Siegfried,
A lot has happened in the field of molecular biology in the last 15 years since the two studies you referenced were conducted. For example, sequencing of the human genome was largely complete in 2003 and finally completed with the sequencing of the last chromosome in 2006. Since then there's been an explosion in the area of genetic mapping tools and today you can find several credible sites offering gene atlas like BioGPS that illustrate the distribution and density of specific genes.
Where all this applies to cluster and migraine headache takes us to the central dogma of molecular biology... DNA <-> RNA -> Protein... essentially genetic expression. The following graphic illustrates this process.
This process of genetic expression takes part in the nuclei in every cell type in the human body, in every chromosome and most genes. Think of the messenger RNA (mRNA) in the graphic above as a sequence of genetic instructions, not unlike computer binary code, or a blue print that ribosomes (protein producing factories) within the cell cytoplasm use to translate or synthesize specific proteins called for in the mRNA blueprint.
The four basic high level instructions in genetic expression are replication, differentiation, up- and down-regulation of protein synthesis and apoptosis, programmed cell death.
For example if the cell in the graphic above is a neuron within the trigeminal ganglia, the protein expressed above could easily be CGRP or SP in which case they would trigger the neurogenic inflammation and nociception, the pain we know as cluster or migraine headache.
Now we can look at a scenario where vitamin D3 helps prevent CH and MH. Although the exact mechanism(s) of action remain unclear, several studies have identified the likely candidates in this scenario. The key candidates involved include molecules of the genetically active vitamin D3 metabolite 1,25(OH)2D3, several molecular forms of retinoic acid, (retinol, retinyl, referred to as reinoids), a vitamin D receptor (VDR) a retinoid-X receptor (RXR) and an RNA sequence. It's interesting to note that the VDR and RXR are also products of genetic expression.
The following graphic illustrates where a molecule of 1,25(OH)2D3 and a molecule of retinoic acid combine to form a heterodimer, a two molecule polymer made of dissimilar molecules, that then attracts and attaches to a VDR and RXR. This complex then attaches to the RNA portion of DNA at a Vitamin D Receptor Element (VDRE) to initiate transcription, the process of making an exact copy of the RNA sequence that's now called mRNA.
This is where things get fuzzy... The likely scenario here is where this particular process involves a genetic sequence responsible for expressing CGRP and in this case, vitamin D3 down-regulates its expression lowering the cellular concentration of CGRP to the point it is no longer capable of triggering CH. Like I said, things get fuzzy here as a 2010 research study identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D3.
So there you have a Navy fighter pilot's thinking how vitamin D3 prevents CH... and yes, I have a degree in chemistry circa '67.
Take care,
V/R, Batch