Mast cells, histamine & friends - our current understanding
About 4 years ago a client came to me with a myriad of symptoms which made no rhyme nor reason. They were doing everything right, their blood tests were at least normal, often optimal, and yet seemingly random symptoms kept getting added to an increasingly long list. Life had become unpredictable, challenging and disquietening. I always try my very best to support clients in solving their health mysteries and so I took a deep dive into the research, online conferences and textbooks and discovered the world of mast cells.
Mast cells are part of our immune system. When provoked they breakdown to release “potpourris of potent mediators”, the most famous of which is histamine. About 80% of the population are understood to have mast cells which respond in a measured and proportionate way to threats such as infection, environmental toxins, mould, excipients in medication or supplements (fillers, dyes, preservatives) and stress. The remaining 20% of the population are understood to have “aberrant” or rogue mast cell mediator expression which means that their mast cells’ response to the same threat is much more significant and debilitating. This rogue behaviour then impacts all cells, tissues, organs and systems causing absolute havoc from not being able to catch a deep breath, not being able to stand up, tinnitus, pain, headaches, edema (swelling), insomnia, anxiety, issues with memory - literally any symptom you can think of. An added layer of complexity is that symptoms can appear and disappear, only to return at a different time of the year, in a different location, in periods of emotional distress, at a different life stage or after a new infection or re-infection.
Of particular significance to my midlife clients is the impact of oestrogen’s spikes and progesterone’s decline during perimenopause. Mast cells have receptors on their surfaces which bind with sex hormones. Progesterone may stabilise mast cells and thereby dampen rogue responses. However, oestrogen can provoke mast cell activation and increase the frequency and intensity of unwelcome symptoms. Prior to perimenopause, the hormonal fluctuations of the menstrual cycle can contribute to the confusing fluctuation of symptoms.
Mast cell behaviour may also be a factor in disordered eating.
Emerging research suggests that mast cells behave in an aberrant way due to variants in assortments of mast cell regulatory genes (this profiling is not yet clinically available). As this research continues, we need to deploy all available means to restore calm to appallingly debilitating chaos. For my part, I have come to think about mast cells at the start of my work with clients. I always ask myself if it is possible that the connection between the many symptoms my client reports is rogue mast cell behaviour. I will look for clues in my client’s blood work and in their health history. I will ask questions around what makes things better, what makes things worse. “When did you last feel well?” is a really useful question as 9 times out of 10 my client will be able to say that “everything was fine until X happened”. Then we make a start together.
If this article resonates with you, you are very welcome to book a free strategy session and we can discuss working together to turn your chaos into calm.
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.
Afrin, L. et. al. (2021) “Diagnosis of mast cell activation syndrome: a global ‘consensus-2’”, Diagnosis, 8(2): 137-152.
Afrin, L “Never Bet Against Occam, Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity” (2016).
