Re: Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials
Boucher  presents a number of arguments in favour of the opinion that vitamin D supplementation has substantial benefits, but this is not clearly shown in our review . Given the study selection protocol, the risk of overlap of original studies is minimal for any given outcome, as we only selected one review per outcome for our analysis. The importance of the supplementation dose and of pre-supplementation 25-hydroxyvitamin D (25-OHD) levels is valid. In our discussion we highlighted that inappropriately low dose or short duration of vitamin D supplementation in the randomised controlled trials might be inadequate to raise the body’s vitamin D concentrations enough to show a difference between the arms of a trial. However, there is no certainty that high doses and long duration would necessarily be effective and it is widely used practice to use such arguments to avoid accepting that an intervention is simply ineffective, as documented in vitamin E, hormone treatment, or invasive cardiac interventions in stable patients cases [3,4]. We also mentioned that large differences in baseline plasma concentrations of 25-OHD in different populations could interfere with the effect of the supplementation, but similarly, this could have an impact in either direction.
Calcium supplementation was discussed in our review mainly because vitamin D and calcium were co-administered in the majority of vitamin D trials. On the other hand, we believe that interactions between multiple vitamins are very difficult to be reliably investigated, unless one specifically designs trials that study the supplementation of multiple vitamins. Finally, to account for the specific problems of observational nutrient intake studies (as the ones described by Ioannidis ) we decided to exclude observational meta-analyses of dietary or supplementary vitamin D intake. Overall, we conclude that trends for survival benefits in subgroups of trials should be seen as exploratory and need further validation.
1. Letter by Boucher [based on her rapid response http://www.bmj.com/content/348/bmj.g2035/rr/693593 ]
2. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.
3. Siontis GC, Tatsioni A, Katritsis DG, Ioannidis JP. Persistent reservations against contradicted percutaneous coronary intervention indications: citation content analysis. Am Heart J. 2009;157(4):695-701.
4. Tatsioni A, Bonitsis NG, Ioannidis JP. Persistence of contradicted claims in the literature. JAMA. 2007;298(21):2517-26.
5. Ioannidis JP. Implausible results in human nutrition research. BMJ. 2013;347:f6698.
Competing interests: No competing interests