One of my most popular posts to date, based on the number of comments, emails, and links back to it, has been my post on Histamine Intolerance.
Histamine is a chemical which occurs naturally in certain foods. This is also one of the chemicals that is released in the body as part of an allergic reaction, causing the typical ‘itching, sneezing, wheezing, swelling’ allergy symptoms. We all have an enzyme (Diamine oxidase [DAO]) which breaks down any histamine that we absorb from a histamine-containing food, so when we eat a food which contains histamine it does not affect us. However some people have a low level of this enzyme, and when they eat too many histamine-rich foods, they may suffer ‘allergy-like’ symptoms such as headaches, rashes, itching, diarrhoea and vomiting or abdominal pain. This is called histamine intolerance. Some studies have also suggested links between histamine intolerance and urticaria, asthma, eczema and anxiety and panic attacks.
This diagram from that original post shows many of the systemic effects of high histamine levels, including;
- Circadian rhythm vigilance
- Abdominal pain and cramps
- Airway constriction
- Nasal obstruction and sneezing
- Low blood pressure
- Cardiac arrhythmia
Now all of these symptoms might seem familiar as they are the same or similar to many of the health complaints we see amongst those seeking help from a paleo-type diet. You wouldn’t have to look too hard on the common sites that post paleo success stories to find many of these issues having been resolved amongst those who took the paleo leap. So does that mean switching to a paleo-type diet fix histamine intolerance? Not quite. And that was part of the prompting for the original post. Following a paleo diet, when you look at the list of foods which may trigger a large histamine release, may actually make things worse.
Reading of all the successes of those who adopt paleo only to be faced with your own lack of progress, can be very disheartening and may see people move away from what was otherwise a good strategy on the basis that “paleo didn’t work for them”. Or, as I’ve mentioned previously, it can lead people to chase shadows, looking for what food *must* be contaminated with gluten, or think that toxins must be being released from their fat stores, to cause such a persistence in symptoms.
Since that original post, I have had many people share their stories and n=1 experiments with me. This is one of the most recent ones I have received…
I have been formally diagnosed with histamine intolerance and I am being successfully treated for it now.
In my case there started with a histamine food link and was initially successfully managed through avoidance of histamine rich (i.e. fermented foods) but accelerated 4 years ago so now I need to stick a preservative free, colour free, low allergy diet which reduces my symptoms dramatically.
4 years ago I developed neurological issues including delirium and anxiety on prescription medication now known to release histamines and within 48 hours of removal was fine…
…My situation is managed through ensuring that drugs do not have a history of allergic reaction and if I react I use phenergan and they are removed and others found. I do not find other anti-histamines help.
I also think there is a hormonal component as my symptoms worsened when I went into menopause and I could not tolerate standard HRT. Treatment with compounded histamine free HRT has really helped although the histamine intolerance seems to make absorption of progesterone difficult.
There is a lot which can be done to relieve the symptoms and the challenge has been to find medical professionals who know about it. I am lucky to have a professor of immunology who has diagnosed me and vouched for the diagnosis with other professionals.
It has taken 4 years and it has been rough (especially the neurological component!) but I have seen dramatic changes to my health using traditional medicine.
That is my experience anyway…..and I hope it helps someone.
In my initial reading around this subject, I learned that the enzyme, Diamine Oxidase, is responsible for degrading histamine in the gut. This enzyme is produced by the enterocytes of the gut mucosa. But like all enzymes produced by, and transporters located in the gut mucosa, if there is any gut damage, then one might reasonably expect the capacity of enzymes, transporters, etc., to be diminished. This is my belief with regard to those who have issues with FODMAP’s, fructose malabsorption, and the like. I don’t see these as being the terminal issues, but rather a symptom of a bigger problem such as gut damage, inflammation, etc. It’s my suspicion that histamine intolerance falls into the same category.
Supporting my notions above, I came across a paper looking at plasma histamine levels and chronic urticaria. Whilst this paper focuses specifically on high plasma histamine levels and urticaria, when it comes to how those high plasma levels occurred, it is unlikely to make much of a difference with regard to any of the other effects that histamine might have. This paper contains some statements of interest;
It has been suggested that pseudoallergic manifestations are not only the result of mast cell activation, but also a consequence of a defect in histamine metabolism. Histamine is metabolized by two pathways, oxidation and methylation. N-methyl transferase methylases histamine in the skin and is active in the liver. Diamine oxidase (DAO) normally degrades histamine, methyl histamine and diamine and it is confined to the small bowel mucosa. The loss of the protective role of mucosal DAO might allow an increased absorption of biological amines.
The researchers focus on the usefulness of a specific test for DAO activity and small intestine mucosa integrity – the plasma post-heparin diamine oxidase (PHD) test. In this test, an intravenous dose of heparin should trigger the release of DAO from the small intestine mucosa into circulation. As DAO is synthesised by mature and undamaged enterocytes (gut cells), if there is any gut damage, as might be seen with coeliac disease, then one might see a reduction in DAO release and therefore reduced activity. This reduced capacity to degrade histamine may lead to large increases in plasma histamine levels (due to increased absorption of histamine from histamine-containing foods, and/or impaired metabolism of the body’s own histamine due to the effect of histamine-liberating foods), and all the downstream effects of this, as listed above.
Within this paper’s study, a group of 10 patients with urticaria were placed on a low antigenic, histamine-free diet for three weeks, followed by a 10-week challenge period reintroducing foods. If any food reintroduced elicited symptoms, that food was re-eliminated. When compared to a control group of patients without urticaria, plasma histamine levels were higher in those with urticaria, while post-heparin DAO activity was reduced or close to the lower limit of what is considered the normal range.
Interestingly, neither DAO activity nor intestinal permeability showed any significant improvement with the low histamine diet. However, one must keep in mind that the diet used in this test is not one specifically designed to improve gut health. That is, it isn’t one that necessarily excluded grains, vegetable oils, sugars, and soy from the diet.
The main findings from this study;
In the present study we found higher histamine plasma levels in CIU patients on free diet compared to controls. After an oligoantigenic and histamine-free diet, plasma histamine levels fell to the same levels of the control group. This finding suggests that histamine plasma levels are dependent on diet in patients with chronic idiopathic urticaria…
In our study, the disappearance or reduction of symptoms after the diet appeared to be correlated with lower histamine plasma levels.
A deficient degradation of histamine by the enzyme diamine oxidase has been hypothesized as a possible cause of an increased absorption of histamine. In our study, post-heparin DAO levels in CIU patients were slightly reduced compared to controls or in the lower part of the normal range. This observation may suggest a subclinical impairment of small bowel enterocyte function that can allow a higher absorption of histamine and higher histamine plasma levels.
However, no significant modification of post-heparin DAO was found after an effective oligoantigenic and histamine-free diet, while a significant clinical improvement was recorded. A possible explanation to this discrepancy is that the diet improved symptoms only by reducing histamine load to the small bowel but did not alter the functional status of intestinal mucosa. However, the reason for relatively low DAO levels remains unexplained and will need further studies to be clarified.
[We] can not establish whether clinical improvement was due to low levels of histamine or low levels of offending antigens in the diet. Furthermore, whether the low histamine plasma levels are caused by the reduced exogenous load or by a fall in mast cell histamine production remains unclear.
In conclusion, this study suggests that pseudo-allergic manifestations of CIU may be related to a subclinical functional impairment of the small bowel. This condition may result in a loss of the protective role of the intestinal mucosa against offending molecules in foods.
So, in this group at least, a condition related to high plasma histamine levels (urticaria) was significantly improved by following a low histamine diet. And it would seem that most, if not all, of this improvement came from a fall in histamine intake and mast cell histamine liberation rather than any increase in enzyme capacity to degrade histamine. Whilst in this group, intestinal permeability was normal, DAO capacity was low compared to controls, possibly signalling that intestinal function was impaired at a sub-clinical level.
A low histamine, non-paleo diet lead to improvements seemingly without any improvement in gut function. Perhaps a paleo diet, aimed at improving gut function, in conjunction with a low histamine diet, might see additional improvements, and in particular, see improvements in those who adopt a paleo, but otherwise high histamine loading, diet and who do not necessarily get the improvements in their health issues that they had hoped for following a paleo diet alone. And we simply cannot discount that there might be a subfraction of individuals with either genetics or other factors (extensive &/or refractory gut damage), that leaves DAO enzyme capacity permanently low. In these people, they may require a life-long low histamine diet in order to minimise issues related to high histamine levels.