Summary

Palmitoylethanolamide (PEA) is a supplement known for various properties, especially its anti-inflammatory and mast-cell stabilising properties.

I currently don’t know a lot about it, but it is frequently mentioned in connection with MCAS, EDS, and chronic pain.

N-Palmitoylethanolamine is structurally related.

Known effects

Mast cell stabiliser. Also reduces inflammation. Neuro-protective. Also used in depression. Effective in reducing pain.

Marked as relevant to myalgic encephalitis, too, due to crossovers with fibromyalgia and long covid. Other research may exist.

Currently not very informed.

Rose takes this like this

The dose in most studies is 300 mg twice a day, and apparently 600 mg for depression.

I don’t currently take this as I’m testing other things, but it looks promising and was recommended by a local pain specialist orthopaedist.

It’s not the cheapest, so I’m waiting until I’ll be able to distinguish the benefit.

Research

Professor Rita Levi-Montalcini on Nerve Growth Factor, Mast Cells and Palmitoylethanolamide, an Endogenous Anti-Inflammatory and Analgesic Compound
https://www.omicsonline.org/open-access/professor-rita-levi-montalcini-on-nerve-growth-factor-mast-cells-and-palmitoylethanolamide-an-endogenous-anti-inflammatory-and-analgesic-compound-2167-0846.1000114.php?aid=12372
Summary of benefits in various pain treatments, including neuropathy, inflammation, and mast cells. Links to other sources.

Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity (2019)
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1671-5
In short, they tested and proved the method of action and how it prevents mast cell degranulation. Excellent for MCAS.

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations (2016)
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13580
The most useful finding here to me seems to be that it confirms PEA’s good safety profile in humans.

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse (2017)
https://www.frontiersin.org/articles/10.3389/fphar.2017.00857/full
Explains how it helps when delivered prior to exposure to an allergen – as mast cell stabilisers generally do.

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution (2015)
https://pubmed.ncbi.nlm.nih.gov/26055231/
Explains the neuroinflammation link and how it can help with mast-cell mediated neurogenic inflammation and neuropatheic pain. It can also be neuroprotective in models of stroke, spinal cord injury, traumatic brain injury, and Parkinson’s.

Could Palmitoylethanolamide Be an Effective Treatment for Long-COVID-19? Hypothesis and Insights in Potential Mechanisms of Action and Clinical Applications (2022)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970234/
Hypothesis based on the acknowledged qualities and how it can probably help in long covid fatigue and myalgia, where mitocondrial dysfunction can be hypothesised.

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study (2022)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326613/
PEA found to be effective in long covid.

Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies (2015)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676767/
Found effective for pain relief in fibromyalgia.

Other sources

Recommended by Ehlers-Danlos expert Pradeep Chopra, MD, among other suggestions in the following presentation on managing chronic pain in EDS:
https://www.ehlers-danlos.com/wp-content/uploads/2022/12/P-Chopra-2018Baltimore-Management-of-Chronic-Pain-in-EDS-S.pdf

Discussed in an ME/CFS blog:
https://www.healthrising.org/blog/2022/12/13/pea-luts-long-covid-chronic-fatigue-syndrome-fibromyalgia/