Dear Colleagues,
As you will see, this issue features two contributions relative to the debate on the possible extra skeletal effects of vitamin D supplementation, in particular on type-2 diabetes (T2DM) and in the field of cancer treatment.
You will note that both authors correctly conclude that in general available trials have not found significant results on these fronts: rather, because they were conducted on populations which on the whole were not vitamin D deficient, they are not able to exclude a protective effect of vitamin D supplementation in subjects who are deficient, especially if we consider that sub-analyses of these subjects actually suggest a positive effect.
We see, for example, that a post-hoc analysis of the randomized clinical trial by Pittas et al. [1] on a small number of participants that had baseline circulating levels of 25-hydroxyvitamin D <12 ng/mL (< 30 nmol/L) showed that the risk of developing T2DM was reduced by 60% in subjects treated with cholecalciferol with respect to those given the placebo (hazard ratio [HR] 0.38, 95% IC 0.18-0.80).
We further find that in the study conducted on patients affected by lung tumors vitamin D supplementation did not on the whole produce the expected results. Yet when patients with early stage adenocarcinoma and low vitamin D levels were selected, supplementation in fact reduced mortality by over 60% with respect to the placebo (HR = 0.37; 95% IC 0.15-0.95). [2]
The time required to assess an outcome may also be fundamental: you will see, for example, that the negative conclusion of the VITAL trial [3] would change if the follow-ups of the first 1-2 years were excluded: such an exclusion, in my opinion, would be reasonable, given the biological latency. In that case, vitamin D supplementation shows a significant – 25% – reduction of death by cancer (HR = 0.75; 95% IC 0.59-0.96).
With regard to the documentation on a significant effect of vitamin D supplementation only in subjects with low baseline 25-hydroxyvitamin D3 levels, it is worth remembering that the literature contains numerous other examples, both skeletal and extra skeletal [4]. Figure 1 shows several examples of different effects of supplementation on some extra skeletal risks with respect to baseline serum levels – low and not low – in supplemented patients.
This should not surprise us [5], in view of the fact that vitamin D acts as a nutrient: it is beneficial when lacking, though not so when it is not lacking…
To conclude, I do not believe that we can affirm today that we are overestimating the possible extra skeletal benefits of vitamin D supplementation. Neither do I think that we can deny them, given that the design and results of clinical trials conducted thus far do not allow us to exclude such benefits.
What do you think?
I hope you enjoy reading this issue.