I confess that this rampant Vitamin D supplementation (including myself) makes me queasy. Biological systems are much more complex than we all imagine. A simplistic model says increasing Vitamin D intake leads to increased Vitamin D uptake, and increasing that is good. The real-world model, given our limited knowledge, appears to be much more complex.
Vitamin D is transported in our serum by a protein known as Vitamin D Binding Protein, or VDP. Free Vitamin D in the serum, which is what we measure with our blood tests, is not bio-active on its own.
Albanes et al found that the highest associations with prostate cancer risk were in men who had higher levels of VDP
and higher levels of Vitamin D. It is suspected that increasing Vitamin D increases VDP levels, but there may be saturation levels or negative feedback processes at work as well.
Once the protein-bound Vitamin D gets to the cell, it has to be picked up by a Vitamin D Receptor (VDR) on the cell surface that then brings it inside. There are known VDR mutations that may inhibit this process, such that no amount of supplementing can overcome it.
As all of us are aware, we have negative feedback mechanisms that control the amount of steroids (and Vitamin D is a steroid) in our bodies. We all know that supplementing testosterone by using LHRH agonists like Lupron causes a complete shutdown of our testosterone-producing mechanism. Continued depletion causes an increase in the number of androgen receptors. Conversely, it is suspected that men who consistently take testosterone at high levels (e.g., bodybuilders) have reductions in the number of androgen receptors expressed on their cells, so that ever higher levels are needed to achieve the same effect. Does a similar effect on VDRs occur with Vitamin D supplementation? Albanes speculates that high levels of complexed Vitamin D may upregulate receptors on PC cells that allow more complexed testosterone to get inside.
We just don't know how all this works and what the interactions are.
- Allen