How Palmitoylethanolamide Works

Overall Health

PEA plays a key role in maintaining homeostasis by regulating many physiological reactions associated with pain and inflammation. Some chronic conditions can deplete PEA, resulting in a hyper-immune response involving glial, microglial and mast cells.

Pain reduction

PEA occurs naturally in the body and in many foods. No side effects have been reported with its use, even at the highest doses. (Gabrielsson 2016)

In a recent meta-analysis of PEA involving a total of 1484 chronic pain patients, those taking PEA reported pain levels an average of 2.7 points lower than the control groups after 60 days

Brain Health

Excessive activation of these satellite, non-neuronal cells has been shown to maintain inflammation and result in neurodegeneration. PEA reduces excessive activation of these cells and decreases neuron loss

What is Luteolin?

Luteolin is a potent bioflavonoid with antioxidant and anti-inflammatory properties. Like PEA, luteolin has several mechanisms of action. It inhibits mast cells, as well as mast cell-dependent T cell activation.* (Theoharides 2018) In addition, it modulates microglial activation and inhibits pro-inflammatory cytokine production. (Dirscherl 2010) It also acts on GABA and opioid receptors in the spinal cord.


PEA occurs naturally in the body and in many foods. No side effects have been reported with its use, even at the highest doses. (Gabrielsson 2016)
The recommended daily dose of Mirica is equivalent to the amount of luteolin found in one artichoke. At this dose luteolin is safe and no side effects have been reported.

Immune system boost

This combination has been shown to reduce pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and chemokines (MIP-1 alpha, MIP-2) significantly more than PEA or luteolin alone. Additionally, PEA with luteolin was shown to reduce oxidative and nitrosative damage more effectively than PEA or luteolin alone.

The benefits of Palmitoylethanolamide.

PEA has piqued the interest of scientists since its discovery in the 1950s. Although large-scale safety and effectiveness studies are only recently starting to emerge, Despite this, PEA shows big potential as a pain reliever and anti-inflammatory.

A growing number of chronic disease sufferers who consume PEA believe it helps them deal with chronic and neuropathic pain.

The science behind PEA.

Scientists are currently researching the effects of PEA on cannabinoid receptor activation. Preliminary studies show PEA may benefit brain, heart, and immunological function.

PEA is a fatty acid that is similar to anandamide, the body’s major cannabinoid joy molecule.

Unlike ordinary fats, amide-containing fatty acids such as PEA and cannabinoids have a direct role in nerve signaling. These fascinating and recently discovered compounds are referred to as “neuroactive lipids.”

Why is PEA important?

One of the main problems with prescription drugs is that they can be addictive and cause a variety of side effects. Palmitoylethanolamide, on the other hand, is a natural substance that has pain-relieving benefits without the risk of addiction or side effects.
PEA also helps reduce inflammation, which is often the root cause of pain.

Palmitoylethanolamide and inflammation

Palmitoylethanolamide (PEA) is a natural anti-inflammatory and pain reliever that has been shown to have similar effects as NSAIDs without the side effects or risks associated with these drugs. PEA works by activating nuclear peroxisome proliferator-activated receptors (PPARs), which regulate inflammation in cells throughout your body.

The activation of PPARs by PEA helps to reduce inflammation in the brain. This is important because chronic inflammation can lead to the development of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. PEA also helps to protect neurons from damage and death, which can further reduce the risk of developing these diseases.

PEA stimulates the energy-boosting, fat-burning, anti-inflammatory PPAR alpha receptor. PEA also inhibits the activity of pro-inflammatory genes and the generation of several inflammatory chemicals by activating this important protein.

Evidence of PEA’s efficacy

PEA (600 mg PEA/day) decreased lower back pain in a trial of over 100 participants. It was so powerful that by the end of the experiment, half of the patients had stopped using any extra medicines.

Palmitoylethanolamide has been shown to improve inflammation and pain in arthritis. A study on inflammation and pain in arthritis showed that patients who took PEA had a significant reduction in pain, joint swelling, and morning stiffness.

Palmitoylethanolamide was also found to be safe and well tolerated in the study.

Synergistic effects when combined with other natural products

When combined with other natural antioxidant molecules like flavonoids, Polydatin, Luteolin, Quercetin, or Silyrmarin, PEA can effectively reduce inflammation.

This quality displays PEA’s ability to work both alone and in conjunction with other natural dietary compounds. Overall, these findings support the idea that PEA is a crucial endogenous inflammatory balancer.

In other words, PEA may be a viable option to anti-inflammatory medicines, or even a complementary therapy.

Research resources

Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy with Different Antioxidant Molecules Present in Diets

A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models

Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain..pdf

Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome