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What to be aware of in PEA: Pure PEA is not always Pure PEA, PEA-opt not always optimum PEA

More and more PEA preparations available. In pots, in blisters, in boxes. What about it? Which one should you choose? Most producers say a lot, for example, that they have the best absorbable PEA, that they are the only ones with ‘GMP PEA’,  and so on. It gets crazier every day. Do not be confused! Here, especially for the consumer and the therapist, an explanation about pure PEA, optimum PEA and PEA Pure products, and about all other PEA products. Which are useful and safe, which are not.

A Simple Instruction: so you do not have to read the rest:

What to be aware of in PEA: safety and efficiency that’s what it is about! Many patients who come to us prefer PEA products with the PEA-opt quality mark. That is because they want a product that is safe and long-term tested, and are also described in the medical journals as safe and physiologically effective. This to date is the only excipient free PEA formulation which to our knowledge leads to increased levels of PEA in the blood. And that is the key for succes!

After all, that is what matters! See further: chart-PEA

Patients ask us how you can be sure that a product actually has the PEA-opt quality mark. That is simple: A PEA product with the PEA-opt quality mark is always marked with the following character:

Of these PEA capsules, it has also been proven that the PEA, from the capsule actually gets into the blood after ingestion. That is pretty relevant!

Our personal preference is given to the capsules which, in addition to PEA, also contain an optimal mix of vitamins from the B complex.

Most importantly, PEA-opt is the only pure PEA formulation to date from which we know the formulation induces therapeutic plasma levels, due to a pilot study in the Netherlands.


Palmitoylethanolamide, PEA cheap is better? Not true!

In 2015, more often we get the question, where can I find cheap PEA? That is not a good question! You should be asking: Where can I find the best PEA? After all, you want the best PEA, which gives you the greatest chance of good pain relief and anti-inflammation. And the safest. Of many recent PEA capsules introduced to the market, safety is completely unclear.

Therefore, you should look for a PEA preparation that meets the main characteristics, which we will discuss in this article.

Keep in mind, cheap so-called pure PEA capsules have never been clinically examined whether they are safe and effective!

We have not found proof that the PEA is 100% pure, except for the PEA with the PEA-opt quality mark. Even PEA preparations that state they are 100% pure, do not have any conclusive evidence!

Now, we will give an example of how it should not be.

‘Pure PEA’ and how it should not be

There are cheap ‘pure PEA’ preparations of unproven quality, with bizarre and unsubstantiated advertising slogans, such as a company that recommends its PEA capsules as: “Best absorbable form ever!” Then you immediately know that something is not right.

In fact, best absorbable means that this form of PEA has been compared with other forms, including the superior formulations of PEA and formulations from the past. You immediately know that something like this is nonsense, because some PEA forms have not been available for a long time, (Impulsin, Palmidrol) and thus cannot be compared. ‘The best absorbable form ever’ is therefore total nonsense!

In the Netherlands, we have been working the longest and most intensively with PEA

Our institute has been working with palmitoylethanolamide for many years.[1] Initially with the Italian products een PEA-houdend product and Glialia. But we quickly switched to a renewed capsule produced in the Netherlands, which contained only clean and pure PEA, the PEA-based PEA composition, and has the PEA-opt quality mark. If we are honest, only een Italiaans bedrijf’s PEA products and the Dutch PEA capsules with the green PEA-opt mark are adequately clinically tested. We now prefer the PEA capsules developed specifically for the nervous system and also are physiologically dosed capsules that contain B-complex (PeaPlex). Both patients and doctors believe that this form is more effective.

Due to our many national and international publications about PEA, a number of Dutch organisations have begun to produce PEA products. What is wise? Which products are useful, which are useless and why? Can you use PEA powder from a random strip, or from any pot? Technically, the answer has already been given, but we will give some more details. Because we are the only one with 6 years of experience in the area of PEA.

We feel obliged to clearly inform the consumer of this. Especially because we receive questions about it almost daily. And because we see failed treatments more often due to the use of new cheap PEAs.

Pure PEA products: only according to optimal preparation processes!

PEA is a very special substance. It is a fatty substance with a crystal structure. This makes it difficult to reduce PEA. If you just grind it, the (cheap) PEA will stick to each other and it becomes a mass of grains which makes it difficult for the body to absorb. You must have a special production process to avoid this. Only then, a PEA preparation is created that can be absorbed into the body optimally.

These optimal preparation processes were invented by only 3 PEA producing companies. The techniques are based on specially invented PEA processing procedures. Only two companies which produce PEA tablets, een Italiaans bedrijf and Innovet, and a capsule-producing company, Russell Science, use these processing procedures. They are therefore patented.

We believe that this should be the guideline in choosing a PEA product. In the Netherlands, these types of standardised PEA preparations now have the Pea-Opt quality mark. In Italy, the PEA preparations also have such a mark (A special Italian quality mark: PEA-um and PEA-m).

Reduced, refined and ultra-fine PEA

In the optimum PEA product, the micrograins PEA stick together as little as possible. In optimum PEA, there is an optimum division between small, fine (in size similar to micronised particles) and ultra-fine (in size similar to ultra-micronised) PEA particles. This can only be achieved by special reduction techniques. Most PEA capsule producers do not own and know those techniques.

Why the choice for specially processed PEA is the best, it became clear for the first time in 1999.

In 1999, the company Innovet, which collaborated with Nobel Prize winner Professor Levi-Montalcini, developed a specially patented reduction process designed to reduce the PEA particles. That reduction must be done in a special way, for the end product to be absorbed into the body properly. That process is called micronisation. To make tablets of the micronised material is not easy either. That Italian company then added all kinds of chemical additives to the PEA, such as magnesium stearate. Initially, we also worked with it.

During this decade, two different companies have been busy developing a new production process, creating even better and finer particles. Both companies have developed and patented a new production process.

One company then chose to continue with the chemical additives (because in their opinion it was the only way) and developed micronised and ultra-micronised tablets PEA.

The other company (Russell Science) has developed a procedure to fill capsules with fine, very fine (**similar to micronised) and ultra-fine (***similar to ultra-micronised) PEA particles.[2] The advantage of this latter procedure was that no chemical and pharmaceutical additives were necessary.[3]

All these reduced and ultra-fine particles of PEA are then perfectly integrated into a capsule. Why optimum? Because research has shown that you need all those particles for an optimum effect, the so-called particle distribution is then optimal because:

  1. Fine particles (about 25 microns) have been examined to prevent inflammation (e.g., prophylaxis of flu),[4]
    2. Very fine PEA particles (between 15-10 micron around) have been examined for joint pains [5],fibromyalgia[6] and peripheral nerve pain such as hernia[7], and
    3. Ultrafine PEA particles have an important influence on the glial tissue, of great importance in chronic pain.[8][9]

In different PEA products, which bear the PEA-opt quality mark, all of these PEA particles are distributed in such a manner that there are at least sufficient small and very small particles present to calm the entire nervous system. That the production companies must follow a patented production process guarantees quality. And that quality is necessary for optimal absorption into the body. Therefore, not every PEA powder meets this requirement.

Finally, we know from the biology of chronic pain that there is inflammation, peripheral nerve abnormalities and central nervous system abnormalities (at glia and the nerve cell level). [10] Therefore, we think that a choice must be made for a PEA product that can work at all three levels.

Tested for years, pure and fine PEA, according to PEA-opt quality mark

  1. These PEA capsules have been extensively and long-term (years) tested in terms of efficacy and safety and there are publications on this in medical journals and medical books!
  2. Secondly, it is important to take a pure form of PEA. The producers of PEA capsules with the PEA-opt quality mark are the only ones on their website which have included an analysis certificate from the beginning, coming from an independent analysis laboratory, showing the high purity of the PEA.
  3. The PEA-opt quality mark is only stated on a PEA preparation when a wide range of conditions are met, including the demonstrable high purity and special distribution in small, fine and ultra-fine PEA particles in each capsule according to a special patented process.
  4. Long-term documented safety of PEA capsules with this vignette: those PEA capsules have been used by many thousands of people for at least 6 years under the supervision of doctors. Safety takes priority over everything else with the use of supplements. Certainly, now that we know that there are also PEA capsules on the market, often cheap, which in addition to PEA also contain other substances that you do not want to get in your body.
  5. After ingestion of these quality mark PEA capsules, the PEA is actually in your blood. That has been measured in the blood.

Combined PEA preparations: PEA with B complex, PEA with DPP-IV, PEA with plant extracts, PEA with resveratrol

In addition to non-optimum PEA capsules, there are also combined PEA preparations available. Some are useful and are based on a logical and scientific basis, others are only motivated by marketing motives and seem to lack logic entirely. We shall discuss a few.

DPP-IV enzymes with PEA

It seems that the combination PEA with the DDPIV enzyme is not useful: the combination is not rational, DPP-IV has never been clinically proven to be effective, and these enzymes may potentially cause diabetes. We therefore choose not to work with such a preparation.

Pea-B-complex: PEA with selected vitamin B

PEA has proven to be effective in many nervous disorders, as is the case with the selected vitamins from the B group. It is particularly good that the producer has chosen physiological doses of nerve-supporting vitamin B. These dosages may in fact be fully utilised by the body. Therefore, the combination of PEA with selected and physiologically dosed B vitamins is probably very useful. Apart from the fact that we are increasingly seeing that large numbers of chronic patients have shortages of vitamins from the B group.

This new combination seems to be very useful to us. Meanwhile we found a series of patients who responded to PEA fairly well, and thereafter could achieve a further improvement with Pea-B complex.

See for a report in the medical literature about the improvement which Pea-Complex brought after Pure Pea: Jan M. Keppel Hesselink. “Autacoids: A New Fundament for Pain Medicine of the 21th Century”. Anaesthesia, Critical Care and Pain Management 1.1 (2016): 3-6.

PEA with plant extracts.

Some combinations like those in the USA preparation, a USA fitness product is not rational, other combinations, such as in PEA with resveratrol, may be useful. The disadvantage is that all these preparations are available in tablets, with chemical additives such as magnesium stearate. Furthermore, some of the plant extracts, especially in Achilles, are not well characterised. The ratio of PEA and plant extracts is also not properly, so that too little PEA comes into the body.

Summary: pure PEA or what?

You do not want to take every PEA capsule referred to as pure PEA. Of the majority of those PEAs, the quality is not clear, or in fact not good. Luckily, the Pea-opt quality mark has changed this. Preparations bearing that quality mark are guaranteed:

  1. Proven in terms of effectiveness and safety: only formulations that were proven to be effective in large studies, are useful to use!
  2. Pure, and also proven pure, demonstrable via the certificate of analysis.
  3. Optimal: contain small, fine and ultra-fine PEA particles, produced according to special patented processes. All this is important for its effectiveness in the body.
  4. Enters the bloodstream and the body: to date to our knowledge only PEA capsules bases on the PEA-opt formulation have been explored and after intake the PEA indeed enters the blood and the body!

December 2015, Prof. Dr. Jan M. Keppel Hesselink; revision February 2016, revision June 2018



[1] Hesselink JM. | Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-? agonist and effective nutraceutical. | J Pain Res. | 2013 Aug 8;6:625-34. doi: 10.2147/JPR.S48653. eCollection 2013.

[2] Hesselink JM. | Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. | Int Med Case Rep J. | 2013 Sep 13;6:49-53. doi: 10.2147/IMCRJ.S51572.

[3] Hesselink JM, Hekker TA. | Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. | J Pain Res. | 2012;5:437-42. doi: 10.2147/JPR.S32143. Epub 2012 Oct 26.

[4] Keppel Hesselink JM, de Boer T, Witkamp RF. | Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold. | Int J Inflam. | 2013;2013:151028. Epub 2013 Aug 27.

[5] Marini I, Bartolucci ML, Bortolotti F, Gatto MR, Bonetti GA. | Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. | J Orofac Pain. | 2012 Spring;26(2):99-104.

[6] Del Giorno R1, Skaper S2, Paladini A3, Varrassi G4,5, Coaccioli S6,5. | Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies. | Pain Ther. | 2015 Dec;4(2):169-78. doi: 10.1007/s40122-015-0038-6. Epub 2015 Sep 3.

[7] Keppel Hesselink JM1, Kopsky DJ1. | Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome. | J Pain Res. | 2015 Oct 23;8:729-34. doi: 10.2147/JPR.S93106. eCollection 2015.

[8] Kopsky DJ, Hesselink JM. | Nerve regeneration in neuropathic pain. | Pain Med. | 2010 Oct;11(10):1576. doi: 10.1111/j.1526-4637.2010.00947.x. Epub 2010 Sep 7.

[9] Cocito D1, Peci E1, Ciaramitaro P1, Merola A1, Lopiano L1. | Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. | Pain Res Treat. | 2014;2014:854560. doi: 10.1155/2014/854560. Epub 2014 May 20.

[10] Keppel Hesselink JM, Kopsky DJ. | Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. | J Pain Res. | 2013 Mar 21;6:239-45. doi: 10.2147/JPR.S42417. Print 2013.