Palmitoylethanolamide (PEA) is rapidly becoming one of my go-to supplements. However, whether I’m teaching physicians or non-health professionals, I find that most people are still unfamiliar with it. Today, I aim to change that, because PEA has so much to offer.

Palmitoylethanolamide is a naturally occurring substance that has garnered significant interest in various health science communities due to its potent anti-inflammatory and neuroprotective properties. PEA belongs to a class of endogenous compounds (produced within an organism, tissue, or cell) known as fatty acid amides, which are involved in a wide range of biological functions, including pain regulation, inflammation modulation, and immune response. Though it has been a subject of study for several decades, PEA’s therapeutic potential has only recently been recognized. This is to say that your physician might not have heard of this yet.

Origins of PEA: Natural and Supplementary Sources

As mentioned, PEA is an endogenous compound, which means that it is synthesized naturally in the body as a response to various stimuli, particularly those that involve pain and inflammation. Actually, it is produced in very small amounts in nearly all tissues of the body, including the brain. Moreover, it can also be found in certain foods such as egg yolk, tomatoes, chocolate, and some animal fats. However, the concentration of PEA in either context is relatively low, which means that the benefits that I am about to discuss are typically not realized via natural processes or by consuming the listed foods.

Biological Systems Impacted by PEA

PEA exerts its effects on multiple biological systems, making it a very versatile compound with wide-ranging potential applications. The list is long, but the systems most notably impacted by PEA include:

1. The Immune System: PEA has been shown to modulate immune responses, particularly by reducing the activity of immune cells that are involved in inflammation.
2. The Endocannabinoid System: PEA interacts with the endocannabinoid system, particularly with receptors such as the peroxisome proliferator-activated receptor-alpha (PPAR-α). While it does not bind directly to cannabinoid receptors like other compounds in the endocannabinoid system, it exerts an “entourage effect,” enhancing the overall efficacy of the system.
3. The Nervous System: PEA’s neuroprotective effects are of particular interest. It helps to protect nerve cells from damage, modulates pain pathways, and has shown promise in conditions where nerve function is compromised. This includes neuropathic pain and neurodegenerative diseases, where PEA may help preserve nerve function and reduce pain.
4. The Microbiome: Emerging research suggests that PEA may also influence gut health, though this area is still under investigation. Nonetheless, it is known to have an impact on the microbiome, and its anti-inflammatory properties could play a role in managing various gut-related issues.

Therapeutic Necessity of PEA Supplementation

As mentioned, while PEA is naturally produced in the body and present in certain foods, the concentrations from either are insufficient to exert any therapeutic effects. For example, chronic pain, inflammation, and neurodegenerative conditions typically require significantly higher concentrations of PEA than what the body can produce or what can be obtained through food. This is to say that supplementation with PEA allows for a therapeutic dosage that can effectively manage these conditions. But that just gets the ball rolling. Let’s take a look at my Top-10 Uses for PEA.

My Top 10 Benefits and Uses of PEA

1. Anti-Inflammatory Properties: Palmitoylethanolamide is widely recognized for its anti-inflammatory effects, achieved by modulating the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins. These cytokines are key drivers of inflammation in various chronic conditions and autoimmune diseases. By decreasing the levels of these inflammatory molecules, PEA helps reduce the overall inflammatory burden on the body. https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp2.300

2. Immune System Modulation: Emerging evidence suggests that PEA may have broader effects on the immune system beyond its anti-inflammatory action. It has the potential to modulate immune responses, which could make it beneficial in conditions where immune dysregulation is a factor, such as certain chronic infections or immune-related disorders. https://www.mdpi.com/2673-9879/3/4/58

3. Pain Management: PEA’s ability to modulate pain makes it a valuable tool in managing both acute and chronic pain conditions. It has been used effectively in neuropathic pain, where conventional painkillers often fall short. PEA’s pain-relieving effects are thought to result from its interaction with the endocannabinoid system and its ability to reduce the hyperactivity of mast cells, which can exacerbate pain. https://link.springer.com/article/10.1186/s13643-018-0934-z

4. Neuroprotection: The neuroprotective properties of PEA are of significant interest in conditions such as multiple sclerosis, Alzheimer’s disease, and other neurodegenerative diseases. PEA helps to protect nerve cells from oxidative stress and inflammation, which are common features in these conditions. By preserving nerve function, Palmitoylethanolamide may slow disease progression and improve the quality of life in patients with neurodegenerative disorders. https://www.mdpi.com/1422-0067/22/6/3054

5. Antimicrobial Properties: While it’s still a little early to know “how,” recent studies have begun to mention PEA’s potential antimicrobial effects. This is to say that its ability to inhibit the growth of certain bacteria is an emerging area of research. https://www.mdpi.com/2076-3921/13/5/600. The process of how this happens is highly complex (because it doesn’t work like traditional antibiotics), but recent studies on its effects on E. coli help us to understand this a little better. https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-11-108

6. Mental Health and Cognitive Function: PEA’s interaction with neurotransmitter systems also suggests potential benefits in mental health. By modulating the release of dopamine and norepinephrine, PEA may help to improve mood, reduce symptoms of depression, and enhance cognitive function. Some studies have even suggested that PEA could be useful in treating mood disorders and improving mental focus and concentration. https://www.mdpi.com/2072-6643/16/4/489

7. Weight Management: PEA has been implicated in the regulation of appetite and metabolism. By enhancing the release of norepinephrine, a neurotransmitter involved in the fight-or-flight response, PEA may help to suppress appetite and increase fat breakdown. This makes it a potential aid in weight loss and management. https://www.mdpi.com/2072-6643/13/8/2589

8. Sports Performance: Though less studied, the potential benefits of PEA in enhancing physical performance are worth noting. By reducing inflammation and modulating pain, PEA could support recovery after exercise and improve overall performance. Its effects on mental focus and energy levels could also provide a boost to athletes. https://link.springer.com/article/10.1186/s40798-024-00732-6

9. Cardiovascular Health and Arterial Plaque: Chronic inflammation is a significant contributor to the development of atherosclerosis, a condition where arterial plaque builds up in the walls of arteries, leading to reduced blood flow and an increased risk of heart attack and stroke. PEA’s ability to reduce inflammation is thought to help slow the progression of atherosclerosis. It makes sense because by modulating the production of pro-inflammatory cytokines and stabilizing mast cells, Palmitoylethanolamide could potentially reduce the inflammatory processes that contribute to arterial plaque formation, offering a novel approach to supporting cardiovascular health. https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.118.311185

10. Digestive Health and Gut Inflammation: As previously mentioned, PEA is also being studied for its potential role in gut health. Chronic inflammation in the gastrointestinal tract can lead to conditions like inflammatory bowel disease (IBD) and other digestive disorders. PEA’s anti-inflammatory properties suggest that it could help reduce inflammation in the gut, possibly offering relief for those with chronic digestive issues. Moreover, it is thought that it can actually positively reshape gut microbiota composition, which means it could potentially help to address dysbiosis. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1143004/full

You should know that the studies that I have provided here are a mere fraction of what is available. And, of course, the list goes on. In fact, let’s discuss some other potential uses that are currently under investigation.

Other Experimental and Potential Uses

Beyond the established benefits, Palmitoylethanolamide is also being investigated for its potential in other areas as well. Some of these experimental possibilities include:

1. Cancer: PEA’s anti-inflammatory and immunomodulatory effects have led researchers to explore its potential in cancer therapy. While still in the early stages of research, it is thought that PEA could potentially help to modulate the tumor microenvironment, making it less conducive to cancer growth. A few examples include: Colon – Cervical – Breast – Etc.
2. Sleep Disorders: The interaction of PEA with the endocannabinoid system suggests potential benefits for sleep regulation. Though not yet thoroughly studied, PEA could potentially help to improve sleep quality, particularly in individuals with chronic pain or inflammation-related sleep disturbances. https://link.springer.com/article/10.1186/s41606-021-00065-3
3. Infectious Diseases: While it’s still a little early to know for sure, PEA might also hold the ability to disrupt biofilms, which means it could potentially be used as an adjunct therapy in treating infections. Biofilms are often resistant to conventional antibiotics, so if PEA has the ability to interfere with their formation, it could potentially enhance the effectiveness of other treatments. https://www.frontierspartnerships.org/articles/10.3389/adar.2023.11359/full
4. Studies Incoming: The more we look, the more we find. Expect more discoveries down the road! And remember, these are just my “Top-10,” not the total list!

How to Use Palmitoylethanolamide for Therapeutic Purposes

Palmitoylethanolamide is available in various forms, including capsules, tablets, and powders. The recommended dosage for therapeutic purposes typically ranges from 600 mg to 1,200 mg per day, depending on the severity of the condition being treated. For chronic conditions, it may be necessary to start with a lower dose and gradually increase to the optimal therapeutic level.

PEA has a fantastic safety profile, and no specific toxic dose has been established. It is generally well-tolerated and side effects are thought to be extremely uncommon, even at higher doses. However, as with any supplement, it is advisable to monitor for any adverse effects (such as potential allergies to fillers in the supplement) and consult with a healthcare professional before starting supplementation, especially in individuals with existing medical conditions or those taking other medications.

Final Thoughts

Palmitoylethanolamide is a very promising compound with a wide range of potential therapeutic applications. From its well-established role in managing pain and inflammation to its emerging potential in areas such as neuroprotection, antimicrobial activity, and even cancer therapy, PEA represents a multifaceted tool in modern medicine. While more research is needed to fully understand the breadth of its effects, the current evidence definitely supports the use of PEA as a safe and effective supplement for a variety of chronic conditions. And as our understanding of PEA continues to grow, it may become an increasingly important part of integrative and functional medicine practices. I guess we’ll see!

Anyway, now you know!

If you are interested in seeing more examples of how PEA could potentially help, you might check out my articles regarding Myasthenia Gravis or Natural Ways to Address Eczema or Psoriasis.

Disclaimers and Safety Considerations

While Palmitoylethanolamide has an extremely strong safety profile, it is important to note that research is ongoing, and some of its potential applications are still in the experimental stages. Individuals with specific health conditions, pregnant or breastfeeding women, and those taking medications should always consult with a healthcare provider before using ANY supplement. Additionally, while PEA may provide relief from symptoms, at this point it should not be considered a cure for any disease. Instead, its use should be part of a comprehensive treatment plan under the guidance of a qualified and competent healthcare professional.

Dr. Robertson is a health researcher and educator, not a physician. The information provided here is not medical advice, a professional diagnosis, opinion, treatment, or service to you or any other individual. The information provided is for educational and anecdotal purposes only and is not a substitute for medical or professional care. You should not use the information in place of a visit, call consultation, or the advice of your physician or other healthcare providers. Dr. Robertson is not liable or responsible for any advice, course of treatment, diagnosis, or additional information, services, or product you obtain or utilize. IF YOU BELIEVE YOU HAVE A MEDICAL EMERGENCY, YOU SHOULD IMMEDIATELY CALL 911 OR YOUR PHYSICIAN.