The full paper is online:

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The results section is:


Quote:

The study enrolled 28 patients with cluster headache, 36 migraineurs, and 36 normal controls. In the patients with cluster headache, the serum 25(OH)D concentration averaged 14.0 ± 3.9 ng/mL and 92.8% had vitamin D deficiency. There was no significant difference among the patients with cluster headache, migraineurs, and controls. In the patients with cluster headache, there was no difference in the serum 25(OH)D concentrations between men and women, cluster and remission periods, first and recurrent attack, presence and absence of daily or seasonal periodicity, and 3-month recurrence. In the 14 patients with seasonal periodicity, patients with periodicity of winter to spring had a trend of lower serum 25(OH)D concentrations than those with periodicity of summer to autumn (12.30 ± 1.58 vs. 16.96 ± 4.69 ng/mL, p = 0.097).

It is interesting in that there isn't anything different in the levels between people with CH, migraine or the controls.

Plus there was no link between levels and:

• male / female
  
• cycle length / remission length
  
• between CHs
  
• periodicity
  

The figures are interesting,  certainly,  but nothing can take away from the fact that,  since it was found vitamin D3 helped with CH and all the work Batch has put in to refine the regimen,  there's terrific numbers of ClusterHeads experiencing great relief from this nightmare.

All being well it'll get even better!

Totally agree Brian, but why don't non-CH'ers not get CH when they have the same D3 related levels?

Mike,

That’s a great question and one I have often pondered.

There has to be something else invipolved in the brain, and the D3 deficiency is just the trigger, not the cause in itself.

Peter.

     I guess I assumed the clusters were never caused by a D3 deficiency. Like a bucket of water that develops a leak, the D3 makes an effective patch even though it didn't create the leak in the first place. Imitrex for example isn't a pain killer but it does prevent the mechanism that causes the pain even though it does nothing to cure the true source of the cluster. Oxygen at high enough levels will cause the blood vessels to constrict ending the pain. As many (most?) of us are or were cigarette smokers damaging our lung's efficiency to absorb o2...perhaps or not that's a link. Maybe even young people that develop clusters and have never been around smoke have a lung deficiency. High altitude with it's lower oxygen levels seems to be a trigger also. Who knows? As long as supplementing D3 seems to help and it is definitely safer than drugs I'm all over it.

Hey Mike,

This is an interesting study but with a Ho Hum conclusion that says minor changes in observed vitamin D3 status with seasons has no effect on headache status.

IMHO, this study is no more than thinly veiled piece of opposition research focused on down-playing the capacity of vitamin D3 to act as a CH or MH preventative.  You can draw your own conclusions as to who would benefit from published results like this.

Hello... the difference between being vitamin D3 deficient and vitamin D3 insufficient ( 14 to 30 ng/mL) is so minor with respect to CH or MH status, there's no way this data could be used to predict headache status.  The change in vitamin D3 status must be significant to make any such assessments.  By significant we're talking a physiological dose that could be expected in nature if the subjects were exposed to whole body UVB radiation from direct sunlight for at least 15 to 20 minutes a day, 5 days a week during the summer months and have a corresponding 25(OH)D response of 60 to 80 ng/mL.

We've known for years CHers and migraineurs with active bouts of headache are vitamin D3 deficient or insufficient.  What the authors of this study neglected to do was investigate the relationship between headache status with a significant change in vitamin D3 status.

We've done that here at CH.com with the online survey of CHers taking the anti-inflammatory regimen with at least 10,000 IU/day vitamin D3.  The following two charts illustrate a clear and unequivocal inverse relationship between vitamin D3 status and CH status.   
In simple terms, if the vitamin D3 status is low (deficient/insufficient) CH status is high with an average of 3 CH/day as illustrated in the first chart.  If the vitamin D3 status is high as in a physiological dose of 10,000 IU/day vitamin D3 with a corresponding 25(OH)D response near 80 ng/mL as illustrated in the second chart, the incidence of CH is low to nonexistent.

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The third chart illustrates the efficacy in responses by day from start of regimen.  It also illustrates the high likelihood that serum vitamin D3 concentrations are the determining factor in favorable responses to this regimen as 25(OH)D concentrations are slow to rise as a response to vitamin D3 dose.  This also points out the need for daily vitamin D3 dosing as it maintains the highest possible serum concentration.

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Had the authors of the above study taken the next obvious step to treat the vitamin D3 deficiencies with therapeutic doses of vitamin D3 (≥ 10,000 IU/day), they would have observed the same results as we have here at CH.com.  At that point, they would have established and reported on a level of efficacy in treating CH and MH with vitamin D3 that Big Pharm doesn't want CHers and MHers to know about.

Take care,

V/R, Batch

There are several conclusions in this paper:

• There was no significant difference among the patients with cluster headache, migraineurs, and controls
  
• In the patients with cluster headache, there was no difference in the serum 25(OH)D concentrations between men and women, cluster and remission periods, first and recurrent attack, presence and absence of daily or seasonal periodicity, and 3-month recurrence.
  
• In the 14 patients with seasonal periodicity, patients with periodicity of winter to spring had a trend of lower serum 25(OH)D concentrations than those with periodicity of summer to autumn (12.30 ± 1.58 vs. 16.96 ± 4.69 ng/mL, p = 0.097).
  

I think the first of these conclusions is highly significant and this aligns with the comments from both Peter and Sean. From the work that Batch et al have done there seems to be a very clear link that for someone with CH, raising their D3 levels sufficiently results in CH stopping or being significantly improved for ~80% of people. But low D3 levels alone are not the sole cause of CH as otherwise a lot of people would have CH and not around 1 in 1000 people.

D3 is a wonderful preventive (6.5+ years CH pain free for me as a result), but the complete understanding of CH relies on identifying the root cause(s) of CH that together with low D3 levels results in CH.

Mike,

Well said.  The root cause of CH remains elusive and is clearly upstream from the effects of vitamin D3 status.  That there are many with low to very low vitamin D3 status who don't have CH is an important part of the puzzle.  What makes them different from CHers?

I've spent over seven years researching the cluster headache syndrome motivated by how and why vitamin D3 has the capacity to prevent CH.  Accordingly, I'll go out on a limb to start the ball rolling by making a SWAG (sophisticated wild-ass guess) that the likely cause of CH involves a constellation of factors.  Among them, the leading factor appears to be the asymmetry occurring during cell division as the fertilized egg becomes an embryo and on to the fully formed brain at birth. 

That asymmetry can exist in morphology (physical arrangement and proximity of nerves and vasculature in and around the left and right trigeminovascular systems) as well as in the density and distribution of astrocytes (star-shaped glial cells) that provide structure and brain maintenance functions including the blood brain barrier.  Astrocytes also have a high density of CGRP receptors and genes that express calcitonin related peptides.  This could also answer the age old question on why CH are predominantly one-sided.

Food for thought...  What say you?

Take care,

V/R, Batch

It could be something that influences things, especially for those where CH is inherited with research showing that children of someone with CH have a chance of about 7% (START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or END PRINTPAGE) with:

Quote:

The segregation analysis suggests that cluster headache has an autosomal dominant gene with a penetrance of 0.30 to 0.34 in males and 0.17 to 0.21 in females. The gene is present in 3% to 4% of males and 7% to 10% of females with cluster headache.

So if CH is present from pre-birth, why does it take a few years for the small number of children who get CH for it to develop? And then why for some people does it take decades?

The SWAG suggests why a CH is one sided, but then the side logically fixed, but people have observed CH changing sides between cycles, during cycles and when a nerve block has been done on one side.

CH has also been observed to happen as a result of blast injury (START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or END PRINTPAGE). Perhaps the blast as kicked off some other process which results in CH?

And the recent work by Todd Rozen (START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or END PRINTPAGE) suggests that tobacco exposure impacts how CHs develop.

Lots of questions, mostly yet unanswered.

Hey Mike,

Great comments!  You're getting warmer to my way of thinking about the pathogenesis of CH.  I think you realize by now my SWAG is a think piece designed to stimulate discussion.  To that end let's take genetic disposition as an example.

Being genetically disposed to a medical condition does not translate to the presentation of that medical condition in most cases.  In fact, there are only a handful of genetic markers that translate to the expression of a medical condition with a high probability. 

I lost two childhood friends and grade school classmates to Hemophilia.  They knew from an early age they suffered from this disorder and that their days were numbered. 

Getting back to CH... The gene patterns capable of expressing the cocktail of peptides responsible for CH can remain dormant for many years or a lifetime without the individual experiencing a CH.  However, if environmental conditions are present that activate these genes into expressing that cocktail of neuroactive peptides, the individual gets hit.

In my case, I didn't have my first CH until I'd been retired from Naval service for nearly a year.  At that point I'd entered a fast-paced corporate working environment as a weapons system technology consultant that kept me cooped up in an air conditioned office 7 days a week. 

Prior to my retirement from the Navy, I'd maintained a physically active work-play schedule that included 4 to 6 hours of week of tennis and weekends sailing at Annapolis, MD near the Naval Academy. In short, prior to my retirement from the Navy, I was likely developing sufficient cutaneous vitamin D3 to prevent my CH.   There were also two wonderful years when my episodic CH cycle that ran from mid April to mid June didn't materialize.   

In both cases, I was out of the office and in the field working with clients. The first was March through May '97 at Marine Corps base Camp Pendleton, CA and Air to Ground Training Center, Twentynine-Palms, CA where I was literally out in the sun 6 to 8 hours daily working with Marine Corps Forward Observers.  The second was spending nearly two months (March and April '98) working along the Amazon from Iquitos down to Caballococha Peru with Peruvian counter drug forces.

I had three more CH pain free stints lasting a week or more after turning chronic in 2004.  All three involved lots of time in the sun.  The last occurred during a cruise to the Mexican Riviera in early 2010 were I spent a good 8 hours a day on deck or on the beach in the sun clad in a bathing suit or shorts and tank top.  I'd been averaging 4 CH/night while sleeping prior to the cruise so took along two tanks of oxygen.  I never used them...  My CH stopped the first day of the cruise and didn't restart until the night after the cruise ship returned to Long Beach CA where the frequency returned to 4 CH/night.   That's when the good idea light came on bright that vitamin D3 was likely a CH preventative.

You mentioned Dr. Todd Rozen's paper on the relationship between smoking and CH.  I had the pleasure and opportunity to work with Todd in 2008 developing many of the 187 multiple choice questions in this survey of 1134 CHers mostly from here at CH.com and Clusterbusters.  My task was to develop questions on oxygen therapy.  I also did the initial analysis of the survey results and found them to be consistent with the cluster survey here at CH.com.

Of particular interest was data on pain location
- 49.1% right-sided
- 44.1% left-sided
- 3.1% bilateral pain: CCH 8.3% vs ECH 1.5%.
- 30.5% stated that pain has changed sides since onset of CH
- 8% stated that pain shifted sides during an individual CH attack

The pain location results are consistent with the SWAG with respect to my hypothesis on the disposition and density of astrocytes highest in CGRP receptors and CGRP expressing genes between left and right trigeminal ganglia.

I still have a copy of the survey database of responses and refer to it frequently.

More food for thought...

Take care,

V/R, Batch