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, predniso
lone 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 predniso
lone can work amazingly well to prevent physical exertion-induced PEM, if taken just before a physical exercise workout:
Note that
@hamsterman was using predniso
lone 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 predniso
lone and
not prednisone as he stated in the quote above. Predniso
lone 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 predniso
lone 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 predniso
lone 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 predniso
lone, and last around 2 to 4 hours for hydrocortisone.
Basically, I do weight-bearing exercises, and take supplements.... but its more complicated than that.
