Histamine Intolerance and Menstrual Migraine

Elimination of Histamines for Migraine?
The Headache woke up today.  Maybe because I did not medicate as much as I did yesterday when traveling home, maybe because of the plane rides yesterday, maybe because of the change in weather, maybe because I am almost stepped off prednisone - who knows??  In order to divert myself I  have been researching mast cell biology, histamine and how it works in the body, and H3 histamine antagonists.  Light reading, eh?

In my research I found the following article in the online archives of the American Journal of Clinical Nutrition: Histamine and Histamine Intolerance (Maintz and Novak, Vol. 85, No. 5, 1185-1196, May 2007) and it had some information on histamine and migraine as relates to women that I had not read before. 

Histamine intolerance is not the same as allergic reactions to food.  According to Victoria Groce at about.com (Histamine Intolerance, June 10,2008)

"Histamine intolerance refers to a reaction to foods that have high levels of naturally occurring histamine; in contrast, during a normal allergic reaction, the body itself produces high levels of histamine in response to a food it perceives as an invader. People with histamine intolerance often have low levels of either of two enzymes -- diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) -- that bind to and metabolize histamine. In these people, histamine can build up over time and cause symptoms throughout the body."

Other causes of histamine build up can be diseases such as mastocytosis or increased intake of substances that contain large amounts of histamines (AJCN, Maintz, et al, 2007).  The symptoms caused by histamine intolerance include migraine headache, gastrointestinal issues, allergic reactions such as hives, runny nose, and even heart arrythmias (Groce, 2008, about.com).

Some of the common triggers for headaches are foods and drinks that are high in histamine, including alchoholic beverages, foods containing yeast, and fermented foods like saurkraut.  Groce states in her article that citrus fruits, while not high in histamine, cause mast cells to release stored histamine so citrus should also be avoided if histamine intolerance is suspected.  She states that DAO capsules can be used to supplement deficient DAO levels to assist in histamine regulation.  Doing a quick internet search I found various formulations of DAO that could be purchased as nutritional supplements fairly inexpensively over the counter. 

Maintz and Novak state that "histamine-intolerant women often suffer from headache that is dependent on their menstrual cycle and from dysmenorrhea."   Besides histamines that are brought into the histamine intolerant body by diet, the female reproductive organs also produce histamine in their cellular structure.  These histamines work with the estrogen/progesterone cycle and enhance the "contractile" properties of the uterus (thus the correlation to dysmenorrhea and higher concentrations of histamines) and also increase concentrations of estrogen.  Perhaps this is why birth control helps some women with menstrual migraine and for others it makes it worse. I'm theorizing (see what happens when I can't sleep?) that high histamine and/or low DAO levels combined with augmented hormones could make histamine intolerant women at higher risk for repeated migraines, rather than helped by control of the menstrual cycle.

DAO levels increase up to 500 fold in pregnancy, which may be why some histamine intolerant women have migraine remission during pregnancy (Maintz, et. al, 2007). Histamines are linked to vasodilation in migraine, and increased number of mast cells (which store histamine) have been measured in other headache conditions like cluster headache (also known as histamine headache) or headaches caused by other health problems like multiple sclerosis.  Triggers such as alcohol can be tied to almost all headache conditions, showing that histamine mediation or intolerance could be part of the mechanism.  The AJCN article gives lists of medications that increase histamine or depress DAO levels (suprisingly verapamil was one), foods high in histamine, and foods that cause histamine release.  Maintz and  Novak give guidelines for how much histamine can be tolerated safely in higer histamine foods, but feel, based on studies, that sensitive individuals might have problems when consuming histamines at about 75% of the upper limit.

There are other articles out there linking H3 histamines (the histamines that directly affect your central nervous system) to sleep and mood disorders, cognitive dysfunction, weight gain, schizophrenia and the functioning of the hypothalmus. One article, "Histamine H3 Receptor Antagonists: Preclinical Promise for Treating Obesity and Cognitive Disorders " (Esbenshade, Fox and Cowart, April 2006 vol. 6 no. 2 77-88) in the online pharmacological journal Molecular Interventions, states that  H3 receptors act

"as..presynaptic autoreceptor[s] to modulate the release of histamine, a neurotransmitter that plays a role in vigilance, attention, impulsivity, and feeding/weight regulation... presynaptic H3 heteroreceptors modulate the release of other important neurotransmitters, such as acetylcholine, norepinephrine, dopamine, and serotonin"

Knowing the concomitant incidence of depression with migraine and associated headache disorders I was not surprised to see that histamine levels in histamine intolerant individuals could also affect such mood regulaors as dopamine and serotonin.  Some medications that are commonly prescribed to headache patients and chronic pain patients (amitriptyline, verapamil, narcotics) either directly affect histamine release or inhibit DAO synthesis.   Just wondering if DAO supplementation would help this also?  Wishing there was a wonder drug that could help every thing for every body!

Not sure (due to lack of sleep or lack of brain cells) if I'm just spouting junk science or if I'm comparing apples to oranges here [guess the oranges should be off the list - citrus = histamine release]. Maybe I am making sense, maybe not, but I am thinking maybe I will order some DAO and see what it does. My luck I will have an allergic reaction to the DAO instead of it helping with my overall histamine levels. The best consistent pain relief I have on a day to day basis are from very old histamine blockers, benedryl or vistaril and phenergan (promethazine). Compazine, which I have been given in ER's for headache prophylaxis, is another very old histamine blocker.

Thinking of trying to eliminate more histamine containing foods from my diet.  I cut out quite a few last year, but have added some back.  Maybe that's why the sudden "flare" of hiving/angioedema?  Fresh fruit is my downfall I think.  Sigh.  I guess I will go to the International Chronic Urticaria  Society web page and check out their low salycilate/low histamine diet lists to refresh my knowledge.  Thinking about the low salycilate diet because aspirin is on the list of histamine releasing/DAO inhibiting drugs and almost all foods contain salycilates (aspirin family).  I have walked this road before, but it doesn't hurt to go down it again to see if now it no longer is a dead end.

Probably no good amount of  sleep tonight for me, as I have amassed my full array of non-narcotic remedies tonight yet The Headache persists. I have a PCP appointment I forgot so hoping to get a few minutes sleep!  Hoping The Headache will behave before then!  I need to be at work.