John,

I'm sorry you're having such a rough time and that the anti-inflammatory regimen hasn't been effective in preventing your CH.

It's cases like yours that grab my attention.  You appear to be doing everything right taking the anti-inflammatory regimen... Your 25(OH)D is up in the green zone... and it's still not working to prevent your CH...  I suspect we're missing something.

For starters, check the type of magnesium you're taking.  We need magnesium supplements with the highest bioavailability, i.e., magnesium malate, magnesium glycinate or magnesium citrate. 

These three salts of magnesium have an 80-90% bioavailability.  Magnesium oxide has a bioavailability of at best 5% and can induce osmotic diarrhea at higher doses.

If you're already taking one of the three magnesium supplements above, cut the calcium supplements for a week to see what happens.

We are what we eat, so the second thing to try is the GOMBS diet. Greens, Onions, Mushrooms, Beans-Berries and Seeds.  A handful of each a day should be sufficient. 

Extra virgin olive oil, almonds and avocados are really good sources of anti-oxidents. I make a mean caesar salad dressing with fresh egg yokes, EVOO, lemon juice and elephant garlic then toss it with romaine lettuce with avocados and sunflower seads and top with fresh grated romano or parmesan cheese. 

See the following links for more on the GOMBS diet:

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A sub-clinical allergy is always a possibility so cut out gluten and peanuts.  Cut out sugar and all prepared foods containing sugar... Whole fresh fruits are ok.

The last suggestion comes off the wall...  Nopalea...  Swing by Costco, Wally World or your local supermarket and pick up a jug of their nopal product.  It can't hurt and it just might help.   

If all of the above fail to improve your situation, see your PCP for the endocrine panel of lab tests or look up an endocrinologist for a complete workup.

One last thought on your oxygen therapy.  What flow rate are you using?  If we can't prevent your CH... we might just be able to improve your abort times with oxygen therapy.  I was chronic for over 5 years and oxygen was all I used... except I used oxygen at flow rates that support hyperventilation... (25 to 40 liters/minute).  The following chart illustrates the benefits of this method of oxygen therapy over traditional oxygen therapy at 15 liters/minute.

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4 of the 7 participants in this pilot study used a 0-60 liter/minute regulator and got the same results as the 3 participants who used an oxygen demand valve.  The seven participants logged a total 366 aborts during the eight weeks each took part in this study. The two methods of oxygen therapy were 99% effective in achieving an abort and as you can see in the above chart, the average abort time was 7 minutes for all attacks between pain levels 3 and 9.

Take care and please keep us posted.

V/R, Batch

Pattik,

Thank you for the wonderful update on your experience with the anti-inflammatory regimen.  In some cases I think episodic CH'ers have a more difficult time trying to determine the effectiveness of this regimen when they first start it.  Like so many other preventatives, a drop in the frequency of our CH can and will co-inside with end of cycle blurring the cause and effect nature of the preventative.

That said, staying on this regimen year-round and sailing through the next regular cycle without a visit from the beast is a very strong indication of effectiveness.   Good on you for sticking with this regimen and for the wonderful update.

JH and Morran, interesting comments on the link between taking additional vitamin A and a cessation of your cluster headache symptoms. 

You may have hit the nail square on the head and connected the dots in answering the question why some CH'ers take so long to respond to this regimen and others don't respond at all...

The biochemistry and molecular biology of vitamin A is almost as fascinating as vitamin D3.  Among it's many benefits is the role it plays in conjunction with vitamin D3 as it applies to genetic transcription and gene expression.

I'm not a doctor or a cellular biologist.  On top of that my schooling in cellular biology and biochemistry circa '62-'67 is sadly out of date... 

In order to put my following discussion in perspective,  vitamin A was discovered in 1914.  However, it wasn't until 1969 that researchers discovered it was metabolized into 1,25(OH)2D3, (calcitriol) and that vitamin D3 receptors existed on human genes. The human genome wasn't completely mapped our until 2003 at NIH.

Accordingly, I'll use the following graphic from Biochemistry for Medics© to show where vitamin A, (retinol), links up with 1,25(OH)2D3, (calcitriol), the active hormonal form of vitamin D3 at the cellular nucleus/genetic level.

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What this graphic illustrates is the physical location and proximity between the Retinoic Acid X Receptor (RXR) and the Vitamin D Receptor (VDR) at a special location on the DNA dual helix called the Vitamin D Receptor Element (VDRE). 

When activated by 1,25(OH)2D (vitamin D3) and retinoic acid (vitamin A), this RXR-VDR complex modulates the transcription of specific genes.   More than 50 genes in tissues throughout the body are known to be regulated by 1,25-dihydroxyvitamin D... and the number is growing...

What are genetic transcription and gene expression?  In layman's language, (my limited understanding), genetic transcription is the first step in gene expression.  Gene expression is the process by which information from a gene is used in the cell to synthesize a functional gene product.  In other words, in response to a signal or stimulus, the cell used vitamin D3 and vitamin A to manufacture a product needed by the body.

Dr. Robert Heaney, MD, one of the Jedi Masters of vitamin D3 therapy explains it best...

"When bound to the vitamin D receptor and a variety of other helper proteins, calcitriol seems to be just the right key to open up the locked stores of DNA information, allowing the cell to transcribe the plans and produce the proteins needed for tissue-specific responses. The helper proteins that are a part of this complex determine the region of the DNA that will be transcribed. Without vitamin D, the ability of the cell to respond adequately to pathologic and physiologic signals is impaired.

For example, the ductal epithelium of the breast requires vitamin D to mount an adequate response to cyclic variation in estrogen and progesterone. Also, macrophages use vitamin D to enable the synthesis of the bactericidal peptides needed to deal with bacterial invaders.

In addition, most of the epithelial structures in the body, which turn over relatively rapidly, use vitamin D to signal the transcription of proteins that regulate cell differentiation, cell proliferation, and apoptosis (programmed cell death)."

So where is all this going?  My theory what this means to us as cluster headache sufferers follows:

My current thinking on the mechanism of action of the anti-inflammatory regimen with 10,000 IU/day vitamin D3 is based on the extrarenal (outside the kidneys) autocrine path of vitamin D3 metabolism that takes place in the periphery at the cellular and nuclear level and that supports genetic expression. 

As such I think 1,25(OH)2D3, (calcitriol), down-regulates or suppresses the calcitonin gene-related peptide (CGRP) [1] that is elevated during cluster headache and migraine attacks. [2]

1.  Durham PL, Sharma RV, Russo AF, Repression of the Calcitonin Gene-Related Peptide Promoter by 5-HT1 Receptor Activation. The Journal of Neuroscience, December 15, 1997, 17(24):9545–9553.

2.  Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache Neuropeptide changes and effects of acute attacks therapies. Oxford Journals>Medicine Brain>Volume117, Issue3 Pp. 427-434.

This is just a SWAG (sophisticated wild-ass guess) backed up by a few related studies at this point... but I'm sticking with it until proven wrong...  and that's going to take some serious research backed by equally serious funding.

As one of the essential elements in genetic expression is vitamin A, that's reason enough for me to include vitamin A as an essential part of the anti-inflammatory regimen.

That also brings us to a practical question...  How much vitamin A should we take as a part of the anti-inflammatory regimen?

A review of available literature indicates the Recommended Dietary Allowance (RDA) for vitamin A is 900 micrograms (mcg) or µg/day (3000 IU) RAE (retinol activity equivalents) for men and 700 µg/day (2333 IU) RAE for women. 

The UL or maximum upper limit that can be taken without adverse effects, is 3000 µg/day RAE.

Owing to wide variations in vitamin A absorption in either form,(beta-carotene, the provitamin and retinol) and metabolism of retinol to retinoic acid, we may need more vitamin A than the RDA... 

How much more?

I'm comfortable in doubling the RDA to 1,800 µg, (6,000 IU) RAE vitamin A/day for four reasons: 

(1) The Nutrition Board at the Institute of Medicine and the Office of Dietary Supplements at NIH tend to be conservative in setting the RDA for vitamins and minerals...  (Remember, it was the folks on the Nutrition Board that set the RDA for vitamin D3 at 400 IU/day.)

(2) The second reason is 1,800 µg/day vitamin A is still only slightly more than half the UL.

(3) Some types of foods are very high in vitamin A (beta-carotene or retinol) as illustrated in the following chart:

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Vitamin A is available in multivitamins and as a stand-alone supplement, often in the form of retinyl acetate or retinyl palmitate. A portion of the vitamin A in some supplements is in the form of beta-carotene and the remainder is preformed vitamin A; others contain only preformed vitamin A or only beta-carotene. Supplement labels usually indicate the percentage of each form of the vitamin. The amounts of vitamin A in stand-alone supplements range widely. Multivitamin supplements typically contain 2,500–10,000 IU vitamin A, often in the form of both retinol and beta-carotene.

(4) A little vitamin A a day goes a long way.  Like any other vitamin, taking too much vitamin A can be harmful.

See the following for more details on vitamin A:

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As always, talk to your PCP or neurologist about this regimen.  If for no other reason... you might just learn them something new about treating CH'ers...  with a safe, inexpensive and very effective cluster headache preventative...

Take care,

V/R, Batch

Sean,

Good question and good on you for getting your brother-in-law started on the anti-inflammatory regimen.  The short answer is there's a wide variety of irritants capable of initiating the cluster headache attack mechanism.  They range from nitroglycerine with a 100% probability of triggering a CH, to alcohol at 70% certain foods on down to petroleum and chemical vapors.

Alcohol in any form and cola have never been a CH trigger for me... but I may be one of the few exceptions to the alcohol trigger.

Although colas are acidic as most contain a small amount phosphoric acid, H₃PO₄ as a food additive to add a tangy flavor, most of the acidity is due to the carbonation with carbon dioxide, CO₂ added under pressure which forms carbonic acid.  That's the same carbonic acid you get when mixing baking powder and water that eventually elevates serum pH triggering vasoconstriction.  The cola syrup is also high in caffeine which acts as a vasoconstrictor.

The bottom line is it's possible that several cans of cola a day can serve as a CH trigger.  That said, my experience drinking diet Coke and the chemistry of cola tell me it's unlikely. 

The best course of action for your brother-in-law is to see his PCP and ask for the lab test for 25(OH)D to determine his vitamin D3 status.

Take care and please keep us posted.

V/R, Batch

Take care

Hey Red Ryder,

Thanks for the feedback on your experience with the anti-inflammatory regimen.  Your 25(OH)D serum concentration is perfectly normal for a CH'er taking the anti-inflammatory regimen. 

My wife has been taking 15,000 IU/day vitamin D3 for nearly 3 years and her 25(OH)D serum concentration stays in a range between 105 and 115 ng/mL.  She is also free of the chronic migraine headaches that haunted her for over 20 years.

Her long time PCP didn't bat an eye at her 25(OH)D lab results but did comment that the rest of her labs and vitals which were quite normal, appear to be from a much younger woman...  This tickled my wife as she kicked the heck out of 75 last Christmas...

The truth about the "toxic" level of 25(OH)D is clouded by a lack of clinical studies for obvious reasons...  That said, there is a tremendous amount of anecdotal information from clinical observations that says the real lower threshold for vitamin D3 intoxication is somewhere North of 200 ng/mL, (500 nmol/L).

Your neurologist was correct in cross-checking your 25(OH)D serum concentration with your total serum calcium...  As long as the total serum calcium concentration stays in the normal rang... serum concentrations of 25(OH)D as high as 150 ng/mL are very safe.

Thanks again for the update and please keep us posted.

V/R, Batch