) [26]. Gastrointestinal side effects were the most common side effects and occurred in 1.6 % of men on beta-sitosterol compared to 0 % on placebo. Erectile dysfunction was reported in approximately 0.5 % of men on beta-sitosterol and none on placebo. The authors of this systematic review concluded that beta-sitosterol “improves urological symptoms and flow measures” but that more long-term studies and standardization of beta-sitosterol preparations were needed. The beta-sitosterols utilized in these studies were known by the names Harzol, Azuprostat, or WA184, usually derived from South African star grass (Hypoxis rooperi or from species of Picea or Pinus). Studies used purified extracts, and three studies used “nonglucosidic B-sitosterol,” again from 60 to 195 mg/day (two of these studies used Azuprostat, 65 mg TID or 195 mg/day with a 70 % beta-sitosterol content). The preparation generally contained 50 % or higher amounts of B-sitosterol. The mean age of participants was 65 years (34–85 year range), mean baseline International Prostate Symptom Score (IPSS) was 15.2 points, maximum urinary flow rate (Q _max) of 10.2 mL/s, postvoid residual urine volumes (PVR) of 73.3 mL, and a prostate size of 49.1 mL. Again, it is of interest that all three studies that used nonglucosidic B-sitosterol found significant improvements in urinary symptoms, Q _max, and PVR compared to placebo. The single study that used a purified B-sitosterol B-D-glucoside preparation (also known as WA184) found no improvement in Q _max, PVR, and prostate size.

The second review was published in 2000 and consisted of similar authors compared to the first review [27]. The results published in this review were identical to those published in the first review. However, there was a discussion of statistical significance and nocturia results in this review that mentioned one study that looked at this impact and found that the weighted mean difference (WMD) was approximately −1.00 times in favor of beta-sitosterol [27, 29]. Test for overall effect of the meta-analysis found a statistically significant impact in favor of beta-sitosterol compared to placebo for IPSS (p < 0.00001, two studies), quality of life (p < 0.00001, one study), patient evaluation of efficacy (p < 0.000011, one study), physician evaluation of efficacy (p < 0.000019, one study), nocturia (p = 0.0089, one study), peak urinary flow (p = 0.011, four studies), peak urinary flow sensitivity analysis (p = 0.00027, three positive studies only included), residual volume (p = 0.000012), residual volume sensitivity analysis (p < 0.00001, three positive studies only included), but not prostate size (p = 0.18, two studies). It is noteworthy that prostate size was reduced compared to placebo in two studies by a mean difference of −6.50 and −4.97 cc, favoring beta-sitosterol, but this was not enough to reach statistical significance, which is of interest because again there is some preliminary evidence that beta-sitosterol could mildly inhibit 5-alpha reductase [32]. The positive results observed in these trials compare with results from pharmaceutical agents. Although beta-sitosterol was considered the active ingredient in these clinical trials, this has not been definitively proven, but it is reasonable to conclude that it is the most likely or primary efficacious ingredient. The need for surgery, acute urinary retention rates, or the overall ability to prevent BPH complications are items that would be more helpful in a more long-term study of beta-sitosterol or any intervention.

The clinical question is why not just try beta-sitosterol, a heart-healthy ingredient with or without medications for BPH? The dosage recommended in cholesterol treatment guidelines is 2,000–3,000 mg a day to reduce LDL by 6–15 %, and in fact in these National Cholesterol Education Panel recommendations it states the following: “Plant stanol/sterol esters (2 g/day) are a therapeutic option to enhance LDL cholesterol lowering” [33]. Keep this in mind when consulting with patients about beta-sitosterol for BPH, because it is important to be able to discuss the efficacious dosages from the older 1990 studies (20–65 mg TID) compared to the heart-healthy guidelines of plant stanol/sterols to reduce LDL cholesterol (2,000–3,000 mg/day). Personally, I have few concerns about whether or not beta-sitosterol would interfere with any prescription BPH medications or cause any drug-supplement reactions, but again this is based on experience and not on any research.

Interestingly, cernilton is a fairly well known dietary supplement in urology because it has been shown to significantly improve quality of life and reduce pain in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) compared to placebo [34–36]. However, it has not been shown in these patients to consistently improve urinary flow measures, and this should be kept in mind when trying to apply this data to the BPH/LUTS studies. Cernilton, the original phytotherapeutic extract, is currently a mixed pollen extract (see the chapter on chronic prostatitis for more detail), and it is generally composed of a water-soluble pollen fraction and an acetone-soluble extract fraction that contains some beta-sterols.

One past meta-analysis has been published on cernilton that included 444 men (163 in placebo-trials and 281 in comparative trials) from four clinical trials that were 12–24 weeks in duration; the mean age was 69 years old (range 42–89 years) [37]. Two studies were placebo-controlled and two were comparative trials against another supplement agent (Pygeum africanum or Paraprost = 265 mg of L-glutamic acid, 100 mg of L-alanine, and 45 mg of aminoacetic acid). Cernilton was not more effective compared to placebo or other comparative interventions in the area of objective measures, including urinary flow rates, residual volume, or prostate size. Cernilton did improve subjective symptoms, such as reduced nocturia compared to placebo, and WMD was −0.40 times per evening. Side effects were mild and rare, and the withdrawal rate was 4.8 % versus to 2.7 % (p = 0.26), and 5.2 % for Paraprost. In these studies, one dose of cernilton contained 60 mg of Cernitin T60, a water-soluble extract fraction, and 3 mg of an acetone-soluble extract fraction known as Cernitin GBX. Cernilton dosages were not reported in three studies, and it was not known if a standardized extract was utilized. In another trial of 12 weeks, men utilized 63 mg of cernilton twice daily. A recent similar review of this meta-analysis arrived at similar conclusions but appeared to be more of an advocate of the potential use of cernilton for BPH [38]. A primary mechanism of action is difficult to determine because an older laboratory study found that it may reduce prostate size [39], but this again was not found in the meta-analysis [37]. Interestingly in the CP/CPPS studies there were suggestive anti-inflammatory and muscle relaxation effects in the prostate and perhaps bladder and urethra [34–36], which could be occurring in the BPH studies.

Interestingly, a study from Shanghai, China, of 240 BPH patients with an IPSS >7 utilized 350 or 750 mg of cernilton twice a day for 4 years [40]. Improvement was more rapid in the high-dose group. The study itself was published in Chinese, but significant improvements for the high-dose (over the low-dose) form were found for IPPS (20–10), prostate volume (38–29 mL), PVR (42–15 mL), and Q _max (10–16 mL/s) and a significantly lower rate of urinary retention and surgery, and there were no significant prostate-specific antigen (PSA) changes. No toxicity or adverse effects were found. This is an interesting clinical trial because it at least raises the question of whether or not utilizing higher dosages of cernilton might make more clinical sense for BPH/LUTS or at least should be tested in a future clinical trial. A primary mechanism of action is difficult to determine because an older laboratory study found that it may reduce prostate size [40], but in the CP/CPPS studies there were suggestive anti-inflammatory and muscle relaxation effects in the prostate and perhaps bladder and urethra [34–36]. Regardless, although this agent certainly has data in chronic nonbacterial prostatitis (CP/CPPS) and could be utilized for this condition, it does not have consistent impressive data for BPH/LUTS, and further clinical research is needed in this area. Personally, I am not concerned about the use of this product with and without conventional medicine in terms of interactions, but again this is based on experience and not clinical research. My biggest concern is that this supplement simply has not received enough recent clinical data or attention.

It is also of interest that a flaxseed-derived supplement made of purified lignan (phytoestrogen) extract (secoisolariciresinol diglucoside, or SDG) at 300 or 600 mg/day showed favorable and significant results compared to a placebo in a clinical trial of 87 participants over a 4-month period [41]. IPSS were reduced by approximately 7 points in the intervention arms compared to 3.5 points in the placebo group, with additional improvements in quality of life. Similar SDG derivatives of a variety of doses have also now been found to preliminarily and significantly reduce cholesterol and glucose values [42, 43]. Whether or not ingesting low-cost flaxseed as well as an SDG supplement will reduce BPH symptoms has not been studied, but it is worthy of an attempt for some individuals because these interventions are at least heart healthy. Dietary flaxseed is one of the largest dietary plant sources of omega-3 fatty acids, fiber, and phytoestrogens [44]. Most flaxseed dietary supplements do not contain fiber but at least are excellent sources of omega-3 and/or phytoestrogens. Regardless, whether the supplements provide some benefit beyond the cost-effective dietary sources (seeds and powder) is questionable, especially in terms of BPH, but this has not been studied. A preliminary clinical trial that examined tissue from BPH patients before and after three rounded tablespoons of ground flaxseed (30 g total per day for 6 months) were utilized daily along with a low-fat diet found significant reductions in PSA, cholesterol, and tissue proliferation rates [45]. A subsequent randomized trial from this same group found that proliferation rates were impacted more by flaxseed alone compared to a low-fat diet in men with prostate cancer [46]. These are encouraging dietary flaxseed studies, but again they were not compared to flaxseed supplements. Thus, one could argue right now that dietary flaxseed powder (2–3 tablespoons per day) and/or an SDG supplement from flaxseed could be utilized with and without conventional therapy. Despite minimal clinical data overall, I am an advocate of flaxseed for BPH and health simply because in the worst-case scenario it is a heart-healthy intervention [43, 44], which is a good “first do no harm” and beneficial approach. Other strong sources of phytoestrogens, such as soy products or soy supplements, have not accumulated positive data in BPH, but at least dietary (not soy dietary supplements) soy products are also heart healthy.

The oil found in the pumpkin (Cucurbita pepo) seed is a commonly used salad oil in Austria, Hungary, and Slovenia, and it is produced by cleaned seeds that are dried, grounded, kneaded, roasted, and then pressed at 100–130 °C [47]. It is of interest that four fatty acids comprise 98 % of the total and include linoleic acid (C18:2, 36–61 %), oleic acid (C18:1, 21–47 %), palmitic acid (C16:0, 9.5–14.5 %), and stearic acid (C18:0, 3–7.5 %). Thus, the majority of the fatty acids in pumpkin seed are mono- and polyunsaturated. It is also high in alpha- and gamma-tocopherol and tocotrienol (vitamin E) and carotenoids, including lutein and zeaxanthin. It is also of interest that pumpkin seed oil contains a high content of plant sterols.

Pumpkin seed oil has preliminary past laboratory data to suggest that it may inhibit testosterone-induced hyperplasia of the rat prostate [48]. Basic science work suggests multiple potential mechanisms of action, including reducing prostate weight, protein content, and prostatic acid phosphatase levels, altering cholesterol metabolism, and increasing the testosterone-to-estradiol ratio [49]. This also suggests a potential preventive role for pumpkin seed oil and BPH.

A past small trial found that the combination of saw palmetto and pumpkin seed oil resulted in a significant increase in Q _max in BPH patients after 3 months [50]. Another older study of pumpkin seed for 12 months demonstrated an improved IPSS of at least 5 points and a 65 % overall improvement [51]. A more recent randomized, double-blind, placebo-controlled trial over 12 months of 47 BPH patients (mean age 53 years and IPSS >8) was published [52]. Subjects received placebo, 320 mg/day pumpkin seed oil, 320 mg/day saw palmetto oil, or the combination of these two nutraceuticals. None of the measurements significantly improved with the combination of pumpkin seed and saw palmetto compared to the single interventions. Prostate volume was not impacted in any group, but the baseline volumes were in the range of 21–27 mL. However, the IPSS scores were significantly reduced after 3 months in all intervention groups (−34 % change with pumpkin seed, −25 % with saw palmetto, and −33 % with combination vs. 10 % with placebo). After 12 months there was a −58 % impact in IPSS compared to baseline in the pumpkin seed group, −50 % with saw palmetto, −75 % with the combination, and −39 % with placebo. There were no significant differences after 12 months in IPSS between intervention groups. Quality of life improved after 3 months in the pumpkin seed or saw palmetto groups and improved after 6 months in the combination groups, but after 12 months there was approximately a 40 % positive change with pumpkin seed or saw palmetto and a 58 % with the combination. Serum PSA was reduced after 3 months in the combination arm and after 12 months was significantly reduced by 42 % (1.2–0.7 ng/mL) compared to baseline. Q _max significantly improved after 6 months in the pumpkin seed–only group (by 14 % or 14.8–16.9 mL/s) and after 12 months in the saw palmetto–only group (51 %, from 14 to 21.2 mL/s), and combination experienced only a 5 % change after 12 months from 20.1 to 21.2 mL/s. One obvious limitation of this study is that the placebo group consisted of only seven subjects and the largest intervention group was the pumpkin seed oil group, with only 16 subjects. Another critical examination of the protocol is that the participants needed to take two capsules in the morning and two capsules in the evening after meals (four total capsules a day) for 12 months, which is not a simplistic compliance-enhancing protocol. Basically, this small clinical trial of a long duration for a BPH supplement study did not demonstrate that the combination of pumpkin seed and saw palmetto was significantly better compared to pumpkin seed only, for example. It may have suggested that utilizing more than one nutraceutical in a regimen may reduce PSA, and it suggests that utilizing either pumpkin seed or saw palmetto or the combination is as safe as a placebo.

Pumpkin seed oil appears to be a safe intervention for BPH that can be utilized with and without conventional treatment options. It seems that 320 mg/day is an appropriate dosage, but there are not enough clinical data thus far to feel confident that it is an effective dietary supplement, but it appears to be a very safe dietary supplement. Regardless, pumpkin seed oil is an option, and it is rich in heart-healthy fatty acids, but if the number of pills daily from any manufacturer is more than one to two pills daily or if cost is an issue, then I would not be as excited to utilize this option for patients.

A 2002 meta-analysis of 18 Pygeum africanum clinical trials (17 were double blind) involving 1,562 men suggested a potential benefit with this supplement [53]. This compound(s) is an extract of the African prune tree. The majority of the studies utilized a standardized extract effective at approximately 75–200 mg per day. In terms of the placebo-controlled trials, one study utilized 75 mg per day, seven utilized 100 mg per day, and four used a 200 mg/day dosage; one study did not report dosage. Mean age was 66 years (range 42–89 years), and nocturia was three times per evening with four studies at baseline. Out of 13 placebo-controlled trials, a total of 12 reported a positive impact on at least one measure of effectiveness (overall symptoms, nocturia, peak urine flow, or residual volume). The mean duration of clinical studies was 64 days (range of 30–122 days), but men were more than two times as likely to report an improvement in overall symptoms, nocturia was reduced by 19 %, residual volume by 24 %, and peak urine flow increased by 23 %.

Again, all of the following providing statistical benefits with pygeum versus placebo:

Nocturia was reduced by almost one episode per night, but this failed to reach statistical significance. Whether or not pygeum actually reduces long-term complications of BPH, such as acute urinary retention, renal issues, or surgery, is not known. Pygeum has not been shown to shrink the prostate gland. The withdrawal rate was similar to placebo at 12 %. Adverse effects were similar to placebo, and the most frequently reported adverse effects were gastrointestinal.

It is also of interest that one of the main components of Pygeum africanum (similar to other nutraceuticals such as pumpkin seed and saw palmetto) consists of phytosterols that include beta-sitosterol [54, 55]. Most of the active substances in the Pygeum bark are lipid-soluble compounds triterpenes, ferulic acid esters, and phytosterols (B-sitosterol, B-sitosterone, and campesterol). However, the problem with pygeum is demand compared to precious supply, in that the bark is derived from an endangered tree [56]. This is not the case with most other BPH nutraceuticals, such as saw palmetto or pumpkin seed, which appear to be in abundance and have arguably a diverse number of heart-healthy compounds beyond beta-sitosterol, including the primary monounsaturated fat found in olive oil (oleic acid) and a variety of other potentially healthy dietary fats that may have the ability to increase HDL and lower cardiovascular events [57–60].

Pygeum africanum in reality has arguably the largest number of consistently positive clinical trials to date compared to almost any other nutraceutical product [53–56, 61], especially since the latest data on saw palmetto have not been impressive, even in moderate to higher dosages [62, 63]. Pygeum has been used in Europe since 1969 for the treatment of mild to moderate BPH. Multiple mechanisms of action have been proposed for pygeum, including the following [53–56, 61]:

Again, an adequate dosage for pygeum for BPH is 75–200 mg of an extract usually standardized to 14 % sterol content or higher, including beta-sitosterol, and generally given in two divided daily doses [53]. One brand sold outside the United States is Tadenan (France), which has been the source for older and more recent laboratory studies that suggest a clinical benefit [61], but the problem of whether or not most other companies are selling the actual pygeum utilized from some past studies, from the endangered African plum tree, or a new or altered version of it is a matter of debate. In other words, in my experience pygeum is fraught with issues, especially quality control, so try to investigate where the actual pygeum was derived before recommending or using it. Should real pygeum even be recommended today because real pygeum is endangered? A final issue with pygeum is the lack of any recent studies that could further define the efficacy of this compound.

One of the largest past reviews of clinical studies of saw palmetto for BPH found some interesting results in 1998 [64]. This analysis reviewed a total of 18 randomized trials (n = 2,939 men) and found that most of the studies were limited by their short duration and study design. However, the existing evidence suggested that this herbal product improves urologic symptoms and flow measures. Compared with the drug finasteride, saw palmetto produced similar improvement in urinary tract symptoms and urinary flow, with fewer side effects. However, saw palmetto had only been compared to current drug therapies for a maximum of approximately 12 months. More data are needed on this herbal product. Interestingly, the dosage of saw palmetto used in most randomized trials at this point in time was 320 mg/day, and this dosage had no effect on PSA levels.

Four years after this notable 1998 review was published, another one by similar authors added three new trials with 230 additional male participants that translated into a meta-analysis of 21 randomized trials. The conclusions were similar, with the authors simply stating that “The results of this update are in agreement with our initial review” [65]. In other words, saw palmetto could be an option that works as well as some pharmacologic agents but with fewer side effects. The authors then updated their original meta-analysis again in 2009 and came to this conclusion: “Serenoa repens was not more effective than placebo for treatment of urinary symptoms consistent with BPH” [66]. In 2012 another follow-up review by similar authors concluded with the following: “Serenoa repens therapy does not improve LUTS or Q _max compared with placebo in men with BPH, even at double and triple the usual dose” [67]. What happened that caused such a reversal in a long-standing recommendation or endorsement for saw palmetto? In the more recent meta-analysis, for example, there were nine new trials added to the analysis that included 2,053 more men (about 65 % increase), and overall there were 5,222 subjects from 30 randomized trials of a 4- to 60-week duration utilized, for example [66].

However, the answer to the question of what caused such a reversal in the saw palmetto enthusiasm lies first in a US government-funded trial called STEP (The Saw Palmetto for Treatment of Enlarged Prostates) [62], followed by the results of a more recent trial called CAMUS (Complementary and Alternative Medicine for Urological Symptoms) [63].

The STEP trial was simply a very well-done clinical trial [62], and the researchers and participants in this study should be commended for being a part of one of the better herbal studies ever completed in urology and in medicine (in my opinion). Saw palmetto enjoys a tremendous amount of sales around the world. Some areas of Europe have made this herbal product a prescription, but in the United States there are literally hundreds of over-the-counter brands. Florida and several coastal states are some of the largest exporters of this herbal product. This herbal product is so well known that it continues to be one of the more popular supplements taken by men to prevent prostate cancer, despite having no relevant evidence that it prevents prostate cancer [68, 69]. However, this is the concerning part, because saw palmetto has never had any credible data that it reduces the risk of prostate cancer. All of the preliminary data were for the improvement of BPH symptoms. Some researchers suggest it has a finasteride (a drug approved for BPH)-type effect, but unlike finasteride (also known as Proscar, Merck & Co., Whitehouse Station, NJ), it has not been shown to have any impact on PSA levels. Regardless, there was an ample need to conduct a non-industry-supported clinical trial to determine if saw palmetto really does have some efficacy. The STEP trial was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the National Center for Complementary and Alternative Medicine (NCCAM) [62].

In the STEP trial a total of 225 men with moderate to severe BPH symptoms were randomized to saw palmetto extract at a dosage of 160 mg twice a day (320 mg a day total) or placebo [62]. The primary outcomes were the change in score on the American Urological Association Symptom Index (AUASI), a subjective measurement completed by patients, and the maximal flow rate (an objective measure completed by the physician). There were also a number of secondary outcomes, including change in the prostate size, urine volume left in the bladder after urinating, quality of life, laboratory values, and side effects. Some of the baseline characteristics of the men that participated in the STEP trial are found in Table 3.1.

When the trial ended after 12 months of treatment, there was no difference between saw palmetto and placebo in all the major areas of study, including:

Numerous criticisms have been raised about this trial when I would lecture to public and health care professional groups, but let me answer some of the most popular inquires to demonstrate just how well this trial was designed and conducted.