Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential?

Stephanie Venn-Watson,Edward A Dennis,Richard Lumpkin

doi:10.1038/s41598-020-64960-y

Stephanie Venn-Watson, Edward A Dennis + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-64960-y

Copy DOI

Abstract

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants. Higher circulating concentrations of OCFAs, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are associated with lower risks of cardiometabolic diseases, and higher dietary intake of OCFAs is associated with lower mortality. Population-wide circulating OCFA levels, however, have been declining over recent years. Here, we show C15:0 as an active dietary fatty acid that attenuates inflammation, anemia, dyslipidemia, and fibrosis in vivo, potentially by binding to key metabolic regulators and repairing mitochondrial function. This is the first demonstration of C15:0’s direct role in attenuating multiple comorbidities using relevant physiological mechanisms at established circulating concentrations. Pairing our findings with evidence that (1) C15:0 is not readily made endogenously, (2) lower C15:0 dietary intake and blood concentrations are associated with higher mortality and a poorer physiological state, and (3) C15:0 has demonstrated activities and efficacy that parallel associated health benefits in humans, we propose C15:0 as a potential essential fatty acid. Further studies are needed to evaluate the potential impact of decades of reduced intake of OCFA-containing foods as contributors to C15:0 deficiencies and susceptibilities to chronic disease.

Highlights

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants
While dietary even-chain saturated fatty acids (ECFAs) have been associated with increased risk of inflammation, heart disease, and type 2 diabetes in humans[12,13,14,15], higher dietary intake and circulating levels of OCFAs have been associated with lower risks of adiposity, chronic inflammation, cardiovascular disease, metabolic syndrome, type 2 diabetes, nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease, pancreatic cancer and other conditions[14,15,16,17,18,19,20,21,22,23,24,25,26,27]
Dual PPARα/δ agonist activities similar to C15:0 were present for C14:0 and C16:0, suggesting that carbon chain length may be a determinant of PPARα/δ binding

Summary

Introduction

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants. In the U.S, during the 20-year period following this initial recommendation, the average individual’s daily intake of whole fat milk was reduced more than 4-fold, from 283 to 65 grams per day, in an effort to lower dietary saturated fats[2,3] Despite this drop in whole fat milk intake, the global prevalence of obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease has increased[4,5,6]. Current dietary saturated fat recommendations do not discriminate between ECFAs and OCFAs, and the growing body of literature demonstrating opposing associations of ECFAs and OCFAs with disease and health have led to calls to refine global saturated fatty acid dietary guidelines[29,30] This may be important since population-wide concentrations of circulating OCFAs are decreasing[31]. We reviewed current scientific literature related to OCFAs, with a lens on potential support for OCFAs as essential dietary fatty acids

Objectives

Methods

Results

Conclusion