Reducing Nighttime Urinary Frequency in MenJuly 2019
By Stephen Harrington
Waking up multiple times during the night to urinate is more than an inconvenience.
It’s one of the most common lower urinary tract symptoms in older men.
The medical term for this is nocturia.
It disrupts sleep patterns, which can lead to a host of health problems, and it’s a frequent cause of falls and resulting fractures.1,2
Current medical therapies offer limited improvements.3
A recently conducted pilot trial evaluated the effect of four nutrient compounds plus melatonin on mild, lower urinary tract symptoms, especially nocturia in healthy, older men.4
The primary study outcome was a decrease in nighttime urination.4
By the end of the study, the number of people suffering from nocturia at all was reduced by 64%. And not a single participant was left waking up more than one time a night.4
This finding can potentially help millions of men who suffer from an overactive bladder to improve their sleep health, while reducing risk for falls and injuries.
A Common Aging Problem
The male urinary tract is prone to problems that worsen with age.
Lower urinary tract symptoms (LUTS) are a broad spectrum of clinical manifestations related to the bladder, urethra, and prostate gland. LUTS affect as many as 70% of men over 80 years of age.5
Besides nocturia, these symptoms can include increased urinary frequency, urgency, incontinence, incomplete bladder emptying, hesitancy, prolonged micturition, dribbling and a weak urine stream.6
The worsening of LUTS as men get older is due to various factors that cause dysfunction of the urinary system.7 An overactive bladder, enlargement of the prostate gland, and damage to the urethra can all contribute to urinary symptoms.
Compounds that incite chronic inflammation in the urinary tract can contribute to the development of LUTS and prostate enlargement.8,9 Men with LUTS have increased levels of plasma pro-inflammatory biomarkers.8
The aging process increases the risk for all of these problems. Obesity, diabetes, high blood pressure, smoking, some medications, nervous system disorders, and others can also contribute to LUTS.10
The Dangers of Nocturia
The most common LUTS, and the one which can lead to the most serious problems, is nocturia, the need to get up to urinate during the night, often more than once.1,2
Nocturia can occur in at least half of all men over 50 years of age.11 Clinically relevant nocturia, defined as having to get up to urinate two or more times each night, increases significantly with advancing age, affecting as many as 62% of those aged 70-80.1
Aside from being annoying, nocturia is also a serious health condition that should not be trivialized. Nighttime urinary frequency has the greatest impact of any of the LUTS on quality of life.1,2,11,12
By disturbing sleep, nocturia can contribute to poor health, lower energy, depression, and increased overall mortality.1,13-16
Frequent nocturia can result in falls. Particularly in older individuals who may suffer from frailty, poor balance, and bad vision, navigating the way to the bathroom multiple times in the middle of the night can be treacherous.
Remedies for Nocturia
Most pharmaceutical approaches to treating LUTS focus on controlling bladder overactivity and obstruction of urine flow. These drugs are far more effective in treating the daytime symptoms of LUTS, but have little impact on nocturia.17
But research has shown that several compounds have beneficial effects on the aging urinary system and can potentially reduce nocturia. A study showed that the following five compounds work together to maximize the relief from nighttime urinary problems.
Beta-sitosterol is a plant sterol isolated from the oils of certain vegetables and nuts. A study in an animal model established this compound is an inhibitor of an enzyme in the prostate gland, called 5a-reductase, which converts testosterone to dihydrotestosterone.18
By reducing the levels of dihydrotestosterone, beta-sitosterol helps reduce age-related prostate enlargement. When the prostate is enlarged, it blocks the flow of urine through the urethra. This contributes to nocturia and other LUTS. Reducing prostate enlargement supports healthy urine flow.19-22
Clinical studies in men with prostate enlargement show beta-sitosterol improves urinary symptoms. In a randomized, double-blind, placebo-controlled study, scoring of LUTS severity was reduced by 50% and measures of quality of life improved by 42%.20
Experimental evidence also points to anti-inflammatory activities of beta-sitosterol.23-25
Pygeum bark extract
Pygeum africanum is the scientific name for the African cherry tree. The bark of this tree has been used in Africa to improve urinary symptoms and bladder discomfort for centuries. Modern science has revealed that this extract works through several mechanisms. In addition to anti-inflammatory effects, it helps control bladder overactivity and reduces prostate enlargement.26,27
Clinical trials of pygeum bark extract have shown a reduction in frequency of nighttime urination. Two meta-analyses of existing studies found an average 19% reduction in nocturia,26,27 and one trial found as much as a 32% reduction in the frequency of nocturnal urination.28
It also has anti-inflammatory properties relevant to prostate enlargement and LUTS.29
Found in tomatoes and some other red or pink fruits and vegetables, lycopene is a carotenoid pigment with anti-inflammatory properties.30 Lycopene naturally tends to concentrate in the prostate gland,31 making it ideal for reducing the inflammation that can contribute to frequent nighttime urination.32
Like beta-sitosterol, lycopene also has the ability to reduce the production of dihydrotestosterone in the prostate, removing one of the major drivers of prostate enlargement.33,34
Lycopene has anti-proliferative properties, which means it helps prevent the abnormal growth of cells. In studies of prostate cells, lycopene blocks cell division, which may help prevent enlargement.35
Lycopene was shown to inhibit pro-inflammatory cytokines such as IL-6 and IL-8, further supporting benefits on LUTS.32,36
In further support of inflammation management relevant to LUTS, the mineral boron has been shown to reduce several markers of inflammation, such as TNF-a, IL-6, and C-reactive protein.37
Boron has effects on other signaling compounds in the body that are associated with development of LUTS and nocturia. It modulates sex hormone function and ameliorates the impact of growth factors, such as IGF-1, which may contribute to prostate enlargement.37,38
Melatonin is a hormone produced by the pineal gland that is involved in the regulation of sleep-wake cycles. Supplemental melatonin can help induce better sleep.
But beyond sleep support, melatonin has been shown to be helpful in treating nocturia. A randomized controlled trial published in the Journal of Urology evaluated its use in men suffering from significant nocturia, waking on average three times each night to urinate.39 In these men, 2 mg of melatonin before bed was superior to a placebo in reducing the frequency of nocturia.
Another human study of melatonin found similar effects. Men receiving the same dose of melatonin reduced the frequency of nighttime urination from an average of 3.4 times per night to 2.6 times per night.40
Successful Pilot Human Trial
A pilot trial studied a group of men with mild nighttime (LUTS) urinary issues to analyze the effects of a formula containing:
- Beta-sitosterol 180 mg
- Pygeum extract (bark) 100 mg
- Lycopene [LycoBeads® from 15 mg natural tomato extract (fruit)]
- Boron (as Albion® bororganic glycine) 10 mg
- Melatonin 2 mg
Healthy men with mild LUTS, aged 45 to 72 years, were recruited for the trial.4 Baseline urinary symptoms including the frequency of nocturia were assessed before treatment began. Subjects were then instructed to take one capsule of the bladder control supplement formula daily, just before bedtime. At the end of the 60-day trial period, urinary symptoms were again evaluated.
At the start of the trial, 87% of men reported some degree of nighttime urination. This included roughly 50% of men who had to get up one time at night, and 37% who reported waking two to three times each night to urinate at the beginning of the study.
At the end of the 60 days, the researchers observed a remarkable improvement in nighttime urination frequency. Those suffering from nocturia declined from 87% at the start of the trial to only 23% by the trial conclusion—a 64% reduction!
Particularly notable was the reduction in the most severe cases of nocturia. While 37% of the men originally complained of waking two or more times each night to urinate, none suffered from this degree of nocturia at the end of the study. The 23% who continued to report nocturia by the study’s end were all a single awakening per night.
This means that those who suffered the most extreme nocturia, and were at highest risk for falls, loss of sleep, and diminished quality of life, all had a significant positive impact on their symptoms. Some of these men went from two or three nightly wakings to none—a major impact for those at greatest risk.
Lower urinary tract symptoms (LUTS) are very common in men as they get older. The most prevalent and potentially dangerous of these symptoms is nocturia, the need to get up one or more times during the night to urinate.
Conventional medical treatments for urinary disorders mostly address daytime symptoms. They do relatively little to remedy nocturia, which can increase risk of falls and related injuries, and can lead to diminishing physical and mental health and increased rate of mortality.
In a pilot clinical study, five compounds that included beta-sitosterol, pygeum bark extract, lycopene, boron, and melatonin were shown to improve LUTS, and reduce the frequency of nighttime urination in men.
These findings can potentially improve quality-of-life in men who suffer urinary symptoms.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Oelke M, De Wachter S, Drake MJ, et al. A practical approach to the management of nocturia. Int J Clin Pract. 2017 Nov;71(11).
- Zumrutbas AE, Bozkurt AI, Alkis O, et al. The Prevalence of Nocturia and Nocturnal Polyuria: Can New Cutoff Values Be Suggested According to Age and Sex? Int Neurourol J. 2016 Dec;20(4):304-10.
- Bergman AM, Sih AM, Weiss JP. Nocturia: an overview of evaluation and treatment. 2015. 2015.
- Hirsh SP, Pons M, Joyal SV, et al. An open-label pilot study to evaluate the efficacy of a prostate health formulation to reduce nocturia in healthy males with lower urinary tract symptoms. Submitted for publication. 2019.
- Parsons JK, Bergstrom J, Silberstein J, et al. Prevalence and characteristics of lower urinary tract symptoms in men aged > or = 80 years. Urology. 2008 Aug;72(2):318-21.
- Lepor H. Pathophysiology of lower urinary tract symptoms in the aging male population. Rev Urol. 2005;7 Suppl 7(Suppl 7):S3-S11.
- Sarma AV, Wei JT. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 2012 Jul 19;367(3):248-57.
- Macoska JA. Chemokines and BPH/LUTS. Differentiation. 2011 Nov-Dec;82(4-5):253-60.
- Ficarra V, Rossanese M, Zazzara M, et al. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Curr Urol Rep. 2014 Dec;15(12):463.
- Haidinger G, Temml C, Schatzl G, et al. Risk factors for lower urinary tract symptoms in elderly men. For the Prostate Study Group of the Austrian Society of Urology. Eur Urol. 2000 Apr;37(4):413-20.
- Miranda Ede P, Gomes CM, Torricelli FC, et al. Nocturia is the Lower Urinary Tract Symptom With Greatest Impact on Quality of Life of Men From a Community Setting. Int Neurourol J. 2014 Jun;18(2):86-90.
- Asplund R, Marnetoft SU, Selander J, et al. Nocturia in relation to somatic health, mental health and pain in adult men and women. BJU Int. 2005 Apr;95(6):816-9.
- Coyne KS, Zhou Z, Bhattacharyya SK, et al. The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA. BJU Int. 2003 Dec;92(9):948-54.
- Everaert K, Anderson P, Wood R, et al. Nocturia is more bothersome than daytime LUTS: Results from an Observational, Real-life Practice Database including 8659 European and American LUTS patients. Int J Clin Pract. 2018 Jun;72(6):e13091.
- Kupelian V, Wei JT, O’Leary MP, et al. Nocturia and quality of life: results from the Boston area community health survey. Eur Urol. 2012 Jan;61(1):78-84.
- Shao IH, Wu CC, Hsu HS, et al. The effect of nocturia on sleep quality and daytime function in patients with lower urinary tract symptoms: a cross-sectional study. Clin Interv Aging. 2016;11:879-85.
- Andersson KE, Van Kerrebroeck P. Pharmacotherapy for Nocturia. Curr Urol Rep. 2018 Feb 9;19(1):8.
- Cabeza M, Bratoeff E, Heuze I, et al. Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate. Proc West Pharmacol Soc. 2003;46:153-5.
- Berges RR, Kassen A, Senge T. Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up. BJU Int. 2000 May;85(7):842-6.
- Berges RR, Windeler J, Trampisch HJ, et al. 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.
- 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.
- 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.
- Valerio M, Awad AB. beta-Sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A.1 murine macrophages. Int Immunopharmacol. 2011 Aug;11(8):1012-7.
- Paniagua-Perez R, Flores-Mondragon G, Reyes-Legorreta C, et al. Evaluation of the Anti-Inflammatory Capacity of Beta-Sitosterol in Rodent Assays. Afr J Tradit Complement Altern Med. 2017;14(1):123-30.
- Loizou S, Lekakis I, Chrousos GP, et al. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res. 2010 Apr;54(4):551-8.
- Ishani A, MacDonald R, Nelson D, et al. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Am J Med. 2000 Dec 1;109(8):654-64.
- Wilt T, Ishani A, Mac Donald R, et al. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002 (1):CD001044.
- Breza J, Dzurny O, Borowka A, et al. 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.
- Andro M-C, Riffaud J-P. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia: A review of 25 years of published experience. Current Therapeutic Research. 1995 1995/08/01/;56(8):796-817.
- Elango P, Asmathulla S. A Systematic Review on Lycopene and its Beneficial Effects”. Biomedical and Pharmacology Journal. 2017;10(4):2113-20.
- Clinton SK, Emenhiser C, Schwartz SJ, et al. cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev. 1996 Oct;5(10):823-33.
- Wertz K, Siler U, Goralczyk R. Lycopene: modes of action to promote prostate health. Arch Biochem Biophys. 2004 Oct 1;430(1):127-34.
- Pagano E, Laudato M, Griffo M, et al. Phytotherapy of benign prostatic hyperplasia. A minireview. Phytother Res. 2014 Jul;28(7):949-55.
- Carson C, 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology. 2003 Apr;61(4 Suppl 1):2-7.
- Schwarz S, Obermuller-Jevic UC, Hellmis E, et al. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008 Jan;138(1):49-53.
- Trejo-Solis C, Pedraza-Chaverri J, Torres-Ramos M, et al. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013:705121.
- Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015 Aug;14(4):35-48.
- Gallardo-Williams MT, Chapin RE, King PE, et al. 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.
- Drake MJ, Mills IW, Noble JG. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202.
- Sugaya K, Nishijima S, Miyazato M, et al. Effects of melatonin and rilmazafone on nocturia in the elderly. J Int Med Res. 2007 Sep-Oct;35(5):685-91.