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histamine intolerance

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 70

84. Is the problem for mast cell patients that they can’t break down histamine properly?

  • Not exactly. Mast cells that are overly activated will make and release more histamine but the activation comes before the histamine, not the other way around. There’s no evidence that indicates that in mast cell disease there is something wrong with the way the body breaks down histamine.
  • Histamine intolerance is not a well accepted diagnosis in the general medical establishment. Histamine intolerance is when patients react to foods and activities that contain or cause the production of histamine in the body. The general thinking on why this happens is that the body doesn’t make enough enzyme to break down the histamine at a normal rate. I have not seen convincing data that histamine intolerance is in fact due to the inability of the body to break down histamine fast enough. Regardless, I know a lot of people who feel better when they take DAO supplements or each DAO rich foods. DAO (diamine oxidase) is one of the enzymes your body uses to break down histamine.
  • Please keep in mind that histamine intolerance is a distinct phenomenon from mast cell disease. In mast cell disease, the problem is that the mast cells are too activated so they release excessive histamine into the body. In histamine intolerance, the mast cells are not overly activated, and the body can’t break down histamine fast enough. This means that even if a person with histamine intolerance makes a normal amount of histamine, their body can’t break it down at a normal rate.
  • It is theoretically possible to have both mast cell disease and histamine intolerance. There’s not a reliable way to test for histamine intolerance beyond symptoms, and there aren’t really robust diagnostic criteria. Some people with suspected mast cell disease test negative despite having mast cell symptoms and responding to treatment. This means that there’s no way to definitively know right now if a trigger causes a reaction because of histamine intolerance or a mast cell reaction beyond having a prior, firm diagnosis of mast cell disease.
  • There is something I find intriguing that may be linked to histamine intolerance. I mentioned diamine oxidase (DAO) above. It is one of enzymes your body uses to break down histamine. The other enzyme your body uses for this is called histamine n-methyltransferase. When this enzyme breaks down histamine, it produces n-methylhistamine.
  • N-methylhistamine is the most common breakdown product of histamine. It is also the molecule that we test for as part of the diagnostic workup for mast cell disease. The reason we test for n-methylhistamine instead of histamine is because histamine is broken down so quickly that n-methylhistamine stays in your body much longer than histamine. We use it as a surrogate marker for histamine since it’s easier to measure.
  • I know a lot of mast cell patients who have flagrant histamine symptoms that repeatedly have normal tests for n-methylhistamine both in blood tests and in 24-hour urine tests. There are a few reasons why this could be but I have started to wonder if the reason those tests come back normal is because your body doesn’t make enough of the enzyme that breaks down histamine in this way. As I said above, there is no real evidence to support this, just something I think about sometimes.


For additional reading, please visit the following posts:

The Provider Primer Series: Mediator testing

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 42

51. What is the difference between mast cell activation syndrome and histamine intolerance?

Histamine intolerance is not widely accepted by the mainstream medical establishment. I haven’t been able to find much about it in the way of peer reviewed literature. That said, it doesn’t seem ridiculous to me. It feels plausible, I just haven’t seen convincing evidence of that yet.

Histamine intolerance is when a patient has symptoms from ingesting something that has a lot of histamine in it, that causes the body to release histamine, or that interferes with the body’s ability to break down histamine. In histamine intolerance, the problem is what is being put into your body rather your body itself. The problem is external, not internal.

Mast cell activation syndrome is when a patient’s mast cells are fundamentally dysfunctional. The problem is internal, not external. There is no evidence at this point that patients with MCAS can’t break down histamine normally with enough time, there’s just so much of it that it takes longer.

Many patients with MCAS (and other mast cell diseases) often have symptoms when they ingest something that has a lot of histamine in it or that causes the body to release histamine. There are two theoretical ways in which ingestion of histamine can cause symptoms: either the histamine released/ingested makes it way to other parts of the body and causes symptoms there directly; or, the histamine released/ingested makes mast cells release more histamine.

Regardless of exactly what is happening, patients with MCAS and histamine intolerance can have identical symptoms to ingesting a trigger. Importantly, MCAS patients may have histamine symptoms from lots of other things, not just ingesting something.

Histamine intolerance is much more commonly discussed in holistic and alternative medicine groups, which is definitely not where my expertise is. If you are aware of some recent data on histamine intolerance, or if I have made a mistake in this post, please let me know so that I can correct it.