A reader message me with a drug that I was not familar with

Hello, my brother has CFS and I would like to ask you a question. We talked to a doctor at the ‘…..’ hospital in Germany who specializes on CFS. The doctor suggested taking Pyridostigmine bromide. What are your thoughts on that?

This is a drug that I am not familiar with and thus interested in finding out more.

First, what is it’s typical use:

Pyridostigmine bromide (PB) is a drug used during the Gulf War as a pretreatment to protect troops from the harmful effects of nerve agents. It has been used for more than 40 years in the routine treatment of myasthenia gravis and may be used following surgery in the reversal of neuromuscular blockade (Williams, 1984).

Gulf War and Health: Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines. (From NIH)

So, if the brother had been involved in the Gulf War, there seem to be some logic to this suggestion. However, constructive logic usually have risk and is inferior to doing research. What I found sent my air-raid alarms sounding.

Results indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for Chronic Multisymptom Illness over time.

Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort [2022]

Ah, ME/CFS had yet another name: Chronic Multisymptom Illness.

And the bad news went on:

• Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment [2022]
  • Exposure to Gulf War Illness-related agents leads to the development of chronic pain and fatigue [2021]

Difference of Opinion?

A reader pointed me to Mestinon on ME-Pedia.org which presents some interesting reads. My ground rules have always been to rely on gold standard sources, that is, peer-reviewed PUBMED articles.

This page does cites issues seen:  gastrointestinal symptoms , Multiple chemical sensitivity (MCS). This page also cites:  there are no clinical trials of Mestinon in ME/CFS. Evidence for it was:

• On Social Media: anecdotal patient reports of Mestinon are mixed [src]
• A single study from 2003, Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports [Full Text] which has not had any published follow up studies in 20 years.
• Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome”.  [2005] was of very short duration and stated “The short duration of follow-up in the present study (4 hours) makes it difficult to intelligently project the long-term efficacy of this treatment.”

My typical reading of OLD thin results is that there were follow up studies that showed no effect or negative effects, hence never submitted for publication (or not accepted by publishers).

Revisited PubMed

PubMed failed me because it did not find this drug by alternative names…

• Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine [2022]
  • This was a single dose test. “Pyridostigmine improves peak Vo₂ in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo₂, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. “
    

Bottom Line

I would declined, and actually ask the doctor for published studies that shows it would help. The evidence is that it would make the symptoms worst. A single dose appears to help, the evidence of the cumulative effect of multiple doses are a worsening of the symptoms.

This is one of the few cases that I would consider writing to the licensing authorities if the doctor response to being presented with the above information is arrogance.

For your brother, I would suggest getting an appropriate microbiome test (being in Germany, my choice would be BiomeSight.com from the UK), and using “Dr. Artificial Intelligence” at https://microbiomeprescription.com/ . Dr.A.I. fees are reasonable (free), with immediate availability once you get the test results. So far the feedback from people using him has been very positive.

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