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The fatty acid amides, compounds formed in the body but also found in certain foods (cited below), modify the activity of the endocannabinoid system. Amongst other things they inhibit the breakdown of the endocannabinoid anandamide, an entourage effect which is relaxing and calming. You may have experienced this at some point in your reckless youth.

The best-known and the most commercialized of these compounds is palmitoylethanolamide, known to its many friends as PEA.

PEA is well-established as an effective (and legal) analgesic and anti-inflammatory alternative to CBD, with anti-convulsant and sleep-enhancing benefits on the side. If you want to try this natural product, which is considerably safer than any of the pharma painkillers, I would recommend the version with the highest bioavailability (1).

Next up is OEA. Oleoylethanolamide, the new kid on the block, offers benefits that overlap with but extend the range of PEA, and opens up new possibilities in health management, weight control and sports nutrition.

Both PEA and OEA produce protective anti-inflammatory and therefore analgesic effects. OEA is slightly more effective than PEA at inhibiting the breakdown of anandamide (2), so if PEA makes you feel good, OEA will likely make you feel a little bit better.

However, whereas PEA is primarily an autocoid, a local response to injury synthesized when needed in all tissues, OEA is mostly produced in the intestines (3, 4) where it acts to induce microbiotal shift, immuno-modulation and, via several routes, satiety (5-10). This leads directly to weight loss and improved metabolic health, combined with cardiovascular benefits.

OEA’s ability to up-regulate AMP-kinase makes it an exercise mimetic (6, 11, 12). This implies enhanced muscle physiology and function (6), the transformation of white (storage) to brown (thermogenic) adipocytes (13), and the gradual reduction of those hard-to-reach deep, intra-abdominal fat deposits (14).

The combination of weight loss and better muscle function (improved body composition, increased power/weight ratio) is particularly relevant to athletic and sporting activities such as cycling and martial arts.

Let’s start with the weight loss angle.

Once OEA has been ingested, it rapidly enters the brain via the circulation (ie 9). Preclinical work and early clinical studies show that when it gets there, it induces hypophagia and weight loss via central PPAR-alpha and dopamine signaling within the hedonic brain centers (6-10). These actions contribute to satiety, and enhanced cognitive function (15, 16).

In addition, OEA provides mood-elevating (17) and other cognitive/therapeutic / neuroprotective effects (18-21).

OEA also acts where it is produced, in the intestines. Parallel research has discovered that OEA has distinct and complementary modulating effects in the gut, shifting the microbiota towards a ‘lean’ bacterial phenotype and gut-specific immune parameters towards those seen with low-fat, high-fiber diets (21).

One of the species elevated by OEA is Akkermansia municiphilla (22). A. municiphilla produces a protein (P-9) that induces GLP-1 secretion (23), and this Wegovy-like action is also likely involved in OEA’s satiety effects. As happens with Wegovy, OEA-induced GLP-1 secretion improves glucose homeostasis and various metabolic parameters including insulin sensitivity (24); which is directly anabolic (25).

OEA has one or two advantages over Wegovy and Mounjaro. It is natural, safe (26, 27), inexpensive, available without a prescription, and available. Sorry, that’s 5 advantages. And it does not require an injection, so that’s 6.

Oral GLP-1 agonist drugs are in the pipeline. Lead candidate Danuglipron seems to work quite well, if you don’t mind the diarrhea, nausea and vomiting (28). Is OEA as good as Danuglipron? You might very well think that; I couldn’t possibly comment (because I don’t want to be whacked by one of Albert Bourla’s unsavory sidekicks), but they look rather similar to me…

OEA affects hunger-sensing, but it is also involved in overall energy management. During fasting, for example, mast cells in the gut release histamine, which increases OEA synthesis in the liver. This kick-starts hepatic ketogenesis, a metabolic program that takes the fatty acids released from your fat depots (when fasting), and converts them to ketone bodies which fuel the brain and the muscles during prolonged fasting and exercise (29).

In addition to the positive metabolic shifts generated by OEA it has been shown to exert multiple vaso- and cardio-protective effects (30), including the up-regulation of antioxidant and anti-inflammatory genes, via PPR-alpha signaling.

To summarize, oleoyl ethanolamide is a fine-tuner of the metabolism, microbiota and immune system, with resulting improvements in health, mood and cognitive function. For the athlete, an OEA program offers an improved power/weight ratio plus enhanced stamina. It’s an attractive package.

Due to OEA’s modes of action it can be usefully combined with proteins and/or amino acid supplements such as leucine, and/or the natural anabolic agent ecdysterone (31). AMP-K activators can be utilised in cyclical programs, switching between OEA and the AMP activator in 2-week phases.

Given the importance of mood and resilience in competitive sports, saffron is a potentially valuable adjunct that will likely build on the mood-elevating and anxiolytic effects of OEA (32). As gut health is another important target in sports (33), OEA’s microbiotal modulation (21) can be logically combined with mixed prebiotic fibers (34).

One last note. OEA is produced in the intestines in response to a fatty meal, and under normal (pre-transitional) conditions its anorectic signal presumably forms one link in the gravitostat, the homeostatic system originally designed to keep us lean and fit (35).

There is evidence that the high-fat content of today’s industrial diet damps OEA signaling (10), and this provides the rationale for topping up with OEA supplements. When given to obese subjects, these supplements have been shown to exert distinct metabolic benefits (36), and to reduce appetite and body weight (37). When included in a dairy-based snack they have the same positive effects in our metabolic first cousins, the mini-pigs (38).

Word to the wise. In mini-pigs, supplemental OEA worked significantly better when given in a drink rather than in a solid snack. Bioavailability is the key. This indicates that enhancing technologies such as Lipisperse® will be critical to the development of OEA in tablets and capsules.

For those who prefer a food source, cocoa, oats, nuts and extra-virgin olive oil contain OEA, albeit at low levels (39).

Olive oil also contains oleic acid, however, and if you consume enough of it (ie prepare all food at home and use olive oil exclusively) you will boost OEA production in your own body, to the extent of reducing appetite (40). This is likely why diets rich in oleic acid are associated with improved body composition (41); and why OEA is currently being considered as a treatment for metabolic dysregulation-associated fatty liver disease (42), formerly NAFLD.

As if that were not enough, evidence is emerging that both oleic acid and OEA have significant anti-cancer properties (ie 43, 44) – which is what you might expect, given the exercise mimetic properties cited above (6, 11, 12).

As EVOO (the extra-virgin stuff) also contains cardio-protective polyphenols (45, 46), I recommend you keep it in the kitchen at all times, and Lipisperse®-enhanced OEA in your pocket. This should help you stay slimmer, and healthier.

Next week: From EVOO to EVA; the importance of being elastic.

References

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