Life Extension Magazine®

Man asleep till morning with no nocturia event

Challenge of Middle-of-the-Night Urination

Nighttime urination (nocturia) is a serious problem for most aging men. A clinical trial with targeted nutrients reduced nocturia in 64% of the study subjects.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in October 2024. Written by: Michael Downey.

Waking up one or more times during the night to urinate is considered a normal part of life for older men.

It doesn't have to be.

Known as nocturia, it's more than just an annoyance.

It's associated with low-quality sleep, falls, heart disease, diabetes, and depression.1

Nocturia affects over 40 million American men,2 and most assume there's nothing they can do about it.

But scientists have identified five compounds that have demonstrated beneficial effects on nocturia and male lower urinary tract issues.3-8

In a 2020 clinical study by Life Extension®, the number of men suffering from nocturia was reduced by 64%. And not a single participant was left waking up more than one time at night.9

This 2020 published study provides fresh scientific support for nutrients that support urinary health in aging men.

Common Male Urinary Symptoms

With age, men are prone to a spectrum of lower urinary tract symptoms related to the bladder, urethra, and prostate gland.

By age 80, as many as 70% of men are affected.10

One of the causes is enlargement of the prostate gland, which is common in older age.11 Other contributing factors include damage to the urethra, obesity, diabetes, high blood pressure, smoking, some medications, and nervous system disorders.12

Lower urinary tract symptoms can include increased urinary frequency, urgency, incontinence, incomplete bladder emptying, hesitancy, prolonged urination, dribbling, and weak urine stream.13

One of the most common symptoms is nocturia, the need to get up to urinate during the night, often more than once.2,14

Health Risks of Nocturia

Man using bathroom in the middle of the night

Nocturia affects at least half of all men over age 50.15 Clinically relevant nocturia, the need to urinate twice or more nightly, increases significantly with age, affecting up to 62% of those aged 70-80.14

It can lead to serious health problems. A quarter of all falls by older individuals happen during the night, and a quarter of these are directly related to nocturia.1

In addition, over 40% of people who have a nighttime awakening have trouble going back to sleep.1 Nightly sleep disturbances caused by nocturia are associated with:1,2,14,16,17

  • Heart disease,
  • Diabetes,
  • Obesity,
  • Poor physical health,
  • Cognitive dysfunction,
  • Depression,
  • Mood changes,
  • Fatigue and exhaustion,
  • Reduced quality of life,
  • Impaired productivity, and
  • Increased overall mortality.

Compounds that Target Nocturia

Medications often are meant to control bladder overactivity and urine-flow obstruction. This helps relieve the daytime urinary symptoms but may have little impact on nocturia.18

Some men are prescribed alpha-blockers, which can cause dizziness as a side effect, making them risky for elderly people.1,19

With the rapidly aging population, researchers have been searching for nutrients that can decrease or prevent nocturia.

They identified five compounds with urinary-health benefits:9

  • Beta-sitosterol,
  • Pygeum bark extract,
  • Lycopene,
  • Boron, and
  • Melatonin.

Beta-Sitosterol Helps Relieve Urinary Tract Symptoms

Beta-sitosterol is a plant compound isolated from the oils of certain vegetables and nuts.

Preclinical evidence indicates that beta-sitosterol possesses a broad range of anti-inflammatory properties.20-23

In an animal model, beta-sitosterol inhibits 5-alpha-reductase, an enzyme in the prostate gland that converts testosterone to a more powerful growth-promoting hormone, dihydro-testosterone.24

In clinical studies of men with prostate enlargement, beta-sitosterol improves urinary symptoms. A randomized, double-blind, placebo-controlled study found that beta-sitosterol reduced urinary symptom severity by 50% and improved quality-of-life scores by 42%.3

Pygeum Bark Helps Reduce Nighttime Urination

The bark of the African cherry tree, or Pygeum africanum, has been used for centuries in Africa to improve urinary symptoms and bladder discomfort.

In France, Pygeum extract has been given to patients suffering from benign prostatic hypertrophy (BPH), enlargement of the prostate, since the 1970s.25 It is still used today for the treatment of BPH-related lower urinary tract symptoms.26

Published studies show that Pygeum bark extracts help control bladder overactivity and reduce prostate enlargement and nocturia.25,27,28 One clinical trial found as much as a 32% reduction in the frequency of urination at night.4

What you need to know

Man running to bathroom with toilet paper

Banish the Nighttime Need to Urinate

  • Older men routinely suffer from an array of lower urinary tract symptoms (LUTS). One of the most common is nocturia, the need to get up at night to urinate, often more than once.
  • Nocturia is more than an inconvenience. It can cause sleep loss, and puts older men at increased risk for falls and fractures. It is also associated with heart disease, physical and mental decline, greater mortality, and more.
  • In a clinical trial conducted by Life Extension®, over 60% of the participants using the combination of beta-sitosterol, pygeum bark extract, lycopene, boron, and melatonin reported relief from nighttime urination symptoms.

Lycopene Helps Prevent Prostate Enlargement

Sliced tomatoes a source of lycopene

Lycopene is a carotenoid pigment found in tomatoes and some other red or pink fruits and vegetables. It's a well-known anti-inflammatory and reduces oxidative stress.29

Lycopene tends to naturally concentrate in the prostate gland, allowing it to deliver its anti-inflammatory effects where they can best help reduce nighttime urination.30

Lycopene also has antiproliferative properties, which help prevent the abnormal growth of cells and may inhibit prostate enlargement. In cell studies, lycopene was shown to slow down prostate cell division.31

Like beta-sitosterol, lycopene reduces the production of the hormone dihydrotestosterone, one of the key drivers of prostate enlargement.32-34

In a clinical trial on prostate cancer patients, lycopene-rich tomato products significantly decreased PSA (prostate-specific antigen) levels, which rise as a man's prostate enlarges (or develops malignant cells).6

Boron Helps Protect the Urinary Tract

The mineral boron reduces several markers of inflammation, including TNF-a (tumor necrosis factor-alpha),IL-6 (interleukin 6), and C-reactive protein.35

Boron also modulates sex-hormone production and reduces the impact of growth factors, such as IGF-1 (insulin-like growth factor 1), which may contribute to prostate enlargement and nocturia.35,36

Boron has additional protective effects in the prostate, specifically blocking growth factors necessary for tumor development.36 In studies, human prostate tumors implanted in mice were smaller by 38% after low-dose boron supplementation, while serum PSA levels fell 89%.36

Men with the highest dietary boron intake have a 54% associated lower risk of prostate cancer compared to those with the lowest intake.5

Melatonin Helps Reduce Nighttime Waking

Melatonin, a hormone produced by the pineal gland, has been shown to have potent anti-inflammatory effects37 and may also reduce oxidative stress and blood pressure.38-40

Melatonin is best known for regulating sleep-wake cycles, and oral melatonin helps induce better sleep in some people.41-43 While a need to urinate can cause men to wake, men occasionally get up to urinate simply because they find their sleep already disrupted.44

A randomized, controlled trial published in the Journal of Urology evaluated melatonin's use in men suffering from severe nocturia, who wake on average three times a night to urinate. In these men, 2 mg of melatonin before bed reduced the frequency of nocturia.7

Another human study found that men receiving 2 mg of melatonin reduced their frequency of nighttime urination from an average of 3.4 times per night to 2.6 times per night.8

Human Trial

A team of Life Extension® researchers conducted a 60-day pilot human trial to investigate whether these five compounds would work together to provide relief from nighttime urinary problems.9

The results of this study were published in 2020 in the journal Global Advances in Health and Medicine.

Researchers gave a blend of the compounds every night just before bedtime to 30 healthy men, aged 45 to 75 years, with mild nocturia.9

The formula contained:

  • Beta-sitosterol (180 mg),
  • Pygeum bark extract (100 mg),
  • Lycopene (from 15 mg of natural tomato fruit extract),
  • Boron (10 mg), and
  • Melatonin (2 mg).

Before treatment, 87% of men reported some degree of nocturia. After 60 days of treatment, only 23% still reported some degree of nocturia—a 64% reduction.

Of the men who continued to report some nocturia after treatment, none reported more than a single awakening per night.

There was also a notable reduction in the most severe cases of nocturia.9

Before treatment, 37% of the men woke two to three times nightly to urinate. After treatment, none of the men woke more than once a night.

This means that all of the men who had suffered the most extreme nocturia—and were at the greatest risk for sleep disruption, falls, and overall mortality2,14-17—experienced a reduction in symptoms.

This represents a potential advance for the 40 million American men currently afflicted with this frustrating and potentially dangerous disorder.

Summary

Many men suffer from nocturia, the need to get up one or more times nightly to urinate.

Man smiling before going to sleep

It can cause significant sleep loss and is linked to heart disease, obesity, diabetes, depression, cognitive dysfunction, and increased mortality.

Scientists have identified five compounds with demonstrated benefits for the male lower urinary tract:

  • Beta-sitosterol,
  • Pygeum bark extract,
  • Lycopene,
  • Boron, and
  • Melatonin.

A clinical study showed that most men who took a blend of these compounds experienced an improvement in lower urinary tract symptoms and reduced frequency of nighttime urination.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Available at: https://www.ncbi.nlm.nih.gov/books/NBK518987/. Accessed February 22, 2021.
  2. 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.
  3. 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.
  4. 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.
  5. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004 Apr;11(4):887-92.
  6. Paur I, Lilleby W, Bohn SK, et al. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. Clin Nutr. 2017 Jun;36(3):672-9.
  7. Drake MJ, Mills IW, Noble JG. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202.
  8. 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.
  9. Hirsh SP, Pons M, Joyal SV, et al. Self-Assessed Benefits of a Prostate Health Formulation on Nocturia in Healthy Males With Mild Lower Urinary Tract Symptoms: An Open Label Study. Glob Adv Health Med. 2020;9:2164956120973639.
  10. 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.
  11. 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.
  12. 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.
  13. Lepor H. Pathophysiology of lower urinary tract symptoms in the aging male population. Rev Urol. 2005;7 Suppl 7(Suppl 7):S3-S11.
  14. 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).
  15. 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.
  16. 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.
  17. 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.
  18. Andersson KE, Van Kerrebroeck P. Pharmacotherapy for Nocturia. Curr Urol Rep. 2018 Feb 9;19(1):8.
  19. Debruyne FMJ. Alpha blockers: are all created equal? Urology. 2000 2000/11/01/;56(5):20-2.
  20. 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.
  21. 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.
  22. Sun Y, Gao L, Hou W, et al. beta-Sitosterol Alleviates Inflammatory Response via Inhibiting the Activation of ERK/p38 and NF-kappaB Pathways in LPS-Exposed BV2 Cells. Biomed Res Int. 2020;2020:7532306.
  23. 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.
  24. 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.
  25. 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.
  26. Salinas-Casado J, Esteban-Fuertes M, Carballido-Rodriguez J, et al. Review of the experience and evidence of Pygeum africanum in urological practice. Actas Urol Esp. 2020 Jan - Feb;44(1):9-13.
  27. 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.
  28. Wilt T, Ishani A, Mac Donald R, et al. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002 (1):CD001044.
  29. Mozos I, Stoian D, Caraba A, et al. Lycopene and Vascular Health. Front Pharmacol. 2018;9:521.
  30. Wertz K, Siler U, Goralczyk R. Lycopene: modes of action to promote prostate health. Arch Biochem Biophys. 2004 Oct 1;430(1):127-34.
  31. 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.
  32. Pagano E, Laudato M, Griffo M, et al. Phytotherapy of benign prostatic hyperplasia. A minireview. Phytother Res. 2014 Jul;28(7):949-55.
  33. Carson C, 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology. 2003 Apr;61(4 Suppl 1):2-7.
  34. Wan L, Tan HL, Thomas-Ahner JM, et al. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prev Res (Phila). 2014 Dec;7(12):1228-39.
  35. Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015 Aug;14(4):35-48.
  36. 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.
  37. Cuzzocrea S, Costantino G, Mazzon E, et al. Regulation of prostaglandin production in carrageenan-induced pleurisy by melatonin. J Pineal Res. 1999 Aug;27(1):9-14.
  38. Zuo J, Jiang Z. Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension. Vasc Med. 2020 Aug;25(4):295-301.
  39. Ahsanova E, Popov V, Bulanova N, et al. Hypotensive Action of Melatonin in Patients with Arterial Hypertension. Eur Cardiol. 2020 Feb;15:e43.
  40. Tordjman S, Chokron S, Delorme R, et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol. 2017 Apr;15(3):434-43.
  41. Srinivasan V, Spence DW, Pandi-Perumal SR, et al. Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. Travel Med Infect Dis. 2008 Jan-Mar;6(1-2):17-28.
  42. Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005 Feb;9(1):41-50.
  43. Sletten TL, Magee M, Murray JM, et al. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Med. 2018 Jun;15(6):e1002587.
  44. Available at: https://my.clevelandclinic.org/health/diseases/14510-nocturia. Accessed February 17, 2021.