Long COVID, PEA and Luteolin

Functional Medicine Research with Dr. Nikolas Hedberg, DC

Palmitoylethanolamide (PEA) is a naturally occurring endocannabinoid-like lipid mediator naturally found in many plants. PEA is analgesic, immunomodulatory, neuroprotective, antipyretic, antiepileptic, anti-inflammatory, anticonvulsant, antibacterial and antiviral. PEA also increases endocannabinoids and it down regulates mast cell activation.

PEA can improve immune system function without increasing inflammation. PEA also regulates fatty acid metabolism, reduces oxidation of fats, and inhibits excessive nitric oxide.

PEA may contribute to enhanced muscle recovery and improved cognition, mood and sleep. PEA may be indicated for anti-aging, immunoenhancement, brain health, allergies, and joint health.

These properties make PEA a perfect compound for managing the difficult symptoms of Long COVID.

Studies on PEA and Long COVID

A recent study entitled, “The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study” looked at the potential benefits of PEA for Long COVID symptoms. Some of the most common Long COVID symptoms include fatigue, brain fog, headache, exercise intolerance, trouble breathing, memory lapse, anosmia, dysgeusia, depression, anxiety, psychosis, nervous asthenia, PTSD, insomnia, delirium and anhedonia.

How was the study done?

33 (10 male and 23 female) patients were given 600 mg PEA twice a day for 3 months. All patients were administered the post-COVID-19 Functional Status (PCFS) scale, to assess meaningful function, before (T0) and at the end of the treatment (T1). None of the patients had any side effects from the PEA.

Study results

All the patients experienced improvement in their Long COVID symptoms as measured by the Post-COVID-19 Functional Status scale.

PEA, Luteolin, and Long COVID Studies

The combination of PEA and Luteolin has been studied extensively, with multiple published papers showing the synergistic benefits of these two compounds. PEA and luteolin have been shown to reduce neuroinflammation by modulating microglia and reducing reactive oxygen species (ROS).

Luteolin is a flavonoid, specifically a flavone, found naturally in fruits, vegetables, and herbs such as celery, parsley, lettuce, spinach, peppers, broccoli, cabbage, carrots, onions (leaves), and apples (skins). Luteolin is similar in structure to quercetin, but luteolin is more potent and is sometimes referred to as a “supercharged” quercetin.

Luteolin has the following properties:

• Anti-inflammatory
• Anti-neurodegenerative (neuroprotective)
• Mast cell stabilizer
• Antioxidant
• Anticancer
• Antiallergy
• Antihypertensive
• Antiviral
• Antidiabetic

Another study entitled, “What Is the Role of Palmitoylethanolamide Co-Ultramicronized with Luteolin on the Symptomatology Reported by Patients Suffering from Long COVID? A Retrospective Analysis Performed by a Group of General Practitioners in a Real-Life Setting” looked at the medical charts of 49 patients with Long COVID who were treated by one of nine doctors in Rome, Italy.

The patients were treated with 700 mg of PEA and 70 mg of luteolin twice a day for 90 days.

No side effects were reported during treatment, nor any drug interactions with their medications.

The authors conclude, “Supplementation with PEALUT (PEA and Luteolin) helped to improve all patient-reported symptoms, especially pain, anxiety and depression, fatigue, brain fog, anosmia and dysgeusia, leading to an overall improvement in patients’ health status.”

PEA and luteolin have been found to be effective for post-COVID loss of smell (anosmia) and memory loss.

The first study entitled, “Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial” was done for 90 days on subjects who took 700 mg of PEA and 70 mg of luteolin once a day combined with olfactory training.

The results of this study found that those supplementing with PEA and luteolin had significant improvements and even resolution of their loss of smell compared to the placebo group who only did olfactory training.

The second study entitled, “Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial” was virtually identical to the first study. Subjects took 700 mg of PEA and 70 mg of luteolin along with olfactory training for 90 days, and they achieved significant results compared to the control group.

The third study entitled, “Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial” set out to see if doubling the dose of PEA and luteolin to 700 mg of PEA and 70 mg of luteolin taken twice a day was superior to just once a day dosing.

The results were surprising because there was no difference between the single dose or doubling the dose. This is good news for patients because this results in a significant cost-savings.

The fourth study entitled, “Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study” used the same dose as the above studies of 700 mg of PEA and 70 mg of luteolin combined with olfactory training and found significant improvements in olfaction and improved memory/brain fog.

The one common thread among all the above studies was the importance of olfactory training along with the PEA and luteolin supplement.

How best to take PEA and Luteolin?

PEA is not well absorbed, so it must be delivered in a specific form called Levagen+. Levagen+ PEA uses LipiSperse technology to enhance the absorption of PEA.

Most of the studies on Levagen+ PEA used 300 mg twice a day with excellent results. For more complex cases, 600 mg twice a day of Levagen+ PEA may provide better results.

The therapeutic dose of luteolin is 100-200 mg a day, since it is a potent flavonoid.

Moss Nutrition’s product PEA Luteolin Select contains 300 mg of Levagen+ PEA and 50 mg of luteolin per capsule. I use one capsule twice a day with meals for most patients, and two capsules twice a day for more complex cases.

Long COVID patients are experiencing more and more viable supplement options, and the combination of PEA and luteolin is now part of my core Long COVID protocol.

Hedberg Institute members can download my Long COVID protocol in the Practice Tools section of your membership area. Hedberg Institute members also get access to all my course material on how to treat Long COVID.