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Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects

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Background: In observational studies vitamin D deficiency is associated with increased risk of infections, whereas the effect of vitamin D supplementation in randomized controlled trials is non-conclusive. Methods: Five hundred and eleven subjects with prediabetes were randomized to vitamin D3 (20,000 IU per week) versus placebo for five years. Every sixth month, a questionnaire on respiratory tract infections (RTI) (common cold, bronchitis, influenza) and urinary tract infection (UTI) was filled in. Results: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin D and 111 in the placebo group completed the five-year study. Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study (p < 0.02), whereas no significant 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.
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Infectious Diseases
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Prevention of urinary tract infections with vitamin
D supplementation 20,000 IU per week for five
years. Results from an RCT including 511 subjects
Rolf Jorde, Stina T. Sollid, Johan Svartberg, Ragnar M. Joakimsen, Guri
Grimnes & Moira Y. S. Hutchinson
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 20,000 IU per week for five years. Results from an RCT including 511 subjects,
Infectious Diseases, 48:11-12, 823-828, DOI: 10.1080/23744235.2016.1201853
To link to this article: https://doi.org/10.1080/23744235.2016.1201853
Published online: 30 Jun 2016. Submit your article to this journal
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ORIGINAL ARTICLE
Prevention of urinary tract infections with vitamin D supplementation 20,000 IU
per week for five years. Results from an RCT including 511 subjects
Rolf Jorde
a,b
,Stina T. Sollid
a,b
,Johan Svartberg
a,b
,Ragnar M. Joakimsen
a,b
,Guri Grimnes
a,b
and
Moira Y. S. Hutchinson
c
a
Department of Clinical Medicine, Tromsø Endocrine Research Group, UiT The Arctic University of Norway, Tromsø, Norway;
b
Division of
Internal Medicine, University Hospital of North Norway, Tromsø, Norway;
c
Division of Head and Motion, Department of Rheumatology,
Nordland Hospital, Bodø, Norway
ABSTRACT
Background: In observational studies vitamin D deficiency is associated with increased risk of infec-
tions, whereas the effect of vitamin D supplementation in randomized controlled trials is non-
conclusive.
Methods: Five hundred and eleven subjects with prediabetes were randomized to vitamin D
3
(20,000IU per week) versus placebo for five years. Every sixth month, a questionnaire on respiratory
tract infections (RTI) (common cold, bronchitis, influenza) and urinary tract infection (UTI) was filled in.
Results: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and
fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin
D and 111 in the placebo group completed the five-year study. Eighteen subjects in the 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.
ARTICLE HISTORY
Received 13 April 2016
Revised 6 June 2016
Accepted 9 June 2016
Published online 29 June
2016
KEYWORDS
Diabetes; respiratory
infection; urinary tract
infection; vitamin D
Introduction
Vitamin D is vital for the calcium metabolism, and severe vita-
min D deficiency leads to rickets in children and osteomalacia
in adults. Vitamin D is produced in the skin upon UV expos-
ure or obtained from the diet where fatty fish is the main
source. For its activation, vitamin D is hydoxylated in the liver
to 25-hydroxyvitamin D (25(OH)D), which is used as a marker
of a subject’s vitamin D status, and then in the kidneys (and
some peripheral tissues) to the active form 1,25-dihydroxyvi-
tamin D (1,25(OH)
2
D).[1] The active form binds to the nuclear
vitamin D receptor (VDR) which is located in tissues through-
out the body, including immune cells,[2,3] and regulates tran-
scription of hundreds of genes, including genes for
antimicrobial peptides and cytokines.[4,5] Vitamin D is there-
fore likely to be important for more than bone health.
Thus, from observational studies there are a number of
indications for an association between vitamin D deficiency
and infectious diseases like tuberculosis, respiratory tract
infections (RTI), influenza and sepsis.[6] As an example, non-
pandemic influenza occurs mostly in temperate climates in
the winter season when the serum 25(OH)D levels are low [7];
influenza pandemics are associated with solar activity cycles
[8]; and even the mortality rates during influenza pandemics
appear related to the level of solar radiation.[9] However,
randomized controlled trials (RCT) with vitamin D supplemen-
tation for treatment and/or prevention of infections have so
far not given conclusive results.[6]
We have recently performed a five-year intervention study
with vitamin D in subjects with prediabetes for the preven-
tion of progression to T2DM. As part of the study the subjects
were asked every sixth month for upper respiratory infections
(common cold, bronchitis, influenza) and urinary tract infec-
tions (UTI) since the last visit. We therefore had the opportun-
ity to evaluate the effect of supplementation with vitamin D
on these infections.
Materials and methods
Study design
The design of the study has been described in detail
before.[10,11] In short, subjects with prediabetes (impaired
fasting glucose (IFG) (serum glucose 6.0–6.9 mmol/L) and/or
impaired glucose tolerance (IGT) (fasting serum glucose
<7.0 mmol/L and 2-h value 7.8–11.0 mmol/L at oral glucose
tolerance test (OGTT) with 75 g glucose) were included.
Subjects with primary hyperparathyroidism, granulomatous
disease, history of urolithiasis, cancer diagnosed in the past
five years, unstable angina pectoris, myocardial infarction or
stroke in the past year were excluded. Pregnant or lactating
women, or women of fertile age with no use of contracep-
tion, were not included.
All visits were performed at the Clinical Research Unit at the
University Hospital of North Norway. At the first visit, a brief
CONTACT Rolf Jorde rolf.jorde@unn.no Division of Internal Medicine, University Hospital of North Norway, NO-9038 Tromsø, Norway
ß2016 Society for Scandinavian Journal of Infectious Diseases
INFECTIOUS DISEASES, 2016
VOL. 48, NO. 11-12, 823–828
http://dx.doi.org/10.1080/23744235.2016.1201853
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clinical examination was performed, and questionnaires on
medical history including infections, medication and vitamin D
supplementation were filled in. Height and weight were meas-
ured wearing light clothing. Fasting blood samples had been
collected at the OGTT, and supplementary non-fasting blood
samples were drawn at this visit. The subjects were then
randomized (non-stratified) in a 1:1 ratio to one capsule vitamin
D (cholecalciferol 20,000 IU (Dekristol; Mibe, Jena, Germany))
per week or an identical looking placebo capsule containing
arachis oil (Hasco-Lek, Wroclaw, Poland). New medication was
supplied every sixth month and unused capsules returned and
counted. The subjects were not allowed to take vitamin D sup-
plements (including cod liver oil) exceeding 400 IU per day.
For the next five years, the subjects met every sixth month
and filled in questionnaires on infections. Adverse events were
specifically asked for. The questions regarding infections were:
have you the last six months had a common cold, and in
that case how many times?
have you the last six months had bronchitis, and in that
case how many times?
have you the last six months had influenza or influenza-
like illness (with fever), and in that case how many times?
have you the last six months had a UTI, and in that case
how many times?
If at the annual OGTT the fasting blood glucose was
>6.9 mmol/L and/or the 2-h value >11.0 mmol/L the subject
was considered to have T2DM, thus ending their participation
in the study, and thereafter retested (if necessary) and fol-
lowed by their general practitioner. Due to the inclusion of
HbA
1c
(alone or in combination with glucose criteria) as a
diagnostic criterion for diabetes in the WHO report from
2011,[12] and the acceptance of this in Norway the year later,
it was also implemented in the present study from November
2012. Thus, if HbA
1c
alone was 6.5%, the subject was
retested with new HbA
1c
measurement and if still 6.5%
diagnosed as T2DM and ending their participation in the
study. Also, if diagnosed elsewhere with T2DM between visits
in the study, participation was ended.
Subjects who developed persistent hypercalcemia (serum
calcium >2.55 mmol/L), and subjects who developed renal
stones, or symptoms compatible with renal stones, were also
excluded. In the initial protocol, subjects who during the
study were diagnosed with cancer, coronary infarction,
unstable angina pectoris, or stroke, were to be excluded from
the study. From October 2011, this was changed to exclusion
of subjects who during the study developed serious disease
making it difficult or impossible to attend scheduled visits. As
part of the safety monitoring, serum calcium was measured
at each of the six-month visit.
Biochemical analyses including serum 25(OH)D were ana-
lyzed as previously described.[11]
Statistical analyses
Normal distribution was evaluated with visual inspection of
histograms and by kurtosis and skewness. Comparisons
between the two groups at baseline and during the study
were performed with Student’s t-test or chi-square tests.
Occurrence of RTI or UTI in the two groups was evaluated
with Cox regression with gender and age as covariates.
p<0.05 (two-tailed) was considered statically significant.
Data are presented as mean ± SD for normally distributed val-
ues and as median (5th, 95th percentiles) for serum parathy-
roid hormone (PTH) that had a non-normal distribution. All
statistical analyses were performed using IBM SPSS version 22
software (SPSS INC, Chicago, IL).
The power calculation of the study was made for the main
endpoint (development of T2DM),[11] and a separate power
calculation for the infection questionnaire was not made.
Ethics
All subjects gave written informed consent. The study was
approved by the Regional Committee for Medical and Health
Research Ethics (REK NORD 81/2007) and by the Norwegian
Medicines Agency (2007-002167-27). The trial is registered at
ClinicalTrial.gov (NCT00685594).
Results
Five hundred and eleven subjects were included in the study;
256 were randomized to vitamin D and 255 to placebo. Their
baseline characteristics are shown in Table 1. The baseline
serum 25(OH)D levels were 59.9 ± 21.9nmol/L in the vitamin
D group and 61.1 ± 21.2nmol/L in the placebo group. During
the intervention period, the mean serum 25(OH)D level in the
vitamin D group increased to 110 nmol/L after 1 year and
thereafter gradually to 122 nmol/L at the end of the study;
whereas the levels remained stable in the placebo group.
After 1 year median serum PTH decreased by 0.5 pmol/L in
the vitamin D group, whereas there was an increase of
0.2 pmol/L in the placebo group (p<0.001). A similar differ-
ence in serum PTH persisted throughout the study. The com-
pliance rate was between 95 and 99% at all visits in both
groups.
During the study, 50 subjects in the vitamin D group and
45 subjects in the placebo group dropped out or were
excluded due to illness; and 103 subjects in the vitamin D
group and 112 in the placebo group developed T2DM. The
study flow including the number of subjects who attended
the annual visits is shown in Figure 1. Regarding the main
endpoint, development of T2DM, or the secondary endpoints
(changes in measures of glucose metabolism and insulin
resistance, serum lipids and blood pressure) there were no
statistically significant differences between the two
groups.[10,11]
No significant differences in adverse events were recorded
as described in detail previously.[11] Regarding calcium-spe-
cific adverse events, two subjects in the vitamin D group and
one subject in the placebo group developed renal stones and
were excluded; one subject in the vitamin D group was
excluded after a serum calcium of 2.64 mmol/L after six
months with a retest value of 2.63 mmol/L (later testing
showed normal serum calcium and PTH values), and two
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subjects in the vitamin D group and one in the placebo
group had single serum calcium values in the range
2.56–2.61 mmol/L that normalized at second testing, and thus
continued in the study.
Infections
At baseline, there were not any statistically significant differ-
ences between the groups regarding infections the previous
six months, although there were considerably more subjects
in the placebo than the vitamin D group who had experi-
enced one or more UTI (20 subjects versus 10) (Table 1).
During the five-year intervention, a total number of 141
UTI events were recorded, 44 (18 incident and 26 recurrent)
in the vitamin D group and 97 (34 incident and 63 recurrent)
in the placebo group. The numbers of subjects who experi-
enced one or more events with RTI or UTI are shown in
Table 2. A statistically significant difference between the two
groups was only seen for UTI, with less UTI in the vitamin D
group. This difference was significant when evaluating sub-
jects who experienced at least one UTI during the study
period (18 in the vitamin D group vs. 34 in the placebo
group, p¼0.018, Pearson’s chi-square test); when also consid-
ering total number of UTI events (p¼0.025, chi-square test,
linear-by-linear association), and when analyzing with Cox
regression for first UTI event after inclusion in the study (HR
0.51; 95% CI 0.29–0.90, age and gender as covariates,
p¼0.021) (Figure 2). The difference regarding UTI was statis-
tically significant in men (3 in the vitamin D group vs. 11 in
the placebo group) (HR 0.26; 95% CI 0.07–0.93, p¼0.038)
(Figure 3), but did not reach statistical significance in women
(15 in the vitamin D group vs. 23 in the placebo group) (HR
0.64; 95% CI 0.33–1.23, p¼0.18).
Although not statistically significant, there were more sub-
jects with prior UTI in the placebo than the vitamin D group
(20 subjects vs. 10 subjects). Since there is a high relapse rate
for UTI, the lower rate of UTI in the vitamin D group during
the study could therefore be due to this baseline difference.
However, during the intervention, 7 of these 10 subjects in
the vitamin D group and 7 of these 20 subjects in the
placebo group had a recurrence during the study. Exclusion
of these 30 subjects in the Cox regression therefore increased,
and not diminished, the difference between the two groups
regarding first UTI (HR 0.38; 95% CI 0.19–0.76), p¼0.006).
Effect of baseline serum 25(OH)D
Baseline serum 25(OH)D levels did not differ significantly
between those with or without an infection the previous six
months (Table 3), nor was the baseline serum 25(OH)D level a
significant predictor of infections during the intervention
study in neither study group (data not shown).
In the group of subjects with serum 25(OH)D above 50
mnol/L at baseline (167 in the vitamin D group and 170 in
the placebo groups) the effect of vitamin D supplementation
regarding first UTI during the study was still significant (HR
0.49; 95% CI 0.25–0.96, p¼0.038). However, in the group of
subjects with baseline serum 25(OH)D below 50 nmol/L (88
subjects in the vitamin D group and the 85 in the placebo
group), the effect did not reach statistical significance
(HR 0.53; 95% CI 0.17–1.64, p¼0.27).
Discussion
In the present study, we have found supplementation with
vitamin D to significantly reduce the occurrence and number
of UTI during a five-year intervention study, whereas no effect
was seen on RTI.
To our knowledge, this is the first RCT reporting effect of
vitamin D on UTI. However, there are several observational
reports linking vitamin D deficiency to UTI. Thus, in a case–
control study by van der Starre et al., adult subjects with UTI
Table 1. Baseline characteristics in the two study groups.
Vitamin D group
(n¼256)
Placebo group
(n¼255)
Male sex, n(%) 161 (62.9) 153 (60.0)
Age (years) 62.3 ± 8.1 61.9 ± 9.2
BMI (kg/m
2
) 30.1 ± 4.1 29.8 ± 4.4
Current smokers, n(%) 59 (23.0) 47 (18.3)
Vitamin D supplement use
a
87 (34.0) 92 (36.1)
Serum 25(OH)D (nmol/L) 59.9 ± 21.9 61.1 ± 21.2
Serum calcium (mmol/L) 2.31 ± 0.08 2.31 ± 0.08
Serum PTH (pmol/L) 5.5 (3.4, 9.7) 5.2 (3.1, 9.6)
Serum creatinine (lmol/L) 69.7 ± 13.6 69.5 ± 13.9
HbA
1c
(%) 5.98 ± 0.28 5.97 ± 0.34
Infections last six months
Common cold (yes/no) 99/157 100/155
Bronchitis (yes/no) 7/249 13/242
Influenza (yes/no) 58/198 43/212
UTI (yes/no) 10/246 20/255
a
Including cod liver oil.
BMI: body mass index; 25(OH)D: 25-hydroxyvitamin D; PTH: parathyroid hor-
mone; HbA
1c
: hemoglobin A1c; UTI: urinary tract infection.
Figure 1. Flow chart of the study.
INFECTIOUS DISEASES 825
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had 28% lower serum 25(OH)D levels than controls [13]; in
children with UTI Tekin et al. found the serum 25(OH)D levels
to be approximately half those in the controls,[14] and a simi-
lar observation was made by Nesir et al. in premenopausl
women [15]; Vaughan et al. found vitamin D deficiency to be
associated with lower urinary tract symptoms in a cohort of
2387 men in the 2005–2006 NHANES [16]; Caretta et al. found
low serum 25(OH)D levels to be associated with urinary tract
symptoms and benign prostate hypertrophy in male subjects
with T2DM [17]; and finally, Kwon et al. found vitamin D defi-
ciency to be an independent risk factor for UTI after renal
transplantation.[18]
There could be several mechanisms for a protective effect
of vitamin D on UTI. It has been shown that vitamin D can
induce production and secretion of the antimicrobial peptide
cathelicidin by bladder epithelial cells [19,20]; vitamin D is
important for innate immunity in defending against bacterial
infections by increasing the neutrophilic motility and
phagocytic function [21]; vitamin D supplementation could
alter the chemical composition of the urine by increasing the
urinary calcium excretion [22]; vitamin D has a direct effect
on muscle function and could contribute to pelvic floor func-
tion and bladder emptying, particularly in women [23]; and in
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 5255 161968549 15
2 38 37 11 8 28 18 3 5
3 2224 329152 3
4 2119 1277 5
51710 4231
61211 11
711711 1
848121
911
10 2 3 1
>10 5 7 2
P vs. placebo (chi-square test) ns ns ns 0.025
Figure 3. Cumulative probability of urinary tract infection (UTI) based on Cox
regression with age as covariate in the 161 men in the vitamin D group and the
153 men in the placebo group.
Figure 2. Cumulative probability of urinary tract infection (UTI) based on Cox
regression with age and gender as covariates in the 256 subjects in the vitamin
D group and the 255 subjects in the placebo group.
Table 3. Baseline serum 25(OH)D levels in subjects with or without infection
last six months before baseline.
Subjects with infection
last six months
Subjects without infection
last six months
N
Serum 25(OH)D
(nmol/L) N
Serum 25(OH)D
(nmol/L)
Common cold 199 59.1 ± 21.0 312 61.4 ± 21.9
Bronchitis 20 52.9 ± 16.6 491 60.8 ± 21.7
Influenza 101 59.9 ± 20.8 410 60.6 ± 21.8
UTI 30 62.9 ± 24.1 481 60.3 ± 21.4
All infections 250 59.8 ± 21.8 261 61.2 ± 21.3
25(OH)D: 25-hydroxyvitamin D; UTI: urinary tract infection.
826 R. JORDE ET AL.
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men, vitamin D appears to be a regulator of prostatic cell
growth, could influence the development of benign prostatic
hyperplasia (BPH), and thereby reduce the likelihood of
UTI.[24]
The effect of vitamin D on BPH is supported by an
observational study where subjects with the highest quintile
of vitamin D intake had a 18% reduced risk of developing
BPH compared to those in the lowest quintile [25]; and
also from an RCT where the vitamin D
3
analog BXL628 was
able to arrest prostate growth in subjects with moderate
BPH.[26] In our study this is of particular interest since the
effect of the vitamin D supplementation was particularly
evident in men.
We did not observe any effect of vitamin D on the occur-
rence of RTI. This is in line with the conclusion in the recent
review by Kearns et al. that included 13 RCTs with vitamin D
for prevention of RTI.[6] Only two of those studies found a
positive effect of vitamin D, whereas the other found no
change in the incidence or severity of RTI or influenza
symptoms.
Our study has two main weaknesses: we used question-
naires with self-reported occurrence of infections without
any bacteriological, virological or serological verification,
and the effect on infections was not a primary endpoint. It
is also remarkable that the effect of vitamin D supplemen-
tation was not related to baseline serum 25(OH)D levels.
Thus, the protective effect of vitamin D was significant not
only in all subjects analyzed together, but also in those
with baseline serum 25(OH)D above 50 nmol/L, a level that
many consider as sufficient at least for bone health.[27]If
our result is not a chance finding, this may indicate that
the threshold for vitamin D effects is different for the urin-
ary tract than for the skeleton.
Our study also have some strengths: the study was per-
formed according to strict RCT rules, the questionnaire was
administered and checked by highly trained nurses, we
included a large number of subjects, and we gave sufficient
vitamin D doses for a long period of time.
In conclusion, there is an abundance of observational stud-
ies regarding vitamin D and health effect, and for almost
every disease examined, high serum 25(OH)D levels appear
beneficial. However, RCTs with vitamin D supplementation
have been disappointing.[28] In view of this, our result with a
positive effect of vitamin D on UTI should be viewed with
caution and more RCTs are clearly needed. In particular, the
unexpected effect in subjects apparently vitamin D sufficient
needs confirmation.
Acknowledgements
The superb assistance from the staff at the Clinical Research Unit (and
in particular Aslaug Jakobsen) and the Department of Medical
Biochemistry at the University Hospital of North Norway is gratefully
acknowledged.
Disclosure statement
The authors do not have a commercial or other association that might
pose a conflict of interest.
Funding information
The study was supported by grants from the Novo Nordisk foundation
(grant number R195-A16126), the North Norway Regional Health
Authorities (grant number 6856/SFP1029-12), UiT The Arctic University of
Norway, the Norwegian Diabetes Association, and the Research Council of
Norway (grant number 184766).
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... The results of our study showed that there is no significant relationship between serum levels of vitamin D and the incidence of UTI in both age groups. This finding is similar to some studies [10,11,13,15]. However, the study of Georgieva et al. showed that serum vitamin D level is inversely related to age [16]. ...
... In a clinical trial study in 2016 conducted by Jorde et al. on 511 pre-diabetic patients matched with the control group, the effect of vitamin D supplementation on the prevention of UTI was evaluated. It was shown that vitamin D supplementation for UTI prevention was more effective in males compared to females [15]. However, the study of Mahyar et al. and Tekin et al., showed no significant differences between vitamin D levels of the case and control groups according to gender [10,13]. ...
... Similar to our study, the study of Mahyar et al. showed that according to weight, height, head circumference and BMI, there were no significant differences between the two groups [13]. Also, this finding is similar to the study of Jorde et al. [15]. In general, BMI does not seem to affect the relationship between vitamin D levels and the prevalence of UTI. ...
Article
Full-text available
Urinary tract infection (UTI) is one of the most common infections in infants and children. The aim of this study is to evaluate the association between vitamin D levels and urinary tract infections in children. This case-control study was performed on 80 children aged 1-12 years with urinary tract infection referred to the pediatric clinic of Mousavi Hospital in Zanjan,Iran. For each patient in case group, an individual of the same age and sex was selected in the control group. Vitamin D was measured by ELISA method. Statistical analysis was performed by SPSS V22 software. In this study, 80 children were divided into two groups of 40 cases (UTI) and control. Serum levels of vitamin D in the case group were significantly lower than in the control group [OR (95%CI) = 3.316 (1.286-8.550), p =0.013)]. In females, serum levels of vitamin D in cases were significantly lower than for controls [OR (95%CI) = (5.417 (1.685-17.417), P-value=0.005)]. No significant relationship was found between serum levels of vitamin D in cases and controls regarding male gender, age and weight. Conclusions: This study showed that vitamin D deficiency has a significant relationship with the prevalence of UTI in children. Vitamin D deficiency and female gender are more frequent risk factors for UTI.
... On the other hand, several studies have associated VD-deficiency with increased odds of urinary tract infections (UTI) [22][23][24], highlighting hypovitaminosis D as a potential modifiable risk factor for bacterial vaginosis among the general population including pregnant women, and emphasizing VD supplementation as a prevention strategy for UTIs [25,26]. This epidemiological data reflect the ability of calcitriol to exert microbicidal activity, which is achieved by transcriptionally inducing antimicrobial peptides expression. ...
... Remarkably, in this study, cord serum calcitriol negatively correlated with maternal bacteriuria only in the UTI-female subgroup, further supporting a sex-dependent differential VD regulation of the immune response and suggesting that placental production of calcitriol may help to attenuate maternal UTI. In agreement with our assumption, in a randomized controlled trial, the supplementation with VD significantly prevented UTI [26]. At the same time, serum calcidiol levels less than 20 ng/mL in pregnant subjects have been shown to represent the only factor associated with UTI [23]. ...
Article
Full-text available
Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D3’s most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn’s sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.
... The use of micronutrients, natural products and vitamins are becoming more popular in different diseases in children (4,8). The use of vitamin D as a supplement in prevention and treatment of UTI and its complications has been reported (9). Moreover, the association between vitamin D and several infectious diseases has been studied for a long time (10). ...
... On the other hand, there is increasing evidence that vitamin D deficiency plays an important role in susceptibility to UTI and administration of vitamin D can prevent it. It was reported that supplementation with vitamin D might prevent UTI (9). In addition to, several studies demonstrated that the low level of 25(OH)D may be a risk factor for UTI (11)(12)(13)(14)(15). Beside the growing evidence on the role of vitamin D supplementation in prevention and treatment of UTI in children, no study has systemically evaluated the association between serum vitamin D level and risk of UTI in children. ...
Article
Full-text available
This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentration and the risk of urinary tract infection (UTI) in children. Human studies reported the serum vitamin D level in children with UTI and healthy controls were collected from PubMed, Scopus, Embase, and Cochrane databases. The strictly standardized mean difference (SSMD) and 95% confidence interval (CI) were calculated to evaluate the relationship between serum vitamin D levels and risk of UTI. The results of analysis showed that serum vitamin D levels in children with UTI were significantly lower than healthy control children (SSMD: 0.891, 95% CI: 0.707–1.075, p < 0.000; SSMD: 0.797, 95% CI: 0.500–1.094, p < 0.000, respectively). It can be concluded that there is a significant negative relationship between serum vitamin D level and risk of UTI in children.
... Based on all of these findings, vitamin D supplementation for prevention of rUTI has become a topic of interest in many recent studies, especially since several interventions, other than antibiotic prophylaxis, for the prevention of recurrent UTI have been tried but so far did not provide a definitive effective answer (112). Jorde et al. (113) conducted a randomized controlled trial on patients with prediabetes who were randomized to vitamin D3 (20,000 IU per week) versus placebo for five years (116 subjects who received vitamin D and 111 who received placebo completed the five-year study). During the 5 year follow up, 18 subjects in the vitamin D group and 34 subjects in the placebo group developed UTI. ...
Article
Full-text available
Recurrent urinary tract infections (rUTI) represent a major healthcare and economic burden along with a significant impact on patient's morbidity and quality of life, even in the absence of well-known risk factors, such as vesicoureteral reflux. Despite numerous attempts to find a suitable therapeutic option, there is no clear benefit of any currently available intervention for prevention of UTI recurrence and its long-term consequences such as hypertension, renal scarring and/or insufficiency. The common treatment practice in many centers around the globe involves the use of continuous low-dose antibiotic prophylaxis, irrespective of various studies indicating increased microbial resistance against the prophylactic drug, leading to prolonged duration and escalating the cost of UTI treatment. Moreover, the rapid appearance of multi-drug resistant uropathogens is threatening to transform UTI to untreatable disease, while impaired host-microbiota homeostasis induced by a long-term use of antibiotics predisposes patients for various autoimmune and infectious diseases. New biomarkers of the increased risk of UTI recurrence could therefore assist in avoiding such outcomes by revealing more specific patient population which could benefit from additional interventions. In this light, the recent findings suggesting a crucial role of urothelial innate immunity mechanisms in protection of urinary tract from invading uropathogens might offer new diagnostic, prognostic and even therapeutic opportunities. Uroepithelial cells detect uropathogens via pattern recognition receptors, resulting in activation of intracellular signaling cascade and transcription factors, which ultimately leads to an increased production and secretion of chemokines, cytokines and antimicrobial peptides into the urinary stream. Emerging evidence suggest that the disturbance of a single component of the urinary tract innate immunity system might increase susceptibility for rUTI. The aim of the current review is to update clinicians and researchers on potential biomarkers of host immune response alterations predisposing for rUTI and propose those well worth exploring further. For this purpose, over a hundred original papers were identified through an extensive PubMed and Scopus databases search. This comprehensive review might enrich the current clinical practice and fill the unmet clinical needs, but also encourage the development of therapeutic agents that would facilitate urinary bacterial clearance by enhancing the host immune response.
... The administration of vitamin D might be used to improve the host response to bacterial urinary tract infections and reduce the infection frequency (63). A randomized trial in prediabetic patients showed that administration of vitamin D resulted in a reduction of UTI unrelated to previous vitamin D levels, an effect that was more prominent in men (64). However, another randomized, triple-blind, placebo-controlled clinical trial was not able to confirm such a benefit (65). ...
Article
Full-text available
Background and objective: To perform a literature update of the past decade on potential role of vitamin D in common urological entities: prostatic malignancy and benign hyperplasia, stone disease, urinary tract infections and male infertility. Vitamin D (or calciferol) is the pivotal regulator of calcium in humans and low levels are associated with bone health in children and adults. Recent research though has spread in several other fields including common urological conditions. Early reports indicate that vitamin D deficiency might be associated with increased risk of prostate cancer and hyperplasia, stone disease, semen impairment and urinary tract infections. Methods: A non-systematic search in PubMed/Medline, Google Scholar, Web of Science, and Embase was performed using the terms “vitamin D” and “benign prostatic hyperplasia/enlargement”, “prostate cancer”, “prostate malignancy”, “urolithiasis”, “nephrolithiasis”, “male infertility”, “urinary tract infections”. The search duration period was set between 2011 and 2021. Exclusion criteria were non-English and retracted studies. Key contents and findings: In prostate cancer, vitamin D deficiency is associated with adverse outcomes, but its usage needs to be clarified. In hyperplasia, correlations are not certain. In contrast, in urolithiasis, the achievement of a normocalciemic status should be considered the primary goal in terms of prevention and reduction of recurrence. Moreover, vitamin D seems to regulate host immunity. In children, pregnant and women of reproductive age, screening for deficiency might be of benefit, whereas supplementation may be used as a secondary tool in the management of urinary tract infections. In infertile men, treating deficiency might be a cost-effective approach instead of a multi-panel empirical antioxidant treatment but its role needs further evaluation. Conclusions Although highest level of evidence still lacking to support vitamin D administration as per guidelines practice, last decade research looks promising in terms of its role and its therapeutic potential. The specific indications, the exact dosages and safety profile need to be established with future research.
... Vitamin D deficiency is common and the proven risk factor for UTIs especially in girls and supplementation with vitamin D could prevent first-time UTI [76]. In a randomized clinical trial, the subjects who received vitamin D3 (20,000 IU per week) for five years showed better prevention against UTI [77]. Together, these results demonstrate that vitamin D supplementation provides a potent weapon in the prevention of UTI. ...
Article
Full-text available
Background Urinary tract infection (UTI) is a common occurrence in females, during pregnancy, and in peri- and postmenopausal women. UTIs are associated with significant morbidity and mortality, and they affect the quality of life of the affected patients. Antibiotic therapy is an effective approach and reduces the duration of symptoms. Development of resistance, adverse effects of antibiotics, and other associated problems lead to establishing the research framework to find out the alternative approaches in controlling UTIs. Natural approaches have been extensively used for the management of various diseases to improve symptoms and also improve general health. Main body Different databases were employed to identify studies reporting on natural options including herbal medicines, vitamins, trace elementals, sugars, and probiotics without time limitations. Conclusion Herbal medicines can be effective at the first sign of the infection and also for short-term prophylaxis. Using vitamins, trace elementals, and/or sugars is an effective approach in preventing UTIs, and a combination of them with other antibacterial agents shows positive results. Probiotics have great potential for the threat of antibiotic over-usage and the prevalence of antibiotic-resistant microorganisms. This study may be of use in developing the efficient formulation of treatment of UTI.
... In the cardiovascular system, an adequate vitamin D status is associated with lower risks of hypertension and cardiovascular dysfunctions [180][181][182][183][184][185]. Optimal vitamin D levels are also important for the treatment and prevention of infectious diseases [186][187][188][189][190]. ...
Article
Full-text available
Simple Summary: We herein describe the relevance of Vitamin D for human health, with a special focus on its role in Neurofibromatosis type 1 (NF1) disease. Indeed, epidemiological studies revealed that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of NF1. NF1 is an autosomal dominant syndrome with a severe predisposition in developing tumors and for which limited treatment options are thus far available. In this context, vitamin D or its analogues has been used to treat both skin and bone lesions in NF1 patients, alone or in association with other therapeutic agents. We provide an exhaustive and detailed analysis of the most relevant preclinical and clinical studies aimed at analyzing the correlation between vitamin D deficiency and NF1 lesion progression. This review can add a valuable contribution to the current knowledge of NF1 disease investigating possible therapeutic strategies to ameliorate NF1 conditions. Abstract: Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production-occurring in the skin and dependent on sun exposure-contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.
Article
Background: The urban lifestyle and environment pose a constant immune challenge to city dwellers. A major such challenge is influenza, which creates substantial public health and socio-economic burdens. The global healthcare paradigm has begun emphasizing the importance and cost-effectiveness of self-care in partnership with healthcare professionals such as community pharmacists for the management of mild ailments. For the general public, micronutrient supplementation is an affordable and potentially feasible self-care strategy for immunity enhancement and disease management. At the same time, micronutrient deficiencies are a serious public health concern in both developing and developed areas. Objective: This review focuses on the clinical evidence for the efficacy and safety of three key micronutrients — vitamins C, D and zinc — on respiratory infections. Key findings: These micronutrients are important for optimal immune function through their complementary roles in supporting both innate and adaptive immunity, as well as epithelial barriers. The need to improve public awareness of self-care in prevention and health management is highlighted by recent public health issues and the global fight against antimicrobial resistance. Community pharmacists could play a crucial role in empowering patient autonomy. Conclusion: With this review we aim to offer insights into the supplementation of these micronutrients as a self-care approach to the management of immune health.
Article
Importance Low serum vitamin D levels have been associated with adverse clinical outcomes; identifying and treating deficiency may improve outcomes. Objective To review the evidence about screening for vitamin D deficiency in adults. Data Sources PubMed, EMBASE, the Cochrane Library, and trial registries through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020. Study Selection Fair- or good-quality, English-language randomized clinical trials (RCTs) of screening with serum 25-hydroxyvitamin D (25[OH]D) compared with no screening, or treatment with vitamin D (with or without calcium) compared with placebo or no treatment conducted in nonpregnant adults; nonrandomized controlled intervention studies for harms only. Treatment was limited to studies enrolling or analyzing participants with low serum vitamin D levels. Data Extraction and Synthesis Two reviewers assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures Mortality, incident fractures, falls, diabetes, cardiovascular events, cancer, depression, physical functioning, and infection. Results Forty-six studies (N = 16 205) (77 publications) were included. No studies directly evaluated the health benefits or harms of screening. Among community-dwelling populations, treatment was not significantly associated with mortality (pooled absolute risk difference [ARD], 0.3% [95% CI, −0.6% to 1.1%]; 8 RCTs, n = 2006), any fractures (pooled ARD, −0.3% [95% CI, −2.1% to 1.6%]; 6 RCTs, n = 2186), incidence of diabetes (pooled ARD, 0.1% [95% CI, −1.3% to 1.6%]; 5 RCTs, n = 3356), incidence of cardiovascular disease (2 RCTs; hazard ratio, 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs; hazard ratio, 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58], or depression (3 RCTs, various measures reported). The pooled ARD for incidence of participants with 1 or more falls was −4.3% (95% CI, −11.6% to 2.9%; 6 RCTs). The evidence was mixed for the effect of treatment on physical functioning (2 RCTs) and limited for the effect on infection (1 RCT). The incidence of adverse events and kidney stones was similar between treatment and control groups. Conclusions and Relevance No studies evaluated the direct benefits or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the effect of treatment on physical functioning and infection.
Article
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Context: Vitamin D deficiency is associated with insulin resistance and risk of future diabetes. Objective: To test if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes (T2DM). Design: Randomized controlled trial performed 2008 - 2015. Setting: Clinical Research Unit at a teaching hospital. Patients: 511 subjects (mean age 62 years, 314 males) with prediabetes diagnosed with oral glucose tolerance test (OGTT) as part of the Tromsø Study 2007 - 2008 were included. 256 were randomized to vitamin D and 255 to placebo. 29 subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events. Interventions: Vitamin D (cholecalciferol) 20,000 IU per week versus placebo for five years. Annual OGTTs performed. Main outcome measure: Progression to T2DM. Secondary outcomes change in glucose levels, insulin resistance, serum lipids and blood pressure. Results: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L (24 ng/ml). 103 in the vitamin D and 112 in the placebo group developed T2DM (HR 0.90; 95 % CI 0.69-1.18, Cox regression, P = 0.45, intention to treat analysis). No consistent significant effects on the other outcomes were seen. Subgroup analyses in subjects with low baseline 25(OH)D yielded similar results. No serious side effects related to the intervention were recorded. Conclusions: In subjects without vitamin D deficiency vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes. Very large studies with inclusion of vitamin D deficient subjects will probably be needed to show such a putative effect.
Article
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Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.
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Objective/purpose: Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia. Methods: A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF. Results: IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production. Conclusion: Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.
Article
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Vitamin D deficiency is frequently found in patients with renal transplants (RTxs). Because vitamin D plays indispensable roles in the immune system, there may be an association between vitamin D deficiency and infection in these patients, but this has not been fully elucidated. Therefore, this study investigated the impact of pre-RTx vitamin D deficiency on urinary tract infection (UTI) development after RTx. We measured 25-hydroxyvitamin D3 (25(OH)D3) levels in 410 patients 2 weeks before they underwent RTx. Vitamin D deficiency was defined as 25(OH)D3 <10 ng/mL. The primary outcome was UTI occurrence after RTx. Cox proportional hazard analysis determined whether vitamin D deficiency was independently associated with UTI. The mean 25(OH)D3 level was 12.8 ± 6.9 ng/mL, and 171 patients (41.7%) were vitamin D deficient. During a median follow-up duration of 7.3 years, the UTI incidence was significantly higher in vitamin D-deficient patients (52 patients, 30.4%) compared with vitamin D-nondeficient patients (40 patients, 16.7%) (P = 0.001). Moreover, multivariate Cox proportional hazard analysis showed that vitamin D deficiency was an independent predictor of UTI after RTx (hazard ratio 1.81, 95% confidence interval 1.11–2.97, P = 0.02). Vitamin D deficiency was an independent risk factor for UTI after RTx; hence, determining 25(OH)D3 levels might help to predict infectious complications after RTx.
Article
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Aim: We aimed to examine whether there is any association between serum levels of 25-hydroxyvitamin D [25(OH)D3] and urinary tract infection (UTI) among children. Methods: White blood cell count, serum C-reactive protein, calcium, phosphorus, alkaline phosphatase, parathormone, and serum 25(OH)D3 levels were measured in 82 children experiencing a first episode of UTI, with no risk factors for UTI, and 64 healthy control children. Results: The mean serum levels of 25(OH)D3 among children with UTI were significantly lower than those of controls (11.7 ± 3.3 vs. 27.6 ± 4.7 ng/ml; p < 0.001). The serum levels of 25(OH)D3 were significantly lower in patients with acute pyelonephritis compared to patients with lower UTI (8.6 ± 2.8 vs. 14.2 ± 3.0 ng/ml; p < 0.001). Within the study group, mean serum levels of 25(OH)D3 among girls were lower than those of boys (10.9 ± 3.4 ng/ml vs. 13.2 ± 4.4 ng/ml; p < 0.001). Multivariate analysis showed that a serum 25(OH)D3 level of <20 ng/ml (odds ratio 3.503, 95% confidence interval 1.621-7.571; p = 0.001) was associated with UTI in children. Conclusions: Our results suggest that vitamin D deficiency may be a risk factor for UTI in children.
Article
Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1 alpha,25 dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), has pleiotropic immune effects. The mechanisms by which 1 alpha,25(OH)(2)D-3 protects against tuberculosis are incompletely understood. 1 alpha,25(OH)(2)D-3 reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion. Coculture with agonists or antagonists of the membrane or nuclear vitamin D receptors indicated that these effects were primarily mediated by the nuclear vitamin D receptors. 1 alpha,25(OH)(2)D-3 reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in infected PBMC and macrophages, indicating that 1 alpha,25(OH)(2)D-3 does not mediate protection via these cytokines. Although NOM was up-regulated by 1 alpha,25(OH)(2)D-3, inhibition of NO formation marginally affected the suppressive effect of 1 alpha,25(OH)(2)D-3 on bacillus Calmette Guerin in infected cells. By contrast, 1 alpha,25(OH)(2)D-3 strongly up-regulated the cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in 1 alpha,25(OH)(2)D-3 stimulated PBMC, although no detectable LL-37 peptide was found in supernatants from similar 1 alpha,25(OH)(2)D-3-stimulated PBMC cultures. A total of 200 mu g/ml of the active peptide LL-37, in turn, reduced the growth of Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that vitamin D contributes to protection against TB by '' nonclassical '' mechanisms that include the induction of antimicrobial peptides.
Article
Background: Observational studies have linked vitamin D status and infectious disease. This association is supported by the presence of the vitamin D receptor and CYP27B1 in immune cells. This review aims to consolidate data from clinical trials that used vitamin D for the treatment or prevention of infectious disease. Methods: The authors searched the term "(vitamin D OR ergocalciferol OR cholecalciferol OR vitamin D2 OR vitamin D3 OR calcitriol) AND (infection OR tuberculosis OR sepsis OR pneumonia)" with limits preset to manuscripts published in English and with human subjects. They identified controlled trials that measured infectious outcomes (eg, incidence and severity of disease, time to disease resolution or recurrence, measures of clinical improvement, mortality). Studies that used analog, topical or micronutrient formulations of vitamin D, assessed only vitamin D status or lacked a comparison group were excluded. The references from eligible manuscripts and from 2 recent reviews were scanned for additional manuscripts. Results: One thousand two hundred eighty-four manuscripts were identified with our search terms, with 60 papers still eligible after review of the title and abstract. Full review of these papers, their references and 2 related reviews yielded 38 manuscripts. Conclusions: Although some prospective studies show positive results regarding vitamin D on infectious disease, several robust studies are negative. Factors such as high variability between studies, the difference in individual responsiveness to vitamin D and study designs that do not primarily investigate infectious outcomes may mask the effects of vitamin D on infections.
Article
Lower urinary tract symptoms (LUTS) may develop more commonly in men with type 2 diabetes mellitus (T2DM). LUTS are often associated with benign prostate hyperplasia (BPH), in general population. An association between LUTS and hypovitaminosis D, and between hypovitaminosis D and type 2 diabetes (T2DM), has also been suggested. Thus, we aim to evaluate possible relationships between hypovitaminosis D, LUTS, and BPH in T2DM men. In this prospective observational study, 67 T2DM males (57.9 ± 9.28 years) underwent medical history collection, International Prostate Symptom Score (IPSS) questionnaire, that allows the identification and grading of LUTS, physical examination, biochemical/hormonal blood tests (fasting plasma glucose, glycated haemoglobin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, LH, total testosterone, estradiol (E2 ), 25-OH-vitamin D, PTH, calcium, phosphate, and PSA) and ultrasound transrectal prostate examination. Subdividing patients into three groups, on the base of 25-OH-vitamin D concentration (sufficiency ≥50; insufficiency >25 < 50; and deficiency ≤25 nm), a significant progressive increase of prostate volume (p = 0.037), IPSS score (p = 0.019), diastolic blood pressure (p = 0.018), and a significant decrease in HDL cholesterol (p = 0.038) were observed. 25-OH-Vitamin D levels were inversely correlated with both IPSS (R = -0.333; p = 0.006) and prostate volume (R = -0.311; p = 0.011). At multivariate analysis, hypovitaminosis D remained an independent predictor of both IPSS and prostate volume. In conclusion, we showed, for the first time, an association between 25-OH-vitamin D deficiency, LUTS, and BPH in T2DM men. © 2015 American Society of Andrology and European Academy of Andrology.
Article
Background Observational studies have linked vitamin D status and infectious disease. This association is supported by the presence of the vitamin D receptor and CYP27B1 in immune cells. This review aims to consolidate data from clinical trials that used vitamin D for the treatment or prevention of infectious disease. Methods The authors searched the term "(vitamin D OR ergocalciferol OR cholecalciferol OR vitamin D2 OR vitamin D3 OR calcitriol) AND (infection OR tuberculosis OR sepsis OR pneumonia)" with limits preset to manuscripts published in English and with human subjects. They identified controlled trials that measured infectious outcomes (eg, incidence and severity of disease, time to disease resolution or recurrence, measures of clinical improvement, mortality). Studies that used analog, topical or micronutrient formulations of vitamin D, assessed only vitamin D status or lacked a comparison group were excluded. The references from eligible manuscripts and from 2 recent reviews were scanned for additional manuscripts. Results One thousand two hundred eighty-four manuscripts were identified with our search terms, with 60 papers still eligible after review of the title and abstract. Full review of these papers, their references and 2 related reviews yielded 38 manuscripts. Conclusions Although some prospective studies show positive results regarding vitamin D on infectious disease, several robust studies are negative. Factors such as high variability between studies, the difference in individual responsiveness to vitamin D and study designs that do not primarily investigate infectious outcomes may mask the effects of vitamin D on infections.