Hi All,
I was
asked by Nas to share a few thoughts on a mast cell activation syndrome (MCAS) hypothesis of POIS. I'm not an expert on mast cells, but I will give my opinion. I don't want to tell anyone else how to think, but my approach to evaluating hypotheses is to test them. And "testing a hypothesis" often means trying to prove it wrong. If I have an idea, I will create a model/hypothesis and then try to prove my own model false (or make the hypothesis fail under some special condition). This process usually allows me to learn something that results in a better hypothesis/model. I say this because I do not want it to seem like I am being critical of any person that is investigating mast cell related causes of POIS.
Critical testing is just my general approach to any scientific question. Hopefully something here is useful in refining mast cell related models of POIS.
Mast cells have two main immune functions:1.
chemotaxis (communicating with systemic immune system and bringing them to the site of a problem)
2. fluid removal (swelling, sweating, sneezing, diarrhea, crying, swelling)
In my opinion,
mast cells perform normal and beneficial roles in helping POIS patients resolve illness. In healthy people, mast cells detect harmful substances, induce chemotaxis of immune cells and facilitate the removal of those harmful substances through bodily fluids. The following diagram is slightly over simplified but still useful for this discussion. A more detailed explanation of the immune response can be found here (
video1,
video2).
Note that if a pathogen is not contained by the systemic immune response, then mast cells and macrophages continue to activate (chemotaxis) in a loop/cycle. If the immune system is unsuccessful at controlling the pathogen, this cycle of mast (or macrophages) activation does not end. There may exist a POISer who also has a mast cell disorder as a second disease. But
I think that POIS patients in general do not have mast cell disorders for some of the following reasons: The 1st reason that MCAS seems unlikely to cause POIS is that
the medical test of mast cell disorders from POISers are all normal.
--5 of us have normal trypase (mast cell activation syndrome) levels (BluesBrother, nanna1, Vandemolen, Muon, Muon's brother).
--2 of us have normal histamine levels (nanna1 tested histamine, Muon tested N-methyl-histamine).
...
--3 of us show normal IgE (allergy) levels (aswinpras06, certainlypois2, Vandemolen)
My MCAS test are found here:
13. Mast cell activation syndrome and mastocytosis: The 2nd reason is that
sleep helps recovery from POIS. The sleep-POIS connection is important because adequate sleep increases immune system function, whereas sleep deprivation suppresses immune system function. This is a strong indicator that the immune system is involved with
helping us recover from a POIS state even while it is creating symptoms.
The 3rd reason is that
no one has found immunoglubin E (IgE antibodies) related to semen in POIS patients. Both the
Waldinger group and the
Jiang (
Ref) group failed to find any connection between semen related IgE and POIS. Also, three POIScenter members report normal IgE levels (
see post). These observations limit the potential triggers for MCAS.
The 4th reason is that
the symptoms of POIS do not match MCAS. For example, anaphylaxis, hives and angioedema are common symptoms of mast cell related illnesses such as mastocytosis and MCAS. Even if every POISer doesn't experience these symptoms, if MCAS was associated with POIS, I would expect these symptoms to be more common. But so far I haven't heard of anyone with POIS reporting orgasm induced anaphylaxis or angioedema. None of the POIS papers discuss these symptoms in POIS patients. One paper mentions hive like symptoms in POIS patients, but this was a small minority. And it appears that these patients can have hives even without an orgasm event.
The Waldinger symptom clusters (
Ref):
The Waldinger diagnostic criteria (
Ref):
Even if a person does have symptoms similar to MCAS, this does not mean that mast cells are involved.
Other immune cells, like M1 macrophages, can also produce MCAS-like symptoms without releasing tryptase. Moreover,
the documented/published symptoms of POIS are much more similar to the symptoms of an influenza viral infection (flu) than they are to MCAS. Like POIS,
sleep, stress reduction and vitamins also help people recover from the flu. With the flu, macrophages and mast cells activate to start a systemic immune response (chemotaxis) that fights the flu virus, and then these cells stablize once the virus has been contained.
However, there is one important difference between POIS and the flu. Several POISers have noted a
left-right asymmetry in POIS symptoms, meaning that some of their symmptoms occur more on one side of the body than the other side. There are several discussions on the POIScenter forum about
Bell's palsy,
myasthenia gravis and
hemicrania continua like symptoms related to POIS. If POIS has a left-right asymmetry in some POIS patients then the cause of POIS should be localized to a specific part of the body. But mast cell are not localized to any specific part of the body. Every tissue in the body has mast cells. So mast cells cannot cause asymmetric symptoms. But a localized pathogen can activate immune cells asymmetrically.
The 5th reason is that
there are other more likely explainations for the inflammation. For example, M1 macrophages can produce symptoms very similar to mast cell degranulation (including chemotaxis) without releasing tryptase. This is consistent with the fact that 5 POISers have tested negative for tryptase (
see post).
Figure from:
Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: Preliminary results (D Hasan, et. al., 2012) Also, a mast cell disorder implies that there is no legitimate or useful reason for mast cells to activate (induce chemotaxis and fluid removal), but a harmful pathogen is a legitimate reason for chemotaxis.
In order to demonstrate that there is a mast cell disorder causing POIS, you would have to rule-out viruses as a cause. Because as long as viruses are replicating in the body,
immune cell activation is the correct immune response. And this immune activation is helpful in correcting the problem, even if the symptoms are undesirable.
Here are a few ideas that may or may not be true/useful:- In terms of immune cells I think that low NK cells or low neutrophils could make symptoms of POIS worse.
- I think high epinephrine (adrenaline) and norepinephrine (noradrenaline) could make symptoms of POIS worse.
- Increased heart rate and blood pressure caused by adrenaline (or histamine) could make symptoms of POIS worse.
- Beta-herpes infections (HHV-5, HHV-6, endothelial viruses) could make symptoms worse.
- Blood vessels appear to play some role in some POIS patients
- MCAS and POIS could have a common cause, but this does not mean that one causes the other
These articles may also help further the discussion:
Post-Orgasmic Illness Syndrome: A Review (2018)Postorgasmic Illness Syndrome: What do we know so far? (2018)
