Palmitoylethanolamide (PEA) Health Benefits
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What is Palmitoylethanolamide (PEA)?

Palmitoylethanolamide (PEA) is produced in the body to regulate [pain][27], inflammation and immunity. Some scientists believe PEA may protect the nerves and brain. Its many purported health benefits are intriguing to a growing number of scientists around the world. New research continues to be published showing additional benefits of PEA.

Many animals and plants also produce PEA. The highest amounts can be found in soy lecithin, soybeans, egg yolk, peanuts, and alfalfa [1].


NOTE: Do not confuse palmitoylethanolamide with phenylethylamine (a stimulant) which is also abbreviated PEA.

Palmitoylethanolamide is classified as a dietary supplement and has therefore not been approved by the FDA for the treatment of any medical conditions. GMP regulations set manufacturing standards for dietary supplements but don’t allow them to make claims about treating specific medical conditions.

As a supplement, PEA is available around the world. In Italy and Spain, PEA is marketed as a food for special medical purposes [2]. PEA is a very popular dietary supplement in Holland, Germany and many other countries, but it is relatively new in the USA.

Since its discovery in the 1950s, researchers have been intrigued by PEA's properties. It shows promise as a painkiller and anti-inflammatory, Many consumers have found PEA to be highly effective at reducing their chronic and neuropathic pain [3].

Several clinical studies have explored the effects of PEA on complex pain.

Scientists are also investigating the effects of PEA on activating the cannabinoid receptors. Research suggests PEA might support brain health, heart health, and healthy immune function [1, 4].

PEA is a fatty acid amid similar to anandamide, the so-called bliss molecule your body makes. Unlike regular fats, amide-containing fatty acids like PEA are directly involved in nerve communication. These intriguing and recently-discovered molecules are called “neuroactive lipids” [5].

PEA is not a cannabinoid. It is not psychoactive. It does not get you high. PEA is a compound that the body produces naturally.

Health Benefits of Palmitoylethanolamide (PEA)

1) Pain Relief

Much evidence backs up PEA’s ability to reduce complex pain. It has been investigated in over 30 clinical trials and a total of ~6k people since the 1970s [3].

The research speaks to PEA’s ability to reduce pain in general, including neuropathic and non-neuropathic pain.

In an analysis of 12 human studies, PEA supplements reduced chronic and neuropathic pain intensity without any serious adverse effects. At least 2 weeks (and up to 2 months) need to pass to achieve chronic pain relief.

PEA was typically given over 3 – 8 weeks at dosages between 300 and 2,400 mg/day. Taking it over a longer period of time strengthens its effects without causing tolerance [1].

In a pivotal trial of over 600 people, PEA (300 or 600 mg/day) strongly reduced sciatic pain, higher dose having a more beneficial effect. PEA reduced pain intensity by over 50% in just 3 weeks, which is rarely seen with most painkillers [6].

PEA reduced lower back pain in a trial of over 100 people (600 mg PEA/day). It was so effective that half of the included participants stopped taking any additional painkillers by the end of the trial [6].

PEA seemed to relieve pain caused by diverse health conditions. To outline some of these studies, PEA was investigated in:

  • Women with pelvic pain caused by endometriosis, an overgrowth of the uterus lining. In a trial of 56 women, PEA (300 mg/day) relieved pain and improved sexual function over 6 months [7]
  • Pain caused by fibromyalgia. In 80 people, PEA reduced the intensity of pain and tenderness when added to the standard treatment ([pregabalin][50]) [8]
  • People with sciatica who don’t respond to painkillers like Oxycodone [9]
  • Diabetics with pain from carpal tunnel syndrome caused by nerve compression (at a higher dose of 1,200 mg PEA/day) [9]
  • Pain after failed back surgery [9]
  • Cancer pain [9]
  • Arthritis pain [9]

Importantly, PEA didn’t cause side effects or drug interactions in any of the above studies.

Animal studies shed further light on its pain-relieving potential. In experimental animals (mice and rats), PEA:

  • Reduced nerve pain from a chemotherapy drug (paclitaxel) [10]
  • PEA’s derivative adelmidrol reduced acute and chronic pain and inflammation [11]
  • Reduced inflammation and lung damage [12]
  • Improved inflammation and pain in arthritis [13]
  • Lowered inflammation from spinal cord injuries [14]

2) Brain Health and Nerve Regeneration

PEA may be beneficial for neurodegenerative diseases and stroke because it seems to help brain cells survive and lower inflammation.

In a study of 250 stroke sufferers, a formulation of PEA improved recovery. It had a beneficial effect on cognitive skills, overall brain health, pain, and daily functioning. The effects were noticeable after 30 days and further improved over another month of supplementation [15].

PEA prevented Parkinson’s disease in mice, reducing damage in the brain and protecting [dopamine][64] neurons. Since the destruction of dopamine neurons is what causes Parkinson’s disease, PEA may be able to prevent this disease or its worsening. Clinical studies are needed to confirm these findings [16, 17].

In another study, PEA enhanced the healing of nerves in mice with spinal cord injuries. It increased neurotrophic factors ([BDNF][67], [NGF][68]), small proteins that help create new brain cells needed to regenerate tissues after traumatic damage of the spinal cord or brain [16, 18].

Aside from its direct effects on brain cells, PEA is important for brain health due to its action on our endocannabinoid system. This system plays diverse roles in behavior, cognition, mood, and seizure risk, among others.

PEA was able to relieve seizures and shorten their duration in rats by activating the endocannabinoid system in the brain. Its effects on seizures have yet to be investigated in humans [19].

3) Supporting Eye Health

PEA’s effects on protecting nerve cells extend to the eyes, naturally as the optic nerve is an extension of the CNS. Healthy nerves in the eyes are crucial for maintaining proper vision.

Retinopathy is an eye disease that can result in vision loss. It’s triggered by inflammatory damage to the nerves in the eye, most commonly caused by glaucoma and diabetes. PEA reduced eye nerve damage in over 9 clinical trials used in doses of 1,800 mg/day [20].

In 32 people with glaucoma, PEA reduced high eye pressure and improved vision over 6 months. PEA supplementation was safe and didn’t cause any side effects [21].

People with glaucoma can choose to undergo laser surgery but risk experiencing high eye pressure shortly after that can cause damage. PEA prevented increases in eye pressure given shortly after laser eye surgery in 15 people [22].

Animal studies revealed how PEA may achieve these benefits. In diabetic rats, it reduced eye key inflammatory substances that break down the blood-retinal barrier. Like the blood-brain barrier protects the brain, this eye barrier is crucial for eye health. It nourishes the eye but prevents harmful substances from entering [23, 24].

4) Symptoms of Depression

In a recent study of 58 people with [depression][77], PEA (1.2 g/day) given over 6 weeks greatly and rapidly improved mood and overall symptoms. PEA was added to antidepressant treatment (citalopram) and lowered symptoms by an impressive 50% [[25][78]].

This clinical study was a follow-up on numerous studies in which PEA improved symptoms of depression in animals.

5) Symptoms of Multiple Sclerosis

The analgesic and anti-inflammatory benefits of PEA make it an ideal candidate for [Multiple Sclerosis][79] (MS), which has a strong autoimmune and inflammatory nature. The first-line therapy (interferon IFN-β1a), on the other hand, often causes serious adverse effects. PEA may increase the effects of this immunotherapy while lowering the negative effects.

As an add-on to standard therapy, PEA reduced adverse effects and pain, improving the quality of life and cognition in a trial of 29 people with rapidly-advancing MS. The supplement also increased blood levels of PEA and anandamide [26].

6) Supporting A Healthy Immune System

As scientists became excited about PEA’s ability to relieve pain and nerve damage, its effects on the [immune system][81] were almost forgotten. In many early studies of over 4k people, PEA could fight the flu virus that causes influenza [4].

Despite achieving good results, the main problem with the initial studies was that egg yolk or other supplements that contained only small amounts of PEA were used. These were not standardized and it’s impossible to know how much PEA they contained. Fast-forward to the late 1970s, studies started using higher-quality PEA supplements [4].

PEA (1,200 mg/day) reduced the duration of the cold and symptoms such as fever, [headaches][84], and sore throat in a study of about 900 young soldiers. In four additional studies, PEA lowered the chances of catching a cold and the severity of symptoms. Additional studies should explore its effects as a standalone supplement and as an add-on to standard therapy [4].

7) Heart Health

Heart attacks result from a total blockage of blood vessels leading to the heart. For the damaged heart tissue to recover, proper blood flow needs to be recovered. In mice, PEA improved the recovery from heart attacks, reduced heart tissue injury, and lowered inflammatory cytokine levels [28].

PEA also reduces high blood pressure in rats and prevents kidney damage by lowering inflammatory substances. It also has specific effects similar to drugs commonly used to lower high blood pressure (ACEI). PEA blocked enzymes and receptors that increase blood pressure by narrowing the blood vessels (angiotensin receptor 1 and angiotensin-converting enzyme) [29].

8) Gut Inflammation

PEA was successfully used to relieve symptoms of inflammatory bowel disease ([IBS][89]) in animals. Mice with chronic gut inflammation have low PEA levels, while PEA supplements normalized bowel movement and prevented damage to the gut lining [2, 30].

In tissues taken by biopsy from people with [ulcerative colitis][92], PEA lowered inflammatory cytokines and the buildup of [neutrophils][93], immune cells that worsen symptoms and contribute to gut damage [2].

The gut damage caused by ulcerative colitis increases the risk of cancer. In mice, PEA prevented normal gut tissue from developing cancerous overgrowth [2].

Adelmidrol is an anti-inflammatory substance made by modifying PEA that can also improved IBS symptoms such as diarrhea and [weight loss][96] in mice [31].

9) Histamine Release

Some scientists think PEA might be a [histamine][98]-release blocker. In animal and cell-based studies, PEA improved eczema and skin allergies by lowering mast cell activation and blocking the release of histamine [2].

In dogs with eczema, PEA helped soothe symptoms by reducing skin inflammation and itching. PEA reduced inflammatory substances (TNF-alpha) and increased endocannabinoids in the skin (2-AG), which altogether strongly diminishes the allergic response [2].

PEA Supplement Dosage & Safety

Current data suggests that PEA is very safe. Long-term PEA supplementation has not been linked to adverse effects in small-scale studies. PEA was used in doses of 300 mg to 2,400 mg/day in clinical studies. Anecdotally, consumers have used doses up to approximately 5000 mg/day without reported side effects.

  • A minimum of 900 mg/day is often recommended to relieve nerve pain, while higher doses have been used (especially for spinal cord injury, diabetic nerve pain, etc.)
  • PEA up to 2.7 g/day are used for reducing damage to eye nerves in people with glaucoma or diabetes
  • For fighting the common cold, 1200 mg/day was the most typical dosage used in studies

People report starting out with a loading dose for the first two months, and then testing lower doses to find a maintenance dose that continues to deliver the expected benefits. The total daily dose can optionally be divided in two (morning and afternoon), ideally with food.

Micronized PEA supplements were used in most studies, some scientists considering them superior to other forms. Micronized PEA is a fine powder that may be better absorbed.

PEA dosage in clinical trials varied from 600 mg to 2400 mg per day.

Mechanism of Action

PEA activates the energy-boosting, fat-burning, and anti-inflammatory [PPAR alpha][36]. By activating this key protein, PEA stops the activity of pro-inflammatory genes and the production of many inflammatory substances [2].

PEA reduces the break-down of anandamide (the bliss molecule). This increases the levels of calming anandamide in your body, helping to combat pain and increase relaxation.

PEA contains palmitic acid in its structure. However, increasing your intake of palmitic acid or other dietary fats will not affect PEA production in the body.

Researchers hypothesize that the best way to get the benefits of PEA are standardized supplements.

Food Sources

Soy lecithin, soy products, alfalfa and egg yolks are some food sources of PEA. However, PEA supplements are a safer and more effective choice.

Even though PEA is made from palmitic acid, including more palmitic acid in your diet will not increase your body’s PEA production. On the contrary, it could increase your risk for various chronic and inflammatory health problems. Therefore, do not confuse palmitic acid (aka palmitate) with palmitoylethanolamide.

Pregnancy and Children

A couple of studies have used PEA in children without any risks. Larger studies would need to confirm the safety of PEA in children.

PEA did not have toxic effects in pregnant animals. It didn’t have any potential to damage cells, cause mutation, or cancer. Long-term PEA given at the highest achievable doses to animals (1 g/kg of body weight) wasn’t toxic. [32].

Text includes multiple sections written by Written by Ana Aleksic, MSc and culled from var

Caveat: Make sure you buy Palmitoylethanolamide and NOT Phenylethylamine (a completely different supplement that’s also sometimes referred to as PEA).

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