Tangerinearmy,

Interesting question...  I'm not a doctor and on top of that, it wouldn't be prudent to offer even a guess answer to your question.

What I have learned in over 20 years with CH is we're all different (within a range of differences) and that at least two things about CH that are consistent, and these are its inconsistency in presentation and that it rarely ever goes away for good.

The last four years experience in working with CH'ers taking the anti-inflammatory regimen, and the results of the online survey of CH'ers taking this regimen to prevent their CH has me thinking in different directions that the neurological community in general who treat this disorder.

Treating cluster headache (CH) patients with the anti-inflammatory regimen represents a paradigm shift from the conventional Standards of Care recommended treatments for CH.   The standards of care recommended treatments address the neurological symptoms of CH as a trigeminal autonomic cephalalgia (TAC) with neurogenic origins in the hypothalamus and manifestations in the trigeminal nerves.  Typical prophylactic treatments include corticosteroids as a transitional preventative while titrating up with the longer-term preventative verapamil, a calcium channel blocker and in some cases, lithium.

The anti-inflammatory regimen is a completely different treatment modality that addresses vitamin and mineral deficiencies as the underlying cause of CH. 

That > 85% of CH patients respond favorably to a daily regimen of vitamin D3, Omega-3 fatty acids and the vitamin D3 cofactors suggests CH is a genetotrophic disease. 

In 1956, Dr. Roger J. Williams, PhD., a brilliant biochemist who discovered the B-vitamin pantothenic acid, coined the term "genetotrophic disease" to describe diseases which resulted from genetically determined nutritional metabolic needs not being met by the individual and which result in poor gene expression. Motulsky has recently argued that many of the common degenerative diseases are the result of the imbalance nutritional intake with genetically determined needs for good health.

If you stop and think about genetotrophic diseases, a number of examples come to mind quite easily that meet its definition…  For example, Scurvy is caused by a lack of vitamin C.  Sailors from England used to take crates of limes with them on long ocean voyages to prevent this disorder and came to the new world sucking on limes to prevent scurvy… and that’s why they’re called “Limeys.”   Another example is Rickets.  It’s caused by a lack of vitamin D3 or the inability to pull calcium from the GI tract.  An iodine deficiency can lead to enlargement of the thyroid a.k.a. goiter.  Beriberi is a disease brought on by a Vitamin B-1 (thiamine) deficiency. There are many other diseases that meet the definition of a genetotrophic disease.

What is also clear, is the CH disorder is also associated with neurogenic inflammation in and around the trigeminal nerves.  As inflammation is the result of an immune system response to insult from a number of sources, CH can also be classified as a chronic neuroimmune disease.

Once you make that distinction,  CH falls in with more than 80 other autoimmune diseases like Multiple Sclerosis, Guillain-Barre syndrome, Rheumatoid arthritis, the irritable bowel diseases: Crohn’s, Ulcerative Colitis, Celiac and IBS.  The list goes on…  That makes CH very likely an autoimmune disease with neurological manifestations that can be treated and prevented by genetic expression made possible with vitamin D3.

Accordingly, there is no question in my mind that the success of the anti-inflammatory regimen with vitamin D3 as a CH preventative represents an "out of the box" new insight into the pathogenesis of CH...  It just needs to be reverse engineered to look at causality.

I'm also firmly convinced that the mechanism of action for this regimen lies with the autocrine/paracrine signaling role vitamin D3 plays at the genetic level triggering genetic expression. 

This is where a 1,25(OH)2D3 molecule combines with one of the retinoid molecules (vitamin A) to form a dimer bridge that then attaches one end to a vitamin D receptor (VDR) and the other to a Retinoid X Receptor (RXR) in a vitamin D response element (VDRE) on a candidate gene.

When this happens, Dr. Robert Heaney explains it best by saying, "vitamin D3 unlocks the cells genetic library of instructions and the cell starts executing them" i.e., genetic expression.

During genetic expression, the cell starts performing one or more of the following internal or intracrine activities:  it replicates, differentiates, starts producing or inhibiting the production of peptides and other active chemical messengers, or the cell dies.

It's the chemical signaling that controls other biological processes where all this gets interesting. If these chemical messengers attach to receptors on its own cell membrane, it's considered autocrine signaling.  If these messengers attach to receptors on adjacent or near by cells it's called paracrine signaling.

In the case of the cells within the hypothalamus which has an important and unique function within the nervous system due to its link to the endocrine system via the pituitary gland.  In this case, genetic expression made possible by vitamin D3 can trigger the release of hormones that travel through the bloodstream as an endocrine signaling mechanism that controls functions organs and tissues elsewhere in the body signalling them to start or stop other functions.

My latest research in this area revealed several studies that indicate there are vitamin D3 receptors and the enzymes needed to hydroxylate vitamin D3 to 25(OH)D and 1,25(OH)2D3 found in brain cells throughout the brain. 

What is particularly interesting is the highest concentrations of these genetic expression precursors are found in the hypothalamus and trigeminal nerves…  With the hypothalamus involved, we're talking the neurogenic head-waters of CH pathogenesis.

If we follow this confluence of findings and add in calcitonin gene-related peptide (CGRP), which several studies have found is produced in the trigeminal ganglia and elevated in the bloodstream during the pain phase of CH and migraine... we have a possible trigger. 

Adding one more factoid that vitamin D3 has been shown to down regulate/suppress the production of CGRP, (quite possibly through genetic expression), we have a viable candidate mechanism of action for vitamin D3's capacity to prevent CH.

I say possible candidate, as a 2010 study identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D3...  Sooo... there are potentially thousands of other candidates for genetic expression made possible by vitamin D3... and any one or more of them could easily play a role in a mechanism of action inhibiting CH pathogenesis...

That said, I'll stick with the CGRP gambit for now as there is corroborating evidence provided by none other than the good Dr. Peter Goadsby and Dr. David Dodick.  These two neurologist have tag teamed on a pair of phase 2 RCTs involving the use of two monoclonal antibodies, ALD403 (Alder BioPharmaceuticals Inc) and LY2951742 (Eli Lilly and Company), both with an appetite for CGRP... to prevent migraine headaches...

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I realize this isn’t a direct answer to your question about prolactin levels… but I hope you find the above interesting.

Take care,

V/R, Batch