Monday, January 14, 2013

Magnesium Part 3: The wrath of histamine

In the first 2 parts of this blog series we went over the importance of magnesium to the metabolic syndrome and lifestyle factors that contribute to magnesium wasting.  If you haven't read those two blogs they can be found here and here.  If you remember from part 1, one of the important functions of magnesium is to help create the histamine metabolizing enzyme Diamine Oxidase (DAO).  In magnesium deficient rats, DAO activity is decreased to 50% after 8 days of magnesium deficiency and it returns to baseline once magnesium is reintroduced back in to the diet(1).  In addition, histidine decarboxylase (HDC) activity is increased in some of the tissues of the magnesium deficient rats, particularly the spleen and peritoneum but not the skin(2).  HDC is an enzyme that makes histamine from histidine, an amino acid.  It is this conversion as well as certain foods that contain and/or liberate histamine that can be potentially problematic for someone with an existing magnesium deficiency.

Histamine intolerance is a condition where histamine accumulates in the body as a result of defective histamine metabolism(3).  This occurs as a result of reduced DAO activity, something that is made worse by a magnesium deficiency as referenced in the above study.  In addition, HDC activity increases which increases the conversion of histidine to histamine in the gut and circulation.  Histidine can be found in most high protein foods and is an essential amino acid.  As histamine accumulates in the body, numerous symptoms related to allergic reactions can occur including rash, GI symptoms, headache, hypotension, heart arrythmia, and a host of other symptoms.  Below is a flow chart of symptoms taken from reference #(3).

It becomes important for a person experiencing these symptoms to do a good job of managing histamine levels.  To do this, one should avoid foods that contain histamine, foods that liberate histamine from mast cells, and foods that block DAO activity.  Foods that contain histamine include alcohol, any food that has undergone microbial fermentation including cheeses, meats, pickled foods/sauerkraut, beans, pulses,  nuts, chocolate, wheat based products, shellfish, canned foods, and smoked meats(4).  Leftovers should be strictly avoided as bacteria act on the histidine in foods quickly, converting it in to histamine even in the refrigerator.  Foods that are known to liberate histamine from mast cells include citrus fruits, chocolate, nuts, papaya, beans/pulses, tomatoes, strawberries, pork, spinach,wheat germ, undercooked egg whites, and food additives(3,4).  Finally, foods that are known to block DAO activity include alcohol, green/black/mate teas, and energy drinks(4).

In addition to minimizing foods that can increase histamine levels in the body, it is a good idea to increase magnesium levels to help support DAO levels and reduce HDC levels.  Another nutrient that appears to be important in supporting DAO levels is Vitamin B6(5,6).  There is also evidence that vitamin B6 may help transport magnesium in to cells, possibly by forming a complex between the two(7).  As far as foods to support DAO activity, one interesting finding is that fat is the only macronutrient that increases DAO levels in the lymphatic system, protein appears to only increase DAO levels in the intestinal lumen while carbohydrate seems to have no effect on DAO levels(8).  Therefore, DAO only enters the circulation in the presence of fat.  If you are experiencing systemic symptoms of histamine intolerance, increasing fat intake may be something you want to look at.  Just make sure you take any oral magnesium supplement away from high fat meals as there is evidence that fat negatively impacts magnesium absorption(9).  However, if the reduction of magnesium absorption is due to utilizing more magnesium for DAO production, this may be a positive effect.

Most of you who have been "enjoying" the paleo autoimmune protocol are probably jumping for joy that you get to eliminate a bunch of other foods.  Ironically enough, some of the foods that are known to negatively impact histamine levels are also FODMAPS.  The point here is that if you are experiencing autoimmune symptoms you should be keeping a strict food journal to identify foods that are triggering responses so that you can compare those foods to foods that are known to cause negative reactions in the body to establish mechanism.  If these foods seem to match up to foods known to negatively impact histamine levels, try that route.  If it's FODMAPS that tend to be causing the problems, remove those foods.  If there doesn't seem to be any rhyme or reason to the reactions and you eat a lot of leftovers, something people who eat a paleo diet do often, try eating only fresh food.  If you want to find out if histamine is a problem, try antihistamines for a couple of days to find out if that ameliorates some of the symptoms.  I wouldn't use that as your solution since it's not a solution, it's a band-aid, but improvement from antihistamines infers that histamine may be a problem.

If you do identify histamine as being the culprit, it is probably a dose/response issue.  What I mean by that is you should find your tolerable dose of histamine and attempt to limit exposure to foods that increase histamine to below that dose.  The absolute fastest way to remedy the situation would be to eliminate those foods altogether, but that doesn't really leave much left if you are already on a paleo diet.  In any case, you may also want to increase magnesium and Vitamin B6 intake to both increase DAO production and reduce HDC production.  It seems fairly apparent that one of the underlying issues in the whole situation is a magnesium deficiency.  My best guess is that correcting the magnesium deficiency corrects the histamine intolerance.  In this situation I would recommend both oral and topical magnesium supplementation to make sure both the gut and your cells are getting their fair share of magnesium.


  1. These histamine posts are fascinating and potentially very helpful. I just wanted to ask about the B6 issue. In researching this I found that H Pylori (which I have), thrives on B6.

    So it seems that HP may contribute to histamine intolerance in the susceptible via this mechanism.

    The problem as I see it is that supplementing B6 may worsen the HP situation, so catch 22.

    1. I'm having good results killing HP with Chlorella and broccoli and cannot live without P5P.

  2. That is a catch-22, Roger. One thing with H. Pylori...It tends to be held in check pretty well with appropriate amounts of stomach acid. If you have low stomach acid you will have a hard time absorbing magnesium. IMO, one of the most important things a person with multiple GI issues needs to do is make sure they have adequate stomach acid. I would certainly correct that because there's no point in taking magnesium if you aren't going to absorb it.

  3. Hi Dave

    Thanks for the reply. I'm going to supplement a little HCL (I can't tolerate much of it) in an attempt to keep the HP down, along with some mastic and manuka, and then perhaps try supplementing the B6 after a couple of weeks. We'll see how that goes.



  4. You always have some very interesting points to make, Dave! I was so excited to hear this post mentioned on the Chris Kresser podcast this week by Steve Wright (of SCD Lifestyle). I love listening to that podcast! Thanks for your work!

  5. Thanks for posting this! Now I'll go look up FODMAPS ...

  6. My dd suffers from acid reflux and histamine intolerance. we have tried supplementing with natural calm and magnesium citrate which had absolutely no added ingredients to it. Both times my dd got horrible stomach cramps, one time she said her bones hurt, she was having a hard time lifting her arms, and it made her constipation worse almost, saw small amt of blood on T Paper. And, we only gave her very small amount, like 1/2 tsp a day. Any idea why this would happen. Scared to try it again.

  7. Hmmmm, are you certain it is from the Mag? Cramps I could see but the other symptoms aren't normally associated with Magnesium. With digestive issues and histamine intolerance I would assume there is some sort of food sensitivity, and red blood in the stool could be an indication of this. Are you aware of any food sensitivities or have you removed any foods from her diet?

  8. Nice Information! I personally really appreciate your article. This is a great website. I will make sure that I stop back again!.
    estrosmart reviews