Possible Role of Vitamin D in Celiac Disease Onset
3.1. Vitamin D and Immune System
3.2. Celiac Disease and Enviromental Factors
3.3. Vitamin D Status in Celiac Disease
3.4. Vitamin D and International Guidelines
Conflicts of Interest
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|Country and Year||Design||Study Population||Method||Outcomes|
|Ivarsson et al. ||Sweden, 2003||Retrospective and prospective study||2151 CD children below 15 years of age.||CD incidence rates were calculated by month of birth, stratified|
for age at diagnosis.
|The risk for celiac disease was significantly higher if born during summer compared|
to winter in children below 2 years of age at diagnosis.
This relative seasonal risk pattern prevailed during a 10-year epidemic of celiac disease, although incidence rates varied threefold.
The incidence was constantly higher among girls, but boys showed a more pronounced seasonal variation in risk.
|Lewy et al. ||Israel, 2009||Retrospective study||431 CD children (239 girls, 192 boys). 138 girls and 81 boys were under the age of 24 months.||Medical records were|
analyzed to obtain both statistical
significance and parameters of rhythms.
|Boys and girls with CD were found to have different seasonality of month of birth.|
Girls diagnosed before age 24 months (peak July–August) had a different seasonality birth from those diagnosed after age 24 months (no rhythm) and showed a different seasonality from
boys with diagnosis above 24 months (peak July). Different seasonality was found in children with a family history of CD.
|Lebwohl et al. ||USA, 2013||Case-control study||351,403 biopsy reports, of which 29,096 from patients with CD. Up to 5 controls for each CD individual were identified by|
Statistics Sweden (total: 144,522).
|The association between summer birth (March–August) and later CD diagnosis was examined through conditional logistic regression.||54.10% of individuals with CD vs 52.75% of controls were born in the summer months. Summer birth associated with a small increased risk of later CD. Stratifying CD patients according to age at diagnosis, the highest OR was found in those diagnosed before age 2 years, while summer birth was not associated with a CD diagnosis in later childhood (age 2–18 years), but had a marginal effect on the risk of CD in adulthood.|
|Unalp-Arida et al. ||USA, 2017||Population-based study||22,277 participants 6 years and older.||Analyzed data on gluten-related conditions from the US National Health and Nutrition Examination Survey, from 2009 through 2014 identifying persons with CD.||0.7% of participants were found to have CD.|
Celiac disease was more common among individuals who lived at latitudes of 35–39° North or at latitudes of 40° North or more than individuals who lived at latitudes below 35° North, independent of race or ethnicity, socioeconomic status or body mass index.
|Capriati et al. ||Italy, 2015||Retrospective study||596 CD patients children (age range 3.5) compared with 439,990 controls||Survey conducted|
at two Italian referral centers for CD in Rome and Bari. The CD database was created to enable retrospective examination of the data of all the consecutive patients born between 2003 and 2010 who had received a diagnosis of CD.
|A summer birth preponderance was observed in CD patients compared to controls.|
Stratifying the case by gender, the summer birth preponderance was maintained for females.
|Country and Year||Design||Study Population||Methods||Vit. D Supplement||Outcomes|
|Imam et al. ||USA, 2014||Retrospective study||83 CD patients: 51 girls and 32 boys (average age at diagnosis, 12.8 and 13.0, respectively)||Medical record review of CD patients and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic.||None receiving vitamin supplements at the time of diagnosis.||Average 25(OH)D vitamin levels 32.8 ng/mL;|
9 patients had mild-to-moderate vitamin D deficiency,
31 patients showed insufficiency of 25(OH)D.
|Villanueva et al. ||USA, 2012||Retrospective study||24 prepubertal CD children and 50 no-CD (age, 3–12 years)||25(OH)D level|
measured by chemiluminescence immunoassay. Height and body weight measured to calculate BMI.
|No supplementation.||No difference in 25(OH)D level between CD and no-CD.|
Non-obese CD had a significantly higher 25(OH)D level than the obese no-CD.
No difference in 25(OH)D level in non-obese.
|Lerner et al. ||Israel and Spain, 2012||Case-control study||272 individuals|
in five groups.
Group 1: 51 Israeli children with CD (age, 6 ± 4 years); Group 5: 59 Spanish children with CD (age,
4 ± 4 years);
Group 2: 56 Israeli children with nonspecific abdominal pain (age, 8 ± 5 years);
Group 3: 84 adults,
parents of group 2 (age, 39 ± 8 years);
Group 4: 22 Spanish adults with CD (age, 44 ± 13 years).
|Vitamin D serum levels investigated|
in CD populations
compared to children
with nonspecific abdominal pain, their parents and
Spanish adult CD patients.
25(OH)D checked by chemiluminescent
|No supplementation.||Groups 5 and 1 had the highest levels compared to groups 4 and 3. Levels in groups 1 and 2 were comparable. Concerning|
25(OH)D sera levels, only the difference between
groups 5 and 4 was statistically significant.
Vitamin D sera levels negatively correlated with
|Tavakkoli et al. ||USA, 2013||Retrospective cross-sectional study||530 CD adult patients||Compared patients with normal vitamin D level (≥30 mg/dL) against those with|
vitamin D insufficiency (20–29 mg/dL) and vitamin D deficiency (<20 mg/dL) with regards to prevalence of autoimmune disorders.
|Patients were not excluded from the study if they were taking vitamin D supplements, but there was no knowledge of supplementation.||25% showed vitamin D deficiency. Similar prevalence of AD |
among those with normal vitamin D (11%), insufficiency (9%) and deficiency (12%).
Vitamin D deficiency was not associated with AD.
Risk of psoriasis was higher in patients with vitamin D deficiency.
|Deora et al. ||Canada, 2017||Single-center cohort study||Medical records of 140 CD children (mean age at diagnosis|
7.8 ± 4.01 years)
|Analysis of the medical records of all children with CD. Routine celiac blood tests carried out at diagnosis|
6 months after starting GFD, then on an annual basis. Histopathological changes of duodenal biopsies at diagnosis
documented using modified MARSH classification. Diet
assessment with proper teaching of GFD at diagnosis, 6 months and 18 months after diagnosis.
|During each clinic visit, an experienced dietitian evaluated the nutritional status and need for micronutrient supplementations.||70% of subjects with serum vitamin D deficiency. No correlation between micronutrient deficiencies at diagnosis and serum tTG IgA antibody titers or the degree of villous atrophy.|
The majority of serum levels of micronutrients normalized after 6 months after beginning GFD, except for vitamin D, which improved but remained subnormal.
|Ahlawat et al. ||USA, 2019||Cross-sectional study||38 newly diagnosed CD patients (10.4 ± 3.0 years old) and 82 controls (11.2 ± 4.2 years old).||25(OH)D|
levels drawn in children with newly diagnosed CD compared with
pediatric outpatients with functional abdominal complaints. Anthropometric
data and vitamin D intake based on milk and multivitamin ingestion were recorded.
|Patients were excluded if they |
single-preparation vitamin D supplements within 3 months of study
enrollment. Multivitamin use was allowed.
|Both groups were similar except for average daily D intake and BMI.|
No statistical difference in mean 25(OH)D levels between CD and controls. Both
groups had high percentages of suboptimal D status.
25(OH)D levels significantly correlated with age
(r = −0.262) and estimated vitamin D intake (r = 0.361).
|Mårild et al. ||Norwey, 2017||Case-control study||416 children who developed celiac disease, 570 randomly selected|
controls and their mothers
|25(OH)D examined in maternal blood from mid-pregnancy, post-partum|
and cord plasma.
Mothers and children genotyped for established celiac disease and vitamin D
|Participants completed a food frequency questionnaire covering|
the period from start of pregnancy until completion around week 22, to evaluate their vitamin D intake while also considering supplements.
|No significant difference in average 25(OH)D between cases|
and controls and no significant linear trend.
for vitamin D deficiency were not associated with CD.
|Sulimani ||Saudi Arabia, 2019||Cross-sectional study||200 adolescent females aged 13–19 years old with vitamin D deficiency||Female adolescent screened for IgA tTG (anti-tissue transglutaminase antibodies).||No vitamin D supplement.||Of the 200 girls, 9 (4.5%) were positive for IgA tTG antibodies; all of whom had serum 25(OH)D < 12.5 nmol/L. A strong|
significant inverse association was found between tTG antibody levels and serum 25(OH)D (R = −0.53) among antibody
negative participants. Positive IgA tTG antibodies were 37.2 times higher among participants with 25(OH)D <
12.5 nmol/L than those whose vitamin D status was higher.
|Bittker ||USA, 2019||Case-control study||332 parents with CD children + 241 parents with no-CD children (controls)||An Internet-based survey was conducted among parents living in the US with at least one biological child between 3 and 12 years old in order to determine if 9 variables are associated with CD, among these: |
vitamin D drop exposure in infancy and vitamin D supplement
exposure between 2–3 years old.
|Two questions examined supplemental vitamin D|
exposure. One focused on the duration of exposure
to vitamin D drops in infancy.
The other on vitamin
D supplementation between 2–3 years of age.
|In this dataset, only vitamin D|
drops administered for more than 3 months was associated with CD children.
|Yang et al. ||USA, Finland, German, Sweden, 2017||Longitudinal prospective observational study||6627 children (years range 0.9–10.0)||Examined the association between maternal use of vitamin D, n-3 fatty acids (FA) and Fe supplements during pregnancy and risk for CD autoimmunity (CDA) and CD in the offspring.||Use of supplements containing vitamin D, n-3 FA and Fe was recalled by 66%, 17% and 94% of mothers, respectively, at 3–4 months post-partum. The mean cumulative intake over the entire pregnancy was 2014 μg vitamin D (SD 2045 μg), 111 g n-3 FA (SD 303 g) and 8806 mg Fe (SD 7017 mg).||Of 6627 enrolled children, 1136 developed CDA at a median 3.1 years of age (range 0.9–10) and 409 developed CD at a median 3.9 years of age (range 1.2–11).|
No statistically significant association between the intake of vitamin D, n-3 FA or Fe, and risk for CDA or CD. Dietary supplementation during pregnancy did not seem to modify the risk for the disease in the offspring.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Vici, G.; Camilletti, D.; Polzonetti, V. Possible Role of Vitamin D in Celiac Disease Onset. Nutrients 2020, 12, 1051. https://doi.org/10.3390/nu12041051
Vici G, Camilletti D, Polzonetti V. Possible Role of Vitamin D in Celiac Disease Onset. Nutrients. 2020; 12(4):1051. https://doi.org/10.3390/nu12041051Chicago/Turabian Style
Vici, Giorgia, Dalia Camilletti, and Valeria Polzonetti. 2020. "Possible Role of Vitamin D in Celiac Disease Onset" Nutrients 12, no. 4: 1051. https://doi.org/10.3390/nu12041051