Biotin

Biotin is a B vitamin and part of the structure of a group of enzymes known as carboxylases.[1] The attachment of biotin to another molecule, such as a protein, is known as “Biotinylation.” Holocarboxylase synthetase (HCS) catalyzes the biotinylation of apocarboxylases (i.e., the catalytically inactive form of the enzyme) and of histones. Biotinidase catalyzes the release of biotin from histones and from the peptide products of carboxylase breakdown. Each carboxylase catalyzes an essential metabolic reaction:

• • Acetyl-CoA carboxylase I and II catalyze the binding of bicarbonate to acetyl-CoA to form malonyl-CoA. Malonyl-CoA is required for the synthesis of fatty acids. The former is crucial in cytosolic fatty acid synthesis, and the latter functions in regulating mitochondrial fatty acid oxidation.
  • Pyruvate carboxylase is a critical enzyme in gluconeogenesis—the formation of glucose from sources other than carbohydrates, for example, amino acids. Methylcrotonyl-CoA carboxylase catalyzes an essential step in the catabolism of leucine, an essential amino acid.
  • These functions are all part of the production of energy.

Selenium

In the journal Experientia, Bedwal and Bahuguna[2] have indicated: “Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. In the Journal of the National Cancer Institute, Taylor et al[3] reported that epidemiologic studies have shown that higher levels of selenium may slow prostate cancer tumor progression, and that selenium seems to accumulate in the prostate, and protect against DNA damage and increase apoptosis in cancer cells. In the Journal of the National Cancer Institute, Yoshizawa et al[4] reported on a case-control study within a prospective study of over 50,000 male health professionals in the U.S. One hundred eighty-one men were diagnosed with advanced prostate cancer and 181 matched controls were included. The results were that there was a significant inverse relationship between toenail selenium content and the risk prostate cancer. Individuals whose toenail selenium content was consistent with an average dietary intake of 159 mcg/day of selenium daily had a 65% lower risk of advanced prostate cancer compared to those with toenail selenium content consistent with an average intake of 86 mcg/day. In Cancer Epidemiology, Biomarkers & Prevention, Nomura et al[5] reported that within a prospective study of more than 9,000 Japanese-American men, a case-control study that examined 249 confirmed cases of prostate cancer and 249 matched controls found the risk of developing prostate cancer was 50% less in men with serum selenium levels in the highest quartile compared to those in the lowest quartile. In the Journal of Urology, Brooks et al[6] reported on a case-control study which found that men with prediagnostic plasma selenium levels in the lowest quartile were four to five times more likely to develop prostate cancer than those in the highest quartile. In the European Journal of Cancer, Brinkman[7] reported the results meta-analysis of 20 epidemiological studies, mainly case-control studies, which found that selenium levels in the serum or toenails were significantly lower in those with prostate cancer.

Zinc research

In the journal Experientia, Bedwal and Bahuguna[8] have indicated: “Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body.” In the Journal of Reproduction and Fertility, Kavanagh[9] indicated: “Human seminal plasma contains citrate, zinc, calcium and magnesium, secreted mainly by the prostate gland, in much higher concentrations than in other body fluids.” The aim of this study[10] was to determine how exercise affects thyroid hormones and testosterone levels in sedentary men receiving oral zinc for 4 weeks. The study included 10 volunteers (mean age, 19.47+/-1.7 years) who did not exercise. All subjects received supplements of oral zinc sulfate (3 mg/kg/day) for 4 weeks and their normal diets. The thyroid hormone and testosterone levels of all subjects were determined at rest and after bicycle exercise before and after zinc supplementation. The results were that TT3, TT4, FT3, and total and free testosterone levels decreased after exercise compared to resting levels before supplementation (p<0.01). Both the resting and fatigue hormone values were higher after 4 weeks of supplementation than the resting and fatigue values before supplementation (p<0.05). The results indicate that exercise decreases thyroid hormones and testosterone in sedentary men; however, zinc supplementation prevents this decrease. Administration of a physiologic dose of zinc can be beneficial to performance. Sexual dysfunction in chronic renal failure patients undergoing hemodialysis is common. It is demonstrated that the zinc level is significantly lower in the hemodialysis patients. In this clinical trial,[11] researchers investigated the effect of zinc supplement therapy on the serum levels of sexual hormones in hemodialysis male patients. Researchers carried out a clinical trial study including 100 of our male patients with end-stage renal disease on hemodialysis. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and zinc plasma level were measured in all of the patients. The patients received zinc supplement (zinc sulfate, 250 mg/day) for 6 weeks, and sex hormones and zinc plasma level were checked again. The results were that serum level of FSH and prolactin did not have any significant changes before and after intervention, but serum level of testosterone, LH, and zinc increased significantly. These results suggest that although zinc administration did not have a definite effect on hemodialysis patients with sexual dysfunction, it can cause increase in the serum level of sex hormones which may improve the sexual function of the patients in some aspects. Zinc deficiency may account for the persistence of gonadal dysfunction in a majority of uremic men despite adequate dialysis. Twenty stable patients having hemodialysis three times a week completed a double-blind trial[12] using either 50 mg of elemental zinc as zinc acetate (10 patients) or placebo (10 patients), orally. At the end of the 6-month study period, a significant increase in the mean (+/- SE) plasma zinc (75 +/- 2 micrograms/dL to 100 +/- 2 micrograms/dL, p less than 0.001), serum testosterone (2.8 +/- 0.3 ng/dL to 5.2 +/- 0.5 ng/mL, p less than 0.001), and sperm count (30 +/- 3 million/mL to 63 +/- 5 million/mL, p less than 0.001) occurred in the zinc-treated group, but not in those receiving the placebo. The zinc-treated group also had a significant fall in serum luteinizing hormone (92 +2- 10 mIU/mL to 49 +/- 26 mIU/mL, p less than 0.005) and follicle stimulating hormone (45 +/- 9 mIU/mL to 25 +/- 7 mIU/mL, p less than 0.05), not seen in the placebo group. Patients receiving zinc had an improvement in potency, libido, and frequency of intercourse not found in the placebo group. These results suggest that zinc deficiency is a reversible cause of gonadal dysfunction in patients having regular hemodialysis. Previously, researchers documented primary testicular failure in adult male subjects with sickle cell anemia. They also reported the occurrence of zinc deficiency and suggested that androgen deficiency may be related to zinc deficiency in such patients. In this study,[13] researchers present data with respect to the efferent of oral zinc supplementation on serum testosterone levels in adult male patients with sickle cell anemia. An increase in serum testosterone, neutrophil zinc, and neutrophil alkaline phosphatase activity ws observed in the zinc-supplemented group in comparison with the group on placebo. Additionally, body weight increased and serum lactic dehydrogenase activity decrease in response to zinc supplementation. Researchers concluded that androgen deficiency in adult male subjects with sickle cell anemia is correctable with zinc supplementation and that the determination of neutrophil zinc and alkaline phosphatase activity in the neutrophils may be utilized as good indicators of body zinc status in such subjects. In eight impotent haemodialysed men with low plasma-zinc levels sexual function, including potency, frequency of intercourse, libido, and plasma testosterone, follicle-stimulating hormone, and luteinising hormone levels, was determined before and after therapy with zinc (four patients) or placebo (four patients). Dialytic administration of zinc strikingly improved potency in all patients and raised the plasma-testosterone to normal in the two with low pretreatment plasma-testosterone levels. Placebo did not improve sexual function in any patient. Zinc deficiency is a reversible cause of gonadal dysfunction in uraemia.[14]

Smilax officinalis

Smilax officinalis root (sarsaparilla) contains about 2% saponins and other varied constituents, including quercetin and phytosterols (beta-sitosterol, stigmasterol, pollinastanol). Smilax is used by some with the expectation that its sterols can be converted into anabolic steroids such as testosterone,[15] and provide testosterone-like effects.[16] However, plant sterols cannot be converted to steroid substances in the body.[17] Smilax may improve appetite and digestion, and some research suggests that it may have hepato-protective and anti-inflammatory activity.[18]

Yohimbine extract

Yohimbine is the active alkaloid in Yohimbe bark. It is reported to have aphrodisiac (increased sex drive) properties. As a matter of fact, in its synthetic form, yohimbine is actually an approved drug for the treatment of impotence, and has been used in a number of studies to treat impotence that resulted from various causes.[19] [20] [21] Yohimbine’s aphrodisiac properties seem to be the result of two physiological functions: One function is its ability to cause a dilation of the blood vessels, particularly those in the genital region. Thus, an increased flow of blood to the pen is may help result in an erection. The second function yohimbine’s ability to block presynaptic alpha-2-adrenergic receptors. This blockage results in an increase in para sympathetic (cholinergic) activity, and a decrease in sympathetic (adrenergic) activity.[22] This is important since male sexual performa nce (arousal) is linked to cholinergic activity and to alpha-2-adrenergic blockage. The results of four independent yet convergent meta-analyses to examine the efficacy of yohimbine in the treatment of erectile disorder are reported. These meta-analyses integrated data from (i) controlled clinical trials of yohimbine (when used alone), (ii) uncontrolled trials examining yohimbine (alone), (iii) controlled trials of yohimbine when used in combination with other drugs, and (iv) uncontrolled trials of yohimbine plus other drugs. Results document a consistent tendency for yohimbine, and for other medications containing yohimbine, to enhance erectile functioning relative to placebo.[23] Researchers systematically reviewed and meta-analyzed all randomized, placebo controlled trials of yohimbine monotherapy for erectile dysfunction to determine its therapeutic efficacy. The secondary aim was to evaluate the safety of yohimbine. We used computerized literature searches and standardized data extraction to rate methodological quality in a meta-analysis using computer statistical software. Results: Seven trials fit the predefined inclusion criteria. Overall methodological quality of these studies was satisfactory. The meta-analysis demonstrated that yohimbine is superior to placebo in the treatment of erectile dysfunction (odds ratio 3.85,95% confidence interval 6.67 to 2.22). Serious adverse reactions were infrequent and reversible. Researchers concluded that the benefit of yohimbine medication for erectile dysfunction seems to outweigh its risks. Therefore, yohimbine is believed to be a reasonable therapeutic option for erectile dysfunction that should be considered as initial pharmacological intervention.[24] The aim of this study[25] was to determine the effectiveness and safety of yohimbine and trazodone used together for the treatment of pure psychogenic impotence. Sixty-three patients who had psychogenic impotence diagnosed on the basis of sexual history, results of physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, partial crossover study comparing placebo with yohimbine (15 mg per day orally) and trazodone (50 mg per day orally) used together. Treatment consisted of two 8-week courses. Patients who initially received placebo for 8 weeks were then switched to the 2-drug combination for 8 weeks. Erectile function, ejaculation, interest in sex, and sexual thoughts were investigated at the end of drug treatment and at 3- and 6-month follow-up. For statistical analysis chi-square, McNemar, and Student’s t test for unpaired data were used. Fifty-five patients (87%) completed the whole treatment schedule. Positive clinical results (complete and partial responses) were obtained in 39 (71%) patients at the end of the drug treatment phase. These results were significantly better than those obtained with placebo (p < 0.01). Positive results were maintained in 32 (58%) and 31 (56%) patients at 3- and 6-month follow-up, respectively. Minor drug-related adverse effects occurred in 6 (11%) of the patients in the yohimbine-trazodone group and in 2 (4%) in the placebo group. The combination of yohimbine and trazodone is a safe and effective first-line treatment for psychogenic impotence.

Catuaba

While many beneficial plants are steeped in myth and legend, few are as widely known and consumed among the natives of the Amazon river basin as catuaba (Erthyroxylum catuaba). Revered as an enhancer of both libido and sexual potency, catuaba is a tree which grows widely across the northern Amazon. This most famous of all reputed aphrodisiac Amazonian plants is the subject of numerous indigenous songs, and the harvesting of catuaba bark—the part used for sexual enhancement—has become big business throughout Brazil. Though science on catuaba is still thin, reports in scientific journals and at conferences have affirmed its sexual enhancing properties, and have broadened interest in its use. In catuaba, a group of alkaloids dubbed catuabine A,B and C are believed to enhance sexual function by stimulating the nervous system.[26] In the Amazon, natives mix a teaspoon of the powdered bark of catuaba in about three fingers of water and let the mixture sit overnight. Some people also made a wine in which the bark of catuaba is soaked for three weeks, and then the strained herbal wine in fusion is drunk. Catuaba fuels desire and performance in bed. The Tupi Indians first discovered the qualities of the plant and composed many songs praising it. Meira Penna states, “…the bark of Catuaba [functions] as a stimulant of the nervous system, above all when one deals with functional impotence of the male genital organs.” He concludes, “it is an innocent aphrodisiac, used without any ill side effects at all.”[27]

Nós de Cachorro

Nó de Cachorro (Heteropteris aphrodisiaca) became known in Brazil and beyond as a result of its aphrodisiac properties. However, it appears to have multiple mechanisms of action, which may be explained by the fact that it is an adaptogen[28] (i.e. herb that has balancing effects on the body). In one study,[29] Nó de Cachorro was shown to improve learning and memory deficits in aged rats, suggesting an anti-aging effect. Another rat study[30] showed that Nó de Cachorro diminished nearly all the Cyclosporine A-induced damage to the testis, demonstrating an affinity for the male reproductive system. Research[31] has also indicated that Nó de Cachorro had a stimulus effect in increasing testosterone secretion, and at 104 mg/day increased sperm production. In addition, research[32] has shown that Nó de Cachorro has an anabolic effect, resulting in more organized collagen bundles and more resistant tendons to support higher loads from intense muscle contraction during exercise.

Muira Puama

The other very most popular sex-enhancing plant among the natives of the northern Amazon River basin is the bark of muira puama (Ptychopetalum olacoides). This plant also has been widely used by natives and non-natives for centuries, to increase libido and improve sexual potency, and is more often than not combined with catuaba. In Brazil, muira puama has long been valued as an aphrodisiac and tonic for the nervous system.[33] More recent research has validated this botanicals traditional use. At the Institute of Sexology in Paris, France, a clinical study with 262 patients complaining of lack of sexual desire and the inability to attain or maintain an erection was conducted using muira puama. Dr. Jacques Waynberg, one of the world’s foremost authorities on sexual function, supervised the study. Within 2 weeks, 62% of patients with loss of libido claimed that the treatment had dynamic effect while 51% felt that muira puama was of benefit with “erection failures.”[34]

Maca

Maca is a hardy perennial plant cultivated high in the Andean Mountain at altitudes from 11,000-14,500 feet. Maca was domesticated about 2000 years ago by the Inca Indians. To the Andean Indians, Maca is a valuable commodity. Because so little else grows in the region, Maca is often traded with communities at lower elevations for other staples like rice, corn, and beans. The dried roots can be stored for up to seven years. Native Peruvians have traditionally utilized Maca since before the time of the Incas for both nutritional and medicinal purposes.[35] Maca has been used medicinally for centuries to enhance fertility in humans and animals.[36] [37] [38] [39] [40] Soon after the Spanish Conquest in the South America, the Spanish found that their livestock were reproducing poorly in the highlands. The local Indians recommended feeding the animals Maca and so remarkable were the results that Spanish chroniclers gave in-depth reports.[41] Even Colonial records of some 200 years ago indicate that payments of roughly 9 tons of Maca were demanded from one Andean area alone for this purpose.[42] [43] Its fertility enhancing properties were supported clinically as early as 1961, when researchers discovered it increased the fertility of rats.[44] Hugo Malaspina, M.D., a cardiologist practicing complementary medicine in Lima, Peru, has been using Maca in his practice for ten years Dr. Malaspina first found out about Maca through a group of sexually active older men who were taking the herb with good results. “One man in this group started taking Maca and found he was able to perform satisfactorily in a sexual relationship with a lady friend. Soon everyone in the group began drinking the powdered Maca as a beverage and enjoying the boost that the root was giving their hormonal functions. I have several of these men as patients, and their improvement prompted me to find out more about Maca and begin recommending it to my other patients.”[45] Chicago physician Gary F. Gordon, former President of the American College for Advancement in Medicine, is also a Maca supporter. “We all hear rumors about various products like Maca,” he says. “But using this Peruvian root myself, I personally experienced a significant improvement in erectile tissue response. I call it nature’s answer to Viagra. What I see in Maca is a means of normalizing our steroid hormones like testosterone, progesterone, and estrogen. Therefore it has the facility to forestall the hormonal changes of aging. It acts on men to restore them to a healthy functional status in which they experience a more active libido.”[46] A chemical analysis conducted in 1981 showed the presence of biologically active aromatic isothiocyanates, especially p-methoxybenzyl isothiocyanate, which have reputed aphrodisiac properties.[47] Initial analysis of Maca indicate that the effects on fertility are a result of the glucosinolates. [48] [49] [50] Today, dried Maca roots are ground to powder and sold in drug stores in capsules as a medicine and food supplement to increase stamina and fertility.[51] [52] Human scientific research has also demonstrated Maca’s benefits. One study[53] investigated the effect of 14 days maca supplementation on endurance performance and sexual desire in trained male cyclists. Eight participants each completed a 40 km cycling time trial before and after 14 days supplementation with both maca extract (ME) and placebo, in a randomised cross-over design. Subjects also completed a sexual desire inventory during each visit. ME administration significantly improved 40 km cycling time performance compared to the baseline test (P=0.01), but not compared to the placebo trial after supplementation (P>0.05). ME administration significantly improved the self-rated sexual desire score compared to the baseline test (P=0.01), and compared to the placebo trial after supplementation (P=0.03). 14 days ME supplementation improved 40 km cycling time trial performance and sexual desire in trained male cyclists. These promising results encourage long-term clinical studies involving more volunteers, to further evaluate the efficacy of ME in athletes and normal individuals and also to explore its possible mechanisms of action. This study[54] was a 12-week double blind placebo-controlled, randomized, parallel trial in which active treatment with different doses of Maca Gelatinizada was compared with placebo. The study aimed to demonstrate if effect of Maca on subjective report of sexual desire was because of effect on mood or serum testosterone levels. Men aged 21-56 years received Maca in one of two doses: 1,500 mg or 3,000 mg or placebo. Self-perception on sexual desire, score for Hamilton test for depression, and Hamilton test for anxiety were measured at 4, 8 and 12 weeks of treatment. An improvement in sexual desire was observed with Maca since 8 weeks of treatment. Serum testosterone and oestradiol levels were not different in men treated with Maca and in those treated with placebo (P:NS). Logistic regression analysis showed that Maca has an independent effect on sexual desire at 8 and 12 weeks of treatment, and this effect is not because of changes in either Hamilton scores for depression or anxiety or serum testosterone and oestradiol levels. In conclusion, treatment with Maca improved sexual desire.

Tribulus Terrestris research

In Ayurveda, the herb Tribulus terrestris has been used in promoting genito-urinary health, supporting sexual activity, and as a general tonic for centuries. An Ayurvedic preparation containing Tribulus terrestris was used to treat fifty patients complaining of lethargy, fatigue and lack of interest in day to day activities. The results showed an overall improvement (45%) in symptoms.[55] Of greater significance are the studies where the standardized extracts of Tribulus terrestris were found to have a stimulating effect on the libido.[56] After conducting a study of Tribulus terrestris in rodents, researchers concluded, “Tribulus terrestris extract appears to possess aphrodisiac activity probably due to androgen [i.e. testosterone] increasing property of Tribulus terrestris.”[57] Similar findings were found in another study on primates, where researchers noted that tribulus increased testosterone in the animals, and another later study on rodents.[58] [59] [60] An extract of Tribulus terrestris (Tribestan; Sopharma, Sofia, Bulgaria) has gained recent interest following promotional presentations of English language translations of Bulgarian pharmaceutical company research. Reportedly, the Tribulus extract elevated circulating testosterone and luteinizing hormone amounts that were depressed in men who were part of infertile couples.[61]

Panax Ginseng Root research

Panax ginseng is native to China, Japan, Korea, and other Asian countries. The fleshy root is considered a tonic, stimulant and stress adaptogen. Adaptogens usually exert no specific biological effects, but tend to normalize adverse conditions of the body. More than 500 studies have been published on ginseng. We can only review a few here. As demonstrated in animals and humans, ginseng improves mental and physical performance and well-being in a variety of circumstances. [62] [63] [64] [65] [66] [67] Furthermore, ginseng enhances fat burning during exercise, thereby sparing valuable muscle stores of glycogen (muscle sugar).[68] Taking Panax ginseng orally seems to improve sexual function in men with erectile dysfunction. This was seen in a double-blind, placebo controlled, crossover study[69] (8 weeks on treatment, 2 weeks of washout and 8 weeks on treatment) in which the effects of Panax ginseng (900 mg. 3 times daily) and a placebo were compared in 45 patients with clinically diagnosed erectile dysfunction. Results were that mean International Index of Erectile Function scores were significantly higher in patients treated with ginseng than in those who received placebo (baseline 28.0 +/- 16.7 and 38.1 +/- 16.6 versus 30.9 +/- 15.7, p <0.01). Scores on questions 3 (penetration) and 4 (maintenance) were significantly higher in the ginseng than in the placebo group (p <0.01). In response to the global efficacy question 60% of the patients answered that ginseng improved erection (p <0.01). Among other variables penile tip rigidity on RigiScan showed significant improvement for ginseng versus placebo.

Ginkgo Biloba Extract research

Ginkgo leaf extract might benefit CNS and vascular conditions by improving circulation. Ginkgo leaf seems to improve blood flow to capillaries throughout the body including in the CNS, eyes, ears, extremities, and other tissues. Ginkgo leaf likely improves circulation by both decreasing blood viscosity and affecting vascular smooth muscle. Ginkgo leaf seems to restore the balance between prostacyclin and thromboxane A2, resulting in improved vasoregulation. Therefore, ginkgo leaf relaxes spasmodic contracting vasculature and contracts abnormally dilated vessels. It is not clear exactly how ginkgo causes vascular contraction and improves venous tone, but these effects might be due to phosphodiesterase inhibition, resulting in increased cAMP levels and release of catecholamines.[70] Some ginkgo constituents may also have a potent relaxing effect on vascular smooth muscle and improve blood flow to the corpus cavernosum; which is thought to be helpful for erectile dysfunction.[71] Overall, ginkgo leaf seems to increase cerebral and peripheral blood flow microcirculation, and reduce vascular permeability.[72] [73]

7-keto-DHEA research

7-keto-DHEA is a metabolite of dehydroepiandrosterone (DHEA) which is formed in the body.[74] Unlike DHEA, 7-keto-DHEA is not converted to androgens and estrogens, and it does not activate androgen receptors.[75] [76] [77] [78] In one study in healthy men age 21 to 47, however, there were small decreases in total blood testosterone levels and small increases in free testosterone levels, but both remained within normal ranges. [79] 7-keto-DHEA is also thought to be beneficial in weight loss by increasing metabolism and thermogenesis. In this randomized, double-blind, placebo-controlled, crossover trial, [80]45 overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 (a combination of 7-Keto, calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol) or placebo. 40 subjects completed the study (30 women, 10 men; mean age, 38.5 years; mean mass index, 32.0 kg/m(2)). During the placebo treatment, resting metabolic rate (RMR) decreased by 3.9% (75+/-111 kcal/day; mean+/-S.D.); however, RMR increased significantly by 1.4% (21+/-115 kcal/day) and 3.4% (59+/-118 kcal/day) during the 7-Keto and HUM5007 treatment periods, respectively (each compared to placebo, P=.001). In this study, the administration of HUM5007 or 7-Keto reversed the decrease in RMR normally associated with dieting, and increased RMR above basal levels HUM5007 and 7-Keto were generally well tolerated and no serious adverse events were reported. Thirty overweight (BMI 31.9 ± 6.2) adults (Age 44.5 ± 11.5) were randomized into a prospective, double-blind, placebo controlled eight week study.[81] [82] Fifteen subjects received 100 mg 7-Keto DHEA twice per day whereas the other 15 subjects received a matching placebo. All subjects exercised three times per week, 60 minutes per session of cross-training (aerobic and anaerobic) under the supervision of an exercise physiologist. In addition, each subject was instructed to follow a diet of about 1800 kcal/d by a registered dietitian. Subjects received biweekly dietary counseling to encourage compliance. The exercise plus 7-Keto DHEA group lost a significant amount of body weight as compared with the exercise plus placebo group (-2.88 kg, p=0.012). When analyzed as a per four week interval, the 7-Keto DHEA group lost 3.17 lbs per interval, whereas placebo lost 1.09 lbs (p<0.01). In terms of actual body composition changes, the exercise plus 7-Keto DHEA group lost 1.8% body fat as compared to 0.57% for the placebo group (p=0.02). When viewed as a change in body fat per four week interval, the 7-Keto DHEA group lost 0.89% body fat per interval as compared to 0.29% for the placebo (p=0.003). Also, 7-keto-DHEA, but not placebo, significantly increased the activity of triiodothyronine (T3) (+17.88 ng/dl vs. 2.75 ng/dl; p<0.05). There were no significant changes in either thyroid-stimulating hormone or T4. There were no significant changes in blood sugar, testosterone, estradiol, liver, renal function tests, vital signs, or overall caloric intake over the eight week study. Nor were there any subjective adverse effects reported throughout the study.

Eleutherococcus Senticosus research

The aim of this study[83] was to examine the effects of Eleutherococcus senticosus (ES) supplementation on endurance capacity, cardiovascular functions and metabolism of recreationally trained males for 8 weeks. Nine recreationally trained males in college consumed 400mg of ES (standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12%) twice daily or starch placebo (P) for 8 weeks according to a double-blind, randomized, placebo controlled and crossover design with a washout period of 4 weeks between the cycling trials. Subjects cycled at 75% VO2 peak until exhaustion. The examined physiological variables included endurance time, maximal heart rate during exhaustion exercise, VO2, rating of perceived exertion and respiratory exchange ratio. The biochemical variables including the plasma free fatty acid (FFA) and glucose were measured at rest, 15 min, 30 min and exhaustion. The major finding of this study was the VO2 peak of the subjects elevated 12% (P < 0.05), endurance time improved 23% (P < 0.05) and the highest heart rate increased 4% (P < 0.05) significantly. The second finding was at 30 min of 75% VO2 peak cycling, the production of plasma FFA was increased and the glucose level was decreased both significantly (P < 0.05) over 8-week ES supplementation. This is the first well-conducted study that shows that 8-week ES supplementation enhances endurance capacity, elevates cardiovascular functions and alters the metabolism for sparing glycogen in recreationally trained males. Eleutherococcus has been touted as the herb that builds Russian athletes. In his review of the Russian scientific literature, Farnsworth notes a single 4 mL dose of a 33-percent ethanolic liquid extract given to five male skiers 1-1.5 hours before a 20-50 kilometer race increased skier resistance to hypoxemia and enhanced their ability to adapt to increased exercise demands. In another summary of the Russian studies, Halstead cites research on runners given either 2 mL (n=34) or 4 mL (n=33) of the extract 30 minutes before participating in a 10-kilometer race. The results were compared to 41 participants who did not take the herb (control). Those who took either 2 or 4 mL of the extract completed the race in an average time of 48.7 minutes and 45 minutes, respectively, compared to 52.6 minutes for the control group. After establishing baseline maximal work loads (control) using bicycle ergometry, six healthy male athletes (ages 21-22) were given 2 mL (150 mg of the dried material) of a 33-percent ethanol extract of Eleutherococcus or a comparable placebo in the morning and evening 30 minutes before meals for eight days. Compared to control, individuals who took the herb had significant increases in overall work performance, including maximal oxygen uptake (p<0.01), oxygen pulse (p<0.025), total work (p<0.005), and exhaustion time (p<0.005). The Eleutherococcus group experienced a 23.3-percent increase in total work and a 16.3-percent increase in time to exhaustion compared to only a 7.5-percent and 5.4-percent increase in respective placebo values (p<0.05).[84]

Research on L-Arginine, Nitric Oxide and blood flow

Note: There is no research on L-arginine AKG for promoting circulation. Studies on ordinary L-arginine supplementation for increasing circulation use much higher doses (e.g. 6 g) than we are using in this formula. Therefore, the claim is limited to its role as a nitric oxide precursor and blood flow. A larger dose wasn’t added since with would negatively impact the taste and cost of the formulation. The main importance of L-arginine is considered to be its role as a precursor (building material) for the synthesis of nitric oxide.[85] Supplemental sources of l-arginine are thought to augment nitric oxide production[86], with the result being a measurable increase in blood flow[87] (i.e., vasodilatation).

Saw Palmetto Extract research

A systematic analysis of two Italian studies[88] was carried out on a total of 70 adult patients with BPH. In one study the patients were treated with Saw Palmetto extract 320 mg/day for 30 days; in the other study the patients received Saw Palmetto extract 320 mg/day or Pygeum africanum 4 capsules of 25 mg/day for 30 days. Both studies showed an improvement versus the baseline of about 50% of dysuria (painful and/or difficult urination) and pollakisuria (excessive daytime urinary frequency), an about 50% increase in micturition (urination) rate with positive effects also in terms of reduction of the micturition rate and of prostate size. Also the tolerability profile was favorable. In a prospective, 3-arm study, Hizli and Uygur[89] examined the efficacy of saw palmetto extract (SPE) 320 mg per day (N = 20), Tamsulosin (TAM) 0.4 mg per day (N = 20) and SPE + TAM (N = 20) in BPH patients. The results showed that the groups were not statistically different with regard to increase in maximal urinary flow rate (Q (max)) and decrease in International Prostate Symptom Score (I-PSS) (P > 0.05). No adverse effect was detected in SPE therapy group. Treatment of BPH by both SPE and TAM seems to be effective alone. None of them had superiority to another and additionally, combined therapy (SR + TAM) does not provide extra benefits. Furthermore SPE is a well-tolerated agent that can be used alternatively in the treatment of LUTS due to BPH. The TRIUMPH study[90] recorded the treatment and outcomes of 2351 newly-presenting LUTS/BPH patients in 6 European countries over a 1-year follow-up period. Over the study period 74.9% of patients were prescribed medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The alpha-blockers were the most effective, with a mean reduction of 6.3 IPSS points. Finasteride was slightly less effective (4.1 points). Significant improvements were seen in 43% of patients on phytotherapy with Saw Palmetto extract or Pygeum africanum compared to 57% of those on finasteride and 68% on alpha-blockers. In a 12-month, double-blind, randomized study[91] that showed equivalent efficacy of Saw Palmetto Extract (SPE) 320 mg/day and tamsulosin 0.4 mg/day (“PERMAL study”), 685 BPH patients with IPSS > or =10 had been analyzed for efficacy. Of these, the 124 patients with severe LUTS (IPSS >19) at randomization were retained for this subset analysis. After a 4-week run-in period, 59 and 65 patients had been randomized to tamsulosin and SPE groups, respectively. The results were that at 12 months, total IPSS decreased by 7.8 with SPE and 5.8 with tamsulosin (p=0.051); the irritative symptoms improved significantly more (p=0.049) with SPE (-2.9 versus -1.9 with tamsulosin). The superiority of SPE in reducing irritative symptoms appeared as soon as month 3 and was maintained up to month 12 (p=0.03). Researchers concluded that SPE 320 mg/day was shown to be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3 months and up to 12 months of treatment. In a multicenter open pilot study of two parallel groups on BPH patients, Vela Navarrete et al[92] tested the hypothesis that infiltrating cells (I.C.) are related with BPH progression, and investigated the response to Saw Palmetto Extract (SPE). Patients were randomized to receive either SPE 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (17 control/12 SPE). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Results showed TNFalpha and IL-1beta were dramatically lower, and IPSS was significantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment in the SPE treated group. The researchers concluded that a significant reduction of some inflammatory parameters in prostatic tissues occurred in patients treated with SPE. Pytel et al[93] assessed the efficacy and tolerability of Saw Palmetto Extract (SPE) 160 mg twice daily administered for 2 years in an open study. One hundred fifty-five men with clinically diagnosed BPH and complaints of prostatic symptoms were enrolled in the study. At 6, 12, 18, and 24 months, the International Prostate Symptom Score (I-PSS), quality of life, and sexual function score were recorded, and urodynamics and biologic values were measured. Adverse events were recorded every 3 months. I-PSS and quality of life improved significantly from baseline at each evaluation time point. At the end of the study and at each evaluation, maximum urinary flow also improved significantly. Prostate size decreased. Sexual function remained stable during the first year of treatment and significantly improved (P = .001) during the second year. Prostate-specific antigen was not affected, and no changes in plasma hormone levels were observed. Nine patients reported 10 adverse events, none related to treatment. Improvements in efficacy parameters began at 6 months and were maintained up to 24 months. These data demonstrate the long-term efficacy and tolerability of SPE and support its use as a first-line medical therapy for uncomplicated symptomatic BPH. Giannakopoulos et al[94] compared two dose regimens of Saw Palmetto Extract (SPE) in 100 male outpatients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), in a 6-month double-blind, randomized, parallel-group study. The patients received two 80-mg tablets twice daily or two 80-mg tablets three times daily. Baseline evaluations included maximum and mean urinary flow rates, postvoid residual urine volume, and International Prostate Symptom Score (I-PSS) total and quality-of-life scores. Both regimens significantly reduced the I-PSS mean total score from baseline values (P<.001); improvements achieved statistical significance after month 3 and were maintained for the duration of the study. Significant improvements from baseline also occurred in quality-of-life scores, maximum and mean urinary flow rates, and residual urine volume (P<.05). The decrease in residual urine with both regimens was highly significant (P<.001). No significant differences in efficacy were noted between the two dose groups, and no treatment-related complications or clinical adverse events occurred. In this clinical study, SPE was a well-tolerated agent that may significantly improve lower urinary tract symptoms and flow measurements in men with BPH. In a randomized, placebo controlled trial, Marks et al[95] tested the effects of a saw palmetto herbal blend versus placebo in 44 men 45 to 80 years old with symptomatic BPH. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. The results showed that the saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25.2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). No adverse effects of saw palmetto herbal blend was noted. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. The authors concluded that saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. Although the secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies. This 3-month double-blind, randomized, parallel-group study[96] compared the efficacy and tolerability of two regimens of the lipido-sterolic extract of Serenoa repens (Permixon) (two 160-mg capsules once daily [OD] and one 160-mg capsule twice daily [BID]) in 100 outpatients with symptomatic benign prostatic hyperplasia (BPH). Both regimens significantly (P < .0001) reduced the International Prostate Symptom Score (I-PSS) mean total score from baseline; improvements achieved statistical significance after the first month and were maintained for the duration of the study. Significant (P < .05) and rapid improvements from baseline to the end of month 1 also occurred in I-PSS quality-of-life (QoL) scores, maximum and mean urinary flow rates, and residual urine volume; this benefit was further increased at month 3 for I-PSS total score and QoL and residual volume, and was maintained for maximum and mean flow rates. A highly significant decrease (P < .001) in residual urine was observed in both groups. No significant differences were noted between regimens. Clinical adverse events occurred at a similar incidence in both groups (BID, 24%; OD, 22%) and were deemed unrelated or unlikely to be related to Permixon. European physicians treat benign prostatic hyperplasia (BPH) with saw palmetto extract (SPE), while American physicians generally disregard SPE because “research is lacking.” The authors investigated this discrepancy with a literature search and a clinical trial. The literature search began with MEDLINE, then expanded to “alternative” databases, including AGRICOLA, EMBASE, IBIS, and Cochrane, plus a manual search of unindexed herbal journals. The clinical trial was an experimental case study in which a 67-year-old man with symptomatic BPH was randomly administered SPE (160 mg standardized extract twice daily) or placebo. Outcome measures included the American Urological Association Symptom Index (AUASI), serum prostate-specific antigen, and prostate volume. Our expanded literature search revealed 58 clinical trials, whereas MEDLINE yielded only 19 clinical trials, or 33% of the total. Our clinical trial measured a baseline AUASI score of 20, which improved to 7 after unblinded administration of SPE. Subsequent double-blinded placebo produced a score of 14, and final single-blinded allotment of SPE produced a score of 11. Prostate-specific antigen was 10.3 ng/mL at baseline and 10.7 ng/mL at trial’s conclusion. Baseline prostatic volume was 92 mL, and end volume was 75 mL. In conclusion, MEDLINE proved inadequate as a stand-alone search engine for locating information about an herbal medicine. Our experimental case study, similar to N = 1 research methodology, proved suitable for clinical evaluation of an herbal medicine in a rural private practice. SPE improved the patient’s BPH. Unstandardized look-alike herbs may act as nontherapeutic placebos and may undermine consumer confidence in herbal medicine.[97] In a 6-month trial,[98] fifty men with previously untreated LUTS and a minimum International Prostate Symptom Score (IPSS) of 10 or greater were treated with a commercially available form of saw palmetto extract (SPE) 160 mg twice per day. The results were that mean IPSS (+/-SD) improved from 19.5+/-5.5 to 12.5+/-7.0 (P <0.001) among the 46 men who completed the study. Significant improvement in the symptom score was noted after treatment with saw palmetto for 2 months. An improvement in symptom score of 50% or greater after treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30% (14 of 47), and 46% (21 of 46) of patients, respectively. The researchers concluded that SPE is a well-tolerated agent that may significantly improve lower urinary tract symptoms in men with BPH. In a 6-month double-blind randomized equivalence study, Carraro et al[99] compared the effects of Saw Palmetto Extract (SPE) 320 mg with those of a finasteride 5 mg in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point. The results were that both SPE and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); SPE improved symptoms with little effect on volume (-6%) and no change in PSA levels. SPE fared better than finasteride in a sexual function questionnaire and gave rise to fewer complaints of decreased libido and impotence. The authors concluded that both treatments relieved the symptoms of BPH in about two-thirds of patients. In a 3-week, double-blind, comparative, parallel-groups study, Grasso et al[100] compared the efficacy and safety of alfuzosin 2.5 mg tid (n = 32) vs saw palmetto extract (SPE) 160 mg bid (n = 31) in sixty-three patients suffering from benign prostatic hyperplasia (BPH). Efficacy was assessed both on clinical symptoms (Boyarsky’s scale, visual analogue scale, clinical global impression), urinary flow rates (uroflowmetry) and residual urinary volume (transabdominal ultrasound). Results showed statistically significant and clinically relevant differences were between the two treatments in favor of alfuzosin for Boyarsky’s total score (decrease from 9.6 +/- 3.0 to 5.9 +/- 3.0, 38.8% for alfuzosin and from 9.3 +/- 2.5 to 6.8 +/- 2.8, 26.9% for SPE) and obstructive score (decrease from 4.9 +/- 2.1 to 3.0 +/- 1.9, 37.8% for alfuzosin; from 4.4 +/- 1.7 to 3.4 +/- 1.8, 23.1% for SPE; p = 0.01 for both). Clinically relevant differences were found between the two treatments for visual analogue scale and overall clinical impression at the end of the study. Furthermore, the increase in quality of micturition was better with alfuzosin. The proportion of responders (increase on day 21 in peak flow rate of at least 25% relative to the baseline values) was in favour of alfuzosin (71.8% and 48.4% for alfuzosin and SPE, respectively; p = 0.057). Both treatments were well tolerated. Wilt et al[101] conducted a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of saw palmetto extract (SPE) in men with symptomatic benign prostatic hyperplasia (BPH). Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with SPE had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with SPE had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to SPE were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with SPE repens (1.1%; P<.001). The reviewers conclude that the evidence suggests SPE improves urologic symptoms and flow measures. Compared with finasteride, SPE produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Gerber[102] conducted a comprehensive review of the literature on the clinical results of saw palmetto in men with lower urinary tract symptoms, as well as mechanism of action. The results were that a variety of potential mechanisms of action of saw palmetto have been demonstrated through in vitro studies, including 5-alpha reductase inhibition, adrenergic receptor antagonism and intraprostatic androgen receptor blockade. Clinical evidence of the relevance of these effects is largely unavailable. The use of saw palmetto in men with benign prostatic hyperplasia is safe with no recognized adverse effects. No effect on serum prostate specific antigen has been noted. Placebo controlled trials and meta-analyses have suggested that saw palmetto leads to subjective and objective improvement in men with lower urinary tract symptoms. Evidence suggests that saw palmetto may have a significant effect on urinary flow rates and symptom scores compared to placebo in men with lower urinary tract symptoms. Braeckman[103] studied the therapeutic effect of a 160-mg, twice-daily, oral dose of Saw Palmetto Extract (SPE) during a 3-month open trial in 505 patients with mild-to-moderate symptoms of BPH. The efficacy of the regimen was evaluated in 305 of these patients. Traditional parameters for quantifying prostatism, such as the International Prostate Symptom Score, the quality of life score, urinary flow rates, residual urinary volume, and prostate size, were found to be significantly improved after only 45 days of treatment. After 90 days of treatment, a majority of patients (88%) and treating physicians (88%) considered the therapy effective. In addition, the serum prostate-specific antigen concentration was not modified by the drug, thus limiting the risk of masking any possible development of prostate cancer during treatment. The incidence of side effects (5%) was low and compares favorably with that reported for existing medical therapies used in BPH patients. The author concluded that SPE appears to be an effective and well-tolerated pharmacologic agent in treating the mictional problems accompanying BPH. Boyle et al[104] conducted a meta-analysis on all available clinical trial data of Saw Palmetto Extract (SPE) o determine its clinical efficacy compared with placebo. All published clinical trial data on SPE (11 randomized clinical trials and 2 open label trials), involving 2859 patients, were used. These trials were disparate in size (from 22 to 592 patients) and duration (from 21 to 180 days). Peak urinary flow rate and nocturia were the two common end points. The statistical analysis was based on a random effects meta-analysis. The results were that the average +/- SE placebo effect on the peak urinary flow rate was an increase of 0.51 +/- 0.51 mL/s. The estimated effect of SPE was a further increase of 2.20 +/- 0.51 mL/s (P <0.001). Placebo was associated with a reduction in the mean number +/- SE of nocturnal urinations of 0.69 +/- 0.15. A further reduction of 0.50 +/- 0.01 episodes of urination (P <0.001) occurred that was attributable to SPE. Some heterogeneity was found among the studies. Treatment duration did not appear to impact either of these effects. This meta-analysis of all available published trials of SPE in the treatment of men with benign prostatic hyperplasia revealed a significant improvement in peak flow rate and reduction in nocturia greater than with placebo. Descotes et al[105] conducted a double-blind placebo-controlled multicentre study to assess the efficacy and tolerability of the 5[alpha]-reductase inhibitor Saw Palmetto Extract (SPE) in patients with symptomatic benign prostatic hyperplasia (BPH) who had previously been shown to be unresponsive to the placebo effect. Following a 30-day single-blind placebo run-in period, 176 nonresponders to placebo (those patients showing <30% improvement in peak urinary flow rate) were randomised to double-blind oral treatment with SPE 160mg twice daily or matching placebo for 30 days. Improvement in dysuria severity was seen in a significantly greater proportion of SPE recipients (31.3%) than placebo recipients (16.1%). Daytime urinary frequency fell significantly in SPE-treated patients (11.3% reduction), but was unchanged in placebo recipients. Nocturnal urinary frequency fell to a significantly greater extent with SPE (32.5% reduction) than with placebo (17.7% reduction). SPE produced a significantly greater increase in mean peak urinary flow rate than did placebo (28.9 vs 8.5%). The global efficacy of SPE was judged by the patients and physicians to be satisfactory or better in 71.3 and 56.6% of cases, respectively; corresponding values for placebo were 67.5 and 47.2%, respectively. The overall tolerability of SPE was comparable to that of placebo. In conclusion, SPE appears to be significantly more effective than placebo and well tolerated in the short term treatment of mild to moderate symptomatic BPH. Romics et al[106] treated 42 BPH patients with SPE for 12 months. The obstructive symptoms, residual volume, mean and maximum flow rates improved significantly by the 6th therapeutic month at the latest. The results seem to prove the effectiveness of the drug. Side effects have not been observed. Wilt et al[107] conducted a systematic review aimed to assess the effects of Saw Palmetto Extract (SPE) in the treatment of LUTS consistent with BPH. Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. In this update, 3 new trials involving 230 additional men (7.8%) have been included. 3139 men from 21 randomized trials lasting 4 to 48 weeks were assessed. 18 trials were double-blinded and treatment allocation concealment was adequate in 11 studies. Compared with placebo, SPE improved urinary symptom scores, symptoms, and flow measures. The weighted mean difference (WMD) for the urinary symptom score was -1.41 points (scale range 0-19), (95%CI = -2.52, -0.30, n = 1 study) and the risk ratio (RR) for self rated improvement was 1.76 (95%CI = 1.21, 2.54, n = 6 studies). The WMD for nocturia was -0.76 times per evening (95%CI = -1.22, -0.32; n = 10 studies). The WMD for peak urine flow was 1.86 ml/sec (95%CI = 0.60, 3.12, n = 9 studies). Compared with finasteride, SPE produced similar improvements in urinary symptom scores (WMD = 0.37 IPSS points (scale range 0-35), 95%CI = -0.45, 1.19, n = 2 studies) and peak urine flow (WMD = -0.74 ml/sec, 95%CI = -1.66, 0.18, n = 2 studies). Adverse effects due to SPE were mild and infrequent. The reviews conclusion was that the evidence suggests SPE provides mild to moderate improvement in urinary symptoms and flow measures. SPE produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events. The long term effectiveness, safety and ability to prevent BPH complications are not known. The results of this update were in agreement with the authors initial review. Fong et al[108] reviewed the evidence of Saw Palmetto Extract (SPE) efficacy in lower urinary tract symptoms in men. The determination was made that SPE is comparable with 5-alpha reductase (finasteride) and alpha-1 antagonist in the treatment of benign prostatic hyperplasia in terms of symptom score and peak urinary flow rate improvement, but has a lower incidence of associated sexual dysfunction. Furthermore, long-term usage (36 months) of SPE decreases the progression rate of the condition as compared with watchful waiting. In addition, the efficacies of SPE are proven in several placebo-controlled trials. The authors conclude that SPE has proven its role in the management of benign prostatic hyperplasia and will remain as a viable first-line treatment option. In the journal European Eurology,[109] Di Silverio et al presented data on a double-blind placebo-controlled study performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving saw palmetto extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction for androgen (AR) and estrogen (ER) receptors and progesterone receptors (PgR). Analysis of ERc and ERn revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. The results were that in the untreated BPH group, ER were higher in the n than in the c fraction: ERn were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with saw palmetto extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group. Pais[110] conducted in-vitro research to determine the potency of saw palmetto extract (SPE), an inhibitor of the 5alpha-reductase isoenzyme type II, in a cell-free test system. On the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione, the inhibitory potency was measured and compared to those of finasteride, an approved 5alpha-reductase inhibitor. The results were that SPE concentration-dependently inhibited 5alpha-reductase type II in vitro (IC(50)=2.88+/-0.45 microg/mL). The approved 5alpha-reductase inhibitor, finasteride, tested as positive control, led to 61% inhibition of 5alpha-reductase type II. Note: Four trials[111] [112] [113] [114] with a total of 764 men with BPH found no significant difference in the effect of Saw Palmetto Extract over placebo. The reason for this lack of significant benefit is not understood. Nevertheless, trials with a total of 3177 men with BPH found that Saw Palmetto Extract did provide significant benefits. Clearly, the preponderance of evidence demonstrates is on the side of Saw Palmetto efficacy.

Pumpkin seed oil

Research has demonstrated that pumpkin seed extract may help provide significant improvement in urinary frequency, nocturia, dysuria and overall assessment of BPH.[115] Scientific reviews have stated that the consumption of pumpkin seeds help to reduce residual urine and the frequent urge to urinate.[116] In two double-blind studies[117] [118], pumpkin seed oil was successfully used in combination with saw palmetto to reduce BPH symptoms. In one open label study, pumpkin seed oil by itself was found to decrease symptoms by 47% and improve quality of life by 46% in patients with BPH. [119] Pumpkin seed oil’s effectiveness in BPH may be a partial function of its ability to improve the function of the bladder and urethra, as shown in animal studies.[120] Doses typically used are 160 to 500 mg daily.

References

[1] Chapman-Smith A, Cronan JE, Jr. Molecular biology of biotin attachment to proteins. J Nutr. 1999;129(2S Suppl):477S-484S. [2] Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. Experientia 1994;50(7):626-40. [3] Taylor PR, Parnes HL, Lippman SM. Science peels the onion of selenium effects on prostate carcinogenesis. J Natl Cancer Inst 2004;96:645-7. [4] Yoshizawa K, Willett WC, Morris SJ, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 1998;90(16):1219-1224. [5] Nomura AM, Lee J, Stemmermann GN, Combs GF, Jr. Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2000;9(9):883-887. [6] Brooks JD, Metter EJ, Chan DW, et al. Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol 2001;166(6):2034-2038. [7] Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? Eur J Cancer 2006;42(15):2463-2471. [8] Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. Experientia 1994;50(7):626-40. [9] Kavanagh JP. Sodium, potassium, calcium, magnesium, zinc, citrate and chloride content of human prostatic and seminal fluid. J Reprod Fertil 1985;75(1):35-41. [10] Kilic M. Effect of fatiguing bicycle exercise on thyroid hormone and testosterone levels in sedentary males supplemented with oral zinc. Neuro Endocrinol Lett. 2007 Oct;28(5):681-5. [11] Jalali GR, Roozbeh J, Mohammadzadeh A, et al. Impact of oral zinc therapy on the level of sex hormones in male patients on hemodialysis. Ren Fail. 2010 May;32(4):417-9. [12] Mahajan SK, Abbasi AA, Prasad AS, Rabbani P, Briggs WA, McDonald FD. Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study. Ann Intern Med. 1982 Sep;97(3):357-61. [13] Prasad AS, Abbasi AA, Rabbani P, DuMouchelle E. Effect of zinc supplementation on serum testosterone level in adult male sickle cell anemia subjects. Am J Hematol. 1981;10(2):119-27. [14] Antoniou LD, Shalhoub RJ, Sudhakar T, Smith JC Jr. Reversal of uraemic impotence by zinc. Lancet. 1977 Oct 29;2(8044):895-8. [15] Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996. [16] Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000 Aug;72(2 Suppl):624S-36S. [17] Barron RL, Vanscoy GJ. Natural products and the athlete: facts and folklore. Ann Pharmacother 1993;27:607-15. [18] Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996. [19] Gitlin M. Psychotropic medications and their effects on sexual function: diagnosis, biology, and treatment approaches. Clin Psychiatry. 1994;55(9): 406-13. [20] Gtlin M. Effects of depression and antidepressants on sexual functioning. Bull Menninger Clin. 1995;59(2):232-48. [21] Jacobsen F. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry. 1992;53(4):119-22. [22] Costa R, Marino A. On the eventual psychotropic, cardiovascular and aphrodisiac properties of yohimbine, an old drug with new indications. Clin Ter. 1989;129(3):159-68. [23] Carey MP, Johnson BT. Effectiveness of yohimbine in the treatment of erectile disorder: four meta-analytic integrations. Arch Sex Behav 1996;25:341-60. [24] Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol 1998;159:433-6. [25] Montorsi F, Strambi LF, Guazzoni G, et al. Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology 1994;44:732-6. [26] Personal communication with Chris Kilham, the Medicine Hunter; 2000. [27] Sing C. Cura com Yoga e Plantas Medicinals. 1979; Rio de Janeiro: Freitas Bastos; 1979:126 [28] Mendes FR, Carlini EA. Brazilian plants as possible adaptogens: an ethnopharmacological survey of books edited in Brazil. J Ethnopharmacol. 2007 Feb 12;109(3):493-500. [29] Galvão SM, Marques LC, Oliveira MG, Carlini EA. Heteropterys aphrodisiaca (extract BST0298): a Brazilian plant that improves memory in aged rats. J Ethnopharmacol. 2002 Mar;79(3):305-11. [30] Monteiro JC, Predes FS, Matta SL, Dolder H. Heteropterys aphrodisiaca infusion reduces the collateral effects of cyclosporine A on the testis. Anat Rec (Hoboken). 2008 Jul;291(7):809-17. [31] Gomes ML, Monteiro JC, Freitas KM, Sbervelheri MM, Dolder H. Association of the infusion of Heteropterys aphrodisiaca and endurance training brings spermatogenetic advantages. Biol Res. 2011;44(3):235-41. [32] Monteiro JC, Gomes ML, Tomiosso TC, Nakagaki WR, Sbervelheri MM, Ferrucci DL, Pimentel ER, Dolder H. More resistant tendons obtained from the association of Heteropterys aphrodisiaca and endurance training. BMC Complement Altern Med. 2011 Jun 28;11:51. [33] Penna M. Notas Sobre Platas Brasilerias. Rio de Janero: Araujo Penna & Cia; 1980:258. [34] Waynberg J. Aphrodisiacs: Contribution to the clinical validation of the traditional use of Ptychopetalum guyanna. Presented at the First International Congress on Ethnopharmacology, Strasbourg, France, June 5-9, 1990. [35] Rea, J., 1992. Raices andinas: Maca. in Bermejo, H. and Leon, J.E., eds., Cultivos marginados, otra perspectiva de 1492. [36] King, Steven, 1986. “Ancient Buried Treasure of the Andes,” Garden, November/December. [37] Johns, T., 1981. The anu and the Maca. Journal of Ethnobiology, 1:208-212 [38] Quiros CF, Epperson A, Hu J, Holle M. Physiological Studies and Determination of Chromosome Number in Maca, Lepidium Meyenii. Economic Botany. 1996;50(2):216-223. [39] Leon, J. 1964. The “Maca” (Lepidium Meyenii) a little known food plant of Peru. Economic Botany. 18:122-127 [40] “Plant Medicine’s Importance Stressed by CSU Professor,” HerbalGram Magazine, Spring 1989, p. 12. [41] Report of an Ad Hoc Panel of the Advisory Committee on Technical Innovation, Board on Science and Technology for International Development, National Research Council, 1989. Lost Crops of the Incas: Little Known Plants of the Andes with Promise for Worldwide Cultivation. [42] Johns, T., 1981. The anu and the Maca. Journal of Ethnobiology, 1:208-212 [43] Quiros CF, Epperson A, Hu J, Holle M. Physiological Studies and Determination of Chromosome Number in Maca, Lepidium Meyenii. Economic Botany. 1996;50(2):216-223. [44] Chacon, R.C., 1961. Estudio fitoquimico de Lepidium meyenii. Dissertation, Univ., Nac.Mayo de San marcos, Peru. [45] Kilham, C., Doctor’s Comments on Maca, www.rain-tree.com/maca.htm [46] Kilham, C., Doctor’s Comments on Maca, www.rain-tree.com/maca.htm [47] Johns, T., 1981. The anu and the Maca. Journal of Ethnobiology, 1:208-212 [48] Report of an Ad Hoc Panel…, 1989. [49] Johns, T., 1981. The anu and the Maca. Journal of Ethnobiology, 1:208-212 [50] Dini, A., et al, 1994. [51] Johns, T., 1981. The anu and the Maca. Journal of Ethnobiology, 1:208-212 [52] Gomez, A., “Maca, Es alternativa Nutricional para el ano 2000.” Informe Ojo con su Salud No. 58 August 15, 1997, Lima Peru [53] Stone M, Ibarra A, Roller M, Zangara A, Stevenson E. A pilot investigation into the effect of maca supplementation on physical activity and sexual desire in sportsmen. J Ethnopharmacol. 2009 Dec 10;126(3):574-6. [54] Gonzales GF, Córdova A, Vega K, Chung A, Villena A, Góñez C, Castillo S. Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia. 2002 Dec;34(6):367-72. [55] Jayaram S, et al. Tribulus. Indian Drugs 1993 ;30(10):498-500. [56] Tomova M. Tibestan: A preparation from Tribulus terrestris. Farmatsiya 1987;37(6):40-42. [57] Gauthaman K, Adaikan PG, Prasad RN. Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats. Life Sci 2002;71(12):1385-96. [58] Gauthaman K, Ganesan AP, Prasad RN. Sexual effects of puncturevine (Tribulus terrestris) extract (protodioscin): an evaluation using a rat model. J Altern Complement Med.. 2003;9(2):257-65. [59] Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction–an evaluation using primates, rabbit and rat. Phytomedicine. 2008;15(1-2):44-54. [60] Adaikan PG, Gauthaman K, Prasad RNV. History of herbal medicines with an insight on the pharmacological properties of Tribulus terrestris. The Aging Male 2001;4:163–169 [61] Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr 2000;72(2):624S-636s. [62] Bombardelli E, Cirstoni A, Lietti A. The Effect of Acute and Chronic Panax Ginseng Saponins Treatment on Adrenal Function; Biochemical and Pharmacological. Proceedings of the 3rd International Ginseng Symposium 1980:9-16. [63] Forgo I, Schimert G. The duration of effect of the standardized ginseng extract G115® in healthy competitive athletes [German]. Notobene Medici 1985; 15(9):636-640. [64] Forgo I. Effects of drugs on physical performance and hormone system of sportsmen. Munch Med Wschr 1983;125:822-24. [65] Dorling E, Korchdorfer AM, Ruckert KH. Do ginsenosides influence the performance? Results of a double-blind study. Notabene Medici 1980; 10:241-246. [66] Forgo I, Kayasseh L, Staub JJ. Einfluss eines standardisierten Ginseng-Extraktes auf das Allgemeinbefinden, die Reaktionsfähigkeit, Lungenfunktion und die gonadalen Hormone. Med Welt 1981; 32(19):751-756. [67] D’Angelo L, Grimaldi R, Caravaggi M. A double blind, placebo controlled study on a standardized ginseng extract on psychomotor performance in healthy volunteers. Journal Ethnopharmacology 1986; 16:15-22. [68] Avakian EV Jr, Evonuk E. Effect of Panax ginseng extract on tissue glycogen and adrenal cholesterol depletion during prolonged exercise. Planta Med 1979; 36(1):43-8. [69] Hong B, Ji YH, Hong JH, et al. A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol 2002;168:2070-3. [70] Campos-Toimil M, Lugnier C, Droy-Lefaix M, et al. Inhibition of type 4 phosphodiesterase by rolipram and Ginkgo biloba extract (EGb 761) decreases agonist-induced rises in internal calcium in human endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:e34-e40. [71] Paick J, Lee J. An experimental study of the effect of ginkgo biloba extract on the human and rabbit corpus cavernosum tissue. J Urol 1996;156:1876-80. [72] Diamond BJ, Shiflett SC, Reiwel N, et al. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000;81:668-78. [73] Campos-Toimil M, Lugnier C, Droy-Lefaix M, et al. Inhibition of type 4 phosphodiesterase by rolipram and Ginkgo biloba extract (EGb 761) decreases agonist-induced rises in internal calcium in human endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:e34-e40. [74] Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A 1995;92:6617-9. [75] Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A 1995;92:6617-9. [76] Davidson MH, Weeks C, Lardy H, et al. Clinical Safety and Endocrine Effects of 7-KETO-DHEA. Abstract presented at: Experimental Biology 98, April 19-22, 1998, San Francisco, CA. Abstract obtained from Humanetics Corporation website. [77] Colker CM, Torina GC, Swain MA, Kalman DS. Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxo-dehydroepiandrosterone on Body Composition and the Endocrine System in Overweight Adults. Abstract presented at 2nd ASEP Annual Meeting, October 14-16, 1999, and published in Journal of Exercise Physiology online, Volume 2 Number 4 October 1999. [78] Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000;23:300-10. [79] Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000;23:300-10. [80] Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007;18(9):629-34. [81] Colker CM, Torina GC, Swain MA, Kalman DS. Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxo-dehydroepiandrosterone on Body Composition and the Endocrine System in Overweight Adults. Journal of Exercise Physiology Online 1999;2(4):Abstract #30. [82] Kalman DS, Colker CM, Swain MA, Torina GC, Shi Q. A randomized double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Thera 2000;61:435-42. [83] Kuo J, Chen KW, Cheng IS, Tsai PH, Lu YJ, Lee NY. The effect of eight weeks of supplementation with Eleutherococcus senticosus on endurance capacity and metabolism in human. Chin J Physiol. 2010 Apr 30;53(2):105-11. [84] Anonymous. Monograph. Eleutherococcus senticosus. Altern Med Rev. 2006 Jun;11(2):151-5. [85] Tapiero H, Mathe G, Couvreur P, et al. I. Arginine. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (France) 2002; 56(9):439-45. [86] Nonami Y. The role of nitric oxide in cardiac surgery. Surgery today (JAPAN) 1997; 27(7):583-92. [87] Cheng JW, Baldwin SN, Balwin SN. L-arginine in the management of cardiovascular diseases. Annals of pharmacotherapy 2001; 35(6):755-64. [88] Mantovani F. Serenoa repens in benign prostatic hypertrophy: analysis of 2 Italian studies. Minerva Urol Nefrol. 2010;62(4):335-40. [89] Hizli F, Uygur MC. A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia. Int Urol Nephrol. 2007;39(3):879-86. [90] Hutchison A, Farmer R, Verhamme K, Berges R, Navarrete RV. The efficacy of drugs for the treatment of LUTS/BPH, a study in 6 European countries. Eur Urol. 2007;51(1):207-15. [91] Debruyne F, Boyle P, Calais Da Silva F, et al. Evaluation of the clinical benefit of permixon and tamsulosin in severe BPH patients-PERMAL study subset analysis. Eur Urol. 2004;45(6):773-9. [92] Vela Navarrete R, Garcia Cardoso JV, Barat A, Manzarbeitia F, López Farré A. BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay. Eur Urol. 2003;44(5):549-55. [93] Pytel YA, Vinarov A, Lopatkin N, Sivkov A, Gorilovsky L, Raynaud JP. Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia. Adv Ther. 2002;19(6):297-306. [94] Giannakopoulos X, Baltogiannis D, Giannakis D, Tasos A, Sofikitis N, Charalabopoulos K, Evangelou A. The lipidosterolic extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a comparison of two dosage regimens. Adv Ther. 2002;19(6):285-96. [95] Marks LS, Partin AW, Epstein JI, et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol. 2000;163(5):1451-6. [96] Stepanov VN, Siniakova LA, Sarrazin B, Raynaud JP. Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens. Adv Ther. 1999;16(5):231-41. [97] McPartland JM, Pruitt PL. Benign prostatic hyperplasia treated with saw palmetto: a literature search and an experimental case study. J Am Osteopath Assoc. 2000;100(2):89-96. [98] Gerber GS, Zagaja GP, Bales GT, Chodak GW, Contreras BA. Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology. 1998;51(6):1003-7. [99] Carraro JC, Raynaud JP, Koch G,et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate. 1996;29(4):231-40. [100] Grasso M, Montesano A, Buonaguidi A, Castelli M, Lania C, Rigatti P, Rocco F, Cesana BM, Borghi C. Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia. Arch Esp Urol. 1995;48(1):97-103. [101] Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 1998;280(18):1604-9. [102] Gerber GS. Saw palmetto for the treatment of men with lower urinary tract symptoms. J Urol. 2000;163(5):1408-12. [103] Braeckman J. The extract of Serenoa repens in the treatment of benign prostatic hyperplasia: A multicenter open study. Current Therapeutic Research. 1994;55(7):776-785. [104] Boyle P, Robertson C, Lowe F, Roehrborn C. Meta-analysis of clinical trials of permixon in the treatment of symptomatic benign prostatic hyperplasia. Urology. 2000;55(4):533-9. [105] Descotes JL, Rambeaud JJ, Deschaseaux P, Faure G. Placebo-controlled evaluation of the efficacy and tolerability of Permixon in benign prostatic hyperplasia after exclusion of placebo responders. Clin Drug Invest 1995; 9:291-7. [106] Romics I, Schmitz H, Frang D. Experience in treating benign prostatic hypertrophy with Sabal serrulata for one year. Int Urol Nephrol. 1993;25(6):565-9. [107] Wilt T, Ishani A, Mac Donald R. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;(3):CD001423. [108] Fong YK, Milani S, Djavan B. Role of phytotherapy in men with lower urinary tract symptoms. Curr Opin Urol. 2005;15(1):45-8. [109] Di Silverio F, D’Eramo G, Lubrano C, Flammia GP, Sciarra A, Palma E, Caponera M, Sciarra F. Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol. 1992;21(4):309-14. [110] Pais P. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II. Adv Ther. 2010;27(8):555-63. [111] Barry MJ, Meleth S, Lee JY, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011;306(12):1344-51. [112] Willetts KE, Clements MS, Champion S, Ehsman S, Eden JA. Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial. BJU Int. 2003;92(3):267-70. [113] Reece Smith H, Memon A, Smart CJ, Dewbury K. The value of permixon in benign prostatic hypertrophy. Br J Urol. 1986;58(1):36-40. [114] Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, Avins AL. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006;354(6):557-66. [115] Lowe F, Ku J, Urology (1996) 48(1):12-20. [116] Brinker F, British Journal of Phytotherapy (1993/94) 3(4):154-176. [117] Carbin BE, Eliasson R. Swed J Biol Med 1989;2:7–9. [118] Carbin BE, Larsson B, Lindahl O. Treatment of benign prostatic hyperplasia with phytosterols. Br J Urol. 1990;66:639–41. [119] Schiebel-Schlosser G, Friederich M. Phytotherapy of BPH with pumpkin seeds – A multicentric clinical trial Zeits Phytother. 1998;19(2):71–6. [120] Zhang X, Ouyang JZ, Zhang YS, et al. J Tongji Med Univ 1994;14:235–8.

---