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123 Days PF And I Think I know Why (Read 441118 times)
Hoppy
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Re: 123 Days PF And I Think I know Why
Reply #2475 - Nov 30th, 2016 at 11:40pm
 
Well! That's another Spring done and dusted without a visit from the beast, and I put it all down to the vitamin D regimen. If you haven't tried it, give it a go, because you never know.

Cheers Hoppy
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thierry
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Re: 123 Days PF And I Think I know Why
Reply #2476 - Dec 21st, 2016 at 2:19pm
 
Hi Batch,
I hope all is well with you.
I am helping a friend who suffers from migraines.
I read in your posts that your wife is now relieved from her migraines thanks to the D3 regimen so I have advised my friend to take it. She has started taking it already and has been taking 30000iu D3 + 400mg calcium + 400mg magnesium every day for the last week. She is noticing some changes in the type of pain and  intensity. She will soon be taking the full regimen when she has all the ingredients.
Do you think the levels of D3 in the body needed to become PF are the same for CH and for migraines ie:200nmol?
Do you think my friend should take 600000iu D3 in the 1st month as per your loading schedule and then stay on 10000iu?

Thank you Batch.

All the best and Happy Christmas
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« Last Edit: Dec 21st, 2016 at 2:20pm by thierry »  
 
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2477 - Dec 22nd, 2016 at 10:27am
 
Hey Thierry,

Good question.  The 2-week and 4-week vitamin D3 loading schedules are indicated when the starting 25(OH)D serum concentration is low, typically ≤30 ng/mL.

There are other times when a 50,000 IU loading dose is needed...  An allergic reaction, surgery, trauma or some kind of infection, (viral, bacterial, fungal).

In either case, knowing the 25(OH)D serum concentration is important.

As far as taking the anti-inflammatory regimen to prevent migraine... it should work "as is"... assuming all the cofactors and the 3-month course of vitamin B 50 are taken and there are no comorbid conditions. 

A comorbid condition could be an allergic reaction, surgery, trauma or some kind of infection, (viral, bacterial, fungal).  It could also be Type 2 Diabetes or one of the metabolic disorders.

If any of these comorbid conditions are present, the basic anti-inflammatory regimen will need some assistance: 

A week of 50,000 IU/day vitamin D3, 25 to 50 mg/day Benadryl (Diphenhydramine HCL), Curcumin (500 mg/day) and vitamin C (1000 mg every 2 hours throughout the day),

Finally there's Coenzyme Q10 or CoQ10.  ~300 mg/day should be sufficient. 

Dr. Peter Sándor, MD, a neurologist in Switzerland lead an RCT using CoQ10 as a migraine prophylaxis...

Abstract

We compared CoQ10 (3 × 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

Hope this helps.

Take care,

V/R, Batch
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thierry
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Re: 123 Days PF And I Think I know Why
Reply #2478 - Dec 23rd, 2016 at 5:42am
 
Hi Batch, thank you for your detailed reply and the continuing help that you so freely give.
My friend told me last night that she feels she is getting high from the D3.
I learned from her only yesterday that she is taking a herbal anti-depressant and cymbalta (anti depressant).
I am not sure what, if anything, the D3 regimen can do in conjunction with the tablets she is taking.
However she could not get to sleep and felt high. She puts it down to the D3 regimen. I informed her that I do not know of the interactions with these types of drugs and that she should either consult a GP or join this site to read around and inform herself further.
All the best

Happy Christmas
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« Last Edit: Dec 23rd, 2016 at 6:32am by thierry »  
 
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2479 - Dec 24th, 2016 at 3:04am
 
Hey Thierry,

Drugs.com lists a "minor" interaction between calcium/vitamin D3 and Cymbalta, but nothing clinically significant.

That said, anything is possible when taking a potent heterocyclic antidepressant like Duloxetine (Cymbalta).  Cymbalta has a number of side effects as well as debilitating withdrawal symptoms, including brain zaps... intense and painful sensations that cloud mental clarity and leave them with shakes, nausea and headaches.

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I'm not a doctor... but I would sure try to taper off Cymbalta...

Take care,

V/R, Batch
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Re: 123 Days PF And I Think I know Why
Reply #2480 - Jan 3rd, 2017 at 11:40pm
 
Hi Batch,

I was wondering what the current recommended regiment is?  There's so many pages to look through!  I've been taking the VD3 regime for about 4yrs, and it's extended my time between cycles from a year to about 18 months, and decreased the number of attacks by about half.  The addition of the Benedryl also helped end my cycle last year.  I'm starting to feel the pings of shadows, and would like to see what the best dosage is , as I know there's always new info!  Thank you for everything you do!  Gold rings on ya!
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Peter510
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Re: 123 Days PF And I Think I know Why
Reply #2481 - Jan 6th, 2017 at 6:54am
 
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Kyle N.
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Re: 123 Days PF And I Think I know Why
Reply #2482 - Jan 19th, 2017 at 3:06pm
 
I have read and heard from a pharmacist that the body does not absorb MK-4, so I've just been taking the MK-7.  Will that suffice?  Also, I've just been eating carrots and drinking V-8 to get my Vitamin A rather than taking any supplements.  Shouldn't this be adequate?
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Peter510
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Re: 123 Days PF And I Think I know Why
Reply #2483 - Jan 19th, 2017 at 4:00pm
 
Kyle,

Welcome. MK7 is perfect. The answer to your Vitamin A question depends on how much you're taking in.

Have a look down through the link I posted in my last post on this thread. It shows you in part 2 exactly what supplements to buy.

Keep us posted on your progress because it helps us all to share info and experience.

Best,

Peter.
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Kyle N.
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Re: 123 Days PF And I Think I know Why
Reply #2484 - Jan 19th, 2017 at 11:40pm
 
Awesome, thank you so much for the reply. For some reason the vitamin store I was at didn't have retinol available under 10,000 IU and I didn't want to overdo it. I'll follow your advice, and I'll definitely post again to share how it goes. Thanks again!
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Clustermom
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Re: 123 Days PF And I Think I know Why
Reply #2485 - Jan 24th, 2017 at 9:26pm
 
It's been a while for me. Hello everyone.
We received my sons blood work for his D and it's high. At 125. What should we do? Stop taking it? I need help please.
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2486 - Jan 25th, 2017 at 2:35am
 
Hey Clustermom,

Good question...  I'm assuming your son's lab for 25(OH)D is 125 ng/mL.  The units of measure are very important as 125 nmol/L would be too low to prevent CH...

The short answer is your son should drop the vitamin D3 dose to 5,000 IU/day until he can obtain lab tests of his serum total calcium and Parathyroid Hormone (PTH). 

If his serum total calcium is within its normal reference range of 8.5 to 10.5 mg/dL, his present 25(OH)D serum concentration of 125 ng/mL is not a problem.  His PTH should be in the lower half of its normal reference range of 17 to 70 pg/mL, or roughly 22 to 35 pg/mL.

The 25(OH)D serum concentration is not an indication of vitamin D intoxication/toxicity.  The real indication someone has been taking too much vitamin D3 for too long a period of time is their serum total calcium concentration will rise above its normal reference range > 85 mg/dL. 

This condition is called hypercalcemia (too much serum calcium.  It is also called hypervitaminosis D or vitamin D3 toxicity.  If that's the case, your son needs to stop taking vitamin D3 for a month, but continue taking the vitamin D3 cofactos: Magnesium, zinc, boron, vitamin A (retinol) and vitamin K2. 

At the end of the 30 days without vitamin D3, have your son tested again for his serum 25(OH)D, total calcium and PTH.  If his total calcium is back within its normal reference range your sun can resume vitamin D3 intake but at a lower dose than he was previously taking.

The questions at this point are what is his cluster headache status and how much vitamin D3 has he been taking during the month prior to the blood draw for his 25(OH)D lab test?

As a side note, I ran my 25(OH)D serum concentration up around 170 ng/mL in the spring of 2015 during an exceptionally heavy pollen fall.  I'd been taking 20,000  IU for a few weeks and during the week prior to my 25(OH)D lab test, I was taking 50,000 IU/day vitamin D3.  I also had labs for my total calcium and PTH.

My total calcium was comfortably within its normal reference range so my PCP, who had a copy of the anti-inflammatory regimen treatment protocol, wasn't overly concerned...  His only comment was "You're running a little hot on the vitamin D3 intake."

Take care and please keep us posted.

V/R, Batch
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« Last Edit: Jan 25th, 2017 at 2:39am by Batch »  

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Re: 123 Days PF And I Think I know Why
Reply #2487 - Jan 25th, 2017 at 7:47am
 
Yes it was 125 no/ml. He has been taking all the cofactors. This is the first episode in 2 years. He started getting ch Dec. 5th and so he did a 30,000 iu loading dose one day then 10,000 iu every day. Only a week ago we started the cofactors.
We found the cluster headache group on Facebook (love it) and they suggested the Life Extension website for blood. We didn't do a full work up just a hydroxyl D blood test. His ch are 4 days gone (he's episodic) hopefully for good. They get lighter towards the end, that's how we know the beast is leaving. So I guess we need a full work up on blood? Then in a month another D?  Thank you so much
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2488 - Jan 25th, 2017 at 9:18am
 
Hey Clustermom,

Great news your son is CH pain free.  I don't do facebook so I'm not sure what that group is putting out.  I've had a few CHers tell me the facebook group may not understand the importance of taking the cofactors.  Vitamin D3 is NOT a monotherapy.  Vitamin D3 cofactors must be taken when the vitamin D3 dose is ≥10,000.

If I were episodic, (I'm a chronic CHer so take this regimen daily/365) I would stay on this regimen year round.  That way I wouldn't need to guess when to ramp up my 25(OH)D in time for the next episodic cycle... that may decide to come early...

The health benefits of this regimen are so great I have my entire family and many friends taking it year round.  At 50 cents a day it is the least expensive insurance for a healthy life.

Take care and please keep us posted.

V/R, Batch
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Re: 123 Days PF And I Think I know Why
Reply #2489 - Jan 25th, 2017 at 10:12am
 
Thanks Batch. They sing your praises! they gave me the cofactors there and had a video of the D3 regimen from a conference. We are ordering a complete blood work now. he will be excited. lol. Also how often should we do the hyproxy d3 test? Just until he is level?
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2490 - Jan 25th, 2017 at 12:28pm
 
I'd test for 25(OH)D at 3 months, 6 months and 12 months from start of regimen during the first year as long as the vitamin D3 dose is stable.  Once a year after that is more than sufficient.
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Re: 123 Days PF And I Think I know Why
Reply #2491 - Feb 8th, 2017 at 9:40am
 
Hey Batch,
I hope this post finds you in excellent spirits, sir! I'm working on a book about cluster headache, and was wondering if you would mind elucidating for me the mechanism by which your fine anti-inflammatory regimen works. I've been trying to avoid taxing your time by contacting you directly, but after spending several hours pouring through various forums on this site and others, I've still not found the information that I need. In my understanding of CH pathology, vasodilation alone cannot fully explain the disease's pain, as evidenced by RCCH patients who have had complete trigeminal root section yet continue to experience attack. Is the benefit of your regimen solely anti-inflammatory? Or are their other, secondary benefits? Thanks in advance for your time, and if this information has already been published, I apologize.
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Re: 123 Days PF And I Think I know Why
Reply #2492 - Feb 9th, 2017 at 10:17am
 
Hi all. After about a year of PF, I'm on here to report that I had an allergic response to something in a supplement that I was taking (still haven't isolated the exact ingredient in it - possibly it contains sildenafil (re: viagara?), which I also know is quite capable of giving me a CH) called 'Libido', which is supposed to help your body boost its testosterone production. The allergic response actually gave me a rash, and also, you guessed it, produced a brief cluster cycle.

This is extremely interesting, because, as Batch points out in this thread, allergic (ie. histamine response) is a potential trigger for CH. What's noteworthy to me, as a former chronic CH'er, is that a histamine response can produce a mini-cycle over two-three days, which I'm only able to break with enough antihistamine (the D3 regimen+an NSAID were insufficient alone). This lends credibility to the possibility that CH may be a condition whereby your body's histamine response mechanism is triggered on the circadian rhythm by something in your body (and in turn, produces inflammation) OR by an actual allergen that simply produces a histamine response. There's inflammation, to be sure, but the inflammation is caused specifically by a histamine response. It's just that in the case of a CH'er, that inflammation happens to press against (crush?) the tri-geminal nerve? In any case, I feel like I'm getting closer and closer to understanding CH, as I can now stop and start the CH's at will if I take a sildenafil or a 'Libido' (starts a cluster), benadryl+D3+NSAID (stops the cycle).

The question of how/why CH's happen in longer clusters may have to do with a histamine response being triggered by something produced within you body, on the circadian rhythm, rather than an external allergen (something you eat/breath in, etc.) Something to consider. So, same mechanism of action (histamine response causing COX2 production ---> inflammation), but a different trigger/catalyst. Now we have to figure out what could be this trigger/catalyst! We're going to nail this disease to the wall if it takes until my breath!
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Re: 123 Days PF And I Think I know Why
Reply #2493 - Feb 9th, 2017 at 11:15am
 
Batch, just read your response to 'Bug' (after posting the previous message here) on his new thread 'Re: Back Again after 3 PF years...Lessons Learned?' and realized that you've made huge progress in understanding how allergens trigger CH! Therefore, I'll paste my response on that thread here, too.
----------------------------------------------------
Batch! This is all excellent information in this thread! I just posted to your main thread about having an allergic reaction which restarted my CHs, and I had been positing that >>something<< can trigger the histamine response without an outside allergen being present, and here you have already addressed this! You're amazing!

"...you'll see there's a logical reason to say the circular CGRP - Histamine chain reaction likely takes place without being triggered by an allergic reaction.  Mast cell degranulation and release of histamine triggered by CGRP could easily explain the rapid spike in pain level during most CH."

Thank you once again for all your research and hard work on CH! I'm going to study the CGRP chain reaction in as much detail as I can! The next question I want answered is, in the absence of an allergen as the trigger, why does the Mast cell degranulation happen essentially on the circadian rhythm during a CH cycle? Why does this happen approximately every 12 or 24 hours?!
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thierry
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Re: 123 Days PF And I Think I know Why
Reply #2494 - Mar 5th, 2017 at 11:18am
 
Hi,
About 3 weeks ago my partner suggested that because my CH cycles are usually in late spring and late autumn, i could take a break from the regimen to see how i get on. She thought it would be good for my liver because she believes that all the supplements could be a bit hard on the liver.
So I stopped taking all the supplements, including the probiotic and tumeric powder.
Coincidentally, 2 nights ago, we also decided to change the side of the bed in which we sleep in, which made changing the side of my body i mostly sleep on. Since the change of side, i now sleep mostly on the side of my CH (the right).
Anyway, 1st night of the change of side i got shadows strong enough to wake me about 2 or 3 hours after falling asleep. last night (2nd night of the change of side in the bed), i woke again at 3 a. m with stronger shadows this time. I had to go and get the dusty O2 tank.
So yesterday i started taking the regimen again with a 60000iu loading dose. I did the same again today and will continue the loading dose for another full week until i get to about 500000iu D3 taken, then i will go back to 10000/day.
I will continue to sleep of the same side of the bed -the new side- and see how I get on with the CH.
Will keep posting here on the development.
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Re: 123 Days PF And I Think I know Why
Reply #2495 - Mar 5th, 2017 at 5:17pm
 
Hi Thierry, like you, I to am a Spring/Autumn clusterhead so during the months of Winter and Summer I cut the regimen intake down to a quarter, i.e. 2000iu vitamin D/day same with all the other co-factors and then come the months the beast comes a calling, I up the regimen to a half, 5000iu/day same with the other co-factors. This keeps the beast at bay for me.

I'm not sure about your sleeping arrangements for the beast to come a calling but, it's never bothered me what side of the bed I sleep on.

Cheers Hoppy
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Re: 123 Days PF And I Think I know Why
Reply #2496 - Mar 5th, 2017 at 6:56pm
 
This is the first part (and working draft) of my mini-series titled:

My Theory of Cluster Headache

The following is a discussion and not a definitive statement.  Like any good finding resulting from the scientific method, the conclusions must be open to challenge with attempts to replicate the underlying methods to see if same or similar results can be obtained.  If it cannot be duplicated with similar results consistent with the theory, the theory is dismissed. 

This theory, more appropriately, the scenario of events leading up to a cluster headache (CH), a.k.a., CH pathogenesis, holds as it’s fundamental premise, that CH is a genetotrophic disease/disorder.  A genetotrophic disease/disorder is caused by genetically determined nutritional needs not being met by the individual and which result in a disease/medical disorder...  in this case, the cluster headache syndrome. (Also applies to other TACs and Migraines)

Readers also need to buy into the concept of genetic expression as well as autocrine and paracrine signaling as the fundamental mechanisms of action by which the anti-inflammatory regimen with vitamin D3, Omega-3 fish oil and the vitamin D3 cofactors prevent CH. 

For readers new to this topic/thread, nearly all the data discussed in this paper come from several hundred CHers posting here at CH.com who have started the anti-inflammatory regimen since December of 2010.   More specific data comes from participants in the online survey of 187 CHers taking the anti-inflammatory regimen as of 15 April 2016.  (It is still online... Take it if you haven't already done so.)

The rest come from my research and old fashion Navy fighter pilot logic... that includes among other things...  "If it's not broken... Don't screw with it",  Occam's razor - that essentially states...  "When looking for an explanation for an occurrence, the simpler one is usually better",  and my long time favorite from Admiral of the Fleet of the Soviet Union Sergey Georgiyevich Gorshkov, a.k.a., "The Father of the modern Soviet Navy."   After viewing a new weapon system claimed to be better than the existing system... he remarked, "'Better' is the enemy of 'Good Enough'"

To date, more than 80% of CHers taking the anti-inflammatory regimen have experienced a significant reduction in the frequency, severity and duration of their CH.  54% of these CHers have experienced a lasting CH pain free response as long as they remain on this regimen.

The basic mechanism of action by which vitamin D3 prevents CH involves the genetically active metabolite of vitamin D3, 1,25(OH)2D3 triggering target genes to express autocrine and paracrine signaling agents to down-regulate or suppress the production of CGRP and likely other neuroinflammatory agents from neurons in the trigeminal ganglia.

Genetic expression involves:
   •      Replication
   •      Differentiation
   •      Up- or Down-Regulation of Genetic  Products
   •      Apoptosis – (Programmed Cell Death – what we hope is happening to cancer cells)

The simple explanation of genetic expression as it applies to vitamin D3 preventing CH involves the genetically active metabolite of vitamin D3, 1,25(OH)2D3, attaching to a vitamin D receptor (VDR) where it unlocks the cell’s genetic library of instructions so the cell can execute them. 

One of the instructions is to create a peptide that signals the cell to down-regulate CGRP production (autocrine signaling) and other near by cells to do the same (paracrine signaling).

The following slides provide a notional illustration of this process that starts with a molecule of the vitamin D3 metabolite 1,25(OH)2D3, attaching to a target gene segment VDR, messenger Ribose Nucleic Acid (mRNA) genesis, genetic transcription and translation leading to the production of autocrine and paracrine signaling agents.

The first slide illustrates a molecule of 1,25(OH)2D3 that has combined with a molecule of vitamin A (retinoic acid) to form a dimer (a two molecule chain) and both have attached to their respective receptors (RXR and VDR) at a vitamin D receptor element (VDRE) on a target gene sequence located on a spiral DNA helix.

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This next graphic illustrates how a set of genetic instructions are replicated and transcribed from a target gene sequence on the DNA helix onto a messenger RNA (mRNA) sequence.

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The final graphic illustrates an mRNA segment with genetic instructions transcribed from the parent gene segment, passing out of the cell nucleus into the cytoplasm where it is taken up by a ribosome.  Ribosomes are the cell’s pharmaceutical factories.  They take in the mRNA genetic instructions then build peptides (proteins) according to the instructions from amino acids in the cytoplasm.

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These new peptides serve as autocrine and paracrine agents that signal the cell and surrounding cells with instructions, in our case neurons within the trigeminal ganglia to down-regulate or inhibit CGRP production as one of the likely mechanisms of action.

With that as a premise, let’s set the stage with a vitamin D3 deficiency/insufficiency.  Results from the survey of 187 CHers taking the anti-inflammatory regimen to prevent their CH indicate CHers with active CH have a mean baseline 25(OH)D serum concentration of 22.8 ng/mL with a range of 4 to 47 ng/mL before starting this regimen.  The following normal distribution curve illustrates the mean baseline 25(OH)D serum concentration before start of regimen.

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At this point in the scenario of events leading to CH, we have the cluster headache canon loaded with black powder and it only needs a spark to fire.

This is where antigens, allergens, trauma, surgery, other comorbid conditions and mast cells come into play.  Mast cells are a type of white blood cell that’s part of our immune system.  They’re found in tissues throughout the body primarily in mucus membranes lining breathing passages and the GI tract, but they are also found around capillaries throughout the body and brain.  It’s these strategic locations that provide mast cells with the opportunity to defend the body against invading pathogens, allergens and other inflammatory agents.

Mast cells are loaded with “granules” filled with all kinds of things our immune system uses to combat pathogens and allergens as illustrated in the following electron microscope image.  As I spent many years in the military, I liken mast cells to an IED/Cluster Bomb spring loaded to  the pissed off position… 

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All it takes is an insult from a pathogen, allergen or byproducts of inflammation and mast cells can either selectively release the contents of these granules or explode (degranulate) rapidly as the cellular biologists call it, releasing a boatload of nature’s pharmaceutical products… in most cases, designed to keep us healthy…  However, if the mast cell degranulation is widespread and occurs too rapidly, anaphylactic shock can occur. 

In our case as CHers, mast cell degranulation releases a flood of histamine and that results in a humongous CH triggering mechanism…  The following graphic illustrates the products of mast cell degranulation.  Note that histamine is released in a matter of seconds and that leukotrienes and prostaglandins are released in a matter of minutes from start of degranulation.

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As a result of this mast cell degranulation, histamine, leucotrienes and prostaglandins are released.  In turn, histamine, leucotrienes and prostaglandins trigger neurons throughout the brain and in particular, the trigeminal ganglia to release calcitonin gene-related peptide (CGRP) and Substance P (SP).  Both trigger neurogenic inflammation and CGRP is directly associated with the terrible pain, a.k.a., nociception in neurology speak of CH and migraine headache (MH).  It gets worse…

The CGRP released in this process in turn triggers mast cells to release more histamine, leucotrienes and prosteglandins resulting in a bi-directional or circular chain reaction that continues until the reactants are consumed… at which point the CH attack ends… for now… 

I am quite confident that the histamine and prostaglandins released as a result of an allergic reaction are responsible for many CHers being refractory to nearly all means of intervention, i.e., oxygen therapy not effective or less effective at best and traditional CH preventatives like verapamil either don’t work or their preventative effect is minimal.  It’s also very likely this flood of histamine and prostaglandins are responsible for busting to become ineffective.

Hopefully, we’re all on the same page at this point…

Regarding the question about the histamine – CGRP circular chain reaction taking place in an absence of allergens...  My first reaction…  No such thing, or at least, it’s highly improbable.  The more likely scenario is this chain reaction initiates with an allergen insult.  After that, the histamine – CGRP circular chain reaction is capable of continuing on its own without further insult by an allergen until running out of one or more of the reactants and the CH ends.  While this appears to be the primary mechanism of action, there’s reason to suspect there are other mechanisms in play…  I’ll get to that a little later.

The simple fact remains there are thousands of potential allergens around us all the time, day and night, no matter the season.   There is a question of how much of a particular allergen it takes to trigger the histamine – CGRP circular chain reaction.  I don’t know the answer, but logic and the law of mass action would suggest the triggering mechanisms are always present and at some point, a threshold will be reached where mast cells start degranulating.

Before we go any further, it’s important to understand the law of mass action so the rest of my discussion will make sense. 

The law of mass action deals with the relationship between a drug, a nutrient like vitamin D3, or an allergen and a receptor (a molecular socket) located on a cell membrane, the cell nucleus or somewhere on a specific gene sequence on a DNA helix.

The law of mass action 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).

In the case of an allergen and mast cell interaction, immunoglobulin E antibodies (IgE), part of the body's immune system, bind to an allergen and then this complex attaches to a receptor on mast cells triggering degranulation.

Circadian and Circannual rhythmicity can be factors in CH pathogenesis due to the central role played by the hypothalamus in our autonomic nervous system.  During circadian and circannual rhythmicity we experience an ebb and flow of hormones and peptides as we transition through day and night, wakefulness and sleep, moon cycles and seasons with long and short days eliciting more or less cutaneous vitamin D3. 

Sleep is the only time our brains can go offline for house cleaning…  I’ve little doubt the chemicals flushed from our brain during this house cleaning are capable of triggering mast cells to degranulate if the conditions are right… and in accordance with the laws of mass action.  That said, circadian and circannual rhythmicity are only one possible explanation for variations in CH cycles.  Seasonal blooms of allergens can just as easily explain the increased frequency of CH cycles during Spring and Fall seasons.

Even living in a hypoallergenic bubble is no guarantee we can be free of allergens.  We have Dermatophagoides pteronyssinus a.k.a. the common house dust mite. 

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These little beasties live in your bedding, carpets and just about anywhere in fabrics touched by humans as their diet is mainly flakes of skin our bodies shed all the time.

Over the course of 10 years, your mattress can easily double in weight because of the accumulation of dust mite debris (let's be real here: dead dust mites and dust mite poo), your dead skin cells, etc.

Before you burn your mattress or buy a new one, buy a hypoallergenic  mattress cover and wash all the bedding and pillows in 140°  F water.  Unfortunately, no matter what you do, you can’t get rid of dust mites completely…  Fortunately, for most of us, our immune systems adapt to the allergic nature of dust mites and their droppings…  as long as the concentrations don’t get too high…
That said, this is another example where the law of mass action applies.  By that I mean if there’s a major bloom of dust mites, the allergic effect will increase to the point where mast cells will start degranulating and release histamine.  If our vitamin D3 status is low, i.e., a 25(OH)D less than 40 ng/mL and mast cells start degranulating…  we’ll experience the circular histamine – CGRP chain reaction and Bang!... we’ll get hit with a cluster headache.

Then there’s the dynamic duo of Demodex folliculorum and Demodex brevis, both frequently referred to as eyelash mites.

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Studies indicate a prevalence as high as 41% among people over 18 years of age who carry these little beasties…  Even if they didn’t, the family dog, cat or any furry pet likely carries a close genetic relative.  Whatever the case, they’re potential allergens.

Even with the best hygiene and super effective house cleaning that kept us completely free of these beasties, we still have hundreds of different colonies of biota numbering in the trillions, living in the GI tract, nasal passages and lungs called the microbiome.  Most of these colonies are beneficial... but some are not, particularly if they leave the GI tract and enter another part of the body.  Yeast and E. coli infections are classic examples.  While infections like these are technically not associated with an allergic reaction, they do result in inflammation and the release of neuroinflammatory peptides that could easily trigger mast cells to degranulate.

Prostaglandin E(2) (PGE(2)),  could easily be the case here as PGE(2) has been found capable of triggering the release of CGRP from trigeminal neurons.  This poses a problem for CHers as first-generation antihistamines are ineffective in blocking prostaglandin receptors.  Fortunately, the Omega-3 fatty acids, are the best treatment in the event prostaglandins are playing a major role in CH pathogenesis.

Then there are mold spores…  The drip pan under your frost-free refrigerator, the air handler in your central heating and air conditioning system, window mounted air conditioners, shower curtains and even your washing machine are all potential breeding grounds for mold.

Viral and bacterial infections can also cause problems for CHers.  For starters, they trigger an immune system response that consumes serum vitamin D3, 25(OH)D and the essential enzymes needed to hydroxylate both to the genetically active vitamin D3 metabolite 1,25(OH)2D3 that helps us prevent CH.  If the scale of the infection is such that mast cells are triggered to degranulate… Bang! We get hit.

Finally, there’s a whole host of metals and chemicals, some industrial and some produced from things we eat or drink…  Aldehydes and ketones produced during the process of metabolizing alcohol and certain vegetable oils are capable of triggering mast cells to degranulate…

The microbiome... colonies of symbiotic/friendly bacteria a.k.a., "biota" living in the GI tract can also become corrupt with "bad" unfriendly biota or decimated by antibiotics or other chemicals causing a bloom of potential allergens...  If this is the case, probiotics are indicated.

In addition there are a number of studies linking migraine and cluster headache to higher and lower concentrations of metals.

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So where does that leave us?  The simple answer is to maintain a healthy immune system.  This is one of, if not the major beneficial side effect of taking the anti-inflammatory regimen to prevent our CH. 

The final questions on the relationship between mast cell degranulation and circadian rhythmicity and why the cycles appear in 12 to 24 hours cycles bring to mind a few basic principles of biochemistry…  Most biochemical reactions associated with human physiology take place at a sweet spot temperature.  For humans, that’s 98.6° F.  These biochemical reactions also work best within a pH range of 7.35 to 7.45, not surprisingly, that’s the normal pH range of human serum.  Remember the Andromeda Strain?

Let’s take the increase in the frequency of CH during sleep as an example.  During sleep, most body functions slow.  Blood pressure, heartbeat and respiration rates all drop and are as low as they ever get during sleep.  While we inhale sufficient oxygen to stay alive, the partial pressure of arterial O2 (PaO2) drops significantly below normal.  The reduced lung ventilation during sleep also allows the partial pressure of arterial CO2 (PaCO2) to rise and arterial pH to drop.   This sets the stage for a perfect storm for CHers.

To be continued...

While you're waiting, please take the time to watch the fascinating documentary titled: Battlefield Cell from the Curiosity Series on the Discovery Channel:

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This video will put you in the same frame of mind that's kept me well outside the box of conventional thinking regarding cluster headache.

Take care,

V/R, Batch
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« Last Edit: Mar 6th, 2017 at 11:36am by Batch »  

You love lots of things if you live around them. But there isn't any woman and there isn't any horse, that’s as lovely as a great airplane. If it's a beautiful fighter, your heart will be ever there
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Hoppy
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Re: 123 Days PF And I Think I know Why
Reply #2497 - Mar 5th, 2017 at 10:00pm
 
Batch, I've read of cluster headaches being referred too, as histamine headaches?

Hoppy
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Batch
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Re: 123 Days PF And I Think I know Why
Reply #2498 - Mar 5th, 2017 at 11:46pm
 
Spot on Hoppy.
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You love lots of things if you live around them. But there isn't any woman and there isn't any horse, that’s as lovely as a great airplane. If it's a beautiful fighter, your heart will be ever there
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Re: 123 Days PF And I Think I know Why
Reply #2499 - Mar 7th, 2017 at 7:05am
 
Wow Batch, that was amazing, thank you.
i am blown away with your knowledge which is the result of a huge amount of research and work. Thank you for sharing so much. You are helping me and i am sure countless others understand and get relief. Thank you

Hoppy, I am going to stay on the full regimen from now on, I might skip a day here and there when i know I'm way off my CH cycles times or if I'm on a long term sun holiday.
I have now been back on the full regimen at loading doses pace for last  4 or 5 days with 60000iu D3/day. The shadows are gone, whatever side of the bed or my body i sleep on.

All the best to all
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