Vitamin D: A 18%! reduction in early infant mortality

A study published earlier this year in the Lancet found a 18% reduction in mortality when women obtained supplements during pregnancy until 90 days post partum including additional 800 ug retinol, 200 IU vitamin D, 10 mg vitamin E, 70 mg ascorbic acid, 1.4 mg vitamin B1, 18 mg niacin, 1.9 mg vitamin B6, 2.6 ug vitamin B12, 15 mg zinc, 2 mg copper, 65 ug selenium and 150 ug iodine. Much of the effect will be due to the vitamin D supplementation although the authors do not seem to be aware of the immune effects of ergocalciferol:

Generally, the biological basis for the effects of maternal MMN supplements is probably complex in view of the ubiquitous role of micronutrients in human biology. Zinc, retinol, iodine, vitamin D, and folic acid have substantial roles in gene regulation and nucleic acid metabolism that are crucial for embryogenesis. Fetal development along the continuum toward birth and infancy needs precise regulation of both energy metabolism and neurological development that could require vitamins B1, B6, B12, and iron. Immunological maturation and transfer of maternal antibody might be affected by zinc as well, and antioxidants such as selenium, vitamin E, ascorbic acid, and riboflavin have been shown to have a role in immune function and cellular viability.

Although reasons for childhood death are not given, these will certainly be found in the respiratory tract. Unfortunately the authors also do not cite an earlier Lancet article

Pneumonia is the most important cause of morbidity and mortality in children aged under 5 years worldwide. Studies in developing countries have suggested an association between nutritional rickets and pneumonia. […] Rickets was present in 210 of 500 cases compared with 20 of 500 controls (odds ratio 22.11). […] Vitamin D or calcium deficiency may be important predisposing factors for pneumonia in children aged under 5 years in developing countries. Efforts to prevent vitamin D deficiency or calcium supplementation may result in significant reductions in morbidity and mortality from pneumonia in these children.

So there is not so much doubt about the efficiency of vitamin D supplementation in reducing wheezing and pneumonia (and even childhood death). But what about the allergy risk? A follow-up letter to the mortality study concludes:

Hence, the findings […] might well be due to intrauterine immunomodulatory effects of maternal nutritional status, with a general boosting of the infants Th2 immune responses during the first months of life. However, the “hygiene hypothesis” contends that polarisation of the immune system towards Th1 cells is needed to reduce the likelihood of allergy and atopy. Could the cost of improved child survival by maternal micronutrient supplementation be an increase in the incidence of allergy and

It looks like the vitamin hypothesis finally gets known to a larger audience. Although still somewhat cluttered by the Camargo studies, this is also the message in a review that appeared today in JACI:

The vitamin D hypothesis is one of the more interesting hypotheses to have been advanced in recent years as an explanation for the increase of asthma and allergies […] Interventional studies on vitamin D supplementation in the future would also be worthwhile, although it is unclear whether this should take the form of nutritional intervention or exposure to sunlight. Furthermore, maternal intervention during pregnancy might be equally important with respect to the vitamin D hypothesis. In summary, it is argued that antigen exposure through inflamed skin or through the gastrointestinal mucosa might be involved in the establishment of allergy and tolerance.

BTW here is a trackback to a nice summary of my recent AAAAI talk.