The Intriguing Role of Histamine in Exercise Responses 2017 Luttrell and Halliwill Brief Abstract In humans, histamine is a molecular transducer of physical activity responses, and antihistamines modify more than 25% of the genes responding to exercise. Although the upstream signal that results in release of histamine within exercising skeletal muscle remains to be identified, it is likely a fundamental exercise response and not an allergic reaction. Key Points Aerobic exercise results in activation of histamine H1 and H2 receptors within the previously exercised muscle, triggering vasodilation and a broad range of responses to exercise. Histamine affects the availability of glucose to skeletal muscle, glucose uptake by skeletal muscle, and insulin sensitivity after exercise. Histamine contributes to the sensations of pain and discomfort as well as loss of muscle strength associated with delayed-onset muscle soreness. Histamine exerts a profound influence on the human transcriptome response to exercise, modifying more than 25% of the genes responding to exercise, including ones involved in such physiological domains as inflammation, vascular function, metabolism, and cellular maintenance. The histamine released during exercise seems to result from mast cell degranulation as well as de novo synthesis of histamine. This response, a fundamental element of exercise, seems to comprise an anaphylactoid reaction and not an allergic reaction to exercise. ____________________
I posted this oldish paper because someone posted it on Twitter and it looked interesting, particularly as lots of people with Long Covid say antihistamines are helping them.
I used to get quite bad hives after exercise (or showering after exercise), usually on my legs near the bottom of my shorts. Always thought it was heat related, and hadn't made this link before.
I wonder if that would fit with the TH2 shift hypothesis for ME, (which would match my experience) in that if the body is already set up to be more sensitive to allergic signals then it might treat the histamine signal from exercise as an inflammatory response. Unfortunately all the antihistamines I have tried have had disastrous side effects, though I found dietary DAO (diamine oxidase) seems to lessen the load from digestion.
I've had really good success with the mast cell protocol of H1/H2 antihistamines and reducing histamine containing foods. For years I've had a bilateral forearm itch that didn't respond to any kind of medication. Now I use it as an indicator of having a histamine response after some foods, notably tomatoes and red wine. If I'm at 20% functioning and something gives me a boost to 30% that 50% increase in functioning feels like I'm on top of the world. Almost anything works, whether that is drugs, complimentary therapies, good news, etc. Sometimes the effects can last for a long time, but I generally find that after a few days, sometimes months or even years, the effect wears off. My red flag is when I have the urge to start doubling the dose. If I'm stranded on a desert island the first ship that goes by generates elation that can last for a long time. Seeing a ship go by every week tends to make them less effective for my sense of well-being. Over the years it also seems that I've often gotten long term benefit from any drug which reduces inflammatory response. This may be true of histamines, mast cell protocols or CCR5 inhibitors, etc. The trick is to remember that they're probably treating the effects but not eliminating the cause.
My husband has LC and has been helped significantly with Piriton (chlorphenamine). We both had allergies in childhood. I can't bring myself to trial the piriton for ME as it feels like I may have a bad reaction and can't risk a relapse at present. Might I ask which anti-histamines you trialled?
I use Reactine (H1) and Pepcid (H2). Pepcid is about the only OTC H2 available in Canada. I've also found Benadryl has a good effect, though it doesn't last as long. The advice is generally to try them until you find ones that work for you. Very late in life I started becoming allergic to bee stings. I've never had an anaphylactic reaction, always swelling from a type IV response. When I started taking antihistamines I recalled a trip to the hospital about 15 years ago due to a bee sting. I had a bad case of hives, etc and they gave me the usual epi + antihistamine drip. I felt incredibly good for days.
I'm guessing that histamine release is fairly fast. My physically-induced PEM had a consistent 24 hr delay, with an abrupt rise, so that seems inconsistent with histamines. Antihistamines had no effect on my ME symptoms or responses. Histamines could explain PEM with shorter delays though. Does cognitive exertion trigger histamine release?
For me, antihistamines give me more mental and physical energy. I can sit and play a game of cards without being cranky and exhausted while waiting my turn to play. I'm much more pleasant and social. PEM has not changed at all. I try to reduce it by enjoying the highs but sticking to a strict routine to avoid the lows.
Of course, I tried Triludan branded Terfenadine which was coincident with heart arrhythmia and then I tried Loratidine as a generic which appeared to cause upper respiratory tract infections to recur which involved extraordinary oedema. I feel much better for not taking either of those and have kind of gone off the whole idea of trying to mess with my immune system like that and instead use linseed oil for omegs3s, vitD and Solgar Turmeric extract as an anti-inflammatory cocktail, which seems to work as long as I take plenty of Mg during my frequent inflammatory crises.
Rather than using anti-histamines, I'm looking into DAO deficiency causing high histamine levels and associated problems from. Add in exercising which causes histamine release, could that be a cause of PEM? I might get tested for DAO deficiency especially since I was low in iodine and it helped to learn that. It could also be why alcohol is a problem for ME, the high histamine. Histamine is also higher around period and DAO drops off a week before period. It all makes some sense. Low levels of DAO can be associated with dizziness, sleep cycle...
