Essential fatty acids and the endocannabinoid system

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A 2002 article in the magazine Biomedicine and Pharmacotherapy1 was one of the first to draw attention to a health problem that has only grown in the last two decades (as evidenced by the more than 3,900 citations in the paper to date): an imbalance of omega-6 essential fatty acids and omega-3 Western diet.

Author Artemis Simopoulos of the Center for Genetics, Nutrition, and Health in Washington, DC, suggests that humans evolved by eating approximately equal amounts of omega-6 and omega-3. In the typical western diet, however, the ratio is at least 15 to 1. Today we eat less fish, nuts, berries and green leafy vegetables, which are major sources of omega-3s and many more cereals, which are rich in omega-6.

Just as soy and corn have displaced nuts and nuts in our diet, omega-6 has essentially displaced omega-3 in our body. It is a zero-sum game with serious health consequences. This dramatic departure from the diet to which humans are genetically adapted – characterized by a large and relatively sudden disparity in the intake of omega fatty acids, as marked by Simopoulos – contributes to chronic health conditions that affect each increasingly the United States and other Western countries such as hypertension and obesity. , diabetes and many cancers.

His observations – and the previous reference to the concept of “therapeutic dose of omega-3 fatty acids” – seemed to anticipate the emergence of the modern global omega-3 supplement industry, which was valued at $ 5.118 billion in 2019 and continues to grow every year. course.2

The endocannabinoid connection

What Simopoulos did not understand at the time, and in fact no one did, was the role in all this of the endocannabinoid system (ECS). He ECS had been first named in the scientific literature only a few years earlier in 1996,3 and no reference is made at all to his article.

Since then, researchers have learned a lot about the role of the ECS when mediating the health effects of “essential” omega fatty acids, so called because they cannot be produced by the body in sufficient quantities and therefore must be ingested. These advances could, in turn, lead to other possible therapies and interventions aimed specifically at ECS to help treat chronic diseases.

While it’s true that there’s a lot more to the story, a story that gets more and more complex the longer you follow it, omega fatty acids interact with ECS in two key ways. The first has to do with the endocannabinoids themselves, which are in fact byproducts of omega fatty acids. Endocannabinoids are compounds that bind to cannabinoid receptors CB1 i CB2, among other receptors and targets of the body.

The second way omega fatty acids interact with ECS specifically involves the CB1 receptor, which concentrates in the brain and nervous system, but also plays a role in inflammatory processes. And inflammation, as we now know, is critical for many chronic diseases.

Arachidonic acid & Synaptamide

The two best studied endocannabinoids, commonly known as anandamide and 2-AG, are chemically derived from arachidonic acid (AA), one of the four main types of omega-6 fatty acids. For anyone even familiar with the role it plays ECS plays to maintain health and homeostasis, the importance of arachidonic acid as a staple of anandamide andAG it should be enough to indicate that omega-6 fatty acids, which are also found in meat, milk, eggs and other sources, are not harmful in themselves.

It turns out that the key is balance. Which brings us back to omega-3. Scientists now understand that two of the three main types of omega-3 fatty acids involved in human physiology: eicosapentaenoic acid (EPA) and docosahexaenoic acid (gave) – also produce derivatives that bind to the CB1 i CB2 receivers. And because they bind to cannabinoid receptors, it is also understood that these omega-3 derivatives are endocannabinoids.

These recently discovered4 endocannabinoids – EPG, EPEA, DPG, i DHEA – There are still no known names in the cannabis or nutrition communities, but maybe someday they will be. DHEA it is also known as “synaptamide” because it has been shown to promote neurogenesis, neuronal development, and synaptogenesis. 5 Scientists still have a lot to learn about how these omega-3-derived endocannabinoids work in the body.

“There’s a lot of interest in endocannabinoids derived from omega-3 fatty acids,” Aditi Das, a professor at the University of Illinois, told Project CBD. Das is helping to lead the global load to identify and characterize these fascinating compounds. “Omega-3 endocannabinoids right now are very mysterious, except for synaptamide, in which people have worked hard.”

Zero sum game

At the very least, it is clear that the two “classic” endocannabinoids (anandamide & 2-AG) derived from omega-6 arachidonic acid and the four recently identified endocannabinoids derived from omega-3 gave i EHPA they have different physiological properties and therefore different effects on the body. A key difference with the implications of chronic disease is that omega-3-derived endocannabinoids appear to suppress inflammation,6 while its omega-6-derived counterparts promote it. (It is worth noting that inflammation is not always bad, as it serves to fight injuries and infections.)

In addition to linking directly to the file CB1 i CB2 receptors, both sets of endocannabinoids also compete for the same biosynthetic enzymes, which are needed to produce them from their fatty acid precursors. Therefore, the balance between omega-3s and omega-6s in the diet can be seen as a zero-sum game: when one goes up, the other goes down.

And this is not just in theory; researchers have seen it happen: “A large set of evidence, which include in vitro-, data on animals and humans, emphasizes that increasing the supply of omega-3 fatty acids results in decreased concentrations of anandamide and 2-AG, while concentrations of DHEA i EPEA increase, ”Dutch scientists reported in a 2019 article exploring the anti-inflammatory effects of omega-3-derived endocannabinoids.7

This impulse and attraction explains how the person’s omega-3 / omega-6 dietary relationship affects not only inflammatory processes, but also the balance and tone of the entire endocannabinoid system. And, from the ECS works to keep homeostasis (another word for balance) within the body in general, this relationship goes a long way to explaining Simopoulos ’understanding in 2002 that when our omega fatty acid intake moves too far proportion with which we have evolved, everything from our brain to the gut can become unbalanced.

Omega-3 deficiency

But this is not the only way that omega and fatty acids ECS interact. The second avenue, as indicated above, goes straight on CB1. And it also has widespread health implications, given the CB1 presence of the receptor in the brain and central nervous system, as well as in other organs and tissues, including the heart, liver, kidneys, eyes, and skin.

In the last decade, researchers have discovered that dietary intake of omega-3 fatty acids has a beneficial effect. CB1 receiver function8 – and, to the point, that its relative absence may contribute to a significant deterioration of the endocannabinoid system.

“The dietary deficiency of omega – 3 has been shown to prohibit the proper functioning of the CB1 receptor, while a diet rich in omega-3 increases the sensitivity of CB1“, Write the authors of a November 2020 review in the European Journal of Neuroscience.9 “These findings support the notion that omega-3 is crucial for the modulatory functions of the endocannabinoid system.”

“Nutrition is about balances”

To return to Simopoulos and his 2002 article for the last time, he does not suggest that all humans should adopt a 1: 1 balance to be healthy. Rather, he points out that an omega-6 to omega-3 ratio of around 2: 1 or 3: 1 appears to be protective against harmful inflammation and a variety of chronic diseases, including cancer. In general, he concludes, the lower the proportion, the better.

Currently, nutritionists seem to agree, recommending a dietary ratio between 1: 1 and 4: 1. (Interestingly, hemp seeds have a ratio of about 3: 1.) But whatever the exact number, Renger Witkamp of Wageningen University in the Netherlands, who studies the intersection between nutrition and pharmacology, said he believes omega fatty acids, ECS, even CBD the “promiscuous” plant cannabinoid that acts on the body in a wide variety of ways; they all have something important to teach us about health. And they also have important lessons for the development of therapeutic products designed to treat chronic diseases, he says.

“Nutrition is about balance. This is how our biology works. If we look at chronic diseases, the diseases of our age, they are lifestyle-related diseases. They originate from imbalances between molecules and not because of a molecule. Therefore, trying to cure these diseases with a single goal and a molecule, in my opinion, is not the right way. And here, “Witkamp concludes,” the endocannabinoid system adapts very well. “


Nate Seltenrich, a freelance science journalist based in San Francisco Bay, covers a wide range of topics such as environmental health, neuroscience and pharmacology.

Copyright, project CBD. Cannot reprint without permission.


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