Hey Kim,

It’s been a while…  A lot has happened with the anti-inflammatory regimen since we last exchanged posts and PMs…  You can pull down a copy of the latest version of the anti-inflammatory regimen CH preventative treatment protocol at the following VitaminDWiki link: 
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Henry Lahore, the brains and brawn behind the VitaminDWiki website posted this treatment protocol for me on 21 January, of this year.  As of yesterday readers at this website have downloaded 3700 copies.  I also maintain a web page on the anti-inflammatory regimen at VitaminDWiki that you can access with the following short URL Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or

What you're likely experiencing with your CH is what I call a Calcitonin Gene-Related Peptide (CGRP) cascade triggered by an allergic reaction where mast cells degranulate/release histamine, heparin and TNFα within seconds of an insult by an allergen.  For a computer programmer this CGRP cascade is like a "do loop", for a chemist like me, it's called a self-sustaining chemical chain reaction where histamine triggers neurons to express and release CGRP which in turn loops back to trigger mast cells to degranulate releasing even more histamine and so on... 

This circular chain reaction continues until it runs out of one or more of the reactants at which point the chemical chain reaction stops… and so do the CH... for now... 

Unfortunately, our bodies recharge mast cells so they produce more histamine and neurons take up the protein building blocks to fabricate more CGRP.  All this happens over a period of one or two hours after the last chain reaction ends and it primes the pumps so to speak, for another self-sustaining chain reaction. Sound familiar?

Under these conditions, none of the standards of care recommended CH interventions are very effective including vitamin D3 and oxygen therapy.  Even prednisone will be marginally effective.

This is where we need a first-generation antihistamine like Benadryl (Diphenhydramine HCL) as it blocks H1 histamine receptors on neuron genes, genes within glial cells that surround neurons and genes within other cell types throughout the periphery capable of expressing CGRP.  The following Gene Atlas from BioGPS illustrates some of the 79 tissue types containing active H1 histamine receptor expressing genes.

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Diphenhydramine also crosses the blood brain barrier to block H1 histamine receptors on neuron and glial genes throughout the brain and in particular, the trigeminal ganglia where the genes expressing CGRP are among the highest density in the brain.

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Second- and third generation "non-drowsy" antihistamines work fine in the periphery, but cannot pass through the blood brain barrier (making them non-drowsy) where we need it most.

It's been my experience after two years of testing where I stop taking the anti-inflammatory regimen until I get hit then try to get back to a CH pain free state with 50,000 IU/day vitamin D3 loading doses...

If that doesn't work, I drop the vitamin D3 dose to 15,000 IU/day and jump on the Benadryl (Diphenhydramine HCL) with a 50 mg loading dose followed by 25 mg every four hours throughout the day and 50 mg at bed time. (For me, that works out to a 25 mg Diphenhydramine tablet at 06:00, 10:00, 14:00, 18:00 and 50 mg at bedtime.) If I stay up late, I throw in another 25 mg at 22:00, but I still take 50 mg at bedtime.

If you miss a dose of Diphenhydramine, during the first few days, the CH beast will jump ugly around the five hour mark from the last dose and remind you to get back on schedule.  On the outside chance I've a low-grade infection cooking away, I take a 1000 mg vitamin C tablet every four hours along with the Diphenhydramine.

After a week to 10 days I start dosing with 25 mg of Diphenhydramine every six hours.  If I remain CH PF after 24 hours, I extend the dosing interval to 25 mg every 8 hours for another 24 hours, then 12 hours then none.  If I remain CH pain free after 24 hours without any Diphenhydramine, then I know that it’s the vitamin D3 that's down-regulating CGRP and in the process, preventing my CH.

Try not to drive as this much Diphenhydramine will make you drowsy.  You'll also sleep like Rip Van Winkle at the drop of a hat.  Cottonmouth is also common so be sure to drink at least 2.5 liters of water a day along with the Omega-3 fish oil and all the other vitamin D3 cofactors. 

I’ve recently added Vitamins B1 and B12 following the initial 3-month course of vitamin B100 complex.  The forms of B1 we need are Benfotiamine or Allithiamine, found naturally in allium vegetables (onions, garlic).  Both pass through the blood brain barrier while other forms of B1 do not.  I take 250 mg/day of the vitamin B1 Benfotiamine and 500 mcg of the vitamin B12 Methylcobalamin.

I added Benadryl (Diphenhydramine HCL) to the anti-inflammatory regimen treatment protocol in June of 2015.  Based on data from the online survey of CHers taking this regimen to prevent their CH, the average year-over-year efficacy of this treatment protocol between December of 2011 and December of 2015 was as follows:  80% of CHers starting this regimen achieved ≤75% reduction in the frequency of their CH in the first 30 days after start of regimen.  In other words, they achieved a reduction in CH frequency from an average of 3 CH/day down to 3 to 4 CH/week.  54% of CHers starting this regimen experienced a complete cessation of CH symptoms in the first 30 days after start of regimen.

Survey data for CHers responding during 2016 indicate a significant improvement in favorable response rate where 93% of CHers starting this regimen experienced ≥75% reduction in the frequency of their CH, 83% in the first 30 days after start of regimen and 73% achieved a complete remission of CH symptoms in the first 30 days after start of regimen.  Again, the only significant change to the treatment protocol was the addition of Benadryl (Diphenhydramine HCL).  Draw your own conclusions.

Regarding GamaCore and the biologic mAbs (monoclonal antibodies with an appetite for CGRP) as a means of treating CH, I wouldn’t get my hopes up too high just yet.  I’ve been a member of the American Academy of Neurology (AAN) for three years and receive at least one or more of their journals a week.  Accordingly, I see the results of RCTs for these methods of controlling migraine.

With respect to the non-invasive vagus nerve stimulator (nVNS), the RCT results indicate it is only marginally effective for ECHers and not effective at all for CCHers.  We’ve a few CHers here at CH.com with the device reporting it works well as an abortive if you get started early in the CH attack. It is not a preventative.  See the following study results at the following link for details then draw your own conclusion.  I’ve done a direct lift of the results and conclusions below.
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Results:
The intent-to-treat population comprised 133 subjects: 60 nVNS-treated (eCH, n = 38; cCH, n = 22) and 73 sham-treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS-treated subjects and 15.1% of sham-treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P  = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double-blind phase and 18/128 subjects in the open-label phase. No serious ADEs occurred.

Conclusion:
In one of the largest randomized sham-controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population.”

Regarding the efficacy of the mAbs as a CH preventative…  there have yet to be any results of RCTs using mAbs to prevent CH published.  All we have are the results from phase 2 RCTs for episodic migraine to use as a gauge.  You can find these results at the following link: Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or

Here is my analysis… Big Pharma is betting hundreds of millions of dollars developing biologics, mAbs, (monoclonal antibodies) and pharmaceuticals that target CGRP as a means to prevent migraine headache and its evil cousin, cluster headache.  There are currently four pharmaceutical companies, Lilly, Amgen, Teva and Alder developing biologics, a.k.a., monoclonal antibodies in the hopes of controlling CGRP as a means of preventing migraine and cluster headache.  Three of these monoclonal antibodies specifically targeting CGRP are galcanezumab (LY2951742 - Lilly), eptinezumab (ALD403 - Alder), and fremanezumab (TEV-48215 - Teva) and one against the CGRP receptor erenumab (AMG-334 - Amgen.)  These four companies will have wagered an estimated $100 million each to bring their monoclonal antibody through FDA approval and first to market as the next great hope of a migraine and cluster headache preventative.

How have they done so far?  I’ll summarize from the link above treating episodic migraineurs who suffer 4 to 14 migraine days a month and treated for 8 to 12 weeks with the following mAbs:

Eli-Lilly’s galcanezumab (LY2951742), 150 mg subcutaneously versus placebo every 2 weeks for 12 weeks. Primary efficacy endpoint was the change in number of migraine days during the third 4-week treatment period (weeks 9–12) compared to the baseline period. Results, 1.2 fewer migraine days a month.

Eptinezumab (ALD-403): Alder Biopharmaceuticals took a slightly different approach with eptinezumab, reasoning that intravenous administration would result in rapidly efficacious dosing with immediate physiological effect.  Results after 8 weeks, 1 fewer migraine days a month.

Fremanezumab (TEV-48215 or LBR-101): Teva Pharmaceuticals investigated fremanezumab in two separate trials for patients with either high-frequency episodic migraine or chronic migraine [40, 41]. Patients with 8 to 14 headache days in 4-week baseline period were randomized to subcutaneous injections of either fremanezumab 225 or 675 mg or placebo every 4 weeks for 12 weeks. Primary efficacy endpoint was the change in number of migraine days during the third 4-week treatment period (weeks 9–12) compared to the baseline period.  Results at endpoint, 2.8 fewer migraine days a month.

Erenumab (AMG-334): Lastly, Amgen has developed a monoclonal antibody against the CGRP receptor, erenumab, in contrast to the other three antibodies that are targeted at the CGRP molecule itself. Patients with episodic migraine (4 to 14 headache days in 4-week baseline period) were randomized to either placebo or one of three doses of erenumab (7, 14, or 70 mg) subcutaneously every 4 weeks for 12 weeks. Primary efficacy endpoint was the change in number of migraine days during the third 4-week treatment period (weeks 9–12) compared to the baseline period.  Results at endpoint for the highest dose, 1.1 fewer migraine days a month.

Why are these companies willing to spend so much to be the first to market what could be the holy grail of preventatives for migraine and cluster headache?  If you thought they really wanted to stop the suffering CHers and migraineurs go through…  you would be wrong…  The answer to this question is simple… With > 12% of the population suffering from migraine headache, these four companies want another Humira (Adalimumab), the golden goose of monoclonal antibodies, costing $4370/month/treatment (2017) and earning $16 Billion a year (2016).

In comparison, the anti-inflammatory regimen CH preventative treatment protocol costs ~55 cents/day ($16.50/month) for the basic regimen with an additional 8 cents a day for a week to 10 days if you add the Benadryl (Diphenhydramine HCL).

There’s a big difference in the mechanism of action in preventing CH between the anti-inflammatory regimen and the monoclonal antibodies.  The genetically active vitamin D3 metabolite 1,25(OH)2D3 acts to prevent the expression of CGRP where the mAbs, (monoclonal antibodies) attack CGRP after it’s been released into the bloodstream or block its receptors as a means of preventing CH.  Our bodies can make cutaneous vitamin D3 if we let them…  The mAbs, will need to be replenished monthly to maintain an as yet, unproven preventative effect.

Sorry to be so jaded…  but that’s the way I see it.  You be the judge.

Take care,

V/R, Batch

Kim,

I love nurses... and I'm impressed you've been taking 10,000 IU/day vitamin D3 for the last six weeks.  Good on you...

What I would do now is pick up and start taking the Omega-3 fish oil and the rest of the vitamin D3 cofactors.  They're essential in effective pharmacokinetics and pharmacodynamics of vitamin D3 and its genetically active metabolite 1,25(OH)2D3.  If my theory holds, it's this metabolite that down-regulates the expression and release of CGRP, the neuropeptide responsible for the neurogenic inflammation and pain we know as CH.

The following photo illustrates the basic anti-inflammatory regimen supplements by brand and doses.

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Magnesium is the most important as the enzymatic process of hydroxylating vitamin D3 to 25(OH)D and 25(OH)D to 1,25(OH)2D3 consumes magnesium rapidly.  I buy the above supplements at Cosco, but you can find most of them at supermarkets and WallyWorld or Sam's.  Take everything with the largest meal of the day.

The next most important item is the Kirkland Adult 50+ Mature Multi.  Try to get this brand as it is formulated with most of the vitamin D3 micronutrient cofactors, i.e., calcium, magnesium, zinc, boron, vitamin A (retinol) and the seven B vitamins.  We just need more magnesium... There's no rush on the vitamin K2, I order LifeExtention's Super K with Advanced K2 complex from iherb.com with the following link:

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If you're not already taking it, I'd start taking 2000 mg/day of vitamin C, 1000 mg at breakfast and another 1000 mg with the evening meal.  It's great for the heart and vascular system and also as a chelating agent to help remove any heavy metals you may have accumulated.

Now for the game changer that will stop the CH beast from jumping ugly and have it high tailing it out of your life...  a week to 10 day course of Benadryl (Diphenhydramine HCL).  I take 25 mg every four hours and 50 mg at bed time.  It will make you drowsy so be very careful driving. 

If I need to drive during the day, I take Children's Benadryl (Diphenhydramine HCL) liquid allergy medicine. 12.5 mg (5 mL in the measuring cap) every 4 hours... Try to hold the liquid in your mouth for a couple minutes for a sublingual application.  This is harder than it sounds as it's terribly sweet.  The lower dose makes it less of a problem driving with less drowsiness.

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When I get home, I go back on the 25 mg tablets...

Your body will tell you when to taper off the Diphenhydramine... I usually extend the dosing interval to 25 mg every 6 hours for a day or two, then 8 hours, then 12 hours then nothing...  As long as you remain pain free at each tapered dose, go for the next longer dosing interval. If you're CH pain free 24 hours after the last dose of Diphenhydramine, that means it's the vitamin D3 that's preventing your CH...

I also push fluids, like 2.5 liters of water a day.

Take care, hugs and please keep us posted.

V/R, Batch