Dr Joneja's Guides to Histamine Intolerance

Dr Janice Joneja, a world expert on histamine intolerance, has published two books on histamine intolerance:

A Beginner's Guide to Histamine Intolerance – read more about it here.

Buy the paperback from Amazon here; buy the e-book from Amazon here.

Histamine Intolerance: The Comprehensive Guide for Healthcare Professionals – read more about it here.

Buy the ebook from Amazon here.

You can buy all of Dr Joneja's books here in the UK or here in the US.

Histamine and tyramine sensitivity – how closely are they linked?


I am a 41 year-old female who was recently diagnosed with MCAD.  I have a much bigger concern than histamine though.  
Tyramine foods lead me to hypertensive crisis.  Even though I am very, very careful, I've still had 3 frightening episodes in the last 4 months.   
Can you please help me understand what mast cell activation and extreme tyramine sensitivity might have in common?  I need to understand the chemistry so that I have a chance in figuring out how to fix this.
I have 3 small children and I'm scared I might end up having a stroke.


Mast cell activation disease (MCAD) refers to several different conditions, all of which involve abnormally large numbers of mast cells which are subject to degranulation by diverse triggers.  Mast cells are white blood cells, mainly located in tissues throughout the body, which produce and store defensive chemicals, called inflammatory mediators, ready to be released in response to a threat to the body.  The mediators are stored within granules in the mast cell. The release of the mediators is termed degranulation as the granules are released from the cells.  One of the first and most powerful of the mediators is histamine. 

However, there are several additional mediators released at the same time, or rapidly thereafter.  Degranulation of mast cells is responsible for allergy, so the symptoms of MCAD are the same as in an allergic reaction.  Because there is an excessive number of mast cells, there will be an excessive quantity of inflammatory mediators released whenever the cells are activated by diverse triggering events. 

However, histamine is only partially responsible for the symptoms of allergy and MCAD, because the additional mediators all have their own unique role to play.  Reducing external sources of histamine, typically by following a histamine-restricted diet, or taking antihistamines to reduce the effects within the body, will only alleviate the symptoms mediated by histamine.  Symptoms caused by the additional mediators will not be affected, so measures to reduce histamine alone will be inadequate in relieving all of the adverse reactions in allergy and MCAD.  Nevertheless, by reducing histamine, many of the most troublesome symptoms can often be reduced to manageable levels.

Dietary tyramine does not usually cause any ill effects, except in people who are (a) taking monoamine oxidase inhibitors (MAOI) drugs, which are principally prescribed for depression, or (b) tyramine intolerant, probably due to a deficiency of the enzyme, monoamine oxidase, which breaks down excess tyramine.

Histamine and Tyramine – what is the connection?

Both histamine and tyramine are biogenic amines.  Amines are chemicals derived from ammonia and biogenic means that they are biologically active.  Biogenic amines play extremely important roles in the body.  Histamine and tyramine are also described as vasoactive amines, which indicates that they can trigger effects in blood vessels, causing vasodilatation (widening) or vasoconstriction (narrowing) of blood cells throughout the body, and thereby affecting blood pressure. However, although there are similarities among such biologically active chemicals, there are many very important differences in their mode of action, and the factors and processes which control their production and their activities.

Function in the Body

Histamine (chemical name: 2-4-imidazolyl ethylamine) is involved in several essential processes including:

  • Acting as a neurotransmitter in the brain and central nervous system, where it conveys signals between nerve cells.
  • Triggering the release of gastric acid in the stomach, which is an important stage in the digestion of protein
  • Protection against threats to the body such as infection and trauma, where it is an essential component of inflammation, the process involved in immunological defence.  In this category we can include allergy.  Allergy can be considered as a misguided attempt by the immune system to protect the body from a “foreign invader” – in this case material that is in itself harmless, but which, being foreign to the body, is perceived as an external threat that needs to be destroyed.  Histamine is an important mediator in this defensive action.

Tyramine (chemical name: 4-hydroxyphenethylamine) is involved in the synthesis (production) of catecholamines such as dopamine, epinephrine and norepinephrine which are neurotransmitters in the sympathetic nervous system.  The sympathetic nervous system is responsible for the fight or flight response.  It is part of the autonomic nervous system, which regulates the body’s unconscious actions.


Both histamine and tyrosine are derived from amino acids.  Amino acids are components of proteins.

Histamine is derived from the amino acid histidine by the action of the enzyme histidine decarboxylase. 
Tyramine in derived from the amino acid tyrosine by the action of tyrosine decarboxylase.

Histidine and tyrosine are present in proteins from most biological materials including animals, plants and other living organisms.


All biological processes are controlled by a complex series of enzymatic reactions which ensure that exactly the right quantity of every active chemical is produced, maintained, or eliminated, to deliver the precise amount required for its optimal functioning in the healthy body.  When there is excess of any biologically active chemical, specific enzymes break down the excess and remove it from the body.

Histamine is broken down by two different enzymes: histamine N-methyltransferase (HNMT) and diamine oxidase (DAO).  DAO is mainly responsible for ensuring that excess histamine in the diet is degraded within the digestive tract before it can enter the body.  It also acts as a “scavenger” within the body to reduce the amount of unnecessary histamine circulating in blood and tissues.

Tyramine is degraded by monoamine oxidases (MOA) of which there are two subtypes, MOA-A and MOA-B.  Usually tyramine in the diet is broken down (metabolized) by MAO-A in the intestinal wall and then in the liver.  This destroys excess tyramine before it can be absorbed and enter circulation, where it is converted into norepinephrine.

When the enzyme systems are not able to break down the excess, which may be because of a genetic defect in enzyme production, or reduction of their activities by external agents such as medications, or other factors, the increase in level can lead to adverse effects.

Excess histamine leads to symptoms resembling allergy, because histamine is an important mediator in allergy and many of the symptoms of allergy are a result of the activity of histamine.

If too much tyramine is ingested, excess norepinephrine can lead to a rapid increase in blood pressure.  If the increase is large and sudden, a hypertensive crisis can occur, which can cause permanent damage to bodily organs, stroke, aneurysm, and very rarely, death.

Although excess histamine and tyramine are often a result of over-abundance of the amines within the body (endogenous), both can be augmented by sources outside the body (exogenous), which may be derived from foods and beverages in the diet.  When the body’s enzyme systems are already deficient, it is important that all means of reducing unnecessary sources of the amines be employed in order to reduce the excess wherever possible.  Following a histamine restricted diet will reduce exogenous (from outside the body) sources of histamine, and a tyramine-reduced diet will similarly reduce dietary sources of tyramine.  From your short description it is clear that you will need to achieve both objectives. 

Biogenic Amines in Food

The good news is that because both biogenic amines are produced by enzymatic breakdown of amino acids, mainly as a result of microbial fermentation, the foods you need to avoid are very similar.  In both cases the majority of the restrictions involve avoidance of fermented food products.  However, there are individual additional sources of both which need to be considered.

A few important points:

  • Both histamine and tyramine sensitivity are conditions in which the adverse effects are only experienced when the amine is consumed in excess.  It is like a bucket filling up with water.  When the bucket overflows, symptoms occur.  No single food is responsible for the excess, it is the accumulated amount that causes the bucket to overflow.  For this reason the “eliminate and challenge” protocol used in identifying allergenic foods, in which a single food is consumed and symptoms monitored for an immediate reaction, does not work.
  • Avoid all the foods on the “Foods to Avoid lists”.  Just selecting a few and consuming others on the restricted list will not achieve the results you need.  However, over time you will be able to be a little more liberal and may include a few of the restricted foods in small quantities as long as you are prepared to suffer through the adverse effects if or when they might occur.
  • Whenever the diet is restricted, it is very important that the eliminated foods be replaced by others with equivalent nutritional value.  It is often easy to avoid foods, but requires more knowledge and work to substitute others.  However, over time the new eating plan becomes the “norm”.
  • Because there is a wide range of alternative foods which will provide all the nutrients you require for a well-balanced diet, you should not lose any weight on this diet.

October 2017

You can buy DAO supplements here in the UK or here in the US. You can buy all of Dr Joneja's books here in the UK or here in the US.

If you found this article interesting, you will find many more articles on anaphylaxis here, and reports of research into anaphylaxis here.
You can also find articles on peanut and tree-nut allergy here, cow's milk allergies here, egg allergy here, histamine intolerance hereand articles on a wide range of other allergic and intolerance reactions to a wide range of other foods here.


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