Nutritional Outlook’s 2020 Best of the Industry Awards, Ingredient Supplier: Gencor

Nutritional OutlookNutritional Outlook Vol. 23 No. 10
Volume 23
Issue 10

The company is carving out its own stake in the PEA market in a big way: with heavy investment in research and development.

Gencor’s Levagen PEA already stars in many products on the market, with more on the way. Photos from GNC, NutriDyn, and Holland & Barrett.

Most mainstream consumers are not widely familiar with the dietary ingredient palmitoylethanolamide (PEA)—yet. Chances are good, however, they might in the years ahead. PEA offers wide-reaching health benefits for humans, with a long history of scientific study to prove it.

Consumers who don’t know PEA might be surprised to learn that PEA has actually been on the research radar for quite a while. Interest in what later would be identified as PEA began prior to the 1940s when researchers realized that feeding dried egg yolk to children suffering from hemolytic streptococcal infection helped prevent them from developing rheumatic fever.1 In 1954, those same researchers discovered that a lipid fraction in egg yolk had anti-inflammatory properties and that similar anti-inflammatory fractions were present in peanut oil and soy lecithin.2 In 1957, researchers identified this lipid fraction as palmitoylethanolamide (PEA).3 Over the next decades, through animal and human clinical studies, scientists learned more about the anti-inflammatory activities and numerous health benefits of PEA.

In 1970, PEA was introduced commercially to the world as a cold-and-flu remedy called Impulsin in the Czech Republic (Czechoslovakia back then).4 Today, PEA is available in the global market as both a food supplement/dietary supplement ingredient, as well as one for topical and veterinary use.5 Its best-known benefits are its anti-inflammatory and pain-relieving properties.

What is PEA, and what makes it so exciting in terms of what it can offer human health? As Gencor explains, PEA is a fatty acid amide produced endogenously by the body. It exerts its benefits via multiple mechanisms. First and foremost, it is an agonist that binds to peroxisome proliferator-activated receptors (PPARα), thereby helping to promote PPARα’s anti-inflammatory and related painkilling effects. PEA is also thought to inhibit degranulation of the mast cells, or immune cells, which ultimately keeps the body from producing pro-inflammatory mediators like TNFα and cytokines. PEA also alleviates pain by activating the transient receptor potential vanilloid type 1 (TRPV1). Finally, research suggests a beneficial relationship between PEA and the endocannabinoid system. This interplay with the endocannabinoid system (ECS) is of high interest especially these days as research on the ECS and cannabinoids grows. Although PEA is part of the endocannabinoid system, it does not bind to the classically known cannabinoid receptors CB1 and CB2; however, it may indirectly activate these receptors by participating in the “entourage effect,” working synergistically with cannabinoids and ultimately influencing physiological outcomes of the ECS. It has also been shown to activate the GPR55 cannabinoid receptors, which are involved in immunomodulatory functions.6

The body itself produces PEA, and PEA is used locally by every tissue in the body. Simply put, the body makes PEA when pain and inflammation occurs. Most importantly, PEA’s action is rapid, which is one of its most valued attributes as an anti-inflammatory and pain reliever.

“Because it is locally produced and is the first responder to any threats to the body, it is fast acting,” explains R.V. Venkatesh, managing director, Gencor (Irvine, CA). “PEA,” he says, “is the body’s first responder to any injuries, inflammation, stresses, pains, infections, etc.”

If the body produces PEA on its own, is there a need to supplement with PEA as a dietary ingredient? Venkatesh explains. “PEA is produced endogenously and used up quickly and on demand by the body. Its action peaks in two hours, which is why it’s fast acting. Once it is depleted, the body takes time to produce it again. That is why supplementing with exogenous PEA helps maintain normal healthy tissue levels of PEA.” Moreover, he says, although PEA is naturally present in such foods as egg yolk, soy, peanuts, and alfalfa, getting enough PEA from these foods usually requires a high intake, “well above what these foods can provide as part of normal daily consumption. This is why supplementation with PEA helps to maintain healthy tissue and levels of PEA.”

Gencor first started its work with PEA eight years ago. Gencor’s branded PEA ingredient, Levagen, launched in 2015 in the U.S. and Canada. The first product to include Levagen was brought to market in 2015 by GNC, which at the time held an exclusive, first-right-of-use license on the ingredient in certain countries. Once that agreement expired, Gencor opened Levagen up to the rest of the market.

To be clear, Levagen is not the first nor the only PEA dietary ingredient on the market. However, Gencor is bringing PEA to market with a splash, armed with impressive human clinical research showing how its proprietary ingredient specifically has a multitude of health applications. In short, it is likely Gencor will play an important role in renewing and raising the profile of an ingredient with such promising benefits.

The first human clinical study Gencor published on Levagen, published in 2019, was conducted in 111 adults experiencing mild-to-moderate knee osteoarthritis.7 Results showed that the ingredient helped relieve pain and other symptoms associated with knee osteoarthritis.

In 2020, Gencor announced the publication of a new study on Levagen—this time on exercise recovery.8 (This study was done on Levagen+, Gencor’s enhanced-dispersibility version of Levagen introduced in 2018.) Following acute and intense exercise, Levagen+ was not found to reduce pain and localized swelling in subjects by reducing pro-inflammatory intramuscular enzymes and cytokines (possibly, the researchers said, due to the “volume of exercise and/or the acute supplementation protocol used”); but, they noted, Levagen+ “was, however, able to reduce myoglobin and increase protein kinase B phosphorylation following exercise.” Protein kinase B plays a key role in muscle building. Myoglobin is a marker for muscle damage, and results showing reduced myoglobin levels indicate a subsequent reduction in muscle damage. The intervention also showed increased lactate levels and therefore an increased exercise threshold. Said the researchers: “Taken together, these results may indicate that PEA supplementation is able to aid in muscle recovery from repeat bouts of exercise performed within three hours.”

The researchers added: “To our knowledge, this is the first study to examine the effects of PEA supplementation on recovery from muscle-damaging exercise.”

These studies are only the start for Gencor. Venkatesh advises that a study on Levagen+ and short-term joint pain is currently being submitted for peer-review publication, this time “focusing on any joint in the body, instead of solely the knee,” and demonstrating that Levagen+ relieved discomfort quickly. He says this study would again be a first for PEA, noting that “Nobody else has done short-term joint-pain studies on all joints for nutraceutical applications.”

Another completed Levagen+ study currently being submitted for peer-review publication compared the effects of Levagen+ and ibuprofen for resolving headaches—again, a first, says Venkatesh—and showing Levagen+ to be as effective, and even faster acting, compared to 400 mg of ibuprofen, he says. This would open Levagen+ up for headache-related products in certain countries. “In Australia and India, we are allowed to make analgesic and pain-relief claims for Levagen+. This is a huge market, and we are working to tap into it,” says Venkatesh.

Then there is sleep. A recently completed study found that Levagen+ significantly reduced the time taken for subjects to get to sleep at night, Venkatesh says—once again, a first for PEA, he adds. This paper will be submitted for peer-review as well.

The company has many other Levagen+ studies in progress, some of which will be completed soon, including trials on seasonal allergies, migraines, cold-and-flu symptoms, the microbiome, and menstrual pain.

The goal, Venkatesh says, is to do more research in healthy subjects. “Most of the research on PEA has been done on diseased patients in the past, as the product was more focused and launched as a food for special medical purposes in Europe as an adjunct to pharmaceutical treatment,” he says. “We have started a lot of work on clinical studies on healthy human subjects in nutraceutical areas.”

Most studies now center on Levagen+, introduced in 2018, which is the cold-water-dispersible version of Levagen that Gencor developed with its sister company, Pharmako Biotechnologies (Cromer, Australia), using Pharmako’s LipiSperse lipid-dispersion technology. Levagen+ stands out in the PEA market because of its enhanced solubility and thus broader product-application potential and absorption in the body. For instance, unlike Levagen which is suited for tablets and capsules, Levagen+ can also go into effervescents, powders, gummies, and more. Generally with PEA, due to its lipophilic nature and thus insolubility in water, “The challenge for PEA has been poor absorption and bioavailability, which is well documented,” Venkatesh points out.

Like for Levagen’s other claims, Gencor has research to back claims about improved absorption and solubility. This year, a pharmacokinetic study was published in the Journal of Nutraceuticals and Food Science confirming that LipiSperse increased the absorption of PEA in Levagen+ above standard PEA formulations—by up to 1.75 times.9

“This was a groundbreaking study,” Venkatesh says. “Levagen+ is the only PEA ingredient in the world that has demonstrated increased bioavailability compared to standard PEA, in a human pharmacokinetic study, which has been peer-reviewed and published….There have been no other pharmacokinetic studies done on PEA showing increased absorption with any other delivery form or system.”

With Gencor’s own research adding to the existing human clinical research that’s already been done on PEA—Venkatesh estimates there are more than 50 published human clinical studies on PEA—“the research on PEA for human health is very strong,” he says. Given how long the ingredient has been researched, “it is one of the most studied products found in the industry,” he adds. PEA has also been found to be safe and without adverse effects, he adds.

Backed by its existing and ongoing research, Gencor is positioning Levagen+ especially for multiple markets within nutraceuticals, including pain and inflammation reduction, reduction of allergies, enhanced sleep, increased calmness and reduced anxiety, immune support, microbiome support, and neuroprotective support.

What products might we see with Levagen and Levagen+ in the future? Only time will tell, but the ingredients are likely to gain more attention as more products hit the market and as Gencor works on expanding its regulatory approvals throughout the world. Gencor’s proprietary PEA ingredients already hold GRAS self-determination in the U.S., as well as approval as a food supplement in Europe, Australia, India, Brazil, Canada, and South Africa. (Venkatesh points out that PEA alone does not require a New Dietary Ingredient notification in the U.S. or a Novel Food application because it has historically existed as a common dietary ingredient in the food supply. It has also not been previously sold or investigated as a drug substance in the U.S. and thus does not run up against any Investigational New Drug challenges.)

There are already numerous products with Levagen and Levagen+ on the market. Just this year, English retailer Holland & Barrett International launched a unique effervescent supplement featuring Levagen, and CBD leader CV Sciences this year introduced a non-CBD immune health line featuring Levagen, with interest stemming from immune-related research already done on PEA.

Products like these two are being marketed as alternatives to the phytocannabinoid CBD. Gencor points out that PEA has some unique attributes that cannabinoids do not. While both act through the endocannabinoid system, Venkatesh explains that “CBD is an endocannabinoid that is supplemented externally. It is not endogenous to your body. That’s one of the key reasons why we compare PEA to CBD; it is something your body is used to producing and processing, while also providing the same, and in many cases greater, benefits.” PEA, as it already exists legally in the market, does not face the same regulatory hurdles CBD currently faces, especially in the U.S., and it currently has a much richer history of published research as well as established dosages—and it is well characterized.

By targeting many of these high-profile nutraceutical spaces, PEA is poised to become better known and more widely used, driven in large part by the work Gencor did in 2020 and that the company says it will continue to do. Says Venkatesh: “We have been instrumental in bringing more attention to PEA in the dietary supplement market with our manufacturing, science, and delivery technologies.”


  1. Coburn AF et al. “The prophylactic use of sulfanilamide in streptococcal respiratory infections, with especial reference to rheumatic fever.” The Journal of Clinical Investigation, vol. 18, no. 1 (January 1939): 147–155
  2. Coburn AF et al. “The effect of egg yolk in diets on anaphlyactic arthritis (passive arthus phenomenon) in the guinea pig.” Journal of Experimental Medicine, vol. 100, no. 5 (October 31, 1954): 425-435
  3. Kuehl Jr. FA et al. “The identification of N-(2-hydroxyethyl)- palmitamide as a naturally occurring anti-inflammatory agent.” Journal of the American Chemical Society, vol. 79, no. 20 (October 1, 1957): 5577–5578
  4. Keppel Hesselink JM. “Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical.” Journal of Pain Research, vol. 6 (2013): 625-634
  5. Gabrielsson L. “Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.” British Journal of Clinical Pharmacology, vol. 82, no. 4 (October 2016): 932-942
  6. Musella A et al. “A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum.” Scientific Reports. Published online August 4, 2017.
  7. Steels E et al. “A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis.” Inflammopharmacology, vol. 27, no. 3 (June 2019): 475-485
  8. Mallard A et al. “The effect of orally dosed Levagen+ (palmitoylethanolamide) on exercise recovery in healthy males—a double-blind, randomized, placebo-controlled study.” Nutrients, vol. 12, no. 3 (March 2020): 596
  9. Briskey D et al. “Increased absorption of palmitoylethanolamide using a novel dispersion technology system (LipiSperse®).” Journal of Nutraceuticals and Food Science. Published online May 3, 2020.
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