Ian,

Welcome to the club...  Trying to convince folks to take some vitamin D3...  even 5,000 IU/day is a thankless task for too many...   It's amazing how many CH'ers apparently prefer to ignore the mounting evidence pointing to the health benefits of vitamin D3 and its capacity to prevent cluster headaches...

Fortunately there are folks like you and Joshua who said...  "Why not..." and have discovered the wonderful benefits of this supplement.  That makes it all worth while...

Take care and persevere... One "Holy Cow" or "Woo Hoo" out of ten tries is a better than average response...

V/R, Batch

DVB, Evan O, B.Baer, DH,

Thank you all for the wonderful updates, feedback and testimony to the effectiveness of the anti-inflammatory regimen as a CH preventative.  It's comments like yours that provide an incentive to so many undecided CH'ers to give this regimen a try.

It's significant to note that the raw efficacy of this regimen is on the climb and is now pushing 80% since more CH'ers started using the vitamin D3 dosing strategy of 20,000 IU/day with a 50,000 IU loading dose once a week discussed in some of my earlier posts.

Seth, the short answer to your question is yes, the cofactors including: magnesium, zinc, boron, vitamin K2 and vitamin A are all essential parts of this regimen.  They aid in the metabolism of vitamin D3 to 25(OH)D3 and on to its active metabolite, 1,25(OH)2D3 that appears to be responsible for preventing our CH.

You can find a good explanation of the vitamin D3 cofactors at the following link:

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You'll see after reading this link that most of the cofactors are available in a well balanced diet...  The problem is, we don't always eat a well balanced diet... so it's best to play the odds in your favor and take the cofactors.

Vitamin A is a late comer to this regimen.  Watch the video of Dr. Robert Heaney, M.D. give a fascinating and compelling presentation titled "Vitamin D: Nutrient, Not a Drug" at the following link.   He explains how and why vitamin A has become another essential part of this regimen:

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Dr. Heaney also brings up the point that there have been over 31 Level A rated RCTs with strong Evidence-based medicine (EBM), dealing with the benefits of vitamin D3 therapy.  True, none of these RCTs were focused on cluster headache, but I think we're providing ample empirical proof of vitamin D3's efficacy as a cluster headache preventative. 

Moreover, we're proving that vitamin D3 doses of 20,000 IU/day are very safe.  There is also ample evidence this regimen can be safely started while also taking physician prescribed cluster headache preventatives like verapamil.

That said... we're still finding too many primary care physicians and neurologists who get their knickers in a wad over sustained doses of vitamin D3 at 10,000 to 20,000 IU/day and serum concentrations 25(OH)D over 30 ng/mL.

For the CH'ers new to this regimen or wanting to start it...  be prepared for push-back from your PCP or neurologist...  Print out the attached study by Garland et al, take it along to your next appointment, and be prepared to discuss it in detail if you do get any push-back.

Please don't be afraid to challenge your PCP or neurologist on this topic... We CH'ers will all come across a PCP or neurologist who needs educating on our disorder and how best to treat it. 

Unfortunately, when it comes to continuing medical education (CME), a requirement to maintain a license to practice medicine in most states, CME on the benefits of vitamin D3 screening and therapy are limited to courses provided by the American Society for Nutrition, CME Program.

Moreover, as most neurologist would sooner attend a Gucci level course of CME on exotic medications proposed as treatments our disorder or the latest studies on the pathophysiology of cluster headaches rather than take a course on the mundane topic of the role of vitamin D3 and nutrition as taught in the American Society for Nutrition, CME Program, it's no wonder most of them are clueless on the topic of vitamin D3.  Most will look at you like you're speaking in tongues when you ask for the lab test for 25(OH)D. 

Accordingly, one of the best charts from the attached study is shown below where over 3,600 people voluntarily took vitamin D3 at various doses and then paid $65 after six months to have their serum concentrations of 25(OH)D measured:

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There are two important things to take away from this chart.  The first is doses of vitamin D3 up to and including 40,000 IU/day do not result in 25(OH)D concentrations high enough to reach the lower threshold for vitamin D3 intoxication at 200 ng/mL.

The second take away is the wide variation in 25(OH)D responses at a given dose of vitamin D3.  As this chart also contains lab test results measured after six months and a year at a given dose, I called the folks at GrassrootsHealth and spoke with one of their MPH statisticians.

She sent the following information on the second lab tests for 25(OH)D, a year after starting a dose of 10,000 IU/day.  25(OH)D concentrations in ng/mL.

             mean      median   min   max    sd
test 2      71          69           20    134    23 

If you use the the 95% confidence band (mean ± 2 X sd, or ±46), these responses fall in a range of 25 to 117 ng/mL.  This is consistent with the data collected in the anti-inflammatory regimen survey.

What this also tells us is a dose of 10,000 IU/day vitamin D3 may not be sufficient for some CH'ers to elevate their serum 25(OH)D into the "green zone" 60 to 110 ng/mL where most CH'ers have gone pain free on this regimen.

If you look at the horizontal line I drew on this chart from 60 ng/mL to where it intersects the lower boundary of the 95% confidence band, you'll see it comes down at a vitamin D3 dose of 20,000 IU/day. 

This indicates 95% of CH'ers who take 20,000 IU/day will have serum concentrations of 25(OH)D in a range of 60 ng/mL up to 125 ng/mL and still not reach the lower threshold for vitamin D3 intoxication at 200 ng/mL

Finally, the investigators of this study concluded that: "Universal intake of up to 40,000 IU vitamin D3 per day is unlikely to result in vitamin D toxicity."

So here are the bottom line conclusions you need to be ready to explain to a doubting PCP or neurologist when you ask for the lab test for 25(OH)D...

1.  The odds are high (better than 75%) of a favorable response to the anti-inflammatory regimen with a significant reduction in the frequency and severity of your CH or going pain free like better than 66% of the CH'ers taking this regimen.

2.  There have been no reports of vitamin D3 toxicity in the 18 months since over 200 CH'ers started this regimen at 10,000 to 20,000 IU/day vitamin D3.

3.  This regimen works for both episodic and chronic CH'ers with an average response time of two weeks, min = 12 hours, max = 1 month.

4.  This regimen can be safely taken with existing standards of care prescription medications for cluster headache.

5.  And finally, at less than 30 cents a day USD, this is the most cost effective cluster headache preventative available to us...

If your PCP or neurologist persists and continues to push back...  ask him or her to please 'splain verapamil side effects and efficacy so you can compare and contrast them with the anti-inflammatory regimen...

Take care and thanks again for the wonderful comments.

V/R, Batch

Hey Joshua,

You had to come off prednisone anyway...  Are the am and pm hits manageable with oxygen or are they hitting at work or in transit?

The short answer is yes...  I'd give 25,000 IU/day a try for a few days to see what happens then drop back to 20,000 IU/day. 

20,000 IU/day should be sufficient to elevate your 25(OH)D into the green zone (60-110 ng/mL).  However, without results from a 25(OH)D lab test, you're shooting in the dark.

Are you still taking the weekly 50,000 IU loading dose and all the cofactors?   How much magnesium are you taking?

Take care and please keep us posted.

V/R, Batch

Hey Joshua,

Sounds like a plan...  (SLAP).  Oxygen will make a big difference...  Do try to get the lab test for 25(OH)D.

Take care,

V/R, Batch

Evan,

Good question.  The short answer is we just don't know how many other factors impede or perturb vitamin D3 metabolism to the extent it becomes ineffective as a CH preventative.

So far the anti-inflammatory regimen appears to work very well without too much interference from other medications, minerals or other vitamins taken at normal levels. 

That said, prednisone may limit vitamin D3 effectiveness to some extent, but there are no studies indicating just how much.

The first phase of vitamin D3 metabolism from vitamin D3, (cholecalciferol) to 25(OH)D3 (calcidiol), takes place in the liver.  If serum concentration of 25(OH)D rises with supplemental vitamin D3 in the doses we take, it's likely the liver is functioning properly.

The second phase of vitamin D3 metabolism from calcidiol to 1,25(OH)2D3, (calcitriol), takes place in the kidneys.  Unfortunately, there's no easy way to determine how effectively the kidneys are metabolizing calcidiol into calcitriol except in overall response like a reduction in the frequency and severity of CH or going pain free.

There are tests like a 24-hour urine collection that check for creatinine clearance that will give a good indication of kidney health.  The creatinine clearance test compares the level of creatinine in urine with the creatinine level in the blood.

Compounding things a little further, it's the 1,25(OH)2D3 that pushes calcium into the blood stream.  If there's insufficient calcium in the gut, 1,25(OH)2D3 pulls it from the bones...  another reason to take at least 500 mg/day calcium with this regimen.

All this is controlled by calcium homeostasis, one of the most powerful regulating mechanisms in the body that maintains serum calcium in a very narrow range.

If the serum calcium concentration is at the upper limit of the normal range, this signals the parathyroids to stop or slow the production of the parathyroid hormone (PTH).  When PTH drops, that signals the kidneys to stop making 1,25,(OH)2D3 and start making 24,25(OH)2D3, an inactive metabolite that's pumped over the side in urine.

If serum calcium is at the low level limit of the normal range, this signals the parathyroids to produce more PTH and that signals the kidneys to make more calcitriol to push more calcium into the blood.

The wild card is the autocrine mode of vitamin D3 metabolism where 25(OH)D3 is metabolized outside the kidneys in body's many different types of cells like our brain and nerve cells.  This is where vitamin A (retinol) comes into play as this mode of vitamin D3 metabolism can't take place unless serum 25(OH)D is high enough and vitamin A is present.

When this happens, 1,25(OH)2D3 enters the cell, triggers a genetic response, where the cell produces what it needs to fix itself.

At this point we don't know which mode of vitamin D3 metabolism is responsible for preventing CH...  I suspect it's a combination of serum concentrations of vitamin D3, 25(OH)D3, 1,25(OH)2D3 and the autocrine mode of vitamin D3 metabolism that takes place in the cells.

Determining the exact cause or causes of an effective response to prevent CH will take detailed RCTs costing several million dollars each...

In the mean time, if a CH'er is having problems controlling CH with the anti-inflammatory regimen and 25(OH)D levels are 60 to 110 ng/mL, the best course of action is to see an endocrinologist for a complete workup.  This will include lab tests for calcium, PTH and related hormones. 

I'm not a doctor so finding a physician trained to recognize proper liver, kidney, thyroid and parathyroid functions is essential.  That's generally an endocrinologist... not a neurologist.

Confusing at best, but I hope this helps...

Take care,

V/R, Batch