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

debored13

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I found this study which says 3,000 mg of Q10 daily for 8 months was found to be safe.
Thanks! Also just thanks in general man, you do some really exhaustive research and also are an inspiration in terms of trying out really experimental things and doing this work, which I know from experience is difficult while very sick. So, cheers
 

debored13

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List of Supplements and Drugs Which Can Reduce PEM

Several supplement and drugs appear to be able to reduce or prevent post-exertional malaise (PEM), by either preventing PEM from physical or mental exertion occurring in the first place, or helping to relieve any PEM that has already appeared.

PEM can be caused both by physical exertion, and also by mental exertion (such as hectic social activity). The mechanism of mental exertion-induced PEM may be different to the mechanism of physical exertion-induced PEM.

The PEM reducers (aka "PEM busters") detailed on this thread have been compiled from other threads about ME/CFS patients' experiences with supplement and drugs that they have observed reduce PEM.



PEM Reducer Supplements and Drugs

The following are the supplements and drugs that ME/CFS patients have found reduce PEM:

Creatine hydrochloride — 2 grams
Citrulline — 1000 mg
Branched-chain amino acids (BCAA) — 5 grams
Co-enzyme Q10 — 800 mg to 1800 mg (this is a very high dose of Q10)
Sodium bicarbonate (baking soda) — ¼ teaspoon (1.5 grams)
Catalase — 600 mg (taken after exercise)
D-ribose — 5 grams, three times daily
Cannabis — taken just as PEM begins to appear prevents PEM from fully manifesting; see the Cannabis section below
Corticosteroids — taken before exertion can completely prevent PEM; see the corticosteroids section below

You can try one or more of the above supplements and drugs during PEM itself, or in advance of any physical or mental exertion that you suspect is going to trigger PEM, and see if they relieve or prevent your PEM.

Most experienced ME/CFS patients know roughly how long their PEM periods tend to last for, so will certainly notice if a supplement can dramatically shorten the severity or duration of their PEM.



PEM Shielders vs PEM Relievers

A PEM reducer supplement or drug may fall into one (or both) of the following two categories:

PEM shielders — help prevent PEM from occurring in the first place. PEM shielders only work properly when taken as a preventative medication before you engage in the physical or mental exertion

PEM relievers — mitigate the severity and duration of PEM only when taken after the exertion has occurred, where the PEM may already have begun to manifest.

It is important to know whether a supplement or drug is a PEM shielder or a PEM reliever, because the former only work when taken before the exertion, and the latter only work when taken after the exertion.

As an example of the difference, @hamsterman found that the corticosteroid drug prednisolone 20 mg is an excellent PEM shielder for both physical and mental exertion, but found that such corticosteroid drugs do not work at all as PEM relievers.

Whereas @hamsterman found that BCAA, Q10, creatine and baking soda work more as PEM relievers, rather than PEM shielders.

Though @TravelChimp said in this post that creatine works for him as both a PEM shielder, as well as a PEM reliever.

And @SOC said Q10 works both as a PEM reducer when taken at a one-off very high dose of 2400 mg (two 1200 mg doses on the same day), but also found Q10 had some mild PEM shielding effects when taken at a dose of 800 mg daily.

Note that this study found 3000 mg of Q10 daily for 8 months was safe.

Cannabis appears to be a good PEM shielder, when taken just as the first signs of PEM appear. See the Cannabis section below for more details.

Nothing however seems to be quite as powerful as corticosteroids for total PEM shielding.



Biochemical Theory of PEM

The above PEM reducers were discovered by various members of this forum, who observed that a supplement or drug they were taking had anti-PEM effects. Interestingly, some of these supplements (but D-ribose, Cannabis or corticosteroids) are known to inhibit exercise-induced lactate (see the athletic exercise studies in this post); that may be their mechanism of action in fighting PEM.

D-ribose likely works by a different mechanism: by helping to replace ATP molecules that may be lost during significant exertion.

In the theory of PEM proposed by Myhill, Booth and McLaren-Howard (briefly explained in this post), they suggest PEM is caused by the loss of ATP molecules that occurs when ME/CFS patients exercise.

According to this theory, you only get over PEM once the body re-manufactures the lost ATP molecules, which can take many days or weeks — hence the why PEM can last for days or weeks. D-ribose speeds up the process of re-manufacturing the lost ATP molecules, thus curtailing the duration of PEM.

Their theory also proposes that a build up of lactic acid during exercise exacerbates and worsens PEM (since lactic acid requires a lot of energy to clear from the body); so that might explain why the above supplements which reduce exercise-induced lactate are PEM relievers: they can help ME/CFS patients get over PEM much more quickly.



Patient Accounts of The Anti-PEM Effects of The Supplements

This post details how D-ribose powder, at the standard dose of 5 grams taken three times daily, consistently curtails PEM from its usual 3 or 4 days, down to just 12 to 24 hours, for ME/CFS patient @arewenearlythereyet.

This post details how for ME/CFS patient @SOC, a very high one-off dose of 2400 mg of co-enzyme Q10 (taken as two 1200 mg doses on the same day) dramatically eliminated a PEM period with 24 hours, a PEM that would normally have lasted 10 to 14 days. The patient also found that 800 mg of Q10 taken daily noticeably raised their PEM threshold (see this post). Cheap sources of bulk Q10 powder are found on purebulk.com.

This post details how regular supplementation with creatine monohydrate 10 grams daily increased energy, and allowed ME/CFS patient @TravelChimp to do much more physical exercise before the PEM was triggered; in other words, this patient found the creatine raised their PEM threshold. Not only that, but when they did get PEM by overdoing it, they noticed their PEM was reduced in severity as a result of the creatine supplementation.

Note that creatine hydrochloride 2 grams daily may be a much better form of creatine to use than creatine monohydrate, as creatine HCl does not cause stomach aches or fluid retention (as the monohydrate form can), and also is much more water soluble and absorbable in the gut, and so you only need to take around ⅕ of the dose (so 10 grams of creatine monohydrate = 2 grams of creatine hydrochloride; ref: 1).

Here is a thread detailing the anti-PEM effects of branched-chain amino acids (BCAAs). @Mary says later in this thread that BCAAs reduce her PEM duration from 2 days to 1 day.

Here is a thread detailing the anti-PEM effects of sodium bicarbonate, catalase, glutathione and others. In the thread, @Mya Symons says that sodium bicarbonate taken just before exercise, and 600 mg of catalase taken just after exercise, has the best anti-PEM effect.



Studies on these Supplements

Athletic performance studies which demonstrate how these PEM reducing supplements also generally improve exercise performance are given in this post. These studies are also listed in Cort's excellent resource about PEM reducers found here.

These athletic performance studies found that the very same supplements that ME/CFS patients on this forum have found prevent or relieve PEM also reduce the recovery period after athletic exercise in healthy people. Several of these studies found that the athletic performance-enhancing supplements work via neutralizing exercise-induced lactate circulating in the blood, and this is probably one of the mechanism by which they reduce PEM.



Cannabis as a PEM Shielder

Several ME/CFS patients have reported that Cannabis is a good PEM shielder: they find if Cannabis is taken just when the first signs of PEM appear, at the first PEM "danger signals", then Cannabis will prevent the PEM from fully manifesting.

Cannabis seems to prevent PEM caused by both physical or mental exertion. Patients report that when they have done too much physical or mental activity, and start to sense the "danger signals" that PEM is about to appear, taking Cannabis pulls them out of the danger zone, so that they can escape PEM.

Interestingly, some ME/CFS patients report that moderate doses of Cannabis do not produce any high at all. This observation is interesting in itself, as Cannabis will normally get people high; but the fact that in ME/CFS, moderate doses of Cannabis often do not cause any high is intriguing. And this is good news for patients who would like to benefit from the anti-PEM effects of Cannabis, but do not want to experience a high just in order to gain these benefits.

To help ensure only moderate doses are taken, Indica Cannabis may be the best choice, rather than Sativa Cannabis. Indica has less of the THC that gets you high, and more of the CBD which acts to counter some of the effects of THC. Whereas by comparison, Sativa has more THC and less CBD.

Of course, the legality of Cannabis varies from region to region, but this option of using moderate dose of a mild Cannabis like Indica to prevent PEM is another useful addition to the list of medications that reduce PEM.

In terms of why Cannabis has this anti-PEM effect: this article says the THC and CBD in Cannabis can affect mitochondria. There are cannabinoid type 1 receptors (CB1) on the mitochondria, which is one of several ways that Cannabis interacts with mitochondria. So maybe that's how Cannabis helps get over PEM, by modulating mitochondrial function.



Corticosteroids as Potent PEM Shielders

Corticosteroids such as prednisone, prednisolone and hydrocortisone are reported to be potent PEM shielders, that when taken just before any physical or mental exertion, can totally prevent any PEM from appearing.

But note that these drugs were found to be useless if taken after the exertion. That is, they do not help if you are already experiencing PEM from a previous period of exertion.

But in ME/CFS these drugs should only be used occasionally, such as once a week; if they are used every day on a long term basis, this can lead to worsening of ME/CFS (possibly because the corticosteroid immune suppression may allow any underlying infections to grow).

Some examples of corticosteroid usage as a PEM shielder to prevent PEM:

Prednisone at a one-off dose of 20 mg or so taken 4 hours before a mentally exerting event (such as socializing). Some ME/CFS patients have vouched this works effectively and reliably (though others report ill effects from this corticosteroid drug). See this thread.

@hamsterman found that prednisolone can work amazingly well to prevent physical exertion-induced PEM, if taken just before a physical exercise workout:

Note that @hamsterman was using prednisolone and not prednisone as he stated in the quote above.

But see the warning in this post, which cautions against using prednisone for any extended period of time, and warns that the PEM protective effects do not work for the whole day, they seem to wear off after about 6 to 8 hours. Prednisone is a strong drug, and has sometimes caused adverse events in ME/CFS patients.

Hydrocortisone at a one-off dose of 80 mg or so taken 30 minutes before a mentally or physically exerting event has also been reported as very effective for preventing PEM due to physical and mental exertion:

Correction: note that @hamsterman was using prednisolone and not prednisone as he stated in the quote above. Prednisolone has the advantage of kicking in faster than prednisone, as the following explains.

The exact time it takes for these corticosteroid drugs to kick in after taking them orally is as follows: prednisone takes around 2.6 hours for the drug to reach peak levels in the bloodstream, whereas prednisolone takes around 1.3 hours, and hydrocortisone takes around 1 to 2 hours. Ref: 1

So when you are taking any of these corticosteroids in advance to prevent PEM from a physical or mental exertion you are about to perform, you need to give them enough time to kick in before starting the exertion, else you "PEM shield" will not be in place.

In terms of how long the "PEM shield" lasts, the plasma half-life of prednisone and prednisolone is 3 to 4 hours, and the plasma half-life of hydrocortisone is 2 hours.

So once your "PEM shield" is active it will last for say one or two half-lives, ie, it may last about 4 to 8 hours for prednisone and prednisolone, and last around 2 to 4 hours for hydrocortisone.
Would the baking soda help because of some neutralizing effect on lactic acid?
 

hamsterman

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My naturopath got me on these adrenal supplements that had bovine adrenal glands. they seemed to help but also hurt in a way, I have the theory that it's just giving you stress hormones that corticosteroids mimic, without helping your body replace them. I had the most substantial energy I'd had for awhile, nothing dramatic (no exercise) but I could actually think and write with vigor. However I was also on LDN and experienced panic attack like symptoms. I think the adrenal cortex contains cortisol and other stress hormones. my cortisol may be low but I'm not sure that corticosteroids/adrenal glandulars are sustainable. I would also wake up with a headache which is a classic stress reaction.
As far as cortisol hormone replacement, that's definitely something that can help a percentage of us... but its not for everyone. Usually people take the saliva test before doing it. Its a delicate balancing act... because the last thing you'd wanna do is take it when you don't need it, or take too much of it for too long, and affect the HPA axis.... and that's even trickier for PWME, since our systems are so hyper-sensitive. There is a subforum here on this subject.

However, I don't use hydocortisone for hormone replacement, I use it as an occasional immunosuppresent, which requires a much higher dose (about 20 times higher). When it acts as an immunosuppresent it stops and/or alters the exertion immune response... which basically makes it impossible for me to PEM while I'm on it. But that's me.

But I'll typically only use it 2-3 times per month for this purpose. And at that frequency, it doesnt have an effect on my HPA axis. But if I were to take that dose for a week, it probably would. And if I continued taking that dose for another week, it would be awful coming off it. Coming off corticosteroids is true 'Hell on Earth', even when you taper. Its one of the few things worse than PEM.
 

debored13

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As far as cortisol hormone replacement, that's definitely something that can help a percentage of us... but its not for everyone. Usually people take the saliva test before doing it. Its a delicate balancing act... because the last thing you'd wanna do is take it when you don't need it, or take too much of it for too long, and affect the HPA axis.... and that's even trickier for PWME, since our systems are so hyper-sensitive. There is a subforum here on this subject.

However, I don't use hydocortisone for hormone replacement, I use it as an occasional immunosuppresent, which requires a much higher dose (about 20 times higher). When it acts as an immunosuppresent it stops and/or alters the exertion immune response... which basically makes it impossible for me to PEM while I'm on it. But that's me.

But I'll typically only use it 2-3 times per month for this purpose. And at that frequency, it doesnt have an effect on my HPA axis. But if I were to take that dose for a week, it probably would. And if I continued taking that dose for another week, it would be awful coming off it. Coming off corticosteroids is true 'Hell on Earth', even when you taper. Its one of the few things worse than PEM.
I did have a saliva test for cortisol and I was fairly low. I just would rather try other things than corticosteroids or even these adrenal glandulars. Next on my list is progesterone or pregnenolone which seem to be better than corticosteroids for some things.
 

debored13

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I did have a saliva test for cortisol and I was fairly low. I just would rather try other things than corticosteroids or even these adrenal glandulars. Next on my list is progesterone or pregnenolone which seem to be better than corticosteroids for some things.
I have also experienced effects similar to those adrenals on low dose naltrexone. It’s always something that I do for a few days and then the effect builds up and I get too tense. I even had high blood pressure readings on it. I think it increases ACTH. It seems like it can be a little too unpredictable as far as HPA axis effects, but it also has Specific immunosuppression effects that could be similar to corticosteroids. I said I would go off naltrexone for god after I had those high-ish bp readings but I start and restart short courses just to deal with awful PEM
 
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Just an update on large-dose hydrocortisone PEM Sheilding
When I was on 60 mg prednisone, I had significant problems with GI and "rebound"--if I took the prednisone in the morning, by evening I was collapsed in bed, with painkillers and a heating pad. I know that hydrocortisone isn't the same, however, I'm curious about how high is your "high dose". My other problem was indication of incipient bone loss. Would love to know your experience and results!
 

hamsterman

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When I was on 60 mg prednisone, I had significant problems with GI and "rebound"--if I took the prednisone in the morning, by evening I was collapsed in bed, with painkillers and a heating pad. I know that hydrocortisone isn't the same, however, I'm curious about how high is your "high dose". My other problem was indication of incipient bone loss. Would love to know your experience and results!
I've never taken that high of a dose, so I can't say for certain. The highest dose of prednisone I've ever been on was 40 mgs, for a nasty Cronhs flareup.... I havent had a flareup for several years though (knock on wood), but I don't remember crashing at night though.

My high dose for PEM protection for prednisone is 25 mgs. But I'm pretty large, so that might be equivilant to 20 mgs for an average-sized individual. From the others I've spoken to who use it for the same purpose... they usually say 20mgs is ideal.

As far as the rebounding at that dose.... I don't get much of a 'crash'. Currently I take it once a week at 10:00am... I usually can feel coming down at about 6pm... where I basically just lie in bed.... but its not painful. The next day I feel basically nothing.

As far as hydrocortisone, I take 80 mgs (which is equiv to 20 mgs of pred)...its only for unforseen PEM-causing situations... I don't get any sorta crash afterwards.

As far as bone density, I go into that in detail on my 'how to' that I'm writing. I really need to finish it soon. :) Basically, I do weight-bearing exercises, and take supplements.... but its more complicated than that.
 

Hip

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I tried DRibose with no effect at all.
Have you specifically tried D-ribose during your PEM periods, to see if it helps shorten the duration of PEM?

According to the (unproven) theory of PEM proposed by Myhill, Booth and McLaren-Howard (explained in this post), PEM is due to the loss of ATP molecules, and D-ribose helps the body re-manufacture those molecules more quickly.
 

perrier

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Have you specifically tried D-ribose during your PEM periods, to see if it helps shorten the duration of PEM?

According to the (unproven) theory of PEM proposed by Myhill, Booth and McLaren-Howard (explained in this post), PEM is due to the loss of ATP molecules, and D-ribose helps the body re-manufacture those molecules more quickly.
Dear Hip

What do you think about injecting ATP? or NADH? Or administering it via IV?
 

Hip

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What do you think about injecting ATP? or NADH? Or administering it via IV?
I am not sure that extracellular ATP provided by injection or by oral supplements would be taken into the cell, where according the above theory of PEM, there is a shortage of ATP molecules during PEM. But note that there is no supportive evidence for this theory of PEM, so it is just a hypothesis.

I've tried the supplement Swanson Peak ATP, which contains 400 mg of ATP disodium per capsule, with no major benefit noticed; although it does tend to perk my mood up very slightly, with what feels like a dopaminergic antidepressant effect.
 

debored13

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I am not sure that extracellular ATP provided by injection or by oral supplements would be taken into the cell, where according the above theory of PEM, there is a shortage of ATP molecules during PEM. But note that there is no supportive evidence for this theory of PEM, so it is just a hypothesis.

I've tried the supplement Swanson Peak ATP, which contains 400 mg of ATP disodium per capsule, with no major benefit noticed; although it does tend to perk my mood up very slightly, with what feels like a dopaminergic antidepressant effect.
I think there have been some studies on injected atp. It seemed risky and to have some cardiovascular effects. without knowing what's causing the loss of energy, injecting straight ATP rather than a cofactor for some of the reactions seems risky.
 

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What about in an IV? In Canada it is available, and it can be added to an IV, a Myers. NADH is also added.
Hi @perrier - have you checked out the discussion we've been having here?

http://forums.phoenixrising.me/inde...ical-mitochondrial-genetic-repair-poll.57797/

I have been doing well with 150mg NAD+ added to a nutrient IV containing high complex B, B5, folinic acid, MB12, HB12, carnitine, magnesium, and taurine. Plus glutathione and molybdenum. Plus PolyMVA.

It has been giving me more energy, for up to 48 hours. Sublingual NAD+ (not NADH) daily is filling in the gaps between IVs.

I was able to do a lot more without thinking about it and felt good. However, it did trigger PEM.

Hydrocortisone and more NAD+ didn't help. BCAAs did. My doctors and I noted most of my aminos were low, similar to Fluge and Mella's PDH blockade amino study. Tyrosine, methionine, ornithine, citrulline, lysine, and NAC have helped other problems, so I'm going to get a custom amino powder, all the commercial ones have the wrong combo of aminos.

My CoQ10 runs high - it isn't being used up though I take it just in case. I also take creatine, d-ribose, B vitamins, and hydrocortisone, and have not noticed a difference with any of them.

On the thread I posted, there are several articles on the benefits of NAD+.

NADH can convert to NAD+, but its one more step and just as expensive. And we want a low ratio of NADH to NAD+, not a high one. And beware of the heavily advertised nicotinamide riboside. It works on healthy athletes in studies, but many of us can't convert it to NAD+.
 

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Currently, if I take 500mg of liposomal glutathione in the morning, before exercise, then follow up exercise with 500mg reduced glutathione capsules, with 2-4 capsules of BCAAs along with the glutathione, most times, I can avoid PEM these days.

When I started out with this strategy, I was able to start in PEM and dig my way out by taking the glutathione and BCAAs.

I also take a lot of glutathione precursors (B vitamins, magnesium, and amino acids) daily and have a glutahione IV once a week.