Research Article| Volume 14, ISSUE 3, P257.e1-257.e6, June 2018

Download started.


Effect of vitamin D and omega-3 on nocturnal enuresis of 7–15-year-old children

Published:February 05, 2018DOI:



      Nocturnal enuresis is known to be a common urinary bladder complication in children. Recent studies have associated vitamin D and omega-3 insufficiency with nocturnal enuresis.


      This was a 2-month randomized, placebo-controlled, double-blind trial to measure the effects of vitamin D, omega-3 supplements, and their combination on nocturnal enuresis among 7–15-year-old children.

      Materials and methods

      Participants (180 children with nocturnal enuresis) were selected from children referred to the Pediatric ward of Imam Reza Clinic in Shiraz, Iran. Demographic information and anthropometric measures were taken. Fasting blood and urine samples were also collected, and serum vitamin D and urine prostaglandin E2 were measured before and after intervention. Enuretic children were randomly assigned to four groups: Group A, vitamin D (1000 IU/day); Group B, omega-3 (1000 mg/day); Group C, both omega-3 (1000 mg/day) and vitamin D (1000 IU/day); and Group D, placebo.


      The results suggested that the study groups were not significantly different regarding demographic and anthropometric measures at baseline. Comparison of different groups revealed that 44.4% of participants in Group A, 28.2% of Group B and 45% of Group C were cured from enuresis (P = 0.03). Serum 25(OH) D was significantly increased in Group A, but urine prostaglandin E2 was not significantly decreased in response to supplementation. Although supplementation with both Group A and Group B were found to be effective, the combined intervention did not increase the effect of each intervention solely.


      The results showed that supplementation with vitamin D and omega-3 could reduce the number of wet nights among 7–15-year-old children with nocturnal enuresis.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Pediatric Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Liu X.
        • Sun Z.
        • Uchiyama M.
        • Li Y.
        • Okawa M.
        Attaining nocturnal urinary control, nocturnal enuresis, and behavioral problems in Chinese children aged 6 through 16 years.
        J Am Acad Child Adolesc Psychiatry. 2000; 39: 1557
        • Yeung C.
        • Chiu H.
        • Sit F.
        Bladder dysfunction in children with refractory monosymptomatic primary nocturnal enuresis.
        J Urol. 1999; 162: 1049
        • Hjalmas K.
        • Arnold T.
        • Bower W.
        Nocturnal enuresis: an international evidence based management strategy.
        J Urol. 2004; 171: 254
        • Bakhtiar K.
        • Pournia Y.
        • Ebrahimzadeh F.
        • Farhadi A.
        • Shafizadeh F.
        • Hosseinabadi R.
        Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of Khorramabad in 2013.
        Int J Pediatr. 2014; 2014
        • Ramakrishnan K.
        Evaluation and treatment of enuresis.
        Am Fam Physician. 2008; 78: 489
        • Glazener C.
        • Peto R.
        • Evans J.
        Effects of interventions for the treatment of nocturnal enuresis in children.
        Qual Saf Heal Care. 2003; 12: 390
        • Vande Walle J.
        • Stockner M.
        • Raes A.
        • Nørgaard J.P.
        Desmopressin 30 years in clinical use: a safety review.
        Curr Drug Saf. 2007; 2: 232
        • Glazener C.M.
        • Evans J.H.C.
        • Peto R.E.
        Tricyclic and related drugs for nocturnal enuresis in children.
        Cochrane Database Syst Rev. 2003;
        • Logan A.C.
        • Lesperance F.
        Primary nocturnal enuresis: omega-3 fatty acids may be of therapeutic value.
        Med Hypotheses. 2005; 64: 1188
        • Li L.
        • Zhou H.
        • Yang X.
        • Zhao L.
        • Yu X.
        Relationships between 25-hydroxyvitamin D and nocturnal enuresis in five- to seven-year-old children.
        PLoS One. Jan 2014; 9: e99316
        • Riccardi D.
        • Traebert M.
        • Ward D.
        • Kaissling B.
        • Biber J.
        • Hebert S.
        • Murer H.
        Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule.
        Pflügers Arch. 2000; 441: 379
        • Leiberman A.
        • Stiller-Timor L.
        • Tarasiuk A.
        • Tal A.
        The effect of adenotonsillectomy on children suffering from obstructive sleep apnea syndrome (OSAS): the Negev perspective.
        Int J Pediatr Otorhinolaryngol. 2006; 70: 1675
        • Mete T.
        • Yalcin Y.
        • Berker D.
        • Ciftci B.
        • Guven S.
        • Topaloglu O.
        • et al.
        Obstructive sleep apnea syndrome and its association with vitamin D.
        J Endocrinol. 2013; 36: 681
        • Aceto G.
        • Penza R.
        • Coccioli M.
        • Palumbo F.
        • Cresta L.
        • Cimador M.
        • et al.
        Enuresis subtypes based on nocturnal hypercalciuria: a multicenter study.
        J Urol. 2003; 170: 1670
        • Koff S.
        Why isn’t desmopressin very effective?.
        Pediatr Nephrol. 1996; 10: 667
        • Nording M.L.
        • Yang J.
        • Georgi K.
        • Hegedus Karbowski C.
        • German J.B.
        • Weiss R.H.
        • et al.
        Individual variation in lipidomic profiles of healthy subjects in response to omega-3 fatty acids.
        PLoS One. Jan 2013; 8: e76575
        • Mutoh S.
        • Ueda S.
        • Yano S.
        • Ikegami K.
        • Sakanashi M.
        Effects of some prostaglandins on urinarybladder and urethraisolated from the dog.
        J Urol. 1983; 38: 219
        • Finkbeiner A.
        • Bissada N.
        In vitro effects of prostaglandins on the guinea pig detrusor and bladder outlet.
        Urol Res. 1981; 9: 281
        • Kielar M.
        • Jeyarajah D.
        • Zhou X.
        • Lu C.
        Docosahexaenoic acid ameliorates murine ischemic acute renal failure and prevents increases in mRNA abundance for both TNF-alpha and inducible nitric oxide synthase.
        J Am SocNephrol. 2003; 14: 389
        • Kliegman R.
        • Nelson W.E.
        Nelson textbook of pediatrics.
        in: Kliegman R.M. Stanton B.F. St Geme III, J.W. Text of pediatrics. 19th ed. Judith Fletcher, Philadelphia2011: 71
        • Winzenberg T.
        • Powell S.
        • Shaw K.
        • Jones G.
        Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis.
        BMJ. 2011; : 1
        • Urashima M.
        • Segawa T.
        • Okazaki M.
        • Kurihara M.
        • Wada Y.
        • Ida H.
        Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
        Am J Clin Nutr. 2010; : 1255
        • Bays H.E.
        Safety considerations with Omega-3 fatty acid therapy.
        Am J Cardiol. 2007; 99: 35c
        • Report of a WHO Expert Committee
        Physical status: the use and interpretation of anthropometry.
        World Heal Organ Tech Rep Ser. 1995; 854: 1
        • Anyanwu O.
        • Ibekwe R.
        • Orji M.
        Nocturnal enuresis among nigerian children and its association with sleep, behavior and school performance.
        Indian Pediatr. 2015; 52: 587
        • Hashem M.
        • Morteza A.
        • Mohammad K.
        • Ahmad-Ali N.
        Prevalence of nocturnal enuresis in school aged children: the role of personal and parents related socio-economic and educational factors.
        Iran J Pediatr. 2013; 23: 59
        • De Bruyne E.
        • Van Hoecke E.
        • Van Gompel K.
        • Verbeken S.
        • Baeyens D.
        • Hoebeke P.
        • et al.
        Problem behavior, parental stress and enuresis.
        J Urol. 2009; 189: 2015
        • Kuznetsova E.
        • Shakhmatova A.A.
        • Prutskova N.
        • Natochin Y.
        Possible role of prostaglandins in pathogenesis of nocturnal enuresis in children.
        Scand J Urol Nephrol. 2000; 34: 27
        • Cao D.
        • Kevala K.
        • Kim J.
        • Moon H.-S.
        • Jun S.B.
        • Lovinger D.
        • et al.
        Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function.
        J Neurochem. 2009; 111: 510
        • Al-Waili N.
        Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.
        BJU Int. 2002; 90: 294