Hi folks!

So a question on vasoconstriction!

As I understand it that's why oxygen and imitrex work well to help reduce clusters. I've read Batch's regimen and have been taking D3 and magnesium, but was surprised to find that magnesium is a vasodilator. I'm sure there's a good reason for that, but would love to hear about the underlying mechanisms.

I regularly take caffeine to help with vasoconstriction, and have been curious about other things I can do to help support that. Right now I do lots of O2, 480mg of verapamil, and finally imitrex should all else fail.

But as always it seems there are other factors that might help keep the pain away, since I'm still getting hit two or three times a night. Salt is in theory a vasoconstrictor too, for example. And if potassium plays a strong role in vasodilation, wouldn't it be best to avoid it?

Any thoughts or explanations would be much appreciated. I know there are thousands of variables that go into clusters, but am trying to figure out how to make the best choices possible. It drives me crazy trying to figure out why some days are better than others (though one can never really isolate individual variables very well).

Thanks!

Hey Lexpecto,

You raise some interesting points... and glad to hear you've started the anti-inflammatory regimen.  I'm confident you'll join the better than 80% of CHers who start this regimen and experience a favorable response.

Calcium and magnesium play a role in in pain mechanisms and muscle functions.  Magnesium also plays a major role in the enzymatic processes that hydroxylate vitmain D3 to it's genetically active metabolite, 1,25(OH)2D3, calcitriol.

So lets look at vasodilation, but first we need to address the question is it a causal factor in CH or a symptom.  A lot of brilliant neurologist far smarter on this topic than me have yet to agree on the answer to this question.  Moreover as you pointed out, the two major standards of care methods of intervention in CH involve mechanisms of action resulting in vasoconstriction.

Being just your average 72 year old retired Navy fighter pilot, I come at this question from out of right field so here's my take...  Calcium supports moscle fiber contraction and magnesium supports muscle fiber relaxation.  It's a Yin Yang thing where both need to be present in balanced proportions.  The real question is what caused the vasodilation.

I've been a full time student of vitamin D3 and its role in preventing CH for the last six years... As such, I've dug up enough information from a lot of RCTs and scientific papers that say, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), histamine, and physiologically active lipid compounds the prosteglandins (PG) all play a role in inflammation and it's logical big brother, vasodilation in and around the trigeminal ganglia.  CGRP is also responsible for the pain we know as cluster headache. Moreover, several studies have found CGRP serum concentrations are elevated in the pain phase of migraine and cluster headache. 

One of the leading candidate mechanisms of action by which vitamin D3 prevents CH deals with its capacity to down-regulate the production of CGRP.

Taking this line of thinking one step further, why would Big Pharma bet tens of millions of dollars on each of two RCTs involving the use of monoclonal antibodies with an appetite for CGRP as a migraine and CH preventative?  Follow the money...

If you follow me so far... and getting back to your original point... magnesium plays a role in vasodilation but it doesn't cause it. 

Regarding oxygen as a vasoconstrictor... that's true.  What is also true is oxygen flow rates that support hyperventilation, or an alternative method of oxygen therapy that involves hyperventilating for 30 seconds then inhaling a lungful of oxygen, both induce respiratory alkalosis.  This is characterized by a lower arterial concentration of CO2 that elevates the pH of arterial blood flow making it more alkaline.  At least three RCTs have confirmed the combination of low arterial CO2 and an elevated arterial pH are more potent vasoconstrictors than oxygen...

Hope I haven't confused you...

Take care,

V/R, Batch

Hey Batch! I'm glad you weighed in, I was hoping you would!

I follow for sure! What's so difficult in dealing with clusters is trying to identify causality as opposed to correlation. Every cycle over the years I try something new to try and find a "helper" mechanism to aid D3/O2/Verapamil/Imitrex.

In the past I was all about an anti-inflammation diet and eating and drinking the most alkaline friendly foods possible and had little success. My thought being, if O2 caused rapid alkatosis, perhaps I could get some relief by reducing inflammation however I could.

This year I've been pushing caffeine hard (unfortunately can't do energy drinks because of the verapamil). But it's maddening trying to figure out why some days are better or worse than others. We naturally want to try and find the variable responsible!

My thought on vasodilation stems from a neuro who said plainly that, "you have to treat these like a vascular headache." That got me thinking- reading through the medical literature it's my best guess that vasodilation is perhaps a resultant cause of the pain, but not the originating event or triggering mechanism. Therefore, if your blood vessels were constricted sufficiently, that triggering mechanism wouldn't be able to start the secondary process (vasodilation) that caused the pain.

To put it another way- there are perhaps two (of probably many more) ways to treat the mechanisms of CH pain. To reduce, change, or eliminate the triggering or maladapted mechanisms that can eventually lead to vasodilation, or to reduce the vasodilation itself and let the triggers continue to fire blindly.

A lot of the literature kind of writes off vasodilation as a "cause" since people were able to get relief using mechanisms that were unrelated (ie taking care of the primary triggers / brain chemistry). But it seems to me that they are two separate approaches that both might work in their own ways.

I'd love to hear your thoughts on this, Batch! Also, some quick questions for you:

1. After extensive googling of vasoconstrictors I've been surprised by some interesting findings. Nearly every drug listed on the wikipedia page has been linked with successful treatment of CH. Adderall, for example, seems to be a wonder drug of sorts for some folks, but it seems very uncommon for CH treatment. Ritalin is more common as another wonder drug, but is often "unreliable". I wonder if this is because it has a short half-life, (ie "the headaches came back several hours later, so it doesn't work") and people were unaware of the vasoconstriction mechanism potentially being the primary mechanism of relief.

I then looked and found that two of the largest triggers, alcohol and smoking, are both vasodilators. Psilocybin is suprisingly a vasoconstrictor. So this is all correlation, mind you, but the significance of the correlation is pretty staggering. Is a treatment plan potentially as simple as avoiding dilators and using constrictors when needed?

2. Any thoughts on potassium? Potassium rich foods seem to cause problems for me. I know this is one of the main channels involved in vasodilation.

3. How about sodium? Theoretically it would vasoconstrict blood vessels, and I'm not finding much from folks about it being a trigger. I feel like this is one of the holdovers from migraine / tension treatments that people often try to eliminate. But perhaps we should do the opposite? Also, maybe this is coincidentally why baking soda helps some folks?

4. Any dietary or lifestyle changes that you're aware of that would promote vasoconstriction?

Hey Lexpecto,

Interesting topic...  Here's my take...  What I think we want is a healthy vasculature capable of constriction and dilation in concert with the body's many homeostatic systems...

As an example... ever wonder why and how the normal body temperature is 98.6º?  The answers are that's the ideal temperature for most biochemical reactions and the processes that keep it there involve homeostasis...  In this case, a vasculature mechanism of action that controls the body's heat loss and heat gain through vasodilation and vasoconstriction as needed.

Another example of homeostasis involves arterial pH, the acid alkaline balancing mechanisms that maintain our arterial pH between 7.35 and 7.45...  Why?  This is the pH range that's optimum for the many biochemical reactions that keep us living and healthy. 

How does our body do this... by controlling the bloodstream CO2 content through respiration rate and kidney filtration.  In this case vasoconstriction and vasodilation play a role in how much blood passes from all over the body to lungs where the CO2 produced in the body through normal metabolism is pumped out with each exhaled breath.

Getting back to cluster headache and vasoactivity...  I'm just a 72 year old retired Navy fighter pilot and not a doctor or molecular biologist...  so I tend to look for an explanation that's easy enough to get my head around... 

In this case, the vasoactivity associated with cluster headache pain is more a symptom than causal factor. There are a sufficient number of studies that have found that calcitonin gene-related peptide (CGRP) is always present in the bloodstream during the pain phase of migraine and cluster headache...  and missing during pain free periods.  Hmmm... I can get my head around that...

There are also a number of studies concluding the genetic expression made possible by vitamin D3, down-regulates/suppresses the production of CGRP in the trigeminal ganglia...  Hmmm...  I can get my head around that  too...

Bottom line... I don't worry about vasodilation or vasoconstriction....

Hope this helps.

Take care,

V/R, Batch