POLL: Do you sweat a lot from a 20 minute walk? Linked to overactive sympathetic nerves, and in turn, reduced Th1 antiviral immune responses

[Hip]

This poll investigates how easily ME/CFS patients sweat after a walk. The answer may relate to a patient's sympathetic nervous system activity, as well as to their immune system competence.

This poll is for ME/CFS patients who are able to do 20 or 30 minute walks at a reasonable pace: do you find you are sweating quite a bit across your torso when you come back home from such walks? Is your shirt, blouse or T-shirt all damp at the end of you walk? Or do you not sweat much at all?

This question assumes you do not live in a very hot and sunny location, which would cause sweating even if you are standing still. Where I live in the UK, summer temperatures are around 20 to 25°C typically (68 to 77°F), and winter temperatures are 5 to 10°C.

I also posted this poll on Reddit ME/CFS, where the poll results indicate a lot of ME/CFS patients have excessive sweating after a walk.


I tend to do a 20 or 30 minute walk once daily were possible, just to get the blood circulating, and for some exercise and fresh air. But when I return home, I find my T-shirt is quite damp with sweat. Not just in the underarm areas: the sweating appears all over my chest and back, so my entire T-shirt is damp. This sweating occurs even in the winter, when it is cold outside and I am dressed up with a jumper and warm coat.

I wonder if other ME/CFS patients perspire a lot from a 20 or 30 minute walk?


I think this sweating from walking might be caused by an overactive sympathetic nervous system (SNS), as this branch of the nervous system controls perspiration, and the medical condition of excess sweating (hyperhidrosis) is known to involve overactivation of the SNS.

For severe cases of hyperhidrosis, a simple surgical operation which cuts the sympathetic nerve in the chest (sympathectomy) is an extremely successful means to permanently cure hyperhidrosis (and can treat Raynaud’s too). Ref: here. So this shows that the SNS is the culprit in excess sweating.


For ME/CFS patients, the significance of having an overactive SNS may be far greater than just the inconvenience of a perspiration-dampened T-shirt: an overactive SNS is generally considered to be immunosuppressive, so having an SNS constantly overactivated may mean you are unable to fully clear viruses from you body.

In particular, the SNS regulates the Th1/Th2 cell balance, and high SNS activation inhibits the Th1 cells which fight viruses and intracellular pathogens, and promotes the Th2 cells which target extracellular bacteria. The paragraphs in the spoiler give the details:

Spoiler: How an activated sympathetic nervous system suppresses Th1 and promotes Th2

SNS regulation of Th1 and Th2 cell differentiation

The SNS regulates the differentiation of Th cells, including autoreactive cells, through the activation of α- and β2-ARs expressed on their cell surfaces. Sympathetic nerves are present adjacent to target immune cells in secondary LOs [lymphoid organs] and the immune cell infiltrates in the tertiary lymph nodules that occur in the affected joints.

In secondary LOs, NE [norepinephrine] released from sympathetic nerves activates β2-ARs [β2-adrenergic receptors] expressed in T cells. This receptor activation inhibits IL-2 production, which subsequently suppresses lymphocyte proliferation required for clonal expansion.

Activation of β2-ARs on Th0/Th1 cells also inhibits cellular and promotes humoral immunity by regulating the phenotypic differentiation of CD4+ Th cells in response to challenge with T cell-dependent antigens. β2-AR stimulation inhibits IFN-γ production by receptor coupling to Gs protein, increased intracellular cAMP production and subsequent phosphorylation of PKA. Reduced IFN-γ limits Th0 cell differentiation towards the Th1 phenotype, and dampens IFN-γ-mediated inhibition of IL-4 production, promoting IL-4 synthesis by Th2 cells.

In this manner, the SNS provides a negative feedback mechanism to restore immune system homeostasis after antigen challenges that activate cellular immunity. Additionally, β2-ARs preferentially inhibit IL-12 and increase IL-10 production by APCs, which subsequently promotes Th2 and inhibits Th1 differentiation.

Source: Sympathetic Nervous System Regulation of Th Cells in Autoimmunity: Beyond Th1 and Th2 Cell Balance.

So the above explains that SNS activation inhibits Th1 and promotes Th2. This is achieved by the SNS stimulating the beta-2 adrenergic receptors (β2-AR). Thus for patients with an overactive SNS, selective beta-2 adrenergic receptor blockers may help prevent the Th1 immunosuppressive action of an overactive SNS. However, there are no FDA approved β2-AR blockers, though the research compounds butaxamine and ICI-118,551 are selective β2-AR blockers.

In addition, some POTS patients may have autoantibodies which activate the beta-2 adrenergic receptors. Ref: here



Just a Reminder:

Th1 cytokines: IL-12, IL-2 and IFN-γ
Th2 cytokines: IL-4 and IL-10

Humoral immunity: involves B-cells which make antibodies that target extracellular pathogens like bacteria. Th2 cells help promote humoral immunity.

Cellular immunity: Involves T-cells which target intracellular pathogens like viruses and intracellular bacteria. Th1 cells help promote cellular immunity. This is the type of immunity we need in ME/CFS if we want to clear intracellular viruses.

If ME/CFS patients have constantly high SNS activation, this might explain why Th2-to-Th1 shifters like oxymatrine do not work for them: oxymatrine clears viruses by boosting the Th1 antiviral response; but if the immune system balance is shifted towards Th2 because of an overactivated SNS, this may thwart the action of oxymatrine.

So if SNS activation can be reduced, there may be better viral clearance in ME/CFS patients, and also Th2-to-Th1 shifters like oxymatrine may work better.



➤➤ Drugs That Reduce an Overactive Sympathetic Nervous System

Beta blockers — "β-adrenoceptor antagonists are used widely to reduce cardiovascular sympathetic tone". Ref: here.

Wyller proposed that beta blockers could be used to inhibit sympathetic nervous system activation in ME/CFS. Some beta blockers target both the beta-1 and the beta-2 adrenergic receptors, and activation of the latter mediates the immunosuppressive effects of the SNS on the desirable Th1 immune response (see explanation in the spoiler above). First generation beta blocker like propranolol, sotalol, timolol and nadolol target both beta-1 and beta-2 adrenergic receptors. Ref: here

Prazosin — reduces blood pressure by blocking alpha-1 adrenergic receptors. "As prazosin treatment ameliorates the symptoms of stress, and it also suppresses the sympathetic activity". Ref: here

Doxazosin — reduces blood pressure by blocking alpha-1 adrenergic receptors. It reduces sympathetic activity. Ref: here

Guanfacine — stimulates alpha-2 adrenergic receptors, which in turn reduce sympathetic nerve impulses from the vasomotor centre to the heart and blood vessels. Ref: here

Benicar (olmesartan) possibly — "it is possible, however, that olmesartan affects the brain, thereby inhibiting the sympathetic nervous system, at least in part, by reducing oxidative stress in the autonomic nuclei". Ref: here. So this might offer an alternative explanation of why the Marshall Protocol (which involves taking Benicar) can slowly improve ME/CFS.

Spironolactone — reduces SNS activity via an aldosterone receptor blockade. Ref: here. This might explain why spironolactone treatment can lead to substantial improvements in EBV ME/CFS.

Clonidine — "in the medulla, clonidine, acting as an alpha-antagonist, inhibits excitatory input to the sympathetic nervous system". Ref: here

Calcium channel blockers diltiazem, nifedipine and verapamil — "may selectively reduce low level (or basal) sympathetic neurotransmission". Ref: here



➤➤ Factors Which Increase Sympathetic Nervous System Activity

Magnesium deficiency — induces sympathetic excitation. Ref: here

Psychological stress — well-known to activate the fight or flight response, which include SNS activation.

LPS (lipopolysaccharide) — "systemic injection of LPS also activates the sympathetic nervous system". Ref: here. A study showed many ME/CFS patients have high levels of LPS, perhaps leaking into the bloodstream from the gut.

 

[Andryr]

I do not sweat a lot after 30 min of walking. Instead, my nose starts running like crazy. Not sure whether it is linked to anything.

 

[Wishful]

Instead, my nose starts running like crazy.

That happens to me during Timothy Grass pollen season (thankfully seems to be ended for this year). In cool wet weather, I react to something related to evergreen trees; I'm guessing fungal spores, possibly from lichens. My type I allergies don't seem to have any relation to my ME.

Regarding sweating, I don't think I sweat more than normal for humans, which is unchanged from before ME.

 

[Hip]

It strange that there is a completely different response to the same poll I place here on Reddit ME/CFS, compared to the results of this PR poll.

On Reddit, lots ME/CFS patients reported sweating a lot, whereas hardly any reported that on PR.

Much better voter turnout on Reddit too, compared to PR.

 

[junkcrap50]

I wasn't going to vote as my answer is sometimes I do, sometimes I don't. But I do think sympathetic overactivi does induce sweating episodes for me in tasks that shouldn't cause any sweating. For instance, very recently I had to repair an electronic by taking it apart and resolder something, and after 15-20mins of I was nearly soaked with sweat. And I was sitting the whole time!

As an FYI, when I was very mild CFS or possibly in a remission (I had 2 different triggering infections, the second worsening me), stressful events would trigger sweating episodes - even when i had no anxiety or even felt like I was stressed. Or, in other words, sweating would be a common stress response for me. For example, in the public library working on a term paper, finding books, I had a sweating "attack". And when I was at a bootcamp type environment for a summer session, when they were going around screaming in faces and putting you on the spot answering stuff, I wasn't that stressed or worried, but was sweating like crazy with all the drill seargents telling me to drink more water instead of screaming at me, lol.

 

[Tsukareta]

I wouldn't be able to walk for that long I guess, even going back to 2020 when I could sprint short distances. I could walk about 1km but my legs would become sore and inflamed and sensitive if I kept walking too far and quickly. Sometimes I will just sweat under the arms for no reason, typically in the morning, its one of many 'phases' of the CFS that I experience and its transient, not consistent.

 

[Rebecca under the papyrus]

When I was still able to walk those 20min I wouldn't sweat. Sweating from exertion is a warning sign for me: Meaning I am worse and have more immune system activity than usual and should slow down/rest. A bit like a healthy person who has a cold or something flu-like and sweats more easily.

 

[sb4]

I seem to have the opposite problem where I barely sweat at all even when baking hot in the sun. I just feel really shitty and when its really hot, my skin gets goose bumps just like what happens when you are cold, I'm pretty sure this is due to sympathetic activation, but still no sweating.

The only bits that do sweat are where skin touches skin, but even then not too much.

It's an interesting hypothesis though, poor viral clearing due to SNS activation.

I was recently on clonidine due to my POTS. It didn't really help. There where bouts where it stopped me from having adrenaline type nightmares. It also resulted in me feeling relaxed which is super rare since getting ill.
Unfortunately it also seemed to make my heart pounding worse and resulted in me being wide awake at 3am.

 

[Hip]

It's an interesting hypothesis though, poor viral clearing due to SNS activation.

It would be interesting if we could selectively target and block beta-2 adrenergic receptor found on T-cells. Activation of this receptor could be a culprit factor preventing viral clearance in some ME/CFS patients.

When the sympathetic nervous system activates this receptor on T-cells, it causes antiviral immunosuppression, because it prevents those T-cells from maturing into Th1 cells which fight viruses and intracellular infections, and instead causes the T-cells to mature into Th2 cells, which fight extracellular bacteria, but are useless for fighting viruses.

One of the oldest theories of ME/CFS is that there are too few Th1 cells, and too many Th2 cells in ME/CFS patients. That is to say, in ME/CFS the so-called Th1/Th2 balance is swung towards the Th2 side, which means ME/CFS patients cannot properly clear viruses.

When Dr Chia was running a clinical trial treating his ME/CFS patients with oxymatrine, a drug that swings the Th1/Th2 balance in the Th1 direction, he did some blood tests on the Th1/Th2 balance in his patients, and he found that all the patients who got better on oxymatrine had their balance swing towards Th1. But in some patients oxymatrine failed to cause a swing to Th1, and these are the patient who did not improve from oxymatrine. See 37:05 in this Dr Chia video.

So this suggests that the Th1/Th2 balance is important for viral clearance and recovery from ME/CFS. To clear viruses, you need the balance to swing to Th1. But it is an activated sympathetic nervous system which swings the balance away from the desired Th1, and pushes the balance towards Th2.

So if you could block the the beta-2 adrenergic receptor found on T-cells, you might be able to swing the Th1/Th2 balance back to Th1, which then might lead to viral clearance.



Having said that, the first generation beta blockers like propranolol block both beta-1 and beta-2 adrenergic receptors, and I am not aware of any ME/CFS patients improving on propranolol.

 

[pattismith]

Spironolactone — reduces SNS activity via an aldosterone receptor blockade. Ref: here. This might explain why spironolactone treatment can lead to substantial improvements in EBV ME/CFS.

There are several ways Spironolactone can help ME/CFS patients (other than reducing SNS activity). It improves metabolism and lower inflammation (and especially endothelial inflammation).
Association with Metformin was recorded beneficial.

https://link.springer.com/article/10.1186/s12902-022-01143-y
https://www.researchsquare.com/article/rs-3028738/v1
https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.119.312954

 

[Wishful]

On Reddit, lots ME/CFS patients reported sweating a lot,

Maybe reading Reddit makes people sweaty. Maybe you need a poll for whether Reddit makes people sweatier than other forums.

Oooh, wait. Maybe it's that "Men sweat; women glow" thing, and there's a male/female imbalance for Reddit.

 

[Hip]

Maybe reading Reddit makes people sweaty. Maybe you need a poll for whether Reddit makes people sweatier than other forums.

Oooh, wait. Maybe it's that "Men sweat; women glow" thing, and there's a male/female imbalance for Reddit.

Might be an age thing: someone said to me recently that the Reddit ME/CFS forum has lots of Generation Z, and PR has a lot of Boomers. I don't know if that is true, nor whether there is an age effect in sweating, but the Reddit results appear to be the inverse of the PR results, which is strange:


Reddit Poll Results:

 

[anne_likes_red]

GenXer here
@Hip I regularly walk on the beach 20+ mins (then rest 10 before walking back home). I usually walk with my husband and we have noticed I get much warmer than he does. It's winter and I'm warm right to the extremities. I don't sweat though.
In case it's of any significance I wear a tracker and keep my heartrate under an aerobic threshold 95% of the time. (Seems to help protect against crashes).

 

[Wishful]

Might be an age thing:

I think this is a good example of why we shouldn't take study results as perfect perspectives on reality. Even on a well-designed study, there could be some strong factor that isn't taken into account. I expect that forums do have age/generational differences, and gender differences, and philosophical differences, and many more. A forum could have had a divisive topic at some time that caused part of the membership to leave, and the resulting change of tone of the remainder would affect whether new readers will join or reject it. That might be a good thesis topic for someone, to later be misapplied for some web site's benefit.

Thanks to this thread, I'll now have a mental image of Reddit members being very sweaty.

 

[Hip]

Maybe I should have written "glow" rather than "sweat"! Maybe some people don't like to associate with sweating!

As in the saying: "horses sweat, men perspire, but women glow".

 

[L'engle]

It strange that there is a completely different response to the same poll I place here on Reddit ME/CFS, compared to the results of this PR poll.

On Reddit, lots ME/CFS patients reported sweating a lot, whereas hardly any reported that on PR.

Reddit is likely to be more younger patients who not been sick as long and are more likely to be able to walk 20-30 minutes. I suspect there will also be more people with other issues such as anxiety self-diagnosing as having ME/CFS.

I can only do walks like that sporadically, and from what people have posted here over the years, a large number of us cannot walk for that length of time at all. So that would account for low number of votes here.
I never sweated to the point of drenching even when I was healthy and very active.

 

[Hip]

I can only do walks like that sporadically, and from what people have posted here over the years, a large number of us cannot walk for that length of time at all. So that would account for low number of votes here.

That could account for the lower number of votes, yes, but cannot really account for the fact that on Phoenix Rising, 85% who can walk for 20 minutes stated they do not sweat at all after this walk; whereas on Reddit only 22% said they do not sweat at all after this walk.

 

[L'engle]

@Hip One issue is that you categorize have only wetness underthe arms as 'not sweating at all' which could confuse people. If your underarms are wet, you probably sweated.

Also there not just an age gap, but a gender gap. Reddit is frequently offputting to women, so that with the age difference could make the numbers seem opposite. People are self-sorting by going to either here or reddit. People with higher metabolisms(more likely younger, more likely male) sweat more, and a lot more women run cold naturally. The exception would be some women going through menopause, but in general I think you'd find women over 35 (typical PR member) sweat a lot less than a typical reddit user(men under 35).

 

[pattismith]

@Hip I forgot one thing about spironolactone, but it's important, this was the first reason I was interested in trying it, it's an hepcidin down regulator

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566021/

 

[Hip]

I forgot one thing about spironolactone, but it's important, this was the first reason I was interested in trying it, it's an hepcidin down regulator

What is this significance of that in relation to the sympathetic nervous system?