C15:0, ferroptosis, and metabolic health: What practitioners should know

Dr. Lara Zakaria is joined by Stephanie Venn-Watson, DVM, MPH, to explore emerging research on pentadecanoic acid (C15:0), an odd-chain saturated fatty acid initially studied through research involving bottlenose dolphins.The conversation connects C15:0 with cell-membrane composition, lipid peroxidation, ferroptosis, iron metabolism, metabolic health, and steatotic liver disease. It also examines research on circulating C15:0 as a biomarker associated with cardiometabolic outcomes and early human trials of C15:0 supplementation. (Imamura 2018) (Sawh 2021) C15:0 has been proposed as a candidate essential fatty acid, however, that classification and a specific human “C15:0 deficiency syndrome” remain emerging hypotheses rather than established clinical diagnoses.Clinical TakeawaysFerroptosis is an iron-dependent form of regulated cell death. First characterized in 2012, ferroptosis involves iron-dependent lipid peroxidation and differs mechanistically from apoptosis and other forms of cell death. (Dixon 2012) Polyunsaturated fatty acids in phospholipids are particularly relevant substrates for ferroptotic lipid peroxidation. (Yang 2016)C15:0 is an odd-chain saturated fatty acid being studied for metabolic effects. Pentadecanoic acid, or C15:0, is found in dairy fat and smaller amounts in other foods. Higher circulating C15:0 has been associated with lower incidence of type 2 diabetes in prospective observational research, but these associations do not establish that C15:0 itself prevents diabetes. (Imamura 2018)Calling C15:0 an “essential fatty acid” remains an emerging scientific proposal. Experimental work has proposed C15:0 as a candidate essential fatty acid based on dietary exposure, biological activity, and associations between circulating levels and health outcomes. More research is needed before C15:0 can be treated as equivalent to the established essential fatty acids linoleic acid and alpha-linolenic acid. (Venn-Watson 2020) (Venn-Watson 2022) Metabolic hyperferritinemia is a recognized clinical framework, but it is not synonymous with ferroptosis or C15:0 deficiency. Metabolic hyperferritinemia describes elevated ferritin occurring with metabolic dysfunction. Ferritin is also an acute-phase reactant, so elevated values require evaluation in clinical context rather than being interpreted as tissue iron overload by themselves. (Valenti 2023)Human C15:0 supplementation evidence is early. Within this broader metabolic context, circulating C15:0 is an emerging biomarker of interest. In a small 12-week randomized, placebo-controlled