The seventy-year story of PEA — and why we built our new balm on it

PEA is a molecule your own body makes. It’s been studied for seventy years, and below you’ll find every trial we know of — named, with its format, its dose, its size and its result, including the ones that came out mixed. Then what’s in our jar, and how much.

Most of the interesting molecules in wellness come from somewhere exotic — a root from one continent, a leaf from another. The one at the heart of our Rapid Comfort Balm comes from somewhere more familiar: you.

PEA — Palmitic Acid Mono Ethanolamide, and that’s the last time we’ll make you read it in full — is a fatty-acid molecule your own body produces, on demand, in the membranes of your cells. It’s in your skin, your muscles, your brain. It’s also in egg yolk, soybeans and peanuts, which is how science found it in the first place. Your body has been making it your whole life, quietly, in precisely the places that are having a hard day.

We didn’t invent it. Your body did. What follows is the story of how a molecule found inside us all became one of the most studied natural compounds in pain and inflammation research — and why, after seven years of building products based on remarkable plant molecules, we chose one we didn’t have to borrow.

A discovery in an egg yolk

In 1939, two American physicians noticed something odd. Alvan Coburn and Lucile Moore were feeding dried egg yolk to children in the poorest districts of New York, and the children who ate it stopped suffering recurrences of rheumatic fever — despite catching the same streptococcal infections as everyone else. Something in the egg yolk was damping down the inflammation. Nobody knew what.

It took until 1957 to find out. Chemists at Merck isolated a crystalline anti-inflammatory factor — from soybean lecithin, as it turned out, though they went on to recover the same compound from egg-yolk phospholipid and from peanut meal — and gave it a name. A paper in the Journal of the American Chemical Society identified N-(2-hydroxyethyl)-palmitamide, our PEA, as “a naturally occurring anti-inflammatory agent” [1].

What happened next is one of science’s stranger detours. In 1970s Czechoslovakia, PEA was manufactured as an actual medicine — 300mg tablets called Impulsin — and put through six double-blind placebo-controlled trials against influenza and the common cold between 1972 and 1977. Nearly 4,000 people took part, around 3,600 of whom completed. One trial ran in the workforce of the Škoda car factory; another in nearly a thousand army recruits. The results were positive; the tablets shipped; and then the Iron Curtain, corporate mergers and the sheer unpatentability of a molecule your body makes for free conspired to bury the whole programme [2]. PEA went back to sleep for twenty years.

The Nobel laureate who woke it up

It was woken by one of the great scientists of the twentieth century. Rita Levi-Montalcini shared the 1986 Nobel Prize in Physiology or Medicine for her discovery of nerve growth factor. In 1993, at 83, she turned her attention to PEA and its chemical relatives, publishing the paper that gave the molecule its modern identity: this family of compounds, she proposed, is the body’s own local damping signal — produced where tissue is stressed, when tissue is stressed, to tell the neighbourhood’s alarm cells (mast cells, in the jargon) to stand down [3]. She called the mechanism ALIA: Autacoid Local Inflammation Antagonism. Autacoid is a lovely, underused word — it means a medicine the body makes for itself.

Later work filled in the machinery. In 2005, researchers showed that PEA works largely through a receptor called PPAR-α — think of it as a dimmer switch inside cells that, when turned, quiets the genes responsible for inflammatory noise. In mice bred without that receptor, PEA’s anti-inflammatory effect disappears entirely [4].

PEA also keeps sympathetic company. It belongs to the same chemical family as the body’s own endocannabinoids and shares the enzymes that make and break them down — though it does not bind cannabinoid receptors itself, and the idea that it indirectly supports that system is well-evidenced in the laboratory and still unproven in people. What is not in question is the shape of the thing: this is a molecule that works with systems you already own rather than overriding them. This is, we’d argue, the most KLORIS-like mechanism imaginable.

So why hasn’t everyone heard of it?

Partly the patent problem — there’s little commercial incentive to run vast trials on a molecule nobody can own. Partly geography: for decades the research tradition lived mostly in Italian, Swedish and Dutch laboratories, published in journals most of the wellness industry never read.

In 2016, three pharmacologists at Umeå University in Sweden — no industry funding, no commercial interest declared — published a critical review of PEA for pain in the British Journal of Clinical Pharmacology. They read sixteen clinical trials and concluded that the available data “support the contention that PEA has analgesic actions and motivate further study” [5]. They were pointed about the quality of what they read: the randomised trials were of variable quality, some data appeared only in graphs, sample sizes were small.

What struck them most was the safety record. Across the whole literature they examined they found essentially one adverse event — and called the rate “remarkable indeed.” They were careful about what that does and doesn’t establish: without access to the study protocols they couldn’t rule out that milder effects simply went unrecorded, and too few people had taken PEA for longer than sixty days to say anything confident about the long term. Within those bounds, though, nearly seventy years after its first paper, PEA’s side-effect profile in trials remains close to indistinguishable from placebo [2, 5]. Your body, after all, has been dosing you with it since before you were born.

What Levagen® is — and why we specified it

PEA has a practical flaw: in its raw form it’s a waxy, crystalline substance that dissolves poorly, and a molecule that won’t disperse can’t do much. Levagen®, made by Gencor to a patented process, is the branded form built to solve this. It exists in more than one version, and the differences matter enough that we’re going to be precise about them, because the studies below are not all studies of the same thing.

Levagen+ pairs the molecule with a dispersion technology called LipiSperse®, developed for capsules and powders; in a human absorption study, it raised total PEA exposure in the blood by around 75% over standard PEA when swallowed [6]. That’s an oral finding, and it tells you nothing about skin. PlexoZome® Levagen® is a liposomal version, used in the topical spray study you’ll read about below. And plain Levagen® — the molecule made to Gencor’s process, without an added dispersion system — is what’s in our jar, carried instead by the balm’s own base of coconut, avocado, sweet almond and beeswax.

So why specify Levagen® at all? Because it is the ingredient the modern clinical research actually uses. When you read “PEA has been studied in randomised controlled trials,” the ingredient in most of those recent trials came from this manufacturer, made to this process, at stated doses. What differs between formats is the delivery system wrapped around it — and we’d rather tell you that ourselves, plainly, than let you find it out afterwards.

In an industry fond of borrowing an ingredient’s research halo while quietly buying something cheaper, we think the honest move is to specify the researched ingredient, show you the studies, and name the format each one used.

What the studies actually show

Everything below is a randomised, double-blind human trial with a control group — placebo in most cases, an active drug in one. Most were funded by Gencor, the ingredient’s manufacturer; that is normal in ingredient research and disclosed in every paper. We’ve named the format, the dose, the size and the result in each one, because a study of capsules is not a study of a balm, and the difference is the whole point.

Joint comfort (oral, Levagen). 111 adults with mild-to-moderate knee osteoarthritis were randomised to 300mg or 600mg of PEA daily in divided doses, or placebo, for 8 weeks. Both PEA groups saw significant reductions in total WOMAC score — the standard osteoarthritis index of pain, stiffness and function — versus placebo, with the 600mg group improving most; physical function reached significance at the higher dose only. Anxiety scores on a standard scale improved in both PEA groups [7].

Exercise recovery (oral, Levagen+). 28 recreationally trained men took 150mg of PEA or placebo around a brutally honest leg-press protocol. Myoglobin — a marker of muscle damage — was significantly lower in the PEA group at one, two and three hours after exercise, as was blood lactate at one and three hours. But reported muscle soreness didn’t differ, and neither did creatine kinase, IL-6 or TNF-α. One damage marker moved and three didn’t, which is exactly the kind of mixed result real science produces and marketing departments usually hide [8].

Sleep (oral, Levagen+). 125 adults with disturbed sleep were randomised to 350mg of Levagen+ or placebo for 8 weeks, and 103 completed. Overall sleep-quality scores improved in both groups alike, with no difference between them. The finding was narrower and more specific than that: among the participants who took longer than ten minutes to fall asleep at the start, the PEA group fell asleep faster by weeks four and eight. Participants also reported feeling properly awake sooner in the morning. A molecule made in the body clearly isn’t a sedative — the finding is about an easier transition, not a knockout [9].

Headache (oral, Levagen+). In a head-to-head trial, 450mg of PEA was compared directly with 400mg of ibuprofen for tension-type headache in 94 adults. Over four hours, both cut pain by roughly 85%, and no significant difference was detected between them [10]. Three things are worth saying about that. There was no placebo arm, so neither result can be separated from a tension headache easing on its own. The trial wasn’t designed to prove equivalence — it was powered to detect a large difference, and didn’t find one, which is not the same as showing the two are equal. And the picture within the data is mixed: PEA resolved severe headaches faster, while ibuprofen did better on the milder ones and on the need for rescue medication. We report all of it with appropriate awe and no product claims whatsoever.

And — the two that matter most to a balm — PEA applied to skin.

Eczema (topical, Levagen+ cream at 1.5%). 72 adults with atopic eczema on the hands and arms were randomised to a cream containing 1.5% Levagen+ or to the identical base cream without it, twice daily for four weeks; 65 completed. That’s a harder test than it sounds: a plain moisturiser is itself useful in eczema, so the PEA had to beat a genuinely active control rather than an inert one. It did, on redness, dryness and overall symptom score (POEM). Quality-of-life scores improved in both groups without separating [11].

Post-exercise knee pain (topical, PlexoZome® Levagen® spray). In 2025, a randomised placebo-controlled trial enrolled 86 adults and tracked 214 individual episodes of post-exercise knee pain. Each episode was treated with a liposomal PEA spray delivering about 5.4mg, or an unmedicated spray. Within an hour, pain scores in the PEA episodes had fallen 55%, against 36% for placebo, and more episodes had resolved completely by the hour’s end — 85% against 73% [12].

Topical PEA, in other words, is not a theoretical extrapolation from capsule studies. Skin delivery has now been tested in humans, twice, and worked both times.

From the research to the jar

Why a balm, then, and not another capsule? Three reasons.

Because the newest evidence says skin delivery works, and skin is where an after-exercise ritual naturally happens [11, 12]. Because a balm gave us somewhere to put everything else we know: arnica, and a working blend of frankincense, lavender, juniper and eucalyptus oils that opens fresh and settles to a whisper. And because a massage is not a delivery mechanism to us; it’s the point.

The balm is 5% Levagen® — 3,000mg of PEA in the 60ml jar. We state it for the same reason we’ve stated the dose in every study above: you can’t judge any of this without the number. For context, the cream in the eczema trial was 1.5%. We went considerably higher, and we’d rather you knew that than assumed it — though a higher concentration is not the same thing as a bigger effect, and nobody has run the study that would tell you where the ceiling is.

Use a small amount, massaged into the area once or twice a day. It melts in fast; take the massage slow — two minutes is the whole ritual, and the two minutes are not incidental to it. This isn’t a switch you flip. It’s something you do at the end of a day that asked a lot of you.

A practical note, since we’ve spent this long on the science. It goes on skin, not in you — but if you take prescribed medication and you’re unsure, ask your pharmacist.

The molecule is the reason the balm exists. The two slow minutes are the reason you’ll keep using it.

This page isn’t finished, either. We survey every new product launch, and when the first people to use the balm tell us what it did for them, we’ll publish what they say — sample sizes and all — right here, under the research.

One last travel note, because it’s our favourite fact about the whole project: a comfort molecule your body already makes is a comfort molecule with nothing to declare. Rapid Comfort Balm contains no hemp-derived ingredients and goes anywhere in the world in your hand luggage — onto a plane, into a kit bag, through any border.

See the Rapid Comfort Balm →

Take the massage slow.

The research

Every study described above is listed here in full, so you can read them yourself:

1. Kuehl FA Jr, Jacob TA, Ganley OH, Ormond RE, Meisinger MAP. “The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent.” Journal of the American Chemical Society, 1957;79(20):5577–5578. https://doi.org/10.1021/ja01577a066
2. Keppel Hesselink JM, de Boer T, Witkamp RF. “Palmitoylethanolamide: a natural body-own anti-inflammatory agent, effective and safe against influenza and common cold.” International Journal of Inflammation, 2013;2013:151028. https://pmc.ncbi.nlm.nih.gov/articles/PMC3771453/
3. Aloe L, Leon A, Levi-Montalcini R. “A proposed autacoid mechanism controlling mastocyte behaviour.” Agents and Actions, 1993;39 Spec No:C145–C147. https://doi.org/10.1007/BF01972748
4. Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, Piomelli D. “The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide.” Molecular Pharmacology, 2005;67(1):15–19. https://doi.org/10.1124/mol.104.006353
5. Gabrielsson L, Mattsson S, Fowler CJ. “Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.” British Journal of Clinical Pharmacology, 2016;82(4):932–942. https://doi.org/10.1111/bcp.13020
6. Briskey D, Mallard AR, Rao A. “Increased absorption of palmitoylethanolamide using a novel dispersion technology system (LipiSperse®).” Journal of Nutraceuticals and Food Science, 2020;5(2):3. https://doi.org/10.36648/nutraceuticals.5.2.3
7. Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. “A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis.” Inflammopharmacology, 2019;27(3):475–485. https://doi.org/10.1007/s10787-019-00582-9
8. Mallard A, Briskey D, Richards A, Mills D, Rao A. “The effect of orally dosed Levagen+™ (palmitoylethanolamide) on exercise recovery in healthy males — a double-blind, randomized, placebo-controlled study.” Nutrients, 2020;12(3):596. https://doi.org/10.3390/nu12030596
9. Rao A, Ebelt P, Mallard A, Briskey D. “Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study.” Sleep Science and Practice, 2021;5:12. https://doi.org/10.1186/s41606-021-00065-3
10. Briskey D, Ebelt P, Steels E, Subah S, Bogoda N, Rao A. “Efficacy of palmitoylethanolamide (Levagen+™) compared to ibuprofen for reducing headache pain severity and duration in healthy adults: a double-blind, parallel, randomized clinical trial.” Food and Nutrition Sciences, 2022;13(7):690–701. https://doi.org/10.4236/fns.2022.137050
11. Rao A, Moussa AA, Erickson J, Briskey D. “Efficacy of topical palmitoylethanolamide (Levagen+) for the management of eczema symptoms: a double-blind, comparator-controlled, randomized clinical trial.” Skin Pharmacology and Physiology, 2023;36(6):288–295. https://doi.org/10.1159/000536670
12. Pellow J, Briskey D, Rao A. “The effect of topical palmitoylethanolamide (PlexoZome® Levagen®) on relief of post-exercise knee joint pain — a randomised double-blind controlled study.” HSOA Journal of Alternative, Complementary & Integrative Medicine, 2025;11(6):604. https://doi.org/10.24966/ACIM-7562/100604

Levagen® and Levagen+® are registered trademarks of Gencor Pacific Ltd. LipiSperse® and PlexoZome® are registered trademarks of Pharmako Biotechnologies Pty Ltd. This article discusses published research on an ingredient. KLORIS products are not medicines and are not intended to diagnose, treat, cure or prevent any disease.