A Study to Evaluate the Effects of a Prostate Health Formulation

Overview

The purpose of this study is to assess the efficacy of a Prostate Health formulation on scores attained from the I-PSS questionnaire. Safety and tolerability of the formulation will also be assessed.

Full Title of Study: “A Pilot, Open-label Study to Evaluate the Effects of a Prostate Health Formulation on Scores Attained From the International Prostate Symptom Score (I-PSS) Questionnaire Among Overall Healthy Male Participants Who Report Lower Urinary Tract Complaints”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Health Services Research
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 27, 2018

Detailed Description

This study is a pilot, open-label study to evaluate the efficacy, safety and tolerability of a Prostate Health formulation. Each subject will receive a specific dose of the formulation once daily. Participants will undergo assessments of blood tests, vital signs, body weight, BMI with completion of questionnaires. The primary objective of the study is to assess effectiveness of the Prostate Health formulation on the I-PSS score. Secondary objectives: 1. To assess the I-PSS "Quality of Life" question score 2. To assess the PSA level 3. To assess the IIEF-5 questionnaire score 4. To assess body weight 5. To assess BMI 6. To assess the score on a questionnaire for health-related quality of life

Interventions

  • Dietary Supplement: Prostate Health formulation

Arms, Groups and Cohorts

  • Experimental: Prostate Health formulation
    • Prostate Health formulation

Clinical Trial Outcome Measures

Primary Measures

  • Mean change on I-PSS score
    • Time Frame: 60 days

Secondary Measures

  • Mean change on the I-PSS Quality of Life question score
    • Time Frame: 60 days
  • Mean change in the PSA level
    • Time Frame: 60 days
  • Mean change on the IIEF-5 questionnaire score
    • Time Frame: 60 days
  • Mean change in body weight
    • Time Frame: 60 days
  • Mean change in BMI
    • Time Frame: 60 days
  • Mean change in the score on a questionnaire for health-related quality of life
    • Time Frame: 60 days

Participating in This Clinical Trial

Primary Inclusion Criteria:

1. Ambulatory, male, 45-75 years of age 2. Having a BMI of 20-35 3. Having an I-PSS score of 1-7 4. Overall healthy and having no difficulty with digestion or absorption of food Primary Exclusion Criteria:

1. Unable to maintain stable exercise and dietary habits throughout the study 2. History of any of the following medical condition(s): diabetes, prostate and/or bladder cancer, arrhythmia, hypotension, hypertension (unless on a stable dose of anti-hypertensive medication for 3 months prior to Baseline/screening and not likely to change medication or dose during the study period), chronic inflammatory or autoimmune disease, gastrointestinal disease (including gastroesophageal reflux and peptic ulcer), biliary obstruction (past or present), cardiovascular disease, hyper- or hypothyroidism (unless on a stable dose of medication for 3 months prior to Baseline/screening and not likely to change medication or dose during the study period), liver or kidney disease, edema with or without congestive heart failure, stroke, bleeding disorders, sleep apnea, insomnia, migraine headaches (within 3 months prior to Baseline/screening), psychiatric disorders, anxiety disorder, known or suspected estrogen-dependent neoplasia, history of thrombosis or embolism, any neurological disorder that could yield cognitive deterioration including Parkinson's disease, stroke, intracranial hemorrhage, head injury, brain tumor(s), normal pressure hydrocephalus or evidence of delirium, confusion, dementia or Alzheimer's disease, or other condition(s) that would preclude participation in the study in the judgment of the PI/Sub-Investigator (Sub-I) 3. Having taken a 5-alpha-reductase inhibitor, alpha- or beta-blocker medication, diuretics, calcium channel blockers, tricyclic antidepressants, or anticholinergic agents 90 days prior to Baseline/screening 4. Having taken testosterone replacement therapy for less than 3 months or unlikely to maintain the same therapeutic regimen (including dose) throughout the study period 5. Having taken pygeum extract, beta-sitosterol, melatonin, lycopene, or boron and unwilling to discontinue use 30 days prior to enrollment (unless permitted to enroll in the judgment of the PI/Sub-I) 6. Having taken saw palmetto, grass pollen extract, flower pollen extract, stinging and dwarf nettle extract, pumpkin seed oil extract, lignan extract, or boswellia serrata extract less than 6 months prior to screening and unwilling to discontinue use 30 days prior to enrollment (unless permitted to enroll in the judgment of the PI/Sub-I) 7. Currently consuming a product containing olestra and unwilling to discontinue use 30 days prior to enrollment 8. Having taken anxiolytics and sedative hypnotics, anticonvulsants, antineoplastics, anti-migraine medication(s), opioid analgesics, monoamine oxidase inhibitors (MAOIs), phosphodiesterase inhibitors, adenosine reuptake inhibitors, dopamine agonists, dopamine antagonists, or immunosuppressants within 30 days prior to Baseline/screening 9. Having taken an anti-inflammatory medication, antihistamine or decongestant within 14 days prior to Baseline/screening 10. Having had a surgical procedure, including prostate or bladder surgery, which would preclude study participation in the judgment of the PI/Sub-I 11. Having any blood coagulation disorder, anemia, vitamin K deficiency, or taking anticoagulant and antiplatelet medication(s) 12. Having abnormal screening laboratory test values: bilirubin > 2.5 x ULN, AST/SGOT and ALT/SGPT > 2.5 x ULN, serum creatinine > 1.5 mg/dL, PSA > 4 ng/mL, abnormal urinalysis (positive proteins, leukocyte, occult blood and nitrites) or any other lab test result(s) that would preclude study participation in the judgment of the PI/Sub-I 13. Currently consumes more than 6 standard alcoholic drinks per week (a standard alcoholic drink is defined as one bottle/can of beer, one glass of wine, or one ounce of hard liquor) 14. Unable or unwilling to abstain from consuming any alcoholic drink within two hours of taking the study product 15. History of known alcohol or substance abuse (eg, opiates, benzodiazepines, or amphetamines) 16. Having smoked any cigarette, electronic cigarette, cigar, pipe, or recreational drug in the past 30 days 17. History of allergy or sensitivity to any component of the study product (as well as pine) 18. Participation in another study within 30 days prior to Baseline/screening 19. Unable or unwilling to avoid consuming grapefruit 20. Having a pacemaker or any internal medical device

Gender Eligibility: Male

Minimum Age: 45 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Supplement Formulators, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Steven Joyal, M.D., Principal Investigator, Life Extension

References

Adjakly M, Ngollo M, Dagdemir A, Judes G, Pajon A, Karsli-Ceppioglu S, Penault-Llorca F, Boiteux JP, Bignon YJ, Guy L, Bernard-Gallon D. Prostate cancer: The main risk and protective factors-Epigenetic modifications. Ann Endocrinol (Paris). 2015 Feb;76(1):25-41. doi: 10.1016/j.ando.2014.09.001. Epub 2015 Jan 13.

Aguilar F, Autrup H, Barlow S et al. Scientific Opinion of the Panel onf Food Additives, Flavourings, Processing Adids and Materials in Contact with Food on a request from the Commission on the safety in use of lycopene as a food colour. The EFSA Journal. 2008;675:1-66.

Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5.

Andro M, Riffaud J. Pygeum Africanum extract for the treatment of patients with benign prostatic hyperplasia: A review of 25 years of published experience. Current Therapeutic Research. 1995;56(8):796-817.

Ansari MS, Gupta NP. Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. Urol Oncol. 2004 Sep-Oct;22(5):415-20. doi: 10.1016/j.urolonc.2004.05.009.

Assar EA, Vidalle MC, Chopra M, Hafizi S. Lycopene acts through inhibition of IkappaB kinase to suppress NF-kappaB signaling in human prostate and breast cancer cells. Tumour Biol. 2016 Jul;37(7):9375-85. doi: 10.1007/s13277-016-4798-3. Epub 2016 Jan 16.

Awad AB, Chen YC, Fink CS, Hennessey T. beta-Sitosterol inhibits HT-29 human colon cancer cell growth and alters membrane lipids. Anticancer Res. 1996 Sep-Oct;16(5A):2797-804.

Awad AB, Chinnam M, Fink CS, Bradford PG. beta-Sitosterol activates Fas signaling in human breast cancer cells. Phytomedicine. 2007 Nov;14(11):747-54. doi: 10.1016/j.phymed.2007.01.003. Epub 2007 Mar 12.

Awad AB, Gan Y, Fink CS. Effect of beta-sitosterol, a plant sterol, on growth, protein phosphatase 2A, and phospholipase D in LNCaP cells. Nutr Cancer. 2000;36(1):74-8. doi: 10.1207/S15327914NC3601_11.

Awad AB, Roy R, Fink CS. Beta-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. Oncol Rep. 2003 Mar-Apr;10(2):497-500.

Azimi H, Khakshur AA, Aghdasi I, Fallah-Tafti M, Abdollahi M. A review of animal and human studies for management of benign prostatic hyperplasia with natural products: perspective of new pharmacological agents. Inflamm Allergy Drug Targets. 2012 Jun;11(3):207-21. doi: 10.2174/187152812800392715.

Barlet A, Albrecht J, Aubert A, Fischer M, Grof F, Grothuesmann HG, Masson JC, Mazeman E, Mermon R, Reichelt H, et al. [Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study]. Wien Klin Wochenschr. 1990 Nov 23;102(22):667-73. German.

Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004 Dec 8;216(1):21-9. doi: 10.1016/j.canlet.2004.06.001.

Barranco WT, Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer. 2006 Mar 27;94(6):884-90. doi: 10.1038/sj.bjc.6603009.

Barry MJ, Fowler FJ Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett AT. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992 Nov;148(5):1549-57; discussion 1564. doi: 10.1016/s0022-5347(17)36966-5.

Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet. 1995 Jun 17;345(8964):1529-32. doi: 10.1016/s0140-6736(95)91085-9.

Bolt HM, Basaran N, Duydu Y. Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data. J Toxicol Environ Health A. 2012;75(8-10):508-14. doi: 10.1080/15287394.2012.675301.

Breza J, Dzurny O, Borowka A, Hanus T, Petrik R, Blane G, Chadha-Boreham H. Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Curr Med Res Opin. 1998;14(3):127-39. doi: 10.1185/03007999809113352.

Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, Klassen TP, Baker G. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006 Feb 18;332(7538):385-93. doi: 10.1136/bmj.38731.532766.F6. Epub 2006 Feb 10.

Chatelain C, Autet W, Brackman F. Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension. Urology. 1999 Sep;54(3):473-8. doi: 10.1016/s0090-4295(99)00147-8.

Chen P, Zhang W, Wang X, Zhao K, Negi DS, Zhuo L, Qi M, Wang X, Zhang X. Lycopene and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015 Aug;94(33):e1260. doi: 10.1097/MD.0000000000001260.

Cui Y, Winton MI, Zhang ZF, Rainey C, Marshall J, De Kernion JB, Eckhert CD. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004 Apr;11(4):887-92.

Culver B, Hubbard S. 1996. Inorganic boron health effects in humans: An aid to risk assessment and clinical judgment. J Trace Elem Exp Med 9:175-184.

Devaraj S, Mathur S, Basu A, Aung HH, Vasu VT, Meyers S, Jialal I. A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr. 2008 Apr;27(2):267-73. doi: 10.1080/07315724.2008.10719699.

DHHS. U. S. Department of Health and Human Services. Center for Drug Evaluation and Research. Guidance for Industry. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapetuics in Adult Heathy Volunteers. 7/2005. http://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf. Accessed 6/21/2016.

Drake MJ, Mills IW, Noble JG. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202. doi: 10.1097/01.ju.0000110442.47593.ea.

Gallardo-Williams MT, Chapin RE, King PE, Moser GJ, Goldsworthy TL, Morrison JP, Maronpot RR. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004 Jan-Feb;32(1):73-8. doi: 10.1080/01926230490260899.

Gooneratne NS, Edwards AY, Zhou C, Cuellar N, Grandner MA, Barrett JS. Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. J Pineal Res. 2012 May;52(4):437-45. doi: 10.1111/j.1600-079X.2011.00958.x. Epub 2012 Feb 21.

Grattan BJ Jr. Plant sterols as anticancer nutrients: evidence for their role in breast cancer. Nutrients. 2013 Jan 31;5(2):359-87. doi: 10.3390/nu5020359.

Gupta R, Sharma AK, Dobhal MP, Sharma MC, Gupta RS. Antidiabetic and antioxidant potential of beta-sitosterol in streptozotocin-induced experimental hyperglycemia. J Diabetes. 2011 Mar;3(1):29-37. doi: 10.1111/j.1753-0407.2010.00107.x.

Hansen MV, Andersen LT, Madsen MT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gogenur I. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat. 2014 Jun;145(3):683-95. doi: 10.1007/s10549-014-2962-2. Epub 2014 Apr 23.

Hays RD, Sherbourne CD, Mazel RM. The RAND 36-Item Health Survey 1.0. Health Econ. 1993 Oct;2(3):217-27. doi: 10.1002/hec.4730020305.

Heber D, Lu QY. Overview of mechanisms of action of lycopene. Exp Biol Med (Maywood). 2002 Nov;227(10):920-3. doi: 10.1177/153537020222701013.

Heindel JJ, Price CJ, Field EA, Marr MC, Myers CB, Morrissey RE, Schwetz BA. Developmental toxicity of boric acid in mice and rats. Fundam Appl Toxicol. 1992 Feb;18(2):266-77. doi: 10.1016/0272-0590(92)90055-m.

Henderson K, Stella SL, Kobylewski S, Eckhert CD. Receptor activated Ca(2+) release is inhibited by boric acid in prostate cancer cells. PLoS One. 2009 Jun 23;4(6):e6009. doi: 10.1371/journal.pone.0006009.

Hendriks HF, Brink EJ, Meijer GW, Princen HM, Ntanios FY. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr. 2003 May;57(5):681-92. doi: 10.1038/sj.ejcn.1601598.

Hevia D, Gonzalez-Menendez P, Quiros-Gonzalez I, Miar A, Rodriguez-Garcia A, Tan DX, Reiter RJ, Mayo JC, Sainz RM. Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer. J Pineal Res. 2015 Mar;58(2):234-50. doi: 10.1111/jpi.12210. Epub 2015 Feb 7.

Ilic D. Lycopene for the prevention and treatment of prostate disease. Recent Results Cancer Res. 2014;202:109-14. doi: 10.1007/978-3-642-45195-9_13.

Jahnke G, Marr M, Myers C, Wilson R, Travlos G, Price C. Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol Sci. 1999 Aug;50(2):271-9. doi: 10.1093/toxsci/50.2.271.

Jian L, Du CJ, Lee AH, Binns CW. Do dietary lycopene and other carotenoids protect against prostate cancer? Int J Cancer. 2005 Mar 1;113(6):1010-4. doi: 10.1002/ijc.20667.

Jung-Hynes B, Huang W, Reiter RJ, Ahmad N. Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells. J Pineal Res. 2010 Aug;49(1):60-8. doi: 10.1111/j.1600-079X.2010.00767.x. Epub 2010 May 27.

Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N. Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model. J Pineal Res. 2011 Mar;50(2):140-9. doi: 10.1111/j.1600-079X.2010.00823.x. Epub 2010 Nov 9.

Kava. In: Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty. [Updated January 6, 2016; Accessed May 24, 2016]. http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=OSU&s=ND&pt=100&id=872&ds =&name=KAVA&searchid=37784702

Kim CH, Yoo YM. Melatonin Induces Apoptotic Cell Death via p53 in LNCaP Cells. Korean J Physiol Pharmacol. 2010 Dec;14(6):365-9. doi: 10.4196/kjpp.2010.14.6.365. Epub 2010 Dec 31.

Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. Br J Urol. 1997 Sep;80(3):427-32.

Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M, Bertram JS, Wood DP Jr. Effects of lycopene supplementation in patients with localized prostate cancer. Exp Biol Med (Maywood). 2002 Nov;227(10):881-5. doi: 10.1177/153537020222701007.

Larre S, Camparo P, Comperat E, Boulbes D, Haddoum M, Baulande S, Soularue P, Costa P, Cussenot O. Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures. Asian J Androl. 2012 May;14(3):499-504. doi: 10.1038/aja.2011.132. Epub 2011 Dec 26.

Lee WH, Isaacs WB, Bova GS, Nelson WG. CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. Cancer Epidemiol Biomarkers Prev. 1997 Jun;6(6):443-50.

Levin RM, Das AK. A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res. 2000 Jun;28(3):201-9. doi: 10.1007/s002409900098.

Li D, Chen L, Zhao W, Hao J, An R. MicroRNA-let-7f-1 is induced by lycopene and inhibits cell proliferation and triggers apoptosis in prostate cancer. Mol Med Rep. 2016 Mar;13(3):2708-14. doi: 10.3892/mmr.2016.4841. Epub 2016 Feb 2.

Litovitz TL, Klein-Schwartz W, Oderda GM, Schmitz BF. Clinical manifestations of toxicity in a series of 784 boric acid ingestions. Am J Emerg Med. 1988 May;6(3):209-13. doi: 10.1016/0735-6757(88)90001-0.

Lomenick B, Shi H, Huang J, Chen C. Identification and characterization of beta-sitosterol target proteins. Bioorg Med Chem Lett. 2015 Nov 1;25(21):4976-4979. doi: 10.1016/j.bmcl.2015.03.007. Epub 2015 Mar 11.

Mace, A.E. (1964), Sample Size Determination, New York: Reinhold Publishing Corporation

Murray FJ. A comparative review of the pharmacokinetics of boric acid in rodents and humans. Biol Trace Elem Res. 1998 Winter;66(1-3):331-41. doi: 10.1007/BF02783146.

Murray FJ. A human health risk assessment of boron (boric acid and borax) in drinking water. Regul Toxicol Pharmacol. 1995 Dec;22(3):221-30. doi: 10.1006/rtph.1995.0004.

Paroni R, Terraneo L, Bonomini F, Finati E, Virgili E, Bianciardi P, Favero G, Fraschini F, Reiter RJ, Rezzani R, Samaja M. Antitumour activity of melatonin in a mouse model of human prostate cancer: relationship with hypoxia signalling. J Pineal Res. 2014 Aug;57(1):43-52. doi: 10.1111/jpi.12142. Epub 2014 May 20.

Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015 Aug;14(4):35-48.

Quiles MT, Arbos MA, Fraga A, de Torres IM, Reventos J, Morote J. Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH). Prostate. 2010 Jul 1;70(10):1044-53. doi: 10.1002/pros.21138.

Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008 Mar;22(3):659-61. doi: 10.1096/fj.07-9574LSF. Epub 2007 Oct 17.

Risk Profile. Beta-sitosterol. CAS No. 83-46-5. http://www.mattilsynet.no/kosmetikk/stoffer_i_kosmetikk/risk_profile_betasitosterol.11370/binary/RiskProfileBeta-Sitosterol. 8/27/2012. Accessed 6/20/2016.

Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26. doi: 10.1038/sj.ijir.3900472.

Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ. Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate. 2005 Apr 1;63(1):29-43. doi: 10.1002/pros.20155.

Schwarz S, Obermuller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008 Jan;138(1):49-53. doi: 10.1093/jn/138.1.49.

Shao A, Hathcock JN. Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol. 2006 Aug;45(3):289-98. doi: 10.1016/j.yrtph.2006.05.007. Epub 2006 Jun 30.

Shenouda NS, Sakla MS, Newton LG, Besch-Williford C, Greenberg NM, MacDonald RS, Lubahn DB. Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo. Endocrine. 2007 Feb;31(1):72-81. doi: 10.1007/s12020-007-0014-y.

Sohn EJ, Won G, Lee J, Lee S, Kim SH. Upregulation of miRNA3195 and miRNA374b Mediates the Anti-Angiogenic Properties of Melatonin in Hypoxic PC-3 Prostate Cancer Cells. J Cancer. 2015 Jan 1;6(1):19-28. doi: 10.7150/jca.9591. eCollection 2015.

Srinivasan V, Pandi-Perumal SR, Brzezinski A, Bhatnagar KP, Cardinali DP. Melatonin, immune function and cancer. Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):109-23. doi: 10.2174/187221411799015408.

Stokinger HE. 1981. The halogens and nonmetals boron and silicon. In: Clayton GD, Clayton FE, eds. Patty's Industrial Hygiene and Toxicology, Vol. 2B. New York: John Wiley and Sons. Pp. 2978- 3005.

Sugaya K, Nishijima S, Miyazato M, Kadekawa K, Ogawa Y. Effects of melatonin and rilmazafone on nocturia in the elderly. J Int Med Res. 2007 Sep-Oct;35(5):685-91. doi: 10.1177/147323000703500513.

Ulbricht CE. An Evidence-Based Systematic Review of Beta-Sitosterol, Sitosterol (22,23- dihydrostigmasterol, 24-ethylcholesterol) by the Natural Standard Research Collaboration. J Diet Suppl. 2016;13(1):35-92. Epub 2015 Aug 13.

von Holtz RL, Fink CS, Awad AB. beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr Cancer. 1998;32(1):8-12. doi: 10.1080/01635589809514709.

Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. eCollection 2014.

Wang Y, Jacobs EJ, Newton CC, McCullough ML. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Int J Cancer. 2016 Jun 15;138(12):2846-55. doi: 10.1002/ijc.30027. Epub 2016 Feb 23.

Wertz K. Lycopene effects contributing to prostate health. Nutr Cancer. 2009;61(6):775-83. doi: 10.1080/01635580903285023.

Wertz K, Siler U, Goralczyk R. Lycopene: modes of action to promote prostate health. Arch Biochem Biophys. 2004 Oct 1;430(1):127-34. doi: 10.1016/j.abb.2004.04.023.

Wilt T, Ishani A, Mac Donald R, Rutks I, Stark G. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;1998(1):CD001044. doi: 10.1002/14651858.CD001044.

Wilt TJ, MacDonald R, Ishani A. beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. BJU Int. 1999 Jun;83(9):976-83. doi: 10.1046/j.1464-410x.1999.00026.x.

Wu K, Erdman JW Jr, Schwartz SJ, Platz EA, Leitzmann M, Clinton SK, DeGroff V, Willett WC, Giovannucci E. Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):260-9. doi: 10.1158/1055-9965.epi-03-0012.

Zhao Y, Chang SK, Qu G, Li T, Cui H. Beta-sitosterol inhibits cell growth and induces apoptosis in SGC-7901 human stomach cancer cells. J Agric Food Chem. 2009 Jun 24;57(12):5211-8. doi: 10.1021/jf803878n.

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