Life Extension Magazine®

Doctor examining older patient’s spine for pain with x-rayed spine

Turn off the Pain Signal

A natural fatty acid called PEA has been shown to reduce inflammatory stimuli at the site of tenderness. This enables PEA to target underlying causes of pain signals without the risks of drugs.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: Michael Downey, Health & Wellness Author.

More than 100 million Americans experience chronic pain.

That number exceeds those suffering from heart disease, cancer, and diabetes—combined.1

Pain-relieving drugs often fail to heal injured tissue. While these drugs can alleviate outward symptoms, they fall short of addressing the underlying causes.

Scientists have discovered a fatty acid naturally found in the body that targets the underlying cause of chronic pain. It works at the pain site to turn off the pain signal.2,3

More importantly, by working at the site of the original injury, this peripherally-acting fatty acid helps break the inflammatory pain cycle. 2,3

Clinical studies show reductions in pain after 14-30 days —and sometimes sooner.4-6

What you need to know

  • Pain-relieving drugs come with inherent risks, and people who rely on these medications may not be aware of the potential damage they can cause.
  • Chronic pain demands treatment that targets its underlying cause at the site of the tissue damage.
  • PEA reduces inflammatory stimuli at the site of tenderness to turn off the pain signal.
  • PEA offers a safe, non-addictive option for those suffering from occasional minor pain and discomfort. In addition, it has been shown to reduce reliance on other pain medications. This may radically alter how pain is managed in the future.

The Problem with Pain Relievers

Common pain relievers come with inherent risks. Yet the over-prescribing of these drugs has become a standard practice—with devastating results:

  • Current users of ibuprofen (for 1-7 days) have 1.48-fold greater odds of suffering a heart attack. 7
  • Current users of naproxen (Aleve®) (for 1-7 days) have 1.53-fold greater odds of suffering a heart attack.7
  • Regularly taking NSAIDs (non-steroidal anti-inflammatory drugs) (such as ibuprofen) increases the risk of kidney impairment by 32%.8
  • Over-prescribing of addictive opioids has led to an epidemic resulting in more than 500,000 deaths since the year 2000.9

Despite the widespread availability of these drugs, more than 116 million American adults still live with chronic pain.10

A Safe Pain-Relief Alternative

Man having back checked by doctor

A safer alternative is urgently needed.

Scientists have been aggressively researching safer alternatives to relieve pain.

This led them to a natural fatty acid compound called PEA (palmitoylethanolamide) that works at the site of tenderness to turn off the pain signal.2,3

In clinical studies of PEA, noticeable reductions in pain were seen after 14-30 days of supplementation—and sometimes in as little as one week.4-6

PEA has an extraordinary safety profile. It does not result in dependence or addiction, because—unlike opioid pain-relievers—it does not involve the body's opioid receptors.

Proper use of PEA represents an innovative, safe, and effective advance in the long-term management of pain.

PEA Blocks Pain

PEA is a fatty acid the body naturally produces to lower inflammation.11,12

In recently published animal studies, researchers demonstrated that PEA downregulates distinct inflammatory and oxidative pathways and significantly relieves chronic inflammatory and neuropathic pain.13,14

Multiple clinical trials and other human studies, involving more than 1,100 participants, have established the validity of PEA as a powerful, peripherally-acting pain reliever.2,3 Peripherally-acting compounds work at the site of the original injury, helping to normalize the body's response to tissue damage.

Unlike commonly used pain-relieving drugs, PEA has no documented cardiovascular or renal risk.2 Clinical studies on PEA highlight its safety and efficacy even when used in combination with common pain relievers.5,15

This type of approach has produced beneficial results, as we'll now see.

PEA Relieves the Most Common Form of Pain

Investigators chose to test PEA against sciatica nerve pain, a condition that involves inflammation and pressure on the main nerve supplying the back portions of the leg. Sciatic pain is one of the most common forms of chronic pain, affecting up to 43% of people.16

For this study, 636 patients with sciatica pain were randomly assigned to receive either a placebo, 300 mg of PEA, or 600 mg of PEA daily.5

After three weeks, both groups of people taking PEA experienced significantly better pain reduction and quality-of-life scores compared to placebo recipients. Those taking the higher dose had the most improved outcomes.5

This study also revealed that PEA provides pain-reducing effectiveness that surpasses most pharmaceutical standards.

Researchers frequently estimate how many patients would need to be treated in order to achieve a 50% reduction in pain. This is known as the "number needed to treat." Any number below five indicates a useful pain intervention, with a measure of one being the statistically perfect ideal.

In this PEA study, the number needed to treat was just under three by the second week of treatment. And by week three, the number needed to treat was down to a virtually unheard-of 1.5!5,17

This indicates that PEA has a remarkably high degree of effectiveness in pain reduction.

PEA Proven Safe and Effective Against Migraines

Migraine headaches are the sixth highest cause of years lost to disability worldwide. 15

There are two major types: migraines with aura and migraines without aura.

Auras are constellations of neurological symptoms that usually occur before the onset of a migraine, though they can also occur during a migraine. Auras can also occur without any migraine headache, and individuals who have migraines with aura can also have migraines in which no aura occurs. Auras usually last just a few minutes and are most commonly visual, though they can affect other senses, verbal ability, or the motor nervous system.18,19

A single-blind, clinical study was conducted to assess the safety and efficacy of PEA in 20 sufferers of migraines who experienced severe pain as well as visual aura. Each was given 1,200 mg of PEA daily for 90 days, and all were evaluated at 30, 60, and 90 days. They also took NSAIDs such as ibuprofen at the onset of an acute attack.

At 60 days, PEA-supplemented patients experienced dramatic improvement in reducing pain symptoms, and this effect continued until the 90-day follow-up. Remarkably, at 90 days, this treatment group demonstrated a reduction in the number of migraine attacks per month and a reduction in the number of painful days. And there were no adverse effects.15

Critically, daily use of PEA allowed patients to reduce the dosage of toxic NSAIDs.15

The Hidden Dangers of NSAID Use
Pill bottles

Some of the most commonly used pain medications are the non-steroidal anti-inflammatory drugs or NSAIDs. These drugs reduce levels of prostaglandins, compounds that initiate acute inflammation and increase sensitivity to pain, by blocking an enzyme called cyclooxygenase which is required for their production.

Because the most common NSAIDs (such as ibuprofen and naproxen) are available over-the-counter, without a prescription, millions of people self-prescribe for their pain control with these drugs.

Unfortunately, despite their wide availability, NSAIDs are not as innocuous as many people believe. While they are generally safe for short-term use over a few days, longer use can be very dangerous, even lethal. Considering that many people use NSAIDs for chronic types of pain, such as back pain or arthritis, this presents a serious problem.

Although NSAIDs reduce inflammation in some parts of the body, prolonged use can cause injury and inflammation in the stomach, leading to gastritis and ulcers. These can be associated with gastrointestinal bleeding and even rupture, which can be life-threatening.22

Even relatively short-term use of NSAIDs is also associated with an increased risk of heart attack and stroke.7,23,24

Even more insidiously, NSAIDs can cause damage to the kidneys.8,25 With prolonged use, this can contribute to the development of kidney failure and the need for dialysis or a kidney transplant. Oftentimes the damage being done is not noticed until it is too late, unless it is detected on blood tests of kidney function.

Although the risk for serious kidney injury with NSAID use appears worst in those with pre-existing kidney disease or other risk factors like high blood pressure, significant damage can occur even in younger, previously healthy individuals.25

The take-home message is that NSAID use should not be taken lightly. It is recommended to limit their use overall, substituting safer alternatives when possible.

Inhibiting Inflammatory Pain Signals

In another study, scientists put PEA to the test against another common type of pain: carpal tunnel syndrome.4

Carpal tunnel syndrome occurs as a result of compression of the nerves that extend through a narrow space in the wrist, and it results in tingling, weakness, or numbness in the hands.

In this study, patients who received no treatment acted as controls, while others were given either 600 mg or 1,200 mg of PEA daily.

After 30 days, the patients taking PEA reported reductions in symptoms and discomfort compared to the controls. They also experienced improvements in nerve conduction studies along the median nerve.4

These improvements are clinical indicators of a reduction in pain-related inflammation and improved function.4

In the compelling studies above, PEA proved to be an effective pain-reliever when compared either to a placebo or to no treatment at all.4,5

Next, scientists set out to evaluate how well PEA would perform when matched against a proven painkilling drug.

PEA Outperforms Ibuprofen

Man having back checked by doctor

To test this, researchers conducted a randomized, placebo-controlled study comparing the pain-relieving effects of PEA to ibuprofen (Advil®, Motrin®).

The patients suffered temporomandibular joint (TMJ) pain, an often chronic condition that causes severe jaw discomfort.6

For the study, 24 patients with TMJ were divided into two groups. One group took 600 mg of ibuprofen three times daily for two weeks, while the other group took 300 mg of PEA in the morning and 600 mg in the evening for the first week and then only 300 mg of PEA twice daily for the second week.6 (The 1,800 mg a day dose of ibuprofen is dangerously high, yet many chronic-pain sufferers take it anyway.)

Within just two weeks, those taking PEA experienced a greater decrease in pain than those taking high-dose ibuprofen. They were also able to open their mouths wider (an indicator of range of motion) and with less pain than those in the ibuprofen group.6

Importantly, PEA accomplished these benefits without any side effects. These results were consistent with a 2018 review that found, "None of the clinical trials with PEA to date have reported treatment-related adverse events."20

A Potential Role for PEA in Neuroprotection

Man having arm checked by Doctor

PEA reduces inflammation at the peripheral site of pain, making it a powerful pain-reliever for chronic pain.4-6 New evidence suggests that PEA may also act in the central nervous system to quench neuroinflammation.

A recent study suggests that PEA's anti-inflammatory effects in combination with levodopa therapy may also help slow the progression of Parkinson's disease.21

Thirty patients with advanced Parkinson's who were being treated with the drug levodopa were given a battery of cognitive tests before and after treatment with PEA. They received 1,200 mg of PEA daily for three months, followed by 600 mg daily for up to a year.21

Investigators documented a significant and progressive reduction in both motor and non-motor symptoms.

Astoundingly, after a year of PEA supplementation, the number of patients who exhibited any symptoms had been reduced—a previously unheard-of reversal in this chronic disease's progression.21

Larger randomized and controlled clinical trials may yet reveal new potential for PEA to reduce neuroinflammation and improve the ability to protect against neurodegenerative diseases.


Chronic pain often involves both peripheral inflammation as well as amplification of the perception of pain within the brain.

Long-term treatment with pain-relieving drugs involves a high risk of adverse effects and fails to target the underlying cause of chronic pain.

PEA functions to suppress painful inflammatory stimuli that persist at sites of injury.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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