Brain Fog, Fast Heart Rate, and Fatigue. Is Pyridostigmine Right for You?
Living with autonomic dysfunction is like being on a boat with a temperamental compass; you never quite know when you'll be thrown off course. My mornings start with a guessing game: will standing up cause a dizzy spell today, or will I make it to the kitchen without clutching the wall? It's a bit like your body's cruise control is out of whack.
I have to be strategic about the simplest things, like taking a hot shower – too long, and I might feel faint from the heat. And meals? They're carefully timed and portioned to avoid sending my heart rate through the roof.
Work requires its own set of tactics. I'm the one with a stash of salt packets and an emergency sports drink in my desk drawer, just in case my blood pressure decides to dip during an important meeting.
Pyridostigmine and Its Treatment History
Pyridostigmine is a medication known for its effectiveness in treating symptoms of myasthenia gravis, a neuromuscular disorder that causes muscles to get weaker as they are used more. Pyridostigmine works as a cholinesterase inhibitor, which means it blocks the enzyme that breaks down acetylcholine, a neurotransmitter that transmits signals between 2 nerve cells and between nerve cells muscles. By preventing the breakdown of acetylcholine, more acetylcholine is able to accumulate in the synapse (junction) between the nerve and muscle, increasing muscle contraction and improving muscle strength. Pyridostigmine also has the ability to modulate the immune system and has even been shown to increase CD4 cell levels in HIV patients whose levels weren’t normalized on standard HIV drugs. Part of pyridostigmine’s immune modulatory function may be due to impact on the vagus nerve - a long nerve that travels through most of the body and sends signals to pockets of immune cells throughout organs, to the GI tract, and much more.
In addition to myasthenia gravis, pyridostigmine has been used off-label to manage symptoms of other conditions such as Postural Orthostatic Tachycardia Syndrome (POTS), where it helps alleviate rapid heart rate and stabilize blood pressure upon standing. It has also been explored as a treatment option for certain symptoms of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), particularly those related to autonomic dysfunction, exertional tolerance, and muscle fatigue. As with any medication, the use of pyridostigmine should be under the guidance of a healthcare professional, with consideration given to its potential benefits and side effects.
Symptoms Treated
In the context of POTS, pyridostigmine can help alleviate symptoms such as:
Lightheadedness or dizziness upon standing
Rapid heartbeat or palpitations
Fatigue and weakness
For those with Long COVID and ME/CFS, pyridostigmine may offer symptom relief for:
Muscle fatigue and weakness
Cognitive dysfunction or "brain fog"
Autonomic nervous system irregularities
The Science Behind Pyridostigmine
Pyridostigmine is a medication that belongs to a class of drugs known as cholinesterase inhibitors. It works by inhibiting the breakdown of acetylcholine, a neurotransmitter that is essential for communication between nerve cells and muscles. By increasing levels of acetylcholine, pyridostigmine enhances communication within the nervous system and strengthens muscle contractions.
In conditions like POTS and ME/CFS, where autonomic dysfunction is present, pyridostigmine's mechanism of action may help by enhancing parasympathetic (vagal) tone. This can potentially improve symptoms like orthostatic intolerance (difficulty standing due to blood pressure changes) and stabilize heart rate variability.
Safety and Efficacy
Pyridostigmine is a medication that has been used for many years, particularly for the treatment of myasthenia gravis, a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles. Its safety and efficacy for this condition are well-established, making it a mainstay of treatment for patients with this disorder.
Common side effects are usually mild and can include gastrointestinal upset, muscle cramps, and increased salivation. More serious side effects, such as bradycardia (slow heart rate) or respiratory difficulties, are less common and typically occur with higher doses.
For off-label uses such as POTS, Long COVID, and ME/CFS, the safety and efficacy of pyridostigmine are less clear due to a lack of large-scale, randomized controlled trials. However, smaller studies and anecdotal evidence suggest that it may be beneficial in managing symptoms related to autonomic dysfunction, such as fatigue and orthostatic intolerance.
In POTS, for example, pyridostigmine is thought to improve orthostatic tolerance by increasing the availability of acetylcholine, thereby enhancing the autonomic ganglia's ability to maintain vascular tone upon standing. Patients with Long COVID or ME/CFS who experience similar autonomic symptoms may also find symptom relief with pyridostigmine.
The Path Forward
Pyridostigmine has been used for years off-label to treat those with autonomic dysfunction. Varying degrees of autonomic dysfunction are commonly seen with conditions like Long COVID and ME/CFS. While pyridostigmine is not a cure, its potential to improve quality of life makes it a valuable option in the treatment arsenal. If you are interested in exploring pyridostigmine as a treatment option, consult with your healthcare provider or visit RTHM Direct to learn how pyridostigmine can help combat a variety of autonomic symptoms and get you back on the path to better health.
Follow the Science
Pyridostigmine has a history of being used off-label for symptoms experienced by people with autonomic dysfunction, such as postural orthostatic tachycardia syndrome (POTS). Because of this benefit, current studies are looking at the potential benefits pyridostigmine may have for those with Long COVID, ME/CFS, and MCAS that also include autonomic dysfunction. Early studies that, when administered during acute COVID-19, pyridostigmine reduces mortality among patients hospitalized for severe COVID-19. Learn more by exploring the following studies below.
Fragoso-Saavedra et al. Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial. Mol Med. 2022 Nov 8;28(1):131. doi: 10.1186/s10020-022-00553-x. PMID: 36348276; PMCID: PMC9644007.
Squires, J., Al-Zayer, S., & Systrom, D. M. (2023). Exercise capacity in myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) treated with long-term pyridostigmine. European Respiratory Journal. https://doi.org/10.1183/13993003.congress-2023.pa4639
Joseph P, Pari R, Miller S, Warren A, Stovall MC, Squires J, Chang CJ, Xiao W, Waxman AB, Systrom DM. Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine. Chest. 2022 Nov;162(5):1116-1126. doi: 10.1016/j.chest.2022.04.146. Epub 2022 May 6. PMID: 35526605.
KANJWAL, K., KARABIN, B., SHEIKH, M., ELMER, L., KANJWAL, Y., SAEED, B., & GRUBB, B. P. (2011). Pyridostigmine in the Treatment of Postural Orthostatic Tachycardia: A Single-Center Experience. Pacing and Clinical Electrophysiology, 34(6), 750-755. https://doi.org/10.1111/j.1540-8159.2011.03047.x
Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation. 2005 May 31;111(21):2734-40. doi: 10.1161/CIRCULATIONAHA.104.497594. Epub 2005 May 23. PMID: 15911704.
Grubb, B. P. (2008). Postural Tachycardia Syndrome. Circulation, 117(21), 2814–2817. https://doi.org/10.1161/circulationaha.107.761643
