In a recent post I advocated that a common UK food like milk or bread/flour should be fortified with vitamin D.
Large number of the British population are classified as vitamin D deficient and clinical cases of rickets have been rising albeit from a very low base. There is robust evidence that increased vitamin D intake or synthesis (from sunlight exposure) would have some clear benefits for bone health and muscle function. The European Food Safety Authority have also concluded that vitamin D contributes to the normal functioning of the immune and inflammatory systems. There are also many other less well established or even speculative claims for the benefits of improved vitamin D status and I listed several such claims found on a search of the BBC news web-site. I advocated food fortification rather than increased used of over-the-counter dietary supplements because such supplements have proved to be an ineffective way of increasing the vitamin and mineral intakes of those likely to benefit from taking them, for example:
- Supplements have no impact on the number of people with poor nutrient intakes in the UK
- Recommendations to take folic acid supplements were ineffective in reducing incidence of neural tube defects whereas food fortification has had an immediate impact wherever it has been adopted.
New findings and arguments
Several newspapers and news web-sites including BBC news have today (16/02/2017) reported claims that vitamin D supplements can reduce the risk of colds and flu. These newspaper reports were prompted by a study published in the British Medical Journal (Martineau et al, 2017 ). This BMJ paper reports the results of a meta-analysis (i.e. a weighted aggregation) of the results of 25 mostly quite small controlled clinical trials of the effects of vitamin D supplements on the incidence of acute respiratory infections like colds and flu. Meta-analyses of controlled trials are considered to be at the top of the hierarchy of evidence in medical research. When the results of these 25 trials are combined, overall they show a highly significant reduction in acute respiratory tract infections in the supplemented subjects. More detailed analysis of subgroups within the results suggests a bigger effect if the supplements were given to those with the lowest blood levels of vitamin D at the outset and that regular daily or weekly dosing was the most effective mode of administration. The authors discuss some technical flaws with the data including the possibility that there have been other small trials that have shown adverse effects of vitamin D that have either not been published or were not found by the authors. Nevertheless the authors conclude that their results suggest a major new potential benefit for improved vitamin D status and they conclude that:
“Our results add to the body of evidence supporting the introduction of public health measures such as food fortification to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common”.
Do these results justify a public health intervention?
An accompanying editorial in the same issue of the BMJ (Bolland and Avenell, 2017 ) considers that these results are insufficient to change clinical practice. They argue that they should be considered as “hypothesis generating only” and probably indicate the need for adequately powered (i.e. large) controlled clinical trials. One reason for their scepticism are the inconsistent findings reported in several other meta-analyses that have addressed this same question: some have reported benefits and others no benefit. They also suggested that the scale of the risk reduction suggested by the results of Martineau and his colleagues is not sufficient to warrant population-wide recommendations or actions. They also suggest that the benefits may not be evenly spread but confined to certain age groups.
The conclusions of Martineau and his colleagues and those of Bolland and Avenell are not necessarily incompatible. Whilst the evidence of Martineau et al may not of itself be sufficient to warrant food fortification or supplement recommendations they do add to the body of evidence suggesting that such changes might be beneficial.
The high levels of vitamin D insufficiency found in large sectors of the UK population, together with strong evidence that better population vitamin D status would improve bone health and muscle function have persuaded Public Health England to recommend that most people should take vitamin D supplements in the winter and that many should take them all year round. However, advice to take supplements is unlikely to have much impact on the levels of poor vitamin D status in the population so I advocate food fortification as a cheap, safe and effective alternative strategy.
A wider perspective
In the last decade there have been at least 25 relatively small (hundreds of subjects or less) controlled clinical trials that have addressed whether vitamin D supplements reduce the incidence of colds and flu. There have also been at least nine meta-analyses where these clinical trial results have been aggregated. Yet still we are unclear about whether these supplements work or not. If one widened one’s selection criteria e.g. including less controlled trials then one could undoubtedly find many more papers where this issue has been addressed. This is clearly a very slow and inefficient process. Lots of relatively small trials with different subject criteria, mode and/or dose of intervention, measure of outcome etc. are often relatively difficult to robustly amalgamate into a convincing meta-analysis. Different groups of meta-analysts therefore come up with different conclusions about what the “totality of clinical trials” indicate. Large, well-controlled trials are expensive but tend to produce clearer outcomes within a more reasonable time-scale. Lots of small trials with variable protocols are often not an effective substitute even when amalgamated in meta-analyses. Still more of these small individually designed trials may cause meta-analyses to continue to oscillate between benefit-no benefit; they will generate more scientific papers and possibly newspaper headlines but probably still not give an unequivocal answer.