Recent large observational data have suggested that ~40% of Europeans are vitamin D deficient, and 13% are severely deficient [
2]. The relevance of this widespread deficiency and necessity for supplementation has been questioned [
3]. Certainly, vitamin D is not a panacea. Because more often than not, trials have included non-deficient individuals, it is not surprising that interventional trials have usually not been able to find a benefit of vitamin D supplementation on clinical outcomes. This was also reflected in meta-analyses on the topic that were carried out with poor methodological standards [
4]. Consequently, many authors have dismissed a role of vitamin D on important clinical outcomes, and suggested that vitamin D may be more an associative than a causal factor in acute and chronic disease.
On the other hand, a low vitamin D status is emerging as a very common condition worldwide, and several studies from basic science to clinical applications have highlighted a strong association with chronic diseases, as well as acute conditions. Moreover, the large amount of observational data currently available are also accompanied by pathophysiological associations of vitamin D with energy homeostasis, and regulation of the immune and endocrine systems [
5].
Recent negative interventional trials may be biased by substantial methodological and study design errors, making it impossible to show the potential contributing role of vitamin D supplementation in a deficient population. Typically, most studies have missed important prerequisites for a nutrient intervention trial: the absence of the problem to be solved—vitamin D deficiency, often ridiculously small sample sizes, and varying interventional regimes regarding dose and metabolite. Even the recent very large trials did not exclusively include deficient populations [
6,
7,
8]. Moreover, interventional regimes have used a one-size-fits-all approach without taking into account individual differences in BMI and vitamin D metabolism.