Supplements and Drugs That Reduce or Prevent PEM (Post-Exertional Malaise)

[sunshine44]

Corticosteroids don’t prevent PEM in my case, actually, they do the exact opposite and cause it.

I took a single 20 mg dose of prednisone before being driven to a park for an afternoon with my wife. The temps were in the mid 60s with a slight breeze and high barometric pressure. We sat in our lounge chairs and relaxed in the sun.

To my surprise the prednisone did the opposite of preventing PEM! I took prednisone at 1215 and my ANS readings prior were low and calm. Stress readings were only at 10 to 18. At about 1430 my ANS started rising, as did my resting heart rate. All I was doing was sitting down. By 1630 my ANS was solid redline, my resting heart rate was back up at 85, and my stress numbers were averaging 75. This lasted until around 0300 when everything began dropping back to normal readings under the influence of the beta-blocker metoprolol. However, the racing ANS for about 12 hours caused me to crash into PEM and my waking body battery was an all time low for wake-up at 43. I was pretty much comatose on the couch for two days and dragging ass the rest of the week.

Two days ago I had to go to a sports doctor. My shoulders had stiffened up and been in daily pain for 6 months and needed to be looked at. After clean X-rays the agreed on the “frozen shoulder” theory. The X-rays did show any bone, tendon, ligament, or cartilage damage, so arthritis was ruled out. The doc said even though it appeared to be “frozen shoulder," it was severe and very atypical case. He gave me two steroid injections, one in each shoulder. My vision was terrible that day and so I was in the whiteout phase of being able to see nothing by flat featureless light. The staff were guiding me all over the building. They did a decent enough job but I could tell they weren’t used to working with severely visually impaired clients.

The doctor told me the pain should start subsiding in three days time, but the stiffness might take a year to work itself out and there isn’t any real way to speed the process. The body needs to slowly breakdown the excess protective tissue surround each joint capsule and reabsorb it. That takes as much time as the body requires.

I received the injections about noon. By 1430 my ANS started skyrocketing, as did my resting heart rate. I was tired from the doc visit and was just resting and napping in a lounge chair outside when everything began rising. By 1800 the ANS was completely redlined at 100% The resting heart rate was back up to 100 to 110 BPM. Stress level numbers were leveling at 85 and heart rate variability clocked in at 10. The autonomic nervous system continued all night in a 100% redline state on the smartwatch charts. My heart rate while sleeping was averaging 90 to 95. I had zero registered REM. My body battery plummeted to 12, and my wake up battery hit an all time low for waking at 13%. That next day I was gutted in a deep post-exertional malaise crash. My ANS chart at 1100 was still a solid block of redline with zero let up. I had a bunch of elevated dysautonomia/PoTS/M.E. symptoms going on.

My ANS is still redlining and I have no idea how long it will last before the beta-blocker metoprolol kicks back in. The prednisone resolved in about 12 hours, but the redlining ANS has after the steroid injections had so far been going for 2 days now. I’m in bed struggling like it was mid winter dictating this because I still can’t see.

Steroids have become a new enemy as they obviously override the beta-blocker. And with the ANS being suppressed daily from the metoprolol, when that beta-blocker is removed or overridden by another drug, the ANS overreacts above and beyond its normal abnormalities.

Therefore, as I said, corticosteroids in my case do not prevent PEM, but do the absolute opposite.

I am so sorry for this awful situation you are enduring

 

[Judee]

I always felt like steroids kinda rev us up (like exercising without actually exercising) hence the PEM.

I can only handle tiny doses of hydrocortisone (Cortef) like maybe an 1/8 of a 5mg pill and still sorta pay for it the next day or so. I haven't taken any for a long while.

The doc said even though it appeared to be “frozen shoulder," it was severe and very atypical case

You might also consider chiropractic treatment. That could possibly be caused by your lower cervical vertebrae being locked up too and radiating to your shoulder. If you do look for a chiro, look for one that uses his hands and adjusts the entire spine (everything that's locked up) on each visit. The drop tables and actuators can be uncomfortable and don't work as well as hands on.

I miss being able to get to my chiropractor. He was so good at getting me out of pain. My Mom too when she was alive.

 

[hips_fan]

Just so we are clear: mental PEM is where you get PEM symptoms (such as increased fatigue, increased brain fog, etc) after a bout of mental exertion (like social chat with friends, talking to someone on the phone for some time, reading, concentrating on a difficult mental task, etc). Typically the PEM will hit the next day, after a bout of mental exertion.

@Hip

Could this be the reason for mental PEM being a bit different than Physical PEM.
Sodium Potassium Pump Dependent on ATP.
This pump is also responsible for pushing excess calcium out from neurons.
Low ATP --> Excess Calcium --> Neurotoxicity

 

[Hip]

Could this be the reason for mental PEM being a bit different than Physical PEM.

Did you have any mechanism in mind?

 

[Hip]

According to Dr Brayden Yellman of the Bateman Horne Center, dextromethorphan (which is found in cough syrup) is a PEM shielder when taken before exertion, or just after the exertion. See timecode 37:14 of this video.

Dextromethorphan is taken at normal doses for PEM (which I think would be 15 to 30 mg).

I've added dextromethorphan to the list of PEM busters in the first post.

 

[hapl808]

According to Dr Brayden Yellman of the Bateman Horne Center, dextromethorphan (which is found in cough syrup) is a PEM shielder when taken before exertion, or just after the exertion. See timecode 37:14 of this video.

Dextromethorphan is taken at normal doses for PEM (which I think would be 15 to 30 mg).

I've added dextromethorphan to the list of PEM busters in the first post.

That's interesting. I've meant to try it as I have awful coughing anyways (I used to take it occasionally when I traveled), and it correlates with a lot of 'good' things. Early days of COVID it was highlighted that people who took DXM had better COVID outcomes (when they were doing various ML analysis of electronic health records).

Also an S1R agonist like fluvoxamine I think.

 

[Hip]

There are also two drugs based on dextromethorphan that may be of interest to ME/CFS patients:

Nuedexta = dextromethorphan + quinidine.

Nuedexta drug is designed to treat emotional lability, which is a listed ME/CFS symptom. Quinidine is added as it inhibits the liver enzyme CYP2D6 responsible for metabolising dextromethorphan, so prolongs the half-life of dextromethorphan.


AXS-05 = dextromethorphan + bupropion.

AXS-05 is designed to treat anhedonia. Anhedonia is not an official ME/CFS symptom, but there are ME/CFS patients who have anhedonia. Here bupropion (Wellbutrin) is added because it again inhibits CYP2D6, thus increasing the half-life of dextromethorphan. But being an antidepressant, possibly bupropion may also help with the anti-anhedonia effect as well.

Studies using this combo to treat anhedonia used a dose of bupropion 100 mg + dextromethorphan 45 mg twice daily. Ref: here.

 

[Springbok1988]

AXS-05 = dextromethorphan + bupropion.

AXS-05 is designed to treat anhedonia. Anhedonia is not an official ME/CFS symptom, but there are ME/CFS patients who have anhedonia. Here bupropion (Wellbutrin) is added because it again inhibits CYP2D6, thus increasing the half-life of dextromethorphan. But being an antidepressant, possibly bupropion may also help with the anti-anhedonia effect as well.

Studies using this combo to treat anhedonia used a dose of bupropion 100 mg + dextromethorphan 45 mg twice daily. Ref: here.

I was on Auvelity (AXS-05) but couldn’t tolerate it for more than five weeks. It made me incredibly tired, out of it, and sick feeling all day, everyday. Dextromethorphan is a CNS depressant and Wellbutrin acts as a stimulant. It made me feel like I was being yanked in to different directions, with the tiredness and sleepiness winning out. I had an awful time with it. I didn’t notice any changes in PEM but that’s not to say others wouldn’t see a benefit.

 

[hips_fan]

I was on Auvelity (AXS-05) but couldn’t tolerate it for more than five weeks. It made me incredibly tired, out of it, and sick feeling all day, everyday. Dextromethorphan is a CNS depressant and Wellbutrin acts as a stimulant. It made me feel like I was being yanked in to different directions, with the tiredness and sleepiness winning out. I had an awful time with it. I didn’t notice any changes in PEM but that’s not to say others wouldn’t see a benefit.

DXM is a NMDA Receptor Antagonist.
NMDA Antagonist prevent excess calcium ions influx through the NMDA receptor.
This has its uses(stimulant tolerance) but this process also causes disassociation.

People who use DXM for avoiding stimulant tolerance use it in low doses.
I have never tried it just read about it.

 

[hips_fan]

DXM is a NMDA Receptor Antagonist.
NMDA Antagonist prevent excess calcium ions influx through the NMDA receptor.
This has its uses(stimulant tolerance) but this process also causes disassociation.

People who use DXM for avoiding stimulant tolerance use it in low doses.
I have never tried it just read about it.

Some More Links if people want to read more about it :-
1)

https://www.reddit.com/r/Nootropics/comments/2tbyma

2)https://www.longecity.org/forum/top...n-as-a-potential-rapid-acting-antidepressant/
3)https://www.reddit.com/r/Nootropics/comments/58mctx/nmda_antagonists_what_is_the_appeal/

 

[L'engle]

Just tried vinpocetine 15mg for the first time about an hour ago. With blueberry extract, and took with food.
We'll see what happens...

 

[L'engle]

I've felt slightly better in the last few hours, but I also took reishi, vitamin A, and mb12. Had a good serving of protein that helps as well. So it's hard to isolate whether vinpocetine helped specifically but I would say I happen to feel better after taking it.

 

[L'engle]

5 days of taking 15mg vinpocetine. Slightly improved feeling of well-being on the first couple of days, more energy for physical activity then crashing. One of the only things I've taken that made me want to take more due to immediate effects.

Less improvement after the first day.

Didn't take any today and now feel worse than ever so I guess it is a withdrawal symptom. As someone said above it seemed to be similar to SSRIs, so that tracks. I don't think I'll keep taking it as this is pretty awful.

One more crossed off the list and also makes it clearer what might happen if I gave in and took SSRIs.

I was hoping it would help with brain fog but even the improvement I did get wasn't in terms of cognition.

I actually didn't plan to test it out but had gone to the store for pomegranate extract and couldn't get that. Vinpo has been on the list for a long time, now I know why I kept putting off trying it.

 

[L'engle]

Just an update, I started fighting something off the day I stopped vinpocetine so that contributed to the crashing. I felt worse and had terrible brain fog for the next few days but it was mainly my immune system.

I might try the vinpocetine again just to take for one day at a time and see if that is manageable occasionally or not. It's not one I would take on a regular basis.

 

[L'engle]

In case anyone finds this useful: I had worsened brain fog for a month after stopping vinpocetine. I don't know if it was because of that but the timing is suspicious. I'd advise caution with this stuff if anyone is still thinking about trying it.

Too bad, the capsules also have blueberry extract and so smell quite pleasant.

 

[kushami]

I know I always say this, but I would love to see what effects PEM shielders are having on cerebral blood flow.

I have a few tiring things to do in the next month – doctor’s appointments, blood tests – and have ordered some hydrocortisone to try a single pre-emptive dose.p on those days.

I don’t get PEM, although I have been wondering lately whether I am inching towards it. I do feel shocking after exerting myself, probably because my cerebral blood flow drops, as that is my main problem.

Will report back.

 

[triffid113]

However, why does mental exertion cause PEM? What substance does mental exertion release that has to be dealt with in the human body?

My guess is that you are short of ATP and the heart and brain are the highest users of ATP in the body.

 

[triffid113]

Excellent summary at the start of this topic.

I got in because there are studies out that came to my awareness to the effect that astaxanthin helps preserve mitochondria from oxidative stress. Perhaps additionally, for mitochondria already destroyed, there is a need for something like PQQ.

In the past I reported PQQ as a possibility to help with fatigue, but if you take it and still have/make too many free radicals they would just destroy any new mitochondria. Astaxanthin has much more antioxidant power than C + E. (You'll have to look it up yourself, if interested). I started taking it 5 years ago. I was wondering if anyone had tried a PQQ + astaxanthin regime to make and retain more ATP to help with fatigue?

To cover all bases, you also need all Kreb cycle nutrients, of which notably most people do not get enough magnesium (I take cal-mag citrate, and I note citrate is on your fatigue-reducing list of supplements - I use citrate because it is non-stone forming and it makes me feel good, unlike other calcium supplements)). Also, you should take active B vitamins because, for instance, the Kreb cycle uses 3 niacin molecules (and 1 or 2 riboflavin molecules) for every turn of the cycle. [The Kreb cycle produces ATP].

ROS = radial oxygen species (free-radicals)

https://www.mdpi.com/2072-6643/14/1/107 - In this paper, we (1) review astaxanthin’s (AX's) well-known antioxidant activity, and (2) expand on AX’s lesser-known role in mitochondrial energy metabolism. ... (1) AX is a strong antioxidant without any pro-oxidant properties. ... One of the most important physiological activities of AX, which is strongly associated with its antioxidant activity, is its anti-inflammatory activity in response to inflammation triggered by ROS-induced oxidative damage. Numerous studies have shown that AX inhibits NFκB signaling in response to oxidative stress, regardless of the source of ROS, cell types, or organ [31,57,58,59,60,61,62,63,64,65,66,67,68]. As a result, AX suppressed NFκB-mediated gene expression of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, iNOS or TNFα, thereby inhibiting the development of inflammation.... (2) The mitochondrion is an organelle that produces energy by electron transport chain (ETC)/oxidative phosphorylation, and oxygen is consumed in this process. Most of the oxygen molecules entering the ETC are reduced to water, but a significant amount escapes in the form of ROS byproducts [72]. AX can significantly inhibit the lipid peroxidation of biological membranes, [such as those inside the mitochondria]. [Various studies] These results suggest that AX may protect mitochondria from oxidative damage caused by ROS production when mitochondria are overloaded under conditions of physiological stress. [Another study shows] AX has a protective effect against oxidative damage caused by mitochondrial dysfunction in these [mitochondrial] cells. ... Oxidative stress disturbs intracellular calcium homeostasis, resulting in calcium leaving the endoplasmic reticulum and entering mitochondria, which causes the mitochondrial membrane [to become a useless sieve or pipe full of holes], and the mitochondria to signal for cell death (apoptosis) [81]. It has been widely reported that AX prevents the ROS-induced calcium influx into mitochondria, protects against mitochondrial dysfunction, and inhibits apoptosis [82,83,84,85,86,87,88]. etc. etc.

Of interest to me: [80]. AX also had a protective effect against ROS-mediated angiotensin II -induced mitochondrial dysfunction. [the effect of high blood pressure and free radicals on mitochondria]

https://www.sciencedirect.com/science/article/abs/pii/S0955286309000242 - Investigating the efficacy of antioxidants, we found that a carotenoid, astaxanthin (AX), decreased physiologically occurring oxidative stress and protected cultured cells against strong oxidative stress. Moreover, AX improved maintenance of a high mitochondrial membrane potential [non-sieve] and stimulated respiration. Additionally, AX improved the ability of mitochondria to remain in a reduced state under oxidative challenge. Taken together, these results suggest that AX is effective in improving mitochondrial function through retaining mitochondria in the reduced state.

https://www.sciencedirect.com/science/article/abs/pii/S0955286309000242 - We concluded that AX treatment stimulated mitochondrial biogenesis and significantly ameliorated insulin resistance through activation of AMPK pathway in the skeletal muscle.

https://www.mdpi.com/2072-6643/13/2/379 - These results suggested that AX protected the functional stability of mitochondria, alleviated mitochondrial oxidative stress and mitochondria-mediated apoptosis, and thus, prevented muscle atrophy.

etc, etc.

 

[Wishful]

My guess is that you are short of ATP and the heart and brain are the highest users of ATP in the body.

To me that doesn't fit, since there's typically a delay much longer than would be expected from ATP depletion. ATP depletion should show an effect quickly, and possibly gradually. My experience is that an activity such as chatting would result in an abrupt switch to PEM maybe an hour after starting.

There many other possibilities that fit better, such as glial activation. Some sort of feedback involving the gut seems plausible too. Cognitive exertion could alter hormones that affect the gut, which in turn affects intestinal permeability, triggering immune activation, triggering glial activation and thus neural function.

 

[hapl808]

There many other possibilities that fit better, such as glial activation. Some sort of feedback involving the gut seems plausible too. Cognitive exertion could alter hormones that affect the gut, which in turn affects intestinal permeability, triggering immune activation, triggering glial activation and thus neural function.

Vaguely one of my beliefs - although whether it's hormone-related or neurotransmitter or what, who knows. But glial activation seems relevant. Wish I could find more things to properly address it, though.