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To cite this article: Rolf Jorde, Stina T. Sollid, Johan Svartberg, Ragnar M. Joakimsen, Guri
Grimnes & Moira Y. S. Hutchinson (2016): Prevention of urinary tract infections with vitamin D
supplementation 20,000IU per week for five years. Results from an RCT including 511 subjects,
Infectious Diseases, DOI: 10.1080/23744235.2016.1201853
Article views: 28
ORIGINAL ARTICLE
Results: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and Diabetes; respiratory
fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin infection; urinary tract
D and 111 in the placebo group completed the five-year study. Eighteen subjects in the vitamin D infection; vitamin D
group and 34 subjects in the placebo group reported UTI during the study (p < 0.02), whereas no sig-
nificant differences were seen for RTI. The effect on UTI was most pronounced in males. The effect of
vitamin D on UTI was unrelated to baseline serum 25(OH)D level.
Conclusion: Supplementation with vitamin D might prevent UTI, but confirmatory studies are needed.
CONTACT Rolf Jorde rolf.jorde@unn.no Division of Internal Medicine, University Hospital of North Norway, NO-9038 Troms, Norway
2016 Society for Scandinavian Journal of Infectious Diseases
2 R. JORDE ET AL.
clinical examination was performed, and questionnaires on between the two groups at baseline and during the study
medical history including infections, medication and vitamin D were performed with Students t-test or chi-square tests.
supplementation were filled in. Height and weight were meas- Occurrence of RTI or UTI in the two groups was evaluated
ured wearing light clothing. Fasting blood samples had been with Cox regression with gender and age as covariates.
collected at the OGTT, and supplementary non-fasting blood p < 0.05 (two-tailed) was considered statically significant.
samples were drawn at this visit. The subjects were then Data are presented as mean SD for normally distributed val-
randomized (non-stratified) in a 1:1 ratio to one capsule vitamin ues and as median (5th, 95th percentiles) for serum parathy-
D (cholecalciferol 20,000 IU (Dekristol; Mibe, Jena, Germany)) roid hormone (PTH) that had a non-normal distribution. All
per week or an identical looking placebo capsule containing statistical analyses were performed using IBM SPSS version 22
arachis oil (Hasco-Lek, Wroclaw, Poland). New medication was software (SPSS INC, Chicago, IL).
supplied every sixth month and unused capsules returned and The power calculation of the study was made for the main
counted. The subjects were not allowed to take vitamin D sup- endpoint (development of T2DM),[11] and a separate power
plements (including cod liver oil) exceeding 400 IU per day. calculation for the infection questionnaire was not made.
For the next five years, the subjects met every sixth month
and filled in questionnaires on infections. Adverse events were
Ethics
specifically asked for. The questions regarding infections were:
All subjects gave written informed consent. The study was
have you the last six months had a common cold, and in approved by the Regional Committee for Medical and Health
that case how many times? Research Ethics (REK NORD 81/2007) and by the Norwegian
have you the last six months had bronchitis, and in that Medicines Agency (2007-002167-27). The trial is registered at
case how many times? ClinicalTrial.gov (NCT00685594).
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Table 2. Number of subjects according to number of events with common cold, bronchitis, influenza-like illness or urinary tract infection during the five-year study
period.
Number of subjects
Common cold Bronchitis Influenza-like illness Urinary tract infection
Number of events Vitamin D Placebo Vitamin D Placebo Vitamin D Placebo Vitamin D Placebo
0 71 73 223 224 137 158 238 221
1 52 55 16 19 68 54 9 15
2 38 37 11 8 28 18 3 5
3 22 24 3 2 9 15 2 3
4 21 19 1 2 7 7 5
5 17 10 4 2 3 1
6 12 11 1 1
7 11 7 1 1 1
8 4 8 1 2 1
9 1 1
10 2 3 1
>10 5 7 2
P vs. placebo (chi-square test) ns ns ns 0.025
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Figure 2. Cumulative probability of urinary tract infection (UTI) based on Cox Figure 3. Cumulative probability of urinary tract infection (UTI) based on Cox
regression with age and gender as covariates in the 256 subjects in the vitamin regression with age as covariate in the 161 men in the vitamin D group and the
D group and the 255 subjects in the placebo group. 153 men in the placebo group.
had 28% lower serum 25(OH)D levels than controls [13]; in Table 3. Baseline serum 25(OH)D levels in subjects with or without infection
children with UTI Tekin et al. found the serum 25(OH)D levels last six months before baseline.
to be approximately half those in the controls,[14] and a simi- Subjects with infection Subjects without infection
lar observation was made by Nesir et al. in premenopausl last six months last six months
women [15]; Vaughan et al. found vitamin D deficiency to be Serum 25(OH)D Serum 25(OH)D
associated with lower urinary tract symptoms in a cohort of N (nmol/L) N (nmol/L)
2387 men in the 20052006 NHANES [16]; Caretta et al. found Common cold 199 59.1 21.0 312 61.4 21.9
Bronchitis 20 52.9 16.6 491 60.8 21.7
low serum 25(OH)D levels to be associated with urinary tract Influenza 101 59.9 20.8 410 60.6 21.8
symptoms and benign prostate hypertrophy in male subjects UTI 30 62.9 24.1 481 60.3 21.4
with T2DM [17]; and finally, Kwon et al. found vitamin D defi- All infections 250 59.8 21.8 261 61.2 21.3
ciency to be an independent risk factor for UTI after renal 25(OH)D: 25-hydroxyvitamin D; UTI: urinary tract infection.
transplantation.[18]
There could be several mechanisms for a protective effect
of vitamin D on UTI. It has been shown that vitamin D can phagocytic function [21]; vitamin D supplementation could
induce production and secretion of the antimicrobial peptide alter the chemical composition of the urine by increasing the
cathelicidin by bladder epithelial cells [19,20]; vitamin D is urinary calcium excretion [22]; vitamin D has a direct effect
important for innate immunity in defending against bacterial on muscle function and could contribute to pelvic floor func-
infections by increasing the neutrophilic motility and tion and bladder emptying, particularly in women [23]; and in
INFECTIOUS DISEASES 5
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[20] Hertting O, Holm , L uthje P, et al. Vitamin D induction of the ment use, and the risk of symptomatic benign prostatic hyperpla-
human antimicrobial peptide cathelicidin in the urinary bladder. sia: results from the prostate cancer prevention trial. Am J
PLoS One. 2010;5:e15580. Epidemiol. 2008;167:925934.
[21] Bikle DD. Vitamin D and the immune system: role in protection [26] Colli E, Rigatti P, Montorsi F, et al. BXL628, a novel vitamin D3 ana-
against bacterial infection. Curr Opin Nephrol Hypertens. log arrests prostate growth in patients with benign prostatic
2008;17:348352. hyperplasia: a randomized clinical trial. Eur Urol. 2006;49:8286.
[22] Gallagher JC, Smith LM, Yalamanchili V. Incidence of hypercalciuria [27] Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary
and hypercalcemia during vitamin D and calcium supplementation reference intakes for calcium and vitamin D from the Institute of
in older women. Menopause. 2014;21:11731180. Medicine: what clinicians need to know. J Clin Endocrinol Metab.
[23] Badalian SS, Rosenbaum PF. Vitamin D and pelvic floor disorders 2011;96:5358.
in women: results from the National Health and Nutrition [28] Theodoratou E, Tzoulaki I, Zgaga L, et al. Vitamin D and multiple
Examination Survey. Obstet Gynecol. 2010;115:795803. health outcomes: umbrella review of systematic reviews and
[24] Adorini L, Penna G, Fibbi B, et al. Vitamin D receptor ago- meta-analyses of observational studies and randomised trials. BMJ.
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