The Impact of Fatty Acid Reporting Methods on Associations with Cardiometabolic Biomarkers

Background: Global dietary guidelines for polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and its metabolite arachidonic acid (ARA), remain debated. Almost all research to date has used fatty acid (FA) data expressed as percent of total FA (% total).

The objective of this study was to determine whether expressing fatty acid (FA) data as % of total or as absolute concentrations alters associations with clinical biomarkers.

Serum FA data obtained via electron capture negative-ion mass spectrometry was obtained from NHANES. Each FA was expressed both as % total and absolute concentration (µmol/L). Associations were examined between individual and total FAs and a panel of lipid and non-lipid biomarkers, including total cholesterol, LDL-C, HDL-C, triglycerides, blood pressure, body mass index, waist circumference, glucose, and insulin.

Associations between LA and clinical biomarkers including triglycerides, cholesterol, HDL-C, BMI, glucose, and insulin, reversed direction depending on whether LA was expressed as % total or as a concentration. Similar reversals were observed for ARA, DHA, DPA, and stearic acid. Increases in total FA levels were accompanied by decreases in % total of several PUFAs and HUFAs, despite rising absolute concentrations. Total FA was positively associated, often strongly, with nine clinical markers and negatively associated with HDL-C.

Expression format significantly impacts observed FA associations. Reliance on % total FA values alone may misrepresent true associations between individual FAs and clinical endpoints, especially when the total fatty acid pool also changes size. To develop effective dietary guidance or clinical recommendations, it is essential to consider the underlying FA biology and total FA pool size when determining whether % total or absolute FA concentrations are more appropriate. Competing Interest Statement Dr. Chilton is a cofounder of Resonance Pharma, Inc (Ann Arbor, MI, USA). This company develops diagnostics for lipid targets. This relationship is managed by the Office for Responsible Outside Interests at the University of Arizona. None of the other authors have any conflicts to report. Funding Statement This work was funded by National Institute of Health (NIH) grant 2R01AT008621-07. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=2011 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data used are available online at https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=2011 https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=2011