Pentadecanoic acid (C15:0) and cardiovascular disease: A narrative review

Abstract

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide despite major advances in prevention and treatment. The odd-chain saturated fatty acid pentadecanoic acid (C15:0), primarily obtained from dairy fat, has been associated with cardiometabolic benefits. To summarize recent advances in understanding the role of pentadecanoic acid (C15:0) in CVD biology and risk, and to identify knowledge gaps and future research priorities. A narrative review was conducted, drawing on 115 PubMed-indexed studies on odd-chain fatty acids (OCFAs) and cardiovascular outcomes, as well as illustrative mechanistic studies of C15:0. This narrative review synthesized evidence from approximately 115 PubMed-indexed studies on OCFAs and cardiovascular outcomes, along with mechanistic studies of C15:0, identified through targeted searches in PubMed, Scopus, and Web of Science from January 2000 through May 2025.

Keywords: Pentadecanoic acid; Cardiovascular disease; Odd-chain saturated fatty acids; Cardiometabolic health; Inflammation; Insulin sensitivity; Mitochondrial function; Dairy fat

Core Tip: Pentadecanoic acid (C15:0), an odd-chain saturated fat concentrated in grass-fed dairy, is increasingly recognized as a “good” saturated fat with cardioprotective potential. Prospective cohorts and a recent meta-analysis show that individuals in the highest C15:0 quintile experience 12%-25% fewer cardiovascular events and approximately 14% less incident type 2 diabetes. Mechanistic studies reveal that C15:0 activates peroxisome proliferator-activated receptors alpha and delta and AMP-activated protein kinase, lowers low-density lipoprotein cholesterol and interleukin-6 and tumor necrosis factor α-driven inflammation, enhances insulin sensitivity, and repairs mitochondrial-endothelial function - findings that prompt calls to test dietary or supplemental C15:0 in randomized trials and to rethink blanket saturated-fat limits.