Infants given extra vitamin D were 29% less likely to develop type 1 diabetes than those not given the supplement, found Christos Zipitis, MBChB, of St. Mary's Hospital for Women and Children here, and Anthony K. Akobeng, M.D., M.P.H., of the Central Manchester and Manchester Children's University Hospitals.

Higher doses appeared to be more effective, they reported online in the Archives of Disease in Childhood.

Vitamin D plays a physiological role in the immune system, and evidence also suggests it protects against cytokine-induced dysfunction of pancreatic beta cells, they wrote. But vitamin D levels and supplement dosages have declined over the last few decades.

"Even in the summer and at lower latitudes, many infants are so thoroughly protected from sun exposure that they produce little endogenous vitamin D," they wrote.

Low population vitamin D levels have led to a resurgence of rickets and hypocalcemia as well as speculation that vitamin D may be contributing to increasing incidence of autoimmune conditions including type 1 diabetes, the researchers said.

Their meta-analysis included four case-control studies and one cohort study on the association between vitamin D supplementation in infancy and subsequent development of type 1 diabetes.

The studies were done in healthy children followed up to ages 15 or 30. None objectively measured vitamin D status, reported total vitamin D intake from diet or sun exposure, or compared ethnic backgrounds in cases and controls. The cohort study likewise did not objectively measure vitamin D status and was not blinded.

In the three case-control studies with sufficient data for meta-analysis, the 1,429 children given vitamin D supplements were 29% less likely to develop type 1 diabetes than the 5,026 participants who were not given supplements (OR 0.71, 95% CI 0.60 to 0.84).

The cohort study likewise found that regular vitamin D supplementation reduced the relative risk of type 1 diabetes significantly (RR 0.12, 95% CI 0.03 to 0.51) as did even irregular use (RR 0.16, 95% CI 0.04 to 0.74).

Higher cumulative doses of vitamin D appeared to increase the benefit of supplementation.

In one study, 10 mg of vitamin D supplements in the form of cod liver oil given one to four times per week reduced type 1 diabetes risk 19% (OR 0.81, 95% CI 0.55 to 1.19) while five or more times a week dosing reduced risk 26% (OR 0.74, 95% CI 0.56 to 0.99).

In another study, regular use of the recommended 2,000 IU vitamin D dose reduced risk compared with regular use of a lower dose (RR 0.22, 95% CI 0.05 to 0.89).

A longer duration of vitamin D supplementation, though, did not appear to substantially improve risk in the one study that looked at this factor (OR 0.69 for less than a year versus 0.64 for more than a year).

Very early supplementation didn't appear to be any better than starting later in infancy in the one study that looked at age at initiation. Cod liver oil supplements from age seven to 12 months were actually associated with lower likelihood of developing type 1 diabetes in later life compared with supplements from zero to six months of age (OR 0.55 versus 0.80).

This may simply reflect longer duration of supplementation, but feeding and other unmeasured variables could also be responsible, the researchers said.

The researchers noted that the findings were limited by the overall moderate quality of the studies included, which may have been subject to recall bias, did not include objective vitamin D measures, and may not have controlled for all potential confounding factors.

Despite these limitations, Drs. Zipitis and Akobeng said that criteria for causality seemed to be fulfilled.

"However, for concrete conclusions to be reached," they cautioned, "adequately powered, randomized controlled trials with long periods of follow-up would be required to establish causality and the best formulation, dose, duration, and period of supplementation."

• Explain to interested patients that the meta-analysis supported the use of vitamin D supplements for infants.
  
  
• Caution patients that the meta-analysis was based on studies of moderate quality without evidence from randomized controlled trials, so further confirmation may be needed.

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