List of "PEM Buster" 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") on this thread were compiled from other forum threads detailing ME/CFS patients' experiences with supplements and drugs they observed reduced or eliminated their PEM.
PEM Reducer Supplements and Drugs
The following are the supplements, drugs and other treatments that ME/CFS patients have found reduce PEM, given in approximate order of efficacy (best or most promising PEM reducers at the top of the list):
Corticosteroids — taken before exertion can completely prevent PEM; see the corticosteroids section. below.
Mestinon (pyridostigmine) 10-180 mg daily— helps some patients entirely avoid PEM.
Cannabis — taken just as PEM begins to appear prevents PEM from fully manifesting; see the cannabis section below.
D-ribose — 5 grams, three times daily.
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) — 2 grams (half of a level teaspoon).
Citrate supplements — 3 grams.
Creatine hydrochloride — 2 grams.
Citrulline — 1000 mg.
Catalase — 600 mg (taken after exercise).
Cold therapy — such as a cold bath.
Cumin (Cuminum cyminum) — level teaspoon of cumin powder; effects last for 3 days.
Chinese skullcap root (Scutellaria baicalensis) — 3 to 6 grams, taken two to three times daily
These anti-PEM supplements and drugs are further detailed 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 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.
If you are going try these high doses of Q10, you may be better off taking the
ubiquinol form, not the more common and cheaper ubiquinone form. This is because blood levels of ubiquinol will continue to rise with increasing dose levels; by contrast, if you take ubiquinone, the blood levels of Q10 will eventually begin to flatten out with increasing dosage. Ref:
here.
@msf found that
Chinese skullcap root is a good PEM shielder, at a dose of 3 to 6 grams, taken two to three times daily.
One
review paper says both baicalin and baicalein (found in Chinese skullcap) and protect mitochondria from oxidative stress. And
one study found baicalin restored the infection-triggered decrease in mitochondrial complex V (aka: ATP synthase, or ATPase). Mitochondrial complex V (ATP synthase)
has been found deficient in ME/CFS. This might explain the anti-PEM effect of Chinese skullcap root.
Chinese skullcap root contains 8 to 16% of baicalin, and 0.2% to 1.2% of baicalein. Ref:
1 So 5 grams of root corresponds to about 500 mg of baicalin. Note that you can buy 95% pure baicalin from
LifeMode, costing $19 for 20 grams. Baicalin bioavailability in rats 2.2%, and half-life around 10 hours. Ref:
1 In the body, baicalin converts into baicalein. Ref:
1
@Wishful finds that
cumin (Cuminum cyminum) effectively blocks physical exercise from causing PEM, as well as reducing any PEM that is already present. So cumin appears to be both a PEM shielder and PEM reliever. He finds just 1 level teaspoon of cumin powder blocks PEM for 3 days. This spice contains cuminaldehyde, which has known mitochondrial effects. Unfortunately
@Wishful says that no other ME/CFS patients so far seem to have benefited from cumin. See also
this thread.
Cannabis appears to be a good PEM shielder/reliever, when taken just as the first signs of PEM appear. See the cannabis section below for more details.
Some ME/CFS patients find
Mestinon (pyridostigmine) taken in doses of 10-180 mg daily eliminates PEM from physical exercise, see
here. Dr David Systrom has a
clinical trial of pyridostigmine for ME/CFS.
Nothing however seems to be quite as powerful as corticosteroids for total PEM shielding.
Biochemical Theory of PEM: How the PEM Busters Work
The above PEM reducer supplements and drugs were discovered by various ME/CFS patients on this forum, who observed that a supplement or drug they were taking had anti-PEM effects.
Interestingly, many of these PEM buster supplements —namely creatine, citrulline, BCAA, Q10, bicarbonate and glutathione — are shown in studies to
inhibit exercise-induced lactate. See the athletic exercise performance studies in
this post. So lactate inhibition may be the mechanism of action of these PEM busters. Lactate inhibition probably does not apply to D-ribose, cannabis or corticosteroids, which likely reduce PEM by other mechanisms.
D-ribose may work 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), it is suggested that 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 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.
Myhill, Booth and McLaren-Howard's 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 more quickly.
Their theory suggests that lactic acid is not the initial cause of PEM (that's due to a shortage of ATP molecules which deliver energy), but lactic acid build-up from exercise further compounds the energy shortage problem of PEM, because to clear lactic acid by converting it back to glucose, it requires considerably more energy than was originally gained from the conversion of glucose to lactic acid.
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. It may be the isoleucine in BCAAs that is responsible for the bulk of the anti-PEM affects, as isoleucine significantly increases glucose uptake. See
this post. BCAAs have been proposed to alleviate exercise-induced fatigue. Ref:
1
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.
Citrate supplements (such as sodium citrate or potassium citrate) may be an alternative to sodium bicarbonate; see
@Mel9's post
below. I would think you need to use doses around 3 grams or so (the sort of dose used for alkalizing). Citrate has the advantage that you can take in on a full stomach, and it will not reduce stomach acid levels (bicarbonate is best not taken when you are digesting food).
Here is a post detailing the anti-PEM effects of
cold therapy (cold baths or swimming in cold water).
@helen1 finds PEM symptoms decrease significantly after cold therapy, especially nausea and weak legs, and finds it is most effective if you catch the PEM early.
Studies on these PEM Buster 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/Reliever
Several ME/CFS patients have reported that
cannabis is a good PEM shielder/reliever: 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 before it manifests.
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, Cannabis indica may be the best choice, rather than Cannabis sativa. 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 active principles in cannabis can affect mitochondria: cannabinoid type 1 receptors (CB1) are found on mitochondria, and THC is an agonist of the CB1 receptor, whereas CBD is an antagonist of this receptor. So maybe that is how cannabis helps avoid 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. When normal doses of these corticosteroids are taken around one or two hours
before any physical or mental exertion, they can totally prevent any PEM from later appearing.
But 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.
Note that it is
normal doses of corticosteroids (eg, prednisolone 20 mg, or hydrocortisone 80 mg) that can prevent PEM, not the
low doses (eg, prednisolone 5 mg, or hydrocortisone 20 mg) that some ME/CFS patients take daily.
And note that normal doses of corticosteroids should only be used occasionally in ME/CFS, perhaps as a maximum of once a week. If normal doses are used every day on a long term basis, this can lead to worsening of ME/CFS (possibly because the corticosteroid Th1 immune suppression may allow any underlying viral infections to proliferate).
Examples of ME/CFS patients using corticosteroids to prevent PEM:
▶︎
@Patrick* found that prednisone at a dose of 20 mg taken a just before a mentally exerting event (such as socializing) was effective at relieving ME/CFS symptoms. Sometimes he would take another 20 mg later in the day. Other ME/CFS patients have vouched this works effectively and reliably (though others report ill effects from this corticosteroid drug). Note that this dosing is only used as a
one-off, not regularly every day.
▶︎
@hamsterman found hydrocortisone at a
one-off dose of 80 mg (or alternatively and equivalently prednisolone 20 mg) taken 30 minutes before a mentally or physically exerting event very effective for preventing PEM due to physical and mental exertion:
Correction:
@hamsterman told me he was actually using predniso
lone and not prednisone as he stated in the quote above. The former takes effect faster.
Note that
@hamsterman said he has the autoimmune disease Crohn's, which causes has extreme fatigue, though thinks he may have ME/CFS as well.
▶︎
@gregh286 found prednisone will block PEM from appearing.
How long for the corticosteroid PEM shield to kick in? Prednisone takes around
2.6 hours for the drug to reach peak levels in the bloodstream, whereas predniso
lone is faster, taking only around
1.3 hours. Hydrocortisone takes around
1 to 2 hours. Ref:
1
So when taking any of these corticosteroids in advance to prevent PEM from a physical or mental exertion you are about to perform, give these drugs enough time to kick in before starting the exertion, else your PEM shield will not be in place. CAUTION: note that there are also timed release versions of prednisone, which only slowly release the drug into your system over several hours, so it might be best to avoid these.
What is the dose equivalence of different corticosteroids? Difference corticosteroid drugs have different strengths: hydrocortisone 80 mg = prednisone 20 mg = predniso
lone 20 mg = methylprednisolone 16 mg = triamcinolone 16 mg = dexamethasone 3 mg = betamethasone 2.4 mg. Source:
here.
How long does the corticosteroid PEM shield last? 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, your PEM shield may last about 4 to 8 hours for prednisone and predniso
lone, and last around 2 to 4 hours for hydrocortisone.
When taking prednisone 20 mg,
@hamsterman found its PEM protection lasted for as long as 8 hours; but when he tried exercising 13 hours after his prednisone, then he crashed. So for a single 20 mg dose of prednisone, around 8 hours would seem the limit of its protective effects. Of course you could take a second 20 mg dose at the 8 hour point, and get another 8 hours of protection.
Efficacy of the corticosteroid PEM shield. This is how effective
@hamsterman found a one-off dose of predniso
lone 20 mg to be at completely eliminating PEM from a major physical workout at the gym:
Note that
@hamsterman was using predniso
lone and
not prednisone as he stated in the quote above. Interestingly enough, after doing this intense cardiovascular exercise once weekly for a year, courtesy of the PEM shielding provided by corticosteroids,
@hamsterman was able to completely cure his POTS (see
here). But his ME/CFS has not improved through exercise. POTS is known to responds well to exercise, whereas ME/CFS does not.
Corticosteroids may lead to major problems if taken daily for weeks in a row. If corticosteroids are used every day on a long term basis of weeks, this can lead to worsening of ME/CFS, perhaps because the immune suppression from the corticosteroids may allow any underlying infections to proliferate (corticosteroids reduce the antiviral Th1 response, reduce T-cell function, and increase the antibacterial Th2 response).
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.
Dr Chia
says two ME/CFS patients who took prednisone daily for two weeks remarkably improved; but when they tapered off they got much worse, and ended up in the hospital. He believes it such extended use of corticosteroids allows enterovirus to proliferate.
The mechanism by which corticosteroids provide a potent PEM shield may relate to their effects on energy metabolism and mitochondrial oxidative phosphorylation.
Mitochondria possess a glucocorticoid receptor, and that receptor regulates oxidative phosphorylation. Refs:
1 2
Interestingly, the over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids. Ref:
1 In
this study of adding theophylline to the corticosteroid regimen of asthma patients, they used a dose of 250 mg of theophylline daily. Theophylline also has a vasoconstriction effect, and is thus useful for POTS, to reduce blood pooling in the legs on standing. Whether theophylline would help ME/CFS patients get the same anti-PEM effects from lower doses of corticosteroids remains to be seen.
