Assessing Pentadecanoic Acid In Vitro

The work on pentadecanoic acid noted here is interesting, but should be taken with a grain of salt given that it is performed in vitro. In general, one should expect any given set of mechanisms in the cell to be associated with many different means of manipulation. It is interesting to see a fatty acid capable of touching on the same mechanisms as rapamycin, but remember that the ability to influence the same mechanistic targets does not necessarily translate to the same ability to produce a modest slowing of aging in animal studies. So the usual advice stands here, to wait for the animal studies before getting too excited.

The BioMAP Diversity PLUS system includes a series of independently run and industry-standard pharmacological assays routinely used to screen and compare molecules for activity profiles and clinical indications as well as safety. Specifically, the BioMAP Diversity PLUS system tests molecules across 12 primary human cell-based systems mimicking various disease states and measures the molecule's effects across 148 clinically relevant biomarkers at four doses. The resulting cell-based phenotypic profile enables valuable insights into potential clinical applications of a compound, as well as identifying shared key activities with other compounds of interest.

Pentadecanoic acid (C15:0), an odd-chain saturated fatty acid, has mounting evidence of being essential to supporting cardiometabolic and liver health. People with low circulating C15:0 concentrations have a higher risk of having or developing type 2 diabetes, heart disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis, as well as specific types of cancer. As an essential fatty acid, C15:0 should, by definition, support healthspan, and longevity. Further, C15:0 has mTOR-inhibiting and AMPK-activating activities shared with rapamycin and metformin, respectively. As such, we compared the primary human cell phenotypic profile of C15:0 with acarbose, metformin, and rapamycin using BioMAP Diversity PLUS to objectively evaluate common clinically relevant cell-based activities supportive of an expanded healthspan and lifespan. Based on our findings, we then reviewed the literature for further evidence of C15:0 as a longevity-enhancing nutrient.

At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

Link: https://doi.org/10.3390/nu15214607

Comments

Interesting. Of note is that most of the research I can find on this acid comes from this same author, who also founded a company currently selling it online (Seraphina Therapeutics). Apparently she was a vet working on dolphins when she discovered higher blood levels of the acid yielded better outcomes, and that lead her on the journey to research and sell this. This doesn't seem like some cash grab / Theranos situation to me, but it's at least a noteworthy conflict that the source of these studies is one author / one company.

They're published in Nature in 2020 describing this along with murine data: https://www.nature.com/articles/s41598-020-64960-y

Another 2022 paper from same author comparing it to omega3 using the same BioMAP panel: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268778

Still, given the low effective dose (35 mg/kg in rats, so ~200mg daily in humans?), naturally occurring in dairy at 1% or so of fat, and existing in the blood already (along with its apparent metabolite C17:0), it seems a fairly safe thing to supplement with to me.

I'd love human data or more data from another author, but seems promising, especially for those of us avoiding dairy?

Posted by: Eric W at November 22nd, 2023 8:57 AM
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