Recent review states that pentadecanoic acid may support cellular stability for better longevity

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A recent paper¹ published in the journal Metabolites makes the case that pentadecanoic acid (C15:0), a newly discovered odd-chain saturated fat, is an essential fatty acid that has a primary role in stabilizing cell membranes and repairing mitochondrial function. According to the paper’s author, Stephanie Venn-Watson, DVM, MPH, deficiency in C15:0 of ≤0.2% total circulating fatty acids increases the risk of ferroptosis, which a type of cell death cause by the peroxidation of fragile fatty acids in cell membranes that combines with iron thus increasing reactive oxygen species, and disabling mitochondria. Ferroptosis is linked to a number of age-related conditions, namely type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Venn-Watson, who is the CEO of Seraphina Therapeutics, which manufacturers a C15:0 supplement called Fatty15, proposes the Cellular Stability Hypothesis, postulating that cell membranes need >0.4% to 0.64% C15:0 to support long term health.

“A somewhat mysterious type of cell death, called ferroptosis, showed up as our C15:0 levels have been declining,” says Venn-Watson, in a press release. “We have demonstrated not only that low C15:0 can lead to ferroptosis and its downstream complications, but that replenishing these levels directly halts all core components of this new cell killer.”

Venn-Watson cites a prospective cohort study that measured C15:0 levels at baseline for more than 4,000 adults with a median age of 60.5 years. On follow-up 16 years later, researchers found that higher C15:0 levels were associated with lower incidence of cardiovascular disease risk in a linear dose-response manner, and all-cause mortality nonlinearly.²

Another study³ of people living in Sardinia, Italy, which is known as a high-longevity zone (HZL) – meaning that high percentage of people living there typically live beyond 80 – found that 60-70 year olds living in the HZL had the highest levels of C15:0 with 0.64% of total fatty acids, while people 80 years or older living in the HZL had 0.42% C15:0 of total fatty acids, People over the ages of 80 living in a low longevity zone had the lowest levels of C15:0 with 0.29% of total fatty acids. That study indicates that C15:0 naturally declines with age, and that people living in HZLs have significantly higher levels of circulating C15:0. In the case of Sardinia, this may be due to the fact that they have a heavy dairy-based diet, primarily from local grass-fed sheep and goat’s milk, which are high in C15:0. One of the factors driving the decline of C15:0 in our diets, says Venn-Watson, is the decline in consumption of whole fat milk.

“There are two big benefits of a discovered nutritional deficiency syndrome,” says Venn-Watson. “The first is that C15:0 can be readily measured to identify people who have low levels. The second is that we can drive meaningful changes in our diets and global nutritional guidelines to help replenish population wide C15:0 levels and fix these deficiencies.”

References

1. Venn-Watson, S. The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome. Metabolites. 2024, 14, 355. DOI: 10.3390/metabo14070355
2. Trieu, K.; Bhat, S.; Dai, Z.; Leander, K.; Gigante, B.; Qian, F.; Korat, A.V.A.; Sun, Q. et al. Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis. Plos Medicine. 2021, 18(9), e 1003763. DOI: 10.1371/journal.pmed.1003763
3. Manca, C.; Carta, G.; Murru, E.; Abolghasemi, A.; Hastimansooreh, A.; Errigo, A.; Cani, P.D.; Banni, S.; Pes, G.M. Circulating fatty acids and endocannabinoidome-related mediator profiles associated to human longevity. GeroScience. 2021, 43, 1783-1798. DOI: 10.1007/s11357-021-00342-0