March 18, 2008 — Children given additional vitamin D were approximately 30% less likely to have type 1 diabetes in later life vs those not given the supplement, according to the results of a systematic review and meta-analysis reported in the March Online First issue of the Archives of Disease in Childhood.

"There is evidence of lower plasma 25-hydroxyvitamin D levels at diagnosis of type 1 diabetes compared to controls," write Christos S. Zipitis, from the Stockport National Health Service Foundation Trust, Stockport, United Kingdom; and Anthony K. Akobeng, from Central Manchester and Manchester Children's University Hospitals, Booth Hall Children's Hospital, Manchester, United Kingdom. "In addition, epidemiological studies suggest that supplementation with vitamin D in infants might be important in conferring protection against the development of type 1 diabetes. In this study, we sought to explore the potential association between vitamin D supplementation in early childhood and reduced risk of type 1 diabetes by conducting a systematic review and meta-analysis of human trials and observational studies."

The investigators searched MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles for controlled trials and observational studies that evaluated the effect of vitamin D supplementation on the risk for development of type 1 diabetes.

There were 5 observational studies (4 case-control studies and 1 cohort study) that met the inclusion criteria, but no randomized controlled trials were identified. The risk for type 1 diabetes was significantly reduced in infants who were supplemented with vitamin D vs those who were not supplemented (pooled odds ratio [OR], 0.71; 95% confidence interval [CI], 0.60 - 0.84) based on a meta-analysis of data from the case-control studies. Findings of the cohort study agreed with the meta-analysis.

Children with higher intakes of vitamin D seemed to be at lower risk for the development of type 1 diabetes, which suggested a dose-response effect. The timing of supplementation also seemed to play some role in the subsequent development of type 1 diabetes.

Limitations of this review include those of the reviewed studies, such as recall bias in the included case-control studies; failure to use an objective method to determine the vitamin D status of cases or controls; lack of quantification of the total amount of vitamin D intake from the diet or that from exposure to the sun; use of healthy controls without prior checking of nondiabetic status; potential confounding factors; and considering cod liver oil as a supplement to be similar to those receiving other forms of vitamin D.

"Vitamin D supplementation in early childhood may offer protection against the development of type 1 diabetes," the review authors write. "The evidence for this is based on observational studies. Adequately powered, randomized controlled trials with long periods of follow-up are needed to establish causality and the best formulation, dose, duration and period of supplementation."

This review received no funding. The review authors have disclosed no relevant financial relationships.

Arch Dis Child. Published online March 13, 2008.

Clinical Context

Study Highlights

• Article search included MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), and the Cochrane Central Register of Controlled Trials (Issue 2, 2007) databases with no limits and the reference lists of articles.
• No randomized controlled trials were found.
• Of 19 relevant articles, 5 observational studies met inclusion criteria: comparison of type 1 diabetes risk between those supplemented with vitamin D vs those not supplemented, control for possible confounders, and adequate data to construct 2 x 2 tables or to determine relative risks or ORs with 95% CIs.
• Cod liver oil supplementation was considered to be similar to vitamin D supplementation.
• 4 case-control studies and 1 cohort study were analyzed.
• 3 case-control studies used patients up to age 15 years, and 1 used patients up to age 30 years.
• 2 investigators graded the validity of each study as moderate risk for bias.
• The authors of these studies were contacted for missing or unclear data.
• Meta-analysis of 4 case-control studies showed decreased risk for type 1 diabetes in 1429 cases with vitamin D supplementation vs 5026 controls (OR, 0.71; 95% CI, 0.60 - 0.84).
• Cohort study also showed lower rate risk for those who received regular vs no supplementation (0.12; 95% CI, 0.03 - 0.51) and those who received irregular vs no supplementation (0.16; 95% CI, 0.04 - 0.74).
• Higher vitamin D doses might be more effective in decreasing risk for type 1 diabetes:
  • In 1 case-control study, OR of type 1 diabetes decreased as cod liver oil use increased from up to 4 times per week (OR, 0.81; 95% CI, 0.55 - 1.19) to more than 5 times per week (OR, 0.74; 95% CI, 0.56 - 0.99).
  • In a cohort study, the risk for type 1 diabetes was lower with regular use of recommended 2000 IU vitamin D dose vs regular use of less than recommended vitamin D dose (relative risk, 0.22; 95% CI, 0.05 - 0.89).
• Type of vitamin D supplement could not be analyzed because of inadequate data.
• In 1 study, the risk for type 1 diabetes did not differ significantly for duration of vitamin D use for less than 1 year (OR, 0.69; 95% CI, 0.52 - 0.93) vs more than 1 year (OR, 0.64; 95% CI, 0.47 - 0.89).
• Risk for type 1 diabetes was lower if cod liver oil was started between 7 and 12 months of age (OR, 0.55; 95% CI, 0.31 - 0.96) vs between birth and 6 months of age (OR, 0.80; 95% CI, 0.61 - 1.06).
• Methodologic limitations of some of the studies included retrospective design; no confirmation of absence of diabetes in healthy children; no comparison of ethnicity between case vs control groups; lack of vitamin D quantification from diet and sun exposure; lack of data about possible confounders, including duration of breast-feeding; and consideration of cod liver oil as similar to vitamin D.

Pearls for Practice

• Vitamin D supplementation in early childhood might reduce the risk for type 1 diabetes by almost 30%.
• The evidence for the relationship between vitamin D supplementation in early childhood and the risk for type 1 diabetes is based on observational studies; randomized controlled trials are recommended to determine causality and optimal dose, duration, and timing of vitamin D supplementation.

CME Test