Post by Batch on Feb 2nd, 2016 at 6:53pm
OK... Just remember... you asked for it.
Cluster Headache - A trigeminal autonomic cephalalgia (TAC) with no known cause and no known cure. Just a lot of treatments to reduce the symptoms...
Starting with the CH cause, the leading neurologists treating CHers swing between a CH pathogenesis with neurogneic origins in the hypothalamus and a pathogenesis with vascular origins in the hypothalamus and trigeminal ganglia.
Possibly the smartest neurologist in the world on all things cluster headache, Prof. Arne May, MD, came out in 2005 with a straddle saying CH has a neurovascular pathogenesis.
I had the opportunity in 2009 to meet with Arne at his UKE facilities, University of Hamburg, Germany for two days of one-on-one meetings with him and additional meetings with him and his staff.
Prof. May used his functional and structural neuroimaging (mostly MRI) and results from several RCTs he's conducted to illustrate his findings and conclusion that CH is neurovascular in origin.
He opines "neuroimaging has broadened our pathophysiological view and has led to successful treatment by deep brain stimulation of the hypothalamus."
That was then... Fast forward to December of 2010 and the advent of the anti-inflammatory regimen with 10,000 IU/day vitamin D3 here at CH.com. Fast forward again to the present.
To date, I estimate at least 600 CHers, most of whom are members of this site have started this regimen. Better than 80% of them have reported a significant reduction in the frequency, severity and duration of their CH in the first month of treatment. 60% them have reported a lasting CH pain free response.
Data from the online survey of 156 CHers taking this regimen tell the same story in the graphic below.
START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!! You need to
or 
END PRINTPAGE
In researching how and why this happens (or doesn't happen) I've been on an epic journey through the pharmacokinetics and phamacodynamics of vitamin D3 for the last five years and the journey isn't over. This search for answers has taken me to the genetic layer... Yes, there is a genetic component of CH, but it's not just from one generation to the next.
We're talking a vitamin D3 genetic history and evolution that dates back a long, long way. The evolution of vitamin D3 dates back over 500 million years to Cambrian period phytoplankton and zooplankton. There was a further major evolution of vitamin D3 with the first vertebrates 420 million years ago where the P450 gene for CYP2R1 was responsible for the enzyme 25-Hydroxylase that hydroxylates vitamin D3 either from exposure to sunlight or from their diet to 25(OH)D, in order to develop and maintain a healthy mineralized skeleton.
Yet another major evolution of vitamin D3 occurred with the first mammals 225 million years ago, where its genetically active form began controlling other hormonal (endocrine) and genetic expression processes through vitamin D3 paracrine and autocrine functions.
The first australopithecine hominins appeared some time after 3 million years ago and the first anatomically modern man, Homo sapiens, appeared roughly 200,000 years ago. In short, there's been a whole lot of vitamin D3 evolution going on...
So what is genetic expression? In the case of CH, that's where vitamin D3 and 25(OH)D enter target cells within the hypothalamus and trigeminal ganglia where they are hydroxylated (adding another [OH] hydroxyl group) by enzymes to 1,25(OH)2D3, calcitriol, the genetically active metabolite of vitamin D3.
During genetic expression, calcitriol attaches to a vitamin D receptor (VDR) on target genes. This unlocks the cell's genetic library of instructions and the cell starts actively executing them.
These genetic expression activities include proliferation (cells reproducing themselves), differentiation (cells changing their functions), up-regulating and down-regulating the production of proteins, peptides and other genetic products and apoptosis (programmed cell death).
For example, calcitonin gene-related peptide (CGRP) is produced by neurons in the hypothalamus and trigeminal ganglia. Several studies have found the serum concentration of CGRP elevated during the pain phase of CH and migraine headaches and very low to nonexistent during the pain free periods. CGRP triggers rapid inflammation and pain. At least two studies have found vitamin D3 down-regulates the production of CGRP.
Are you starting to connect the dots?
To put this in a larger perspective, 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. That means it is very likely that suppression of CGRP by vitamin D3 isn't the only possible mechanism of action by which vitamin D3 prevents CH.
In 1956 Dr. Roger J. Williams, PhD., the 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.
So where does that take this discussion on the cause of CH?
Given that better than 82% of CHers respond to the anti-inflammatory regimen with 10,000 IU/day vitamin D3 leads us to a possible conclusion that CH is likely a genetotrophic disease, caused in part by a vitamin D3 deficiency. We've proven this hypothesis several hundred times over the last five years. A few of us have also proven this hypothesis by stopping the intake of vitamin D3 and have our CH return.
I can hear the wheels turning... What about the 18% who don't respond to this regimen?
So far based on information collected from CHers here at this site and data from the online survey of CHers taking this regimen, the answer is a combination of comorbid medical conditions and not enough vitamin D3.
The comorbid conditions include bacterial and viral infections, surgery and trauma, diseases that result in an abnormally low systemic pH, i.e., diabetic ketoacidosis, and allergic reactions. All of these medical conditions result in an immune system response and inflammation, both of which place a competing demand on available serum concentrations of vitamin D3 and its metabolites.
For example, there are at least two studies that have shown a drop in 25(OH)D serum concentrations of up to 40% following knee surgery. We've also had a pain free CHer on a steady state maintenance dose of 10,000 IU/day vitamin D3 report falling out of remission within thee days following a fractured ankle.
In short, solve the comorbid medical conditions and half that 18 percent that didn't respond initially start responding.
I'm not ready to go into taking a higher maintenance dose of vitamin D3 than 10,000 IU/day just yet as that is going to require a change in the anti-inflammatory treatment protocol and direct supervision by a physician with mandatory lab tests.
I'll get the proposed change out when it's been blessed by the physicians who use it on a regular basis. That's going to take a few weeks to a month as I just sent my latest anti-inflammatory treatment protocol out for comment a few days ago.
So, is the anti-inflammatory regimen a CH cure? That depends on your definition of cure. For now, the short answer is no. What we do have is a way of life and a good quality of life with other health benefits as long as we take this regimen.
And this brings us to allergic reactions and their relationship to CH. When neurons within the hypothalamus and trigeminal ganglia are insulted by histamine from an allergic reaction, they trigger the release of CGRP and Substance P. Although both are implicated in the cluster headache pathogenesis, CGRP has been found to trigger rapid neurogenic inflammation and severe pain.
The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and CGRP, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and CGRP; thus, a bidirectional link between histamine and the neuropeptides in neurogenic inflammation is established.
What all this means is a simple allergic reaction can trigger a bidirectional chain reaction and self-sustaining perfect storm within the brain producing more CGRP and Substance P than can be down-regulated or suppressed by vitamin D3... hence no response or at best, only a limited response to the anti-inflammatory regimen.
In other words a CHer suffering from an allergy whether obvious or sub-clinical, (no outward or obvious symptoms) becomes refractory to the anti-inflammatory regimen's capacity to prevent CH...
This same mechanism likely accounts for some CHers being refractory to most other CH prophylaxis and likely makes oxygen therapy less effective with longer abort times.
Regarding floaters... There's no medical evidence that I'm aware of that links cluster headache to the release of floaters.
Floaters can have several other causes like head trauma and eye surgery... The most common cause of floaters comes with age... The eye is normally spherical in shape and filled with a clear jello like substance called vitreous humor that fills the space between the lens and the retina of the eyeball of humans and other vertebrates.
As we age, the posterior portion of the vitreous humor next to the retina begins to liquefy. Believe it or not, this is a good thing to have happen. This process is called posterior vitreous humor detachment. Once this happens, any disturbance of the retina causes clumps of cells, usually blood cells, to break loose and float around in the liquefied vitreous humor... These are called floaters as they drift across the field of view like a fly buzzing through the room.
There's another process that occurs with age and that is the eyeball starts to change shape going from a near perfect sphere to an elongated grape like structure. This elongation creates tension on the retina if posterior vitreous humor detachment has not occurred. It's this tension that leads to a spontaneous retinal detachment.
At 71, I've had all of the above happen to me including floaters long before my first CH... In my case, a Navy ophthalmologist preformed a multi-stepped surgical procedure to correct this problem.
The first step was go in through the side of my eye with a miniature roto rooter and minature slurp gun to remove the posterior portion of my vitreous humor. This is called a posterior vitrectomy. The next step was to insert an even smaller slurp gun behind the detached retina to aspirate the fluid that had collected there. The next step was to spot weld the retina back in place with a laser spot welder. The final step was to refill the eye with a saline solution to bring it back to the proper shape.
Needless to say, I still have floaters on occasion, but I've found that a few days at 20,000 IU/day vitamin D3 makes the floaters go away.
In closing this epistle according to Batch, I'll leave you with a few thoughts to ponder. If you buy into the notion that CH is a genetotrophic disease caused in part by a lack of vitamin D3, then it's entirely possible the rest of the TACs will respond to the anti-inflammatory regimen...
We've not had the opportunity to test this hypothesis. That said, we do know this regimen works to prevent migraine headaches with a few modifications.
This leads me to think that invasive surgical procedures used to relieve the symptoms of CH like deep brain stimulation (DBS), Occiptal Nerve Stimulation (ONS), gamma knife legation of trigeminal nerves are all crude and unnecessary when vitamin D3 actually treats the cause more effectively for a lot less money while providing other health benefits.
I'm confident that 10 years from now, neurologists will look back at DBS, ONS and gamma knife legation of trigeminal nerves as being closely akin to frontal lobotomies that were preformed up until the mid 1950s.
For you youngsters, a frontal lobotomy is where a neurosurgeon goes into the brain through a hole in the temple area and severs the nerve fibers linking the left and right frontal lobes of the brain. There were over 40,000 lobotomies performed in the US.
If you watched the movie, One Flew Over the Cuckoo's Nest, the character R.P. McMurphy played by Jack Nicholson, was given a frontal lobotomy and basically turned into a vegetable.
Finally, it turns out there are several neurologists using vitamin D3 treatment protocols very similar to the anti-inflammatory regimen to treat a growing number of autoimmune diseases like multiple sclerosis, irritable bowel syndrome, lupus, and rheumatoid arthritis.
How many of you have had a cold or the flu since you started taking the anti-inflammatory regimen?
Take care,
V/R, Batch
Cluster Headache - A trigeminal autonomic cephalalgia (TAC) with no known cause and no known cure. Just a lot of treatments to reduce the symptoms...
Starting with the CH cause, the leading neurologists treating CHers swing between a CH pathogenesis with neurogneic origins in the hypothalamus and a pathogenesis with vascular origins in the hypothalamus and trigeminal ganglia.
Possibly the smartest neurologist in the world on all things cluster headache, Prof. Arne May, MD, came out in 2005 with a straddle saying CH has a neurovascular pathogenesis.
I had the opportunity in 2009 to meet with Arne at his UKE facilities, University of Hamburg, Germany for two days of one-on-one meetings with him and additional meetings with him and his staff.
Prof. May used his functional and structural neuroimaging (mostly MRI) and results from several RCTs he's conducted to illustrate his findings and conclusion that CH is neurovascular in origin.
He opines "neuroimaging has broadened our pathophysiological view and has led to successful treatment by deep brain stimulation of the hypothalamus."
That was then... Fast forward to December of 2010 and the advent of the anti-inflammatory regimen with 10,000 IU/day vitamin D3 here at CH.com. Fast forward again to the present.
To date, I estimate at least 600 CHers, most of whom are members of this site have started this regimen. Better than 80% of them have reported a significant reduction in the frequency, severity and duration of their CH in the first month of treatment. 60% them have reported a lasting CH pain free response.
Data from the online survey of 156 CHers taking this regimen tell the same story in the graphic below.
START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!! You need to
or END PRINTPAGEIn researching how and why this happens (or doesn't happen) I've been on an epic journey through the pharmacokinetics and phamacodynamics of vitamin D3 for the last five years and the journey isn't over. This search for answers has taken me to the genetic layer... Yes, there is a genetic component of CH, but it's not just from one generation to the next.
We're talking a vitamin D3 genetic history and evolution that dates back a long, long way. The evolution of vitamin D3 dates back over 500 million years to Cambrian period phytoplankton and zooplankton. There was a further major evolution of vitamin D3 with the first vertebrates 420 million years ago where the P450 gene for CYP2R1 was responsible for the enzyme 25-Hydroxylase that hydroxylates vitamin D3 either from exposure to sunlight or from their diet to 25(OH)D, in order to develop and maintain a healthy mineralized skeleton.
Yet another major evolution of vitamin D3 occurred with the first mammals 225 million years ago, where its genetically active form began controlling other hormonal (endocrine) and genetic expression processes through vitamin D3 paracrine and autocrine functions.
The first australopithecine hominins appeared some time after 3 million years ago and the first anatomically modern man, Homo sapiens, appeared roughly 200,000 years ago. In short, there's been a whole lot of vitamin D3 evolution going on...
So what is genetic expression? In the case of CH, that's where vitamin D3 and 25(OH)D enter target cells within the hypothalamus and trigeminal ganglia where they are hydroxylated (adding another [OH] hydroxyl group) by enzymes to 1,25(OH)2D3, calcitriol, the genetically active metabolite of vitamin D3.
During genetic expression, calcitriol attaches to a vitamin D receptor (VDR) on target genes. This unlocks the cell's genetic library of instructions and the cell starts actively executing them.
These genetic expression activities include proliferation (cells reproducing themselves), differentiation (cells changing their functions), up-regulating and down-regulating the production of proteins, peptides and other genetic products and apoptosis (programmed cell death).
For example, calcitonin gene-related peptide (CGRP) is produced by neurons in the hypothalamus and trigeminal ganglia. Several studies have found the serum concentration of CGRP elevated during the pain phase of CH and migraine headaches and very low to nonexistent during the pain free periods. CGRP triggers rapid inflammation and pain. At least two studies have found vitamin D3 down-regulates the production of CGRP.
Are you starting to connect the dots?
To put this in a larger perspective, 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. That means it is very likely that suppression of CGRP by vitamin D3 isn't the only possible mechanism of action by which vitamin D3 prevents CH.
In 1956 Dr. Roger J. Williams, PhD., the 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.
So where does that take this discussion on the cause of CH?
Given that better than 82% of CHers respond to the anti-inflammatory regimen with 10,000 IU/day vitamin D3 leads us to a possible conclusion that CH is likely a genetotrophic disease, caused in part by a vitamin D3 deficiency. We've proven this hypothesis several hundred times over the last five years. A few of us have also proven this hypothesis by stopping the intake of vitamin D3 and have our CH return.
I can hear the wheels turning... What about the 18% who don't respond to this regimen?
So far based on information collected from CHers here at this site and data from the online survey of CHers taking this regimen, the answer is a combination of comorbid medical conditions and not enough vitamin D3.
The comorbid conditions include bacterial and viral infections, surgery and trauma, diseases that result in an abnormally low systemic pH, i.e., diabetic ketoacidosis, and allergic reactions. All of these medical conditions result in an immune system response and inflammation, both of which place a competing demand on available serum concentrations of vitamin D3 and its metabolites.
For example, there are at least two studies that have shown a drop in 25(OH)D serum concentrations of up to 40% following knee surgery. We've also had a pain free CHer on a steady state maintenance dose of 10,000 IU/day vitamin D3 report falling out of remission within thee days following a fractured ankle.
In short, solve the comorbid medical conditions and half that 18 percent that didn't respond initially start responding.
I'm not ready to go into taking a higher maintenance dose of vitamin D3 than 10,000 IU/day just yet as that is going to require a change in the anti-inflammatory treatment protocol and direct supervision by a physician with mandatory lab tests.
I'll get the proposed change out when it's been blessed by the physicians who use it on a regular basis. That's going to take a few weeks to a month as I just sent my latest anti-inflammatory treatment protocol out for comment a few days ago.
So, is the anti-inflammatory regimen a CH cure? That depends on your definition of cure. For now, the short answer is no. What we do have is a way of life and a good quality of life with other health benefits as long as we take this regimen.
And this brings us to allergic reactions and their relationship to CH. When neurons within the hypothalamus and trigeminal ganglia are insulted by histamine from an allergic reaction, they trigger the release of CGRP and Substance P. Although both are implicated in the cluster headache pathogenesis, CGRP has been found to trigger rapid neurogenic inflammation and severe pain.
The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and CGRP, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and CGRP; thus, a bidirectional link between histamine and the neuropeptides in neurogenic inflammation is established.
What all this means is a simple allergic reaction can trigger a bidirectional chain reaction and self-sustaining perfect storm within the brain producing more CGRP and Substance P than can be down-regulated or suppressed by vitamin D3... hence no response or at best, only a limited response to the anti-inflammatory regimen.
In other words a CHer suffering from an allergy whether obvious or sub-clinical, (no outward or obvious symptoms) becomes refractory to the anti-inflammatory regimen's capacity to prevent CH...
This same mechanism likely accounts for some CHers being refractory to most other CH prophylaxis and likely makes oxygen therapy less effective with longer abort times.
Regarding floaters... There's no medical evidence that I'm aware of that links cluster headache to the release of floaters.
Floaters can have several other causes like head trauma and eye surgery... The most common cause of floaters comes with age... The eye is normally spherical in shape and filled with a clear jello like substance called vitreous humor that fills the space between the lens and the retina of the eyeball of humans and other vertebrates.
As we age, the posterior portion of the vitreous humor next to the retina begins to liquefy. Believe it or not, this is a good thing to have happen. This process is called posterior vitreous humor detachment. Once this happens, any disturbance of the retina causes clumps of cells, usually blood cells, to break loose and float around in the liquefied vitreous humor... These are called floaters as they drift across the field of view like a fly buzzing through the room.
There's another process that occurs with age and that is the eyeball starts to change shape going from a near perfect sphere to an elongated grape like structure. This elongation creates tension on the retina if posterior vitreous humor detachment has not occurred. It's this tension that leads to a spontaneous retinal detachment.
At 71, I've had all of the above happen to me including floaters long before my first CH... In my case, a Navy ophthalmologist preformed a multi-stepped surgical procedure to correct this problem.
The first step was go in through the side of my eye with a miniature roto rooter and minature slurp gun to remove the posterior portion of my vitreous humor. This is called a posterior vitrectomy. The next step was to insert an even smaller slurp gun behind the detached retina to aspirate the fluid that had collected there. The next step was to spot weld the retina back in place with a laser spot welder. The final step was to refill the eye with a saline solution to bring it back to the proper shape.
Needless to say, I still have floaters on occasion, but I've found that a few days at 20,000 IU/day vitamin D3 makes the floaters go away.
In closing this epistle according to Batch, I'll leave you with a few thoughts to ponder. If you buy into the notion that CH is a genetotrophic disease caused in part by a lack of vitamin D3, then it's entirely possible the rest of the TACs will respond to the anti-inflammatory regimen...
We've not had the opportunity to test this hypothesis. That said, we do know this regimen works to prevent migraine headaches with a few modifications.
This leads me to think that invasive surgical procedures used to relieve the symptoms of CH like deep brain stimulation (DBS), Occiptal Nerve Stimulation (ONS), gamma knife legation of trigeminal nerves are all crude and unnecessary when vitamin D3 actually treats the cause more effectively for a lot less money while providing other health benefits.
I'm confident that 10 years from now, neurologists will look back at DBS, ONS and gamma knife legation of trigeminal nerves as being closely akin to frontal lobotomies that were preformed up until the mid 1950s.
For you youngsters, a frontal lobotomy is where a neurosurgeon goes into the brain through a hole in the temple area and severs the nerve fibers linking the left and right frontal lobes of the brain. There were over 40,000 lobotomies performed in the US.
If you watched the movie, One Flew Over the Cuckoo's Nest, the character R.P. McMurphy played by Jack Nicholson, was given a frontal lobotomy and basically turned into a vegetable.
Finally, it turns out there are several neurologists using vitamin D3 treatment protocols very similar to the anti-inflammatory regimen to treat a growing number of autoimmune diseases like multiple sclerosis, irritable bowel syndrome, lupus, and rheumatoid arthritis.
How many of you have had a cold or the flu since you started taking the anti-inflammatory regimen?
Take care,
V/R, Batch
