Histamine: Friend or Foe?

Histamine is a neuro-immuno-endocrine system mediator¹ that plays a role in the control of smooth muscle contractions in the respiratory and digestive tracts  and is produced by the body.² Histamine can also be introduced into the body in foods that have undergone microbial decarboxylation of histidine by fermenting bacteria, a process that can also occur in the gut by the microbiome.²

Blood histamine levels fluctuate based on the circadian rhythm.² Physical and psychological stress hormones can increase the production and secretion of histamine from mast cells, which when coupled with a change to the permeability of the intestinal epithelium, leads to increased histamine absorption.²

Histamine management within the body

Histamine-N-methyltransferase (HNMT)

Methylation catalysed by the enzyme histamine-N-methyltransferase (HNMT) can degrade intracellular histamine.²

Diamine oxidase - DAO

The body can inactivate histamine by a process called oxidative deamination, which is catalysed by diamine oxidase (DAO) requiring vitamins B6 and C and the minerals zinc and copper to enter circulation and degrade extracellular histamine.²

Intestinal secretion of DAO from the cells lining the intestines is constant to manage exogenous histamine levels, however, physical activity and stress can increase the production of histamine from L-carnosine.² Damage to the small intestinal mucosa and enterocytes leading to a reduction in DAO activity can increase the amount of histamine reabsorbed into the bloodstream, leading to increased circulating histamine.²

Mast cell degranulation can also be inhibited by the flavonoid and antioxidant luteolin, which prevents the release of histamine.²

Histamine intolerance

Histamine Intoxication

Histamine can provide a generally self-limiting toxic effect when high histidine fish are processed poorly resulting in bacterial decarboxylation producing histamine.²

Signs of histamine intoxication include: 

• Sweating 
• Nausea 
• Vomiting 
• Diarrhoea 
• Burning mouth
• Tongue and face swelling 
• Headaches
• Palpitations 
• Hypotension 
• Respiratory distress²

Histamine Intolerance

Histamine intolerance (HIT) can also occur when a person is unable to eliminate adequate levels of histamine due to decreased DAO activity.¹ HIT is also referred to as DAO deficiency and may be genetic,¹ leading to excess histamine presenting as: 

• Itching
• Redness
• Swelling
• Cramps
• Bloating
• Diarrhoea
• Reflux
• Swelling of the lips tongue and Eustacian tube
• Sneezing
• Nasal swelling
• Phlegm
• Cough
• Asthmatic symptoms
• Palpitations
• Blood pressure changes
• Headache
• Dizziness
• Heart rhythm disorders ²

Histamine Intolerance and the Menstrual Cycle

Women may experience premenstrual migraines association with HIT due to the relationship between histamine and female sex hormones, with histamine directly influencing ostradiol synthesis and less so, progesterone.²

Interestingly, HIT can present with increased symptoms during the different phases of the menstrual cycle, with a reduction in symptoms during the luteal phase when there is adequate DAO present.²

Premenopausal women display higher DAO levels in the luteal phase, with HIT associated with painful menstruation.¹

Dietary sources of Histamine

Foods can be rich in histamine including cheese, wine, tomatoes, spinach, fish, chicken, fermented foods, alcohol, additives, stabilisers, flavourings and cocoa.²

Diagnosing Histamine Intolerance

Diagnosis of HIT is done through a process of elimination of alternative causes for the symptoms, and through dietary elimination and observation for a reduction in symptoms¹ and should be done with the support of a nutritionist to ensure that a balanced diet is maintained.

As we enter Spring, notorious for the increase in hay fever presentations, check in with your body and reach out if you think high histamine could be something that you need to investigate.

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References

1. Hrubisko, M.; Danis, R.; Huorka, M.; Wawruch, M. (2021). Histamine Intolerance—The More We Know the Less We Know. A Review. Nutrients 2021, 13, 2228. https://doi.org/10.3390/nu13072228  
2. Kovacova-Hanuskova, E., Buday, T., Gavliakova, S., & Plevkova, J. (2015). Histamine, histamine intoxication and intolerance. Allergologia et Immunopathologia, 43(5), 498–506. https://doi.org/10.1016/j.aller.2015.05.001 

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