What does a Free Fatty Acids (FFA) (non-esterified) test check?

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From the Guidelines

A free fatty acids (non-ester) test checks the level of unbound fatty acids circulating in the bloodstream, which is an independent risk factor for sudden cardiac death (SCD) but not fatal myocardial infarction (MI) 1. This test is primarily used to evaluate metabolic disorders, insulin resistance, and conditions affecting fat metabolism.

  • The test specifically measures fatty acids that are not attached to glycerol (non-esterified), which are released from fat tissue when the body needs energy.
  • Elevated levels of free fatty acids can indicate conditions such as diabetes, obesity, metabolic syndrome, or starvation, as these conditions often involve impaired insulin function or increased fat breakdown. The test is useful because free fatty acids play a crucial role in energy metabolism, and abnormal levels can contribute to insulin resistance and cardiovascular disease, as supported by the association of high total, very low-density lipoprotein (VLDL), or low-density lipoprotein (LDL) cholesterol levels with increased risk of VT/SCD 1.
  • The test typically requires fasting beforehand, as recent food intake can significantly affect free fatty acid levels.
  • Results are interpreted alongside other metabolic markers to provide a comprehensive assessment of metabolic health and fat metabolism. It is essential to note that while dietary n-3 PUFA may confer protection from arrhythmic death in subjects with and without documented underlying CHD, a small multicenter, double-blinded, randomized, placebo-controlled trial of n-3 PUFA has challenged this belief, showing a trend toward a higher incidence of VT/VF in patients randomized to fish oil 1.

From the Research

Free Fatty Acids (Non-Ester) Test

The free fatty acids (non-ester) test checks for the levels of free fatty acids in the blood.

  • Free fatty acids are implicated in the pathogenesis of insulin resistance and atherosclerosis 2.
  • Elevated levels of free fatty acids are associated with metabolic syndrome, insulin resistance, and type 2 diabetes mellitus 3, 4, 5.
  • The test is used to assess the risk of developing cardiovascular disease and metabolic syndrome.

Association with Metabolic Syndrome and Insulin Resistance

  • Free fatty acids are positively correlated with insulin resistance and triglyceride levels 2.
  • Elevated levels of free fatty acids are found in patients with metabolic syndrome compared to those without 2.
  • Free fatty acids are associated with markers of endothelial activation, such as E-selectin and ICAM-1 2.

Mechanisms of Insulin Resistance

  • Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes 6.
  • Local accumulation of fat metabolites, such as ceramides, diacylglycerol, or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signaling and glucose transport 6.
  • Inflammation and oxidative stress are also potent mechanisms that could lead to a state of insulin resistance 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Free Fatty Acids: Circulating Contributors of Metabolic Syndrome.

Cardiovascular & hematological agents in medicinal chemistry, 2018

Research

Obesity and free fatty acids.

Endocrinology and metabolism clinics of North America, 2008

Research

Free fatty acids, insulin resistance, and type 2 diabetes mellitus.

Proceedings of the Association of American Physicians, 1999

Research

Free fatty acids and insulin resistance.

Current opinion in clinical nutrition and metabolic care, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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