Mast Cell Disorders and ME/CFS | note from Dr Charles Shepherd following last night’s BBC programme | 16 March 2017

We have been receiving a lot of inquiries about an item in a BBC TV programme last night that covered Mast Cell Disorders and a possible link to ME/CFS.

The eight-minute item appeared in episode 4 in the Incredible Medicine: Dr Weston’s Casebook series on BBC2. You can watch it using the following link (start watching at 41.10 minutes):

The programme is available to watch on the BBC iPlayer for the next 29 days.

Dr Charles Shepherd, medical adviser to the ME Association, comments:

Although mast cell disorders have a number of symptoms and triggering factors in common with ME/CFS, and I know of a small number of people with ME/CFS who have been diagnosed with a mast cell disorder, or are being investigated for this condition, there isn’t any robust research evidence to indicate that mast cell disorders are linked to ME/CFS, or that they are more common if you have ME/CFS.

There is, however, some interesting research evidence to indicate that mast cells could be implicated in the pathogenesis of ME/CFS and that this connection could therefore help to explain why tricyclic antidepressants such as amitriptyline can sometimes be of benefit in ME/CFS.


Mast cells and their mediators have been implicated in inflammatory diseases, including ME/CFS.

Mast cells are located perivascularly (= in blood vessels) in close proximity to neurons (= nerve cells) in the thalamus and hypothalamus, (= parts of the brain) especially the median eminence, where they are juxtaposed to corticotropin-releasing hormone (CRH)-positive nerve processes.

CRH activates mast cells to release vascular endothelial growth factor (VEGF), which could participate in neurogenic inflammation and contribute to the pathogenesis of ME/CFS. Such mediators may be released locally in the brain or may cross the blood-brain-barrier (BBB), which can be disrupted by stress, subsequent to mast cell activation.

Given the above, we hypothesized that TCAs may be helpful through inhibition of mast cell release of pro-inflammatory mediators.



Dr Charles Shepherd
Hon Medical Adviser, ME Association


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