Connor C Tseng, Jingyi Zhang, Sadichhya Shahi, Martha Waricoy, Lindsey Gordon, Kaylee R Fisher, Spencer D Camp, Colin Miller, Timothy C McCall, Patrick G Corr, Mikhail Kogan, Leigh A Frame
Circulating C15:0 occupies a distinct position within lipidomic networks associated with metabolic resilience, inflammatory balance, membrane integrity, and neurologic health. The observed associations likely reflect shared metabolic regulation, dietary exposure, and enzymatic flux rather than direct fatty-acid synergy. These findings support the interpretation of C15:0 as a clinically relevant nutrient embedded within broader lipid metabolism and provide evidence to inform ongoing evaluation of its status as an essential fatty acid.
BACKGROUND AND AIMS: Pentadecanoic acid (C15:0) is an odd-chain saturated fatty acid increasingly proposed as a candidate essential fatty acid due to emerging evidence linking it to metabolic, inflammatory, and cellular resilience. However, its metabolic context within broader fatty-acid networks remain insufficiently characterized.
METHODS: We conducted a retrospective clinical chart review of 449 patients at an academic integrative medical center between January 2018 and March 2024. Circulating C15:0 and related fatty acids were measured using the NutrEval® comprehensive metabolic assessment. Patients were stratified by C15:0 reference ranges; due to the small sample size, the normal and high reference range groups were combined (low: <0.07 % total fatty acids; normal/high: ≥0.07 % total fatty acids). Linear regression models compared pentadecanoic acid to various fatty acids. Significance thresholds were determined using BH-adjusted p-values (FDR <0.05).
RESULTS: Of the 449 patients, 69/449 (15.4%) were in the "low" cohort. C15:0 demonstrated significant positive associations with several odd-chain and very long-chain saturated fatty acids, including palmitoleic acid (16:1 n7), margaric acid (C17:0), tricosanoic acid (C23:0), behenic acid (C22:0), and lignoceric acid (C24:0), as well as select omega-6 polyunsaturated fatty acids, including arachidonic acid (AA), gamma-linolenic acid (GLA), dihomogamma-linolenic acid (DGLA), and docosatetraenoic acid (DTA). Significant negative associations were observed with stearic acid (C18:0), nervonic acid (24:1 n9), vaccenic acid (18:1 n7), eicosadienoic acid (20:2 n6), and the linoleic acid:DGLA ratio. These patterns suggest coordinated regulation across lipid classes rather than isolated biochemical effects.
CONCLUSIONS: Circulating C15:0 occupies a distinct position within lipidomic networks associated with metabolic resilience, inflammatory balance, membrane integrity, and neurologic health. The observed associations likely reflect shared metabolic regulation, dietary exposure, and enzymatic flux rather than direct fatty-acid synergy. These findings support the interpretation of C15:0 as a clinically relevant nutrient embedded within broader lipid metabolism and provide evidence to inform ongoing evaluation of its status as an essential fatty acid.