Mast cells & stress

Psychological stress is the most common trigger of mast cell activation.

Conditions that involve mast cells and worsen with stress include asthma, eczema, deep swelling with no apparant cause (angioedema), irritable bowel syndrome, shortness of breath, polyuria (passing an excessive volume of urine), pain and palpitations.

Corticotropin-releasing hormone (CRH) is secreted by the paraventricular nucleus of the hypothalamus in response to stress. CRH stimulates mast cells which then release “potpourris of potent mediators” including histamine, heparin, tryptase and tumour necrosis factor (TNF). These mediators then go forth and can cause havoc in any bodily system.

This phenomenon is very real and, in my opinion, mast cell activation should be considered in every client who presents with a myriad of unexplained symptoms. In the recently published update on the global consensus-2 diagnostic criteria for mast cell activation syndrome, the authors wrote “Lack of diagnosis facilitates harmful dismissal and gaslighting”. This is a very important statement and reflects the experience of clients who come to see me after many years of going around the houses and not being taken seriously when they describe waxing and waning symptoms which make life extraordinarily difficult.

There is an important intersection here with genetics. As you know, I run Lifecode Gx reports for my clients. The Nervous System report shows us:

• how sensitive you are to stress hormones (ADRB1 and ADRB2),

• how quickly stress hormones leave your system (COMT, MAOA),

• how easily you find your “off” switch (ALPL, GAD1, GAD2, GABRA2).

We can easily imagine a perfect storm of a genetic predisposition to feel adrenaline more acutely, clear adrenaline more slowly and struggle to access a calmer state of mind or restorative sleep. It is also worth noting that COMT has more than one job. As well as deactivating adrenaline, COMT is involved in deactivating oestrogen. Is it any wonder that when oestrogen spikes during perimenopause that COMT can become overburdened and both adrenaline and oestrogen remain active for longer?Stress resilience goes out the window and seemingly random (but very real) symptoms proliferate.

The first step towards feeling better is to understand what is happening. The next is to know how to move forward towards better health efficiently and effectively. I can help you to do both.

Sources:

Afrin, L. et. al. (2026) “Progress in mast cell activation syndrome: the global consensus-2 diagnostic criteria at six years”, Diagnosis, doi: 10.1515/dx-2026-0016.

Theoharides, T.C. (2020) “The impact of psychological stress on mast cells”, Annals of Allergy, Asthma and Immunology, 125, pp. 388-392.