Mercola J. Molecular and cellular mechanisms of pentadecanoic acid. World J Biol Chem 2025; 16(4): 111258 [DOI: 10.4331/wjbc.v16.i4.111258]
Corresponding Author of This Article
Joseph Mercola, Researcher, Midwestern University, 555 31st Street, Downers Grove, IL 60515, United States. drm@mercola.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Dec 5, 2025; 16(4): 111258 Published online Dec 5, 2025. doi: 10.4331/wjbc.v16.i4.111258
Molecular and cellular mechanisms of pentadecanoic acid
Joseph Mercola
Joseph Mercola, Midwestern University, Downers Grove, IL 60515, United States
Author contributions: Mercola J was the sole author responsible for study conception and design, data acquisition and interpretation, manuscript preparation and revision, final approval of the version to be published, and agrees to be accountable for the integrity of the work in all respects.
Conflict-of-interest statement: The author is the founder of a nutritional supplement company. While the company does not currently manufacture or sell C15:0 products, the author has explored potential product development in this area. This review was conducted independently, and all cited research was performed by third-party laboratories.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph Mercola, Researcher, Midwestern University, 555 31st Street, Downers Grove, IL 60515, United States. drm@mercola.com
Received: June 26, 2025 Revised: July 15, 2025 Accepted: October 10, 2025 Published online: December 5, 2025 Processing time: 161 Days and 11.3 Hours
Abstract
Pentadecanoic acid (C15:0) is an odd-chain fatty acid, the β-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux; higher circulating levels are associated with reduced type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, and mortality. Summarize the cellular and molecular mechanisms underlying these associations. A comprehensive literature search (2000-2025) identified studies of C15:0’s mechanistic actions in vitro and in vivo, and multi-omics studies focused on receptor binding, signaling cascades, gene expression, and comparative pharmacology. C15:0 is a dual partial peroxisome proliferator-activated receptor α/δ agonist. It activates AMP-activated protein kinase, suppresses mechanistic target of rapamycin, and selectively inhibits histone deacetylase 6. It augments succinate-driven complex II respiration, preserves mitochondrial membrane potential, limits reactive oxygen species, and attenuates interleukin-6 (IL-6) – triggered Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B p65 signaling, lowering monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and IL-6. Across the BioMAP® human-primarycell platform – which tests 12 distinct primary human cell systems such as endothelial cells, fibroblasts, macrophages, and T-cells – C15:0 (17 µM) produced statistically significant changes in 36 mechanistically diverse biomarkers. This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. C15:0 engages receptor targets that converge on enhanced lipid oxidation, cellular energetics, and inflammation resolution. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.
Core Tip: Pentadecanoic acid (C15:0) is portrayed as the first essential odd-chain saturated fat that ignites fat-burning through partial peroxisome proliferator-activated receptor α/δ agonism, activates AMP-activated protein kinase while damping mechanistic target of rapamycin, revives complex II via succinate anaplerosis, and uniquely inhibits cancer-linked histone deacetylase 6. It also blocks Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B, using the BioMAP® human-primary-cell platform – which tests 12 distinct primary human cell systems such as endothelial cells, fibroblasts, macrophages, and T-cells – C15:0 (17 µM) produced statistically significant changes in 36 mechanistically diverse biomarkers. By eliciting broad, multi-pathway modulation that mirrors the phenotype produced by metformin and rapamycin – yet with no detectable cytotoxicity – C15:0 emerges as a safe, affordable “nutrapharmaceutical” poised to counter metabolic, inflammatory, and age-related diseases.
