Mestinon, AKA Pyridostigmine, is an acetylcholinesterase inhibitor typically used to treat myasthenia gravis- a neuromuscular disease. It is a drug that can markedly reduce fatigue and enable patients to exercise in general disorders.
ME Specialists and Mestinon
Pulmonologist, Dr. David Systrom, specialises in patients with disorders beneath the exercise intolerant umbrella. As cardinal symptoms of ME include post-exertional malaise and exercise intolerance, Dr. Systrom has begun to focus on this patient cohort. He has conducted invasive cardiopulmonary exercise testing on ME patients that can determine oxygen usage and blood flow abnormalities.
Over the past three years, Dr. Systrom has given Mestinon to hundreds of his exercise intolerant ME patients with autonomic nervous system anomalies. He has found that it has provided many patients with their lives back and “really helped many people.” Dr. Systrom encourages his ME patients to slowly increase their exercise levels, typically on a recumbent bike while on Mestinon. Dr. Systrom’s ME theories and rationale for using Mestinon can be found here.
An ME patient of Dr. Systrom experienced a miraculous recovery on Mestinon and her story can be found here. She gradually titrated her dosage upwards to 180mg a day, presumably taken in smaller doses e.g. 60mg three times per day.
Dr. Goldstein has included Mestinon in a list encompassing his favourite drugs for ME patients. He has noted that it has improved patients’ fatigue, cognitive impairment, muscle weakness and muscle aches. Dr. Goldstein believes that Mestinon may benefit ME patients due to the drug increasing growth hormone levels which are typically low in ME patients. His recommended dosages are in the 30mg-60mg a day range.
Dr. Teitelbaum has written briefly on Mestinon and has an interest in its ability to increase growth hormone in ME patients. He cites research by Dr. Robert Bennett that has found low growth hormone levels in ME patients. Dr. Teitelbaum also parrots Dr. Bennett’s finding that Mestinon can increase growth hormone levels when used at a dosage of 30-60mg taken 3-4 times daily. Renowned cardiologist, Dr. Blair Grubb, also has many of his POTS patients on Mestinon.
Studies
A Japanese case study by Kawamura et al. found that all three ME patients experienced positive “dramatic effects” from the Mestinon. The subjects had experienced ME for 3, 10 and 15 years and had dysautonomia and EBV titers. The patients responded to a daily dose of either 10mg or 30mg of Mestinon and were on the drug for one month. The authors concluded by strongly recommending small doses of oral Mestinon (10mg per day) in ME patients with:
- Mild impairment of autonomic functions.
- A positive EBV test (anti-VCA IgG).
- An increase (40% plus) in response to the repetitive nerve stimulation test.
A Fibromyalgia study by Jones et al. found that patients experienced a significant improvement in sleep and anxiety after taking Mestinon. 154 out of the 165 Fibromyalgia patients completed the study with the authors theorising that the Mestinon helped due to improving vagal tone and therefore sleep and anxiety.
A study by Kanjwal et al. examining Mestinon usage on POTS patients found that 168 out of the 203 subjects were able to tolerate the drug. 55% experienced a reduction in fatigue after taking the treatment. 51% of those who tolerated the Mestinon experienced an improvement in orthostatic intolerance.
A study by Arvat et al. found that 60mg of Mestinon causes an increase in growth hormone. A study by Berwaerts et al. found that ME patients tended to have reduced nocturnal secretions of growth hormone. At one stage, Dr. Cheney believed low growth hormone was instrumental in the pathogenesis of ME. His musings about this can be found here.
Potential Mechanisms of Action in ME Patients
Mestinon may benefit ME patients due to:
- Increasing oxygen and blood flow to the muscles’ mitochondria.
- Increasing growth hormone levels.
- Improving parasympathetic nervous system and vagus nerve functioning.
- Increasing acetylcholine and thus promoting REM sleep, improving muscle movements and enhancing cognitive faculties.
- Raising exercise tolerance.
My Experience with Mestinon
My planned Mestinon dosing schedule involved an initial dose of 15mg and if tolerated, a gradual increase to 15mg taken 4 times a day. If I didn’t reap any benefits at this dose, I planned to venture up to 60mg taken 3 times per day (180mg per day total). I began a 15mg dose of Mestinon on the afternoon of the 1st of September. What followed was quite extreme sleepiness and drowsiness for the next 7 hours until I went to sleep at my normal bedtime.
The next day I trialled 15mg of Mestinon taken just before bedtime with the hope that this Mestinon-induced drowsiness would improve my sleep. Unfortunately my sleep was worse than normal! I would continuously wake just before my normal waking time. I also experienced more severe restless legs syndrome during this period. Another downside of the Mestinon was the next day sleepiness I would still inevitably endure. After a week of taking the 15mg dose of Mestinon before bedtime that was inducing continual poor sleep and RLS, I decided to cease the medication.
Dosage and Side Effects
In myasthenia gravis, the dosage of Mestinon is typically in the ballpark of 180mg a day (often taken in several smaller dosages). ME patients have generally used much lower doses, generally 30mg a day, although some patients have ventured up to 180mg a day. The Kawamura et al. case study on ME patients taking Mestinon recommended 10mg a day. In contrast, Dr. Systrom seems to encourage patients to gradually increase the dosage to 180mg a day if lower doses are tolerated. Dr. Goldstein is more moderate in his approach, recommending ME patients take 30-60mg per day.
Dr. Systrom states that any side effects are generally minor and may include diarrhea, gastrointestinal issues or twitching muscles. Anecdotally online, some ME patients have reported side effects that are typically gastrointestinal and transient. The Kanjwal et al. POTS study found the most common side effects to be gastrointestinal in nature with 19% experiencing this symptom. The Jones et al. Fibromyalgia study found that Mestinon was generally well tolerated. Mestinon should be used with caution in patients with diabetes or asthma.
Conclusion
Due to the side effects of sleepiness and also ironically, poor sleep, I only managed to take a low dosage of Mestinon for one week. It is therefore difficult to ascertain if it would have evoked any positive effects if taken longer and at a higher dose. The patients that may benefit most from Mestinon are; exercise intolerant patients with autonomic nervous system anomalies, patients with low levels of growth hormone, those with POTS or those with EBV and an increase in response to the nerve stimulation test. Mestinon is generally well tolerated with gastrointestinal side effects the most likely. Anecdotally online, there are a reasonable number of patients who have taken Mestinon, with some calling it a “miracle drug” for them, on the flip side, others have reported no effect or side effects.
Living With Chronic Fatigue Syndrome 
Thanks for doing all this research! Personally I found that I cannot take this medication in the afternoon or evening or else it keeps me up all night. Thus I must take in the morning, or at least before 2 pm. I can only tolerate about 3.5 mg of a 60 mg pill, taken 1-2 times per day (yes it is hard to split a pill up like that, so you can also try the liquid version). I have not been able to get up higher than that. When I get up higher than that it makes me quite shaky. It also increases my hemorrhoids significantly. Ugh. But it does give me energy. I’m still experimenting with this drug and dose, and with its supplement equivalent, called Huperzine A (I found I respond exactly the same way to the supplement as I do to the medication, in all respects, including the positive and the negative effects). Another thing I will note is that when there is a crash Mestinon and Huperzine A do not seem to override the crash. Another words, the crash is still a crash and the drug does nothing. But I am also taking a tiny dose. I have three warnings for those who wish to try either Mestinon or Huperzine A: one is to start at a much much smaller dose than you think you should start at, because this can cause severe G.I. issues at first. Mostly it will make you poop an awful lot until you become acclimated to the medication or supplement. Secondly, do your research first before taking this, because this drug has been scarily implicated in Gulf War Illness, especially with regards to when it is taken concurrently with, or when the person taking it is also exposed to, pesticides. Third, it may give you energy, so be careful taking it in the late afternoon or evening, or you may have trouble sleeping. And lastly, I found that taking it can sometimes override my exhaustion, sort of like taking speed, which in the end can induce a bad crash if you are not super careful about not pushing past what your body is actually capable of doing.
@R
Thanks for the comment!
It is my understanding that Mestinon is more likely to produce an energetic or stimulating effect than a drowsy result- I think my experience was an aberration as I haven’t come across anyone online that has had a similar experience. Out of all the anecdotal reports of ME patients trying this treatment I have read, you are the first one I have come across who can’t tolerate doses of more than 10mg but have tried and can tolerate lower doses. I was prescribed the 60mg tablets which I was already struggling to divide into quarters!
I am always on the lookout for an elusive treatment that will treat a crash, it is unfortunate that Mestinon doesn’t seem to be this treatment. I would like to echo your sentiments regarding not pushing past what your body is capable of while on Mestinon- or any treatment for that matter. Thanks again for the comment and all the great info.
Hi Cfssufferer,
I have recently started Mestinon at 15mg. I went up to 30mg 10 days ago & all it has done is make me even MORE fatigued. I take my dose & then 30 min later, I crash. I’ve tried taking before bed but it doesnt really help sleep at night. I’m frustrated bc I have severe dysautonomia & was thinking this would help.
@Sherri It’s unfortunate that you’ve experienced more fatigue as a result of the Mestinon. Some patients report being able to tolerate lower doses than you are trying but this is something that should be discussed with your physician. I always struggle knowing how long to persist with a treatment before giving up; especially when side effects are involved. Like you, I had high hopes that the Mestinon would help me in some way and I’m sorry to hear that it hasn’t helped you. Thanks for leaving your Mestinon trial info here. All the best
I have tried it, up to 60 mg a day. I had severe side effects: intense muscle weakness, low blood pressure, trouble with talking. All my ME symptoms got worse. My doctor is a cardiologist and he gives it to many patients, of whom many report improvement. I was an exception. So keep an eye out, this can happen too. My immediate side effects stopped a day or two after I took my last dose, and now I’m recovering from the whole setback for weeks.
@alma I’m sorry to hear that you had such a poor experience with the Mestinon. I hope your symptoms start to stabilise and you find a treatment that helps soon. Wishing you the best in health.
I have scoured the internet for as many anecdotal reports of ME patients trying Mestinon as I could find. Based on each patient’s comment online, I have attempted to categorise them in order to gain some perspective on how ME patients have seemingly fared with Mestinon. This is what I have found:
8/38= Major benefits
11/38= Moderate benefits
5/38= Mild benefits
2/38= Benefits but with side effects
6/38= No effect
4/38= Mild or moderate side effects
2/38= Severe exhaustion or severe muscle weakness
These numbers are clearly not scientific in rigour but do give some indication that Mestinon seems to be potentially benefiting at least a subgroup of ME patients. I haven’t included any doctor anecdotal reports or anything from the above article in these numbers. In regards to other treatments ME patients have trialled, these numbers are fairly impressive. I should stipulate that there are many flaws with my ‘anecdotal poll’ not least that patients who had experienced benefits may be more likely to comment on how a treatment has affected them. Also, I cannot vouch that every patient I have included has ME/CFS.
I should also emphasise the anecdotally wide range of dosages that ME patients are individually responding to. Some patients have reported anything over 10mg being too much for them and an optimal dose of around 5mg. Other patients have reaped maximum benefit at up to 60-180mg. Mestinon is available in 10mg or 60mg tablets. ME doctors and researchers seem to be unified in advocating a low starting dose of Mestinon and a very gradual increase if no side effects are noticed. Patients online have also often noted that mild symptoms experienced while on Mestinon are often transient. As always, consult your physician before commencing any treatment and follow their advice.
Very helpful!