New study finds pentadecanoic acid metabolizes into full-acting endogenous cannabinoid called pentadecanoylcarnitine

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A recently published study¹ conducted by Seraphina Therapeutics (San Diego, CA) and funded by the Office of Naval Research, discovered an endocannabinoid called pentadecanoylcarnitine (PDC), which is metabolized from an emerging essential fatty acid called pentadecanoic acid (C15:0). This newly discovered endocannabinoid may have far-reaching health benefits and offers greater insights into the way C15:0 impacts our overall health.

C15:0 is manufactured by Seraphina Therapeutics and marketed as a dietary supplement called Fatty15. An odd chain saturated fatty acid, C15:0 was discovered during research investigating the health outcomes of aging dolphins. Researchers found that dolphins with poorer health outcomes had significantly lower levels of C15:0 in their system compared to those that were healthier, despite receiving the same diets and healthcare. Subsequent research has found that C15:0 may play an important role in liver and cardiovascular health, and may even offer greater health benefits than the omega-3 fatty acid eicosapentaenoic acid (EPA). There are currently 30 peer-reviewed studies demonstrating the potential health benefits of C15:0.

In this most recent study, researchers discovered that C15:0 is metabolized into PDC, which is only the second-known endogenous molecule that can fully activate both the cannabinoid (CB) 1 and 2 receptor. Researchers did this by going back to the metabolomics data collected from dolphins in the initial discovery of C15:0. “We looked for high-ranking metabolites, as in the metabolites that predicted the healthiest aging dolphins…to see if any of those among the high-ranking group were related to pentadecanoic acid. Right there at the top was PDC, so we then went to a second set of metabolomic data in which we gave dolphins a higher C15:0 diet,” explained Stephanie Venn-Watson, DVM, MPH, the study’s lead author, as well as CEO and co-founder of Seraphina Therapeutics to Nutritional Outlook.

That second set of metabolomic data found that C15:0 levels rose in conjunction with a high C15:0 diet, and along with it rose PDC levels. PDC was then evaluated for dose-dependent cell-based activities by measuring its effects on 148 clinically relevant biomarkers across twelve primary human cell systems mimicking various disease states. Its mechanisms of action were assessed across 78 cell-based target assays.

The results showed that PDC had dose-dependent anti-inflammatory activities, lowering interleukin 1 alpha (IL-1α), interferon-inducible T-cell alpha chemoattractant (ITAC), monocyte chemoattractant protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10), across cell systems relevant to treating cardiovascular, immune, neoplastic, pulmonary, and skin diseases. Additionally, PDC was found to be a dose-dependent agonist of the CB1 and CB2 receptors, a dose-dependent antagonist of both histamine H1 and H2 receptors, demonstrating a potential role as an antihistamine nutrient, as well as a dose-dependent agonist of the serotonin 1A and 1B (5-HT1A and 5-HT1B) receptors, demonstrating a potential role as a serotonin mimic. This research not only validates the therapeutic potential of C15:0, but also that of PDC, though further research is necessary on that front.

“Our current priority is to help understand C15:0 as an essential fatty acid, and to help understand the benefits that are being conferred to people,” said Venn-Watson. “Knowing that C15:0 levels have been declining among the population because our sole source of C15:0 is whole-fat dairy and there are ongoing dietary recommendations to avoid all forms of saturated fats, what’s most urgent to us is the potential for global population-wide C15:0 deficiencies, now linked to deficiencies in PDC, which can have impacts across our bodies and mind.”

“These findings help underline the urgent need to address nutritional guidelines around saturated fats, and so the more we find, the nutritional and scientific community will start and continue to work around C15:0 and PDC, so that we can understand as much as possible,” Venn-Watson concluded.

Reference

1. Venn-Watson S et al. “Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health.” Scientific Reports, vol 12 (August 23, 2022): 13717, https://doi.org/10.1038/s41598-022-18266-w