What is Palmitoylethanolamide?
Palmitoylethanolamide (PEA) is a naturally occurring compound that has anti-inflammatory, neuroprotective, and pain-relieving properties. PEA has been used for decades in managing chronic pain and neuroinflammatory conditions. In Long COVID, it is being investigated as a therapy to reduce symptoms such as fatigue, brain fog, and sensory disturbances. PEA is often combined with luteolin, a natural compound with strong antioxidant and anti-inflammatory properties. Luteolin is thought to complement PEA by further reducing oxidative stress and neuroinflammation, particularly in the brain.
How PEA Helps with Long COVID
- Reducing Neuroinflammation – Many Long COVID symptoms are believed to stem from inflammation in the nervous system. PEA and luteolin work together to calm overactive immune cells in the brain (like mast cells and microglia).
- Improving Fatigue and Mood – Through its modulation of inflammatory pathways and possible support for mitochondrial function, PEA may help reduce fatigue and depressive symptoms.
- Restoring Sensory and Cognitive Function – Some studies show improvement in anosmia (loss of smell), dysgeusia (loss of taste), and brain fog with PEA-Luteolin treatment.
What the Research says
Emerging studies suggest that PEA (palmitoylethanolamide)—especially when combined with luteolin—may help relieve common Long COVID symptoms like fatigue, brain fog, loss of smell, and low mood. Research in both clinical and observational settings has shown meaningful improvements in energy, cognition, and overall well-being, with a strong safety profile. Experts believe PEA may work by calming neuroinflammation and supporting nerve recovery.
Key Studies on PEA and Long COVID:
Clinical Trials and Studies Showing Positive Effect:
- This 2022 retrospective cohort study included 33 Long COVID patients. Those receiving PEA (600 mg twice daily for 8 weeks) showed significant improvements in fatigue, anosmia, and cognitive dysfunction. Fatigue scores dropped, while the control group saw no meaningful change.
- This longitudinal study followed 185 Long COVID patients given a PEA-luteolin combination for 90 days. Olfactory and cognitive functions improved in patients treated with the PEA-luteolin combination. No serious side effects were reported.
- This retrospective analysis tracked 49 Long COVID patients treated with PEA-luteolin for 90 days. Significant symptom improvements were reported in fatigue, brain fog, pain, mood, and smell/taste loss. Overall health status improved with no adverse events.
- This case report described a 71-year-old man recovering from ICU-related nerve injury after severe COVID-19. He received PEA-luteolin (400 mg + 40 mg twice daily) for 6 months and experienced significant neurological recovery.
- This observational study included 98 COVID-19 survivors with neuropsychiatric symptoms. Those who took m/umPEA (600 mg twice daily) for 3 months reported significant improvements in depression and fatigue.
Theoretical Support:
- This review outlines how PEA may reduce neuroinflammation, oxidative stress, and mitochondrial dysfunction—key contributors to Long COVID symptoms. The authors propose that PEA may counteract the cytokine storm (a severe immune overreaction where the body releases too many inflammatory molecules too quickly) and support neurological recovery.
Final Thoughts
Palmitoylethanolamide, especially in combination with luteolin, is emerging as a promising natural therapy for Long COVID. Clinical studies have reported improvements in fatigue, cognition, smell/taste, and mood—with a good safety profile. Typical doses range around 300 – 1200 mg daily. Always start with the lowest dose and adjust from there. While more randomized controlled trials are needed, current evidence supports its potential role in managing persistent symptoms. As always, it’s best to consult a healthcare professional before starting any supplement or treatment.