Could child vitamin A supplementation have long-term health effects?

Mason et al. raise issues concerning the widely implemented high-dose vitamin A supplementation programme for young children in low-to-middle income countries, because the programme may no longer be having the beneficial effects on child mortality seen in randomized controlled trials 20 years ago.1 The high-dose vitamin A supplementation programme was originally instituted after vitamin A was unexpectedly found to protect against child death as well as vision loss.1 However, the mechanism by which vitamin A reduced child mortality was never specifically identified, so vitamin A could be protecting against something which is now no longer relevant to child mortality in low-to-middle income countries. For example, vitamin A protects against specifically diarrhoeal disease and possibly measles, but not pneumonia,2 when control of childhood infectious diseases has improved in low-to-middle income countries over the past 20 years.1 These issues concerning short-term effects may well be addressed by the next review of the high-dose vitamin A supplementation programme due in 2016.3 What might perhaps also be relevant is whether high-dose vitamin A supplementation has any long-term effects. When the high-dose vitamin A supplementation programme was started, vitamin A and its precursor β-carotene, like many vitamins and minerals, were seen as potentially protective against a broad range of diseases affecting children and adults in low- and high-income countries, including infections,4 cardiovascular disease5 and cancer,6 so there was no reason to think that vitamin A would be anything other than beneficial. However, for adults in high-income countries these observed protective effects have now largely been refuted by randomized controlled trials which instead suggest that high doses of vitamin A could increase mortality.7 Moreover, since David Barker re-ignited interest in early-life drivers of chronic diseases,8 chronic diseases are much more seen as products of exposures throughout life. Taking these two developments together raises the question as to whether high-dose vitamin A supplementation in young children in low-to-middle income countries could have long-term effects on susceptibility to the adult chronic diseases which are now becoming more common globally.9 Vitamin A has pleiotropic effects and plays a physiological role in many processes connected with chronic diseases, such as atherosclerosis,10 lipids,11 hormones12,13 and obesity,14 which might also need to be taken into account in any evaluation of the costs and benefits of a vitamin A supplementation programme. Whether these effects are in any way related to mode of delivery—increased intake of relevant foods such as carrots, as food fortification, or as supplementation at different doses—could also be considered. Conflict of interest: None declared.