Hey Adam,

Thanks for the detailed feedback and sorry you're not responding to this regimen.   It's been my experience in working with hundreds of CHers that there's almost always a reason why it's not effective for some CHers.

While the raw favorable response rate to this regimen is a little over 80% of the CHers who start it, I've spent the last five years working with CHers who fall into the other 20% and my track record so far is better than average in getting them to respond...

You've taken the right step to obtain your 25(OH)(D serum concentration.  Knowing it will help determine if you need an additional loading dose of vitamin D3, a higher maintenance dose or both. 

As your records are detailed with respect to vitamin D3 dosing, it's reasonable to expect your 25(OH)D serum concentration is around 80 ng/mL...  I've worked with severl CHers who needed to elevate their serum 25(OH)D above 100 ng/mL (under a physicians' supervision with frequent labs for serum 25(OH)D, calcium and PTH). 

What I didn't see is the 3-month course of vitamin B 50 complex.  If you're taking the B 50 now, great.  If not, start it now.  A tablet a day for 3 months only.

That leaves a week to 10-day course of Benadryl (Diphenhydramine HCL) as the next step.  Diphenhydramine is a first-generation antihistamine that crosses the blood brain barrier to block H1 histamine receptors.  Allegra (Fexofenadine) is a second-/third-generation antihistamine so is less able to pass through the blood brain barrier to block H1 histamine receptors so will be less effective for CHers in your condition.

I've recently found that Children's liquid Benadryl (Diphenhydramine HCL) can be very effective at lower doses due to the sublingual application.  Several CHers have reported 12.5 mg of the liquid Diphenhydramine, (5 mL in the measuring cap) in the morning and another 12.5 mg an hour prior to bed helps a great deal without becoming too drowsy.  Swirl the contents under your tongue and between your cheeks and gums for 3 to 4 minutes without swallowing.  It's very sweet but tolerable.

If the frequency of your CH drop to zero, continue the liquid Chidren's Benadryl for another day then drop back to one 12.5 mg dose prior to bed for a couple days then discontinue completely.  If the CH kick up again, I'd go back on the liquid Benadryl for another week then taper.

In addition to the Benadryl, pick up a good probiotic.  I take Nature's Bounty Probiotic 10.  Take as directed on the box until the bottle's empty.  It also helps to start taking Vitamin C.  I take a 1000 mg tablet every two hours during the day for a total of 6 grams a day.  I continue taking the vitamin C at this dose until I've been PF for at least a week then drop to one or two tablets a day.

A good diet can also help.  No sugars or bread.  Proteins - fur, fin and feather are ok.  Max out on green, red and yellow veggies plus lots of fresh fruits.  A GOMBS diet is also helpfule.  GOMBS stands for Greens, Onions, Mushrooms, Beans-Berries, Seeds - Nuts.  At least a handful of each a day and preferable with each meal.  See the following links:

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If you haven't figured it out by now, I'm chronic and and I do get hit...  Usually as a result of doing a very silly thing once a year...  I stop taking the entire regimen until I get hit.  I call this a burn-down test of my 25(OH)D reserves.  Under normal conditions, it can take a week or more for the CH beast to start making house calls...  On a couple occasions, it only took a day.

Once I get hit or detect the CH beast prowling around, I usually start a loading dose of 50,000 IU/day for 3 to 5 days then taper back down to my maintenance dose of 10,000 IU/day.  I'm usually CH pain free within 12 hours... but there have been a couple occasions where it took a week to 10 days to get completely CH pain free.  What I've given you above has worked every time for me...

Please let us know how all this works for you.

Take care,

V/R, Batch

Adam,

Thanks for the feedback and good question on the children's liquid Benadryl.  Yes, swallow what's left.  I've taken the tablet form of Benadryl (Diphenhydramine HCL) for over two years during the high pollen count period covering March and April and again in the fall when leaf mold is high.  25 mg in the morning and another 25 mg before bed keeps me CH pain free.

I discovered the Diphenhydramine helped kick start the vitamin D3 and get me back pain free in March of 2015.  Our home is situated in an area I carved out of deep woods with lots of large Alder and Maple trees surrounding the house.  My black pickup takes a hit in the high pollen count March-April period from Alder and Big Leaf Maple trees.

I'd returned from two weeks travel to find my black pickup truck looking like someone had dumped a bag of Portland cement on it... 

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I had the obvious symptoms of allergic rhinitis within a few hours of returning home.  12 hours later, the CH beast jumped ugly. A few days loading vitamin D3 at 50,000 IU/day had no effect.  Then the clue bird made a low pass... Treat the allergy... 

After researching the options and reading a few papers on neurogenic inflammation associated with allergic reactions, I selected Diphenhydramine as a first-generation antihistamine...  It worked.  Less than 24 hours later, I was again CH pain free.

I started posting about my experience with Benadryl (Diphenhydramine HCL) a few days later and so far, several other CHers who have tried it reported similar favorable results. 

I started a burn-down test of my 25(OH)D reserves while fishing in Alaska in August figuring my serum 25(OH)D at 109 ng/mL and the good clean Alaskan air would keep me pain free for at least two weeks or longer.  I was wrong.  Two days after stopping the vitamin D3 I got hit. Not hard, but hard enough to let me know I had a problem.

I had my basic kit of anti-inflammatory regimen supplements but no Benadryl... Then it dawned on me.  We had added a new shed roof to the side of the house a few days earlier and as a part of that process, replaced some siding under the eves that had evidence of water damage.  Behind the siding we found 1940s era news papers that had been used as insulation...  The newspapers were loaded with dried mold... Two days loading vitamin D3 at 50,000 IU day had little effect.  I still got hit once a night.

The small general store in Pelican had no Benadryl tablets but they did have the Children's Allergy Relief liquid Benadryl (Diphenhydramine HCL) so I started it at 12.5 mg (5 mL) twice a day...  The second night after starting it, I was again sleeping CH pain free.

Regarding the probiotic... Nearly 70% of our immune system resides in and around the gut.  A number of RCTs have found keeping the gut healthy and happy with probiotics can have a beneficial outcome by building a stronger immune system.

I checked clinicaltrials.gov and found 781 studies listing probiotics as a method of intervention for a wide array of medical conditions and diseases.  One of these studies is presently enrolling by invitation for the prevention of migraine headache using a probiotic as the intervention.

Regarding your question on how many CHers take longer than 30 days to respond to this regimen, the survey data indicates 10%.  Three of the chronic types took two months to respond.  This is consistent with over five hears of posts from CHers taking this regimen for the first time and having a similar problem like yours.

After some serious reading, it appears that the process of preventing CH with vitamin D3... and Diphenhydramine HCL, conforms to the law of mass action...

At its most fundamental level, the interaction of a drug or nutrient, in this case, 1,25(OH)2D3, the genetically active metabolite of vitamin D3, with its receptors at the genetic level and Benadryl (Diphenhydramine HCL), follow the law of mass action.  That law dictates that:

• The combination of drug (also called ligand) and receptor depends on the concentrations of each

• The amount of drug-receptor complex formed determines the magnitude of the response

• A minimum number of drug-receptor complexes must be formed for a response to be initiated (threshold)

• As drug concentration increases, the number of drug-receptor complexes increases and drug effect increases

• A point will be reached at which all receptors are bound to drug, and therefore no further drug-receptor complexes can be formed and the response does not increase any further (saturation)

There is ample medical evidence that these basic principals of vitamin D3 pharmacokinetics and pharmacodynamics are directly related to the vitamin D3 dose, dosing interval, duration of exposure, the serum concentration of 25(OH)D (both basal and therapeutic level) and the relative density of VDR in target tissues.

That's a long-winded answer to a question you didn't ask directly...  What I'm saying... in simple terms... is stick with this regimen... You're doing the right things...  It could take a bit longer, but the odds are in your favor it will work.

Take care and please keep us posted,

V/R, Batch

Adam,

It's good to hear you're sticking with this regimen.  I also think you're spot on linking CH and allergic reactions.  In condensing the results from several research papers and studies including one by Dr. Peter Goadsby that found CGRP levels elevated during the pain phase of migraine and cluster headache then connecting the dots, I'm inclined to think histamine plays a role in every cluster headache.  After all, histamine headache was another name for cluster headache.

One paper in particular by A C Rosa and R Fantozzi titled: The role of histamine in neurogenic inflammation published in the British Journal of Pharmacology in 2013, lays out a detailed pathophysiology easily leading to the same conclusion.

"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 neuropeptides in neurogenic inflammation is established."

I liken the "bidirectional link between histamine and neuropeptides" i.e., CGRP as a circular firing squad with our trigeminal ganglia in the middle... If I understand this process correctly, this circular/bidirectional chain reaction happens during every garden variety cluster headache.  It also continues until it runs out of reactants, at which point the headache ends. 

Taking it one step further, if you add the insult resulting from a flood of histamine caused by an allergic reaction elsewhere in the body, the resulting CH can easily become refractory... Even the genetically active vitamin D3 metabolite, 1,25(OH)2D3 cannot resolve one of these cluster headaches at a maintenance dose of 10,000 IU/day and serum 25(OH)D concentrations around 80 ng/mL.

This is where 50,000 iU loading doses of vitamin D3 and Diphenhydramine HCL come into play.  Genetically active 1,25(OH)2D3 has been found to down-regulate/inhibit the production of CGRP in nerve cells.  A first-generation antihistamine like Diphenhydramine passes through the blood brain barrier to block H1 histamine receptors... and this would appear to inhibit the bidirectional chain reaction that triggers the release of CGRP which in turn, triggers the release of more histamine.

Eicosapentanoic acid (EPA), one of the polyunsaturated fatty acids (PUFA) in Omega-3 Fish Oil, acts to inhibit proinflammatory mediators so is considered an anti-inflammatory agent...  This is why it is part of the anti-inflammatory regimen.  Doubling the the daily Omega-3 fish oil dose (2 to 4 grams/day) has helped some CHers gain control over their CH.

If push comes to shove, my hole card in regaining control of CH is curcumin.  It also acts as an anti-inflammatory agent.  400mg/day with food has helped a few CHers regain control of their CH.

So there you have it.  I've gone from hypothesis with a reasoned prediction of a possible causal correlation between a vitamin D3 deficiency and cluster headache, to a working theory that provides a tested and substantiated explanation of the efficacy of vitamin D3 and the cofactors as a CH preventative.  Of course there are likely other factors involved, but this set appears to hit the sweet spot with few detractors. 

I forgot to ask in our earlier exchanges, do you have oxygen therapy available?  My initial intent in developing the anti-inflammatory regimen was to use it to improve my abort times with oxygen therapy...  It just worked too well...

Take care and please keep us posted.

V/R, Batch

Adam,

Thanks for the detailed and learned reply... and copy puzzle...

Sneeze and Histamine can be mutually exclusive.  The sneeze reflex can also also triggered by irritations or phlegm in the trachea not caused by an allergic reaction.

Having cluster headache without oxygen therapy available as an abortive is like bleeding profusely without a blood transfusion available. 

If used properly (with the right breathing technique or adequate oxygen flow rate 15 to 40 liters/minute) and early at the first sign of an approaching attack (even before the pain phase), oxygen therapy can be very effective as a CH abortive with an average abort time of 7 minutes for CH at pain levels 3 through 9. 

If the CH is already at pain level 10, starting oxygen therapy will be useless so hang on... you're in for some heavy sledding.

Ask your neurologist for an Rx for oxygen therapy.  Have the Rx written as follows:

"Oxygen therapy as an abortive for Cluster Headache.  Administer STAT with non-rebreathing oxygen mask at 15 to 25 liters/min for up to 15 minutes at first indication of attack up to 12 X per Day."

If needed, the Diagnostic and Treatment Codes follow:

   ICD-9-CM Diagnosis Codes:
        Episodic Cluster Headaches – 339.01
        Chronic Cluster Headaches  – 339.02

   ICHD-II Codes:
       Episodic Cluster Headaches – 3.1.1
       Chronic Cluster Headaches  – 3.1.2

    ICD-10 NA Codes:
       Episodic Cluster Headaches – G44.01
       Chronic Cluster Headaches  – G44.02

If needed, the Healthcare Common Procedure Coding System (HCPCS) Codes for Home Oxygen Therapy follow:
     Equipment:
               E0424-E0425 Stationary compressed gaseous oxygen system
            E0430-E0431 Portable gaseous oxygen system

     Contents:
           E0441 Oxygen contents, gaseous, 1 month’s supply = 1 unit

     Modifiers:
           QG - Prescribed amount of oxygen is greater than four liters per minute (LPM)

As to what to try next... I would:

1.  Skip all NSAIDs - Instead, drink a Baking Soda Tonic an hour after each meal and before bed.  The recipe is on the Arm & Hammer box...  1/2 teaspoon Baking Soda in 4 ounces of water (Half a glass)

Rationale:  Baking soda (sodium bicarbonate) is one of the safest and most versatile substances around; it's useful not only for baking but for countless medicinal and household purposes. 

You may have a low arterial pH (too much acid).  A low pH can increase the frequency and intensity of CH.  The Baking Soda Tonic will help elevate a low arterial pH making it less acid and more alkaline.

2.  Skip the calcium supplement for at least a week,

3. Double the Omega-3 fish Oil dose,

4. Double the magnesium dose (400 mg with breakfast and 400 mg with the evening meal.

5.  As Diphenhydramine HCL is causing an increase in CH frequency, ask your pharmacist for an alternative first-generation antihistamine and dose.

6. Pick up some curcumin.  I've taken 400 mg/day with food.  That much curcumin is equal to three or four chicken curry dinners.

7. Continue taking vitamin C at 1000 mg every two hours. 

8.  See your PCP for another round of labs for serum 25(OH)D, total calcium and PTH.

Take care and please keep us posted.

V/R, Batch

Hey Slacker, Thierry,

Great question and topic that deserve both an answer and discussion.

To be honest, I've yet to select a brand (type) of curcumin for the simple reason I've not needed to take it... or at the very least, I didn't think I needed to take curcumin. 

That doesn't mean I haven't researched curcumin.  For example, there have been a total of 136 curcumin studies registered in clinicaltrials.gov, 130 in the last 15 years and 120 such studies in the last 10 years and 84 in the last five years.  I use clinicaltrials.gov as a barometer of interest and as you can see, the interest in curcumin is rising.

More importantly for this discussion, 14 of these studies examined the pharmacokinetics of curcumin preparations, with eight of these studies occurring in the last 5 years.

So let's start with pharmacokinetics, or in simple terms, what the body does to a pharmaceutical or in our case a nutraceutical... food or supplement containing health-giving additives and having medicinal benefit. 

A pharmacokinetic study deals with the absorption, metabolism and tissue distribution as important parameters to render a compound to be used as a therapeutic agent. 

So let's start with absorption of a given substance.  It's measured in terms of serum concentration in weight or molar (molecular weight) concentration per volume of serum, i.e., nanomoles per liter (nmol/L), maximum concentration (C_max), Time to maximum concentration (T_max), Time to half-life (T_1/2) where 50% of the substance remains in serum, and total area under the curve (AUC) that basically tells us how long we can expect a therapeutic benefit to last and when we would need to take another dose.

Once you've got your head around pharmacokinetics, take a look at the following study selected from clinicaltrials.gov at the following link.  It's a well constructed randomized clinical trial (RCT), randomized, crossover and single blinded (subject), that compares the pharmacokinetics of different curcumin formulations.  Read the graphs carefully as you'll find they use different scales for plasma concentrations.

The strength of an RCT is based on the avoidance of bias.  Moreover, if it is an objective study, it eliminates the Gucci factor of slick promotional adds that attempt to sell refrigerators to nomadic reindeer herders. To that extent, be sure to read the section titled "Conflict of interest."

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If you take the next step to identify a particular product, you need to consider the pharmacodynamics... what the substance does to the body and bang for the buck... I've checked, you'll find a wide range of prices per capsule from 17 cents up to 60 cents.  It also appears curcumin's basic mechanism of action is much like vitamin D3 as it involves genetic expression resulting in the down-regulation of inflammatory agents.

All this still leaves us with the basic question, which brand (type) works best to help prevent CH?

I'll be the first to admit I don't have all the answers and this is clearly the case with Curcumin.  I've tended to lean towards suggesting curcumin formulations containing piperine (black pepper), primarily based on improved absorption and bang for the buck basis.  That said, there are other formulations which result in significantly higher serum concentrations and larger AUCs.

Again, at this point, we still don't know which brand (type) curcumin is best in preventing CH... and therein lies the beauty and strength of this forum...  We try different brands (types) and report the results.

Hope this helps.

Take care,

V/R, Batch