Metabolic Effects of Linoleic Acid-Rich Oil Compared to a Blend Oil in Adults With Insulin Resistance

Background

Non-communicable diseases (NCDs) are among the leading causes of morbidity and mortality worldwide. A healthy diet may help reduce the risk of these conditions by modulating the availability of nutrients and metabolites. However, the underlying mechanisms are not fully understood and may even lead to misconceptions.

A common example is the widespread belief that a high intake of omega-6 polyunsaturated fatty acids (PUFAs) is harmful to health. Without strong scientific support, some have advocated limiting dietary linoleic acid (LA)-the predominant PUFA in human diets-under the assumption that it competes biochemically with omega-3 fatty acids, thereby reducing their beneficial effects. Nevertheless, meta-analyses of prospective cohort studies have shown that higher LA intake or circulating levels are associated with lower total and LDL cholesterol, reduced cardiovascular disease risk, and a lower incidence of type 2 diabetes. These findings highlight the need to reassess the biological effects of LA and its potential role in metabolic regulation. To support evidence-based dietary recommendations promoting LA intake, well-controlled intervention studies are needed to better understand its cardiometabolic effects.

Hypothesis

Elevated blood levels of linoleic acid (LA), in response to increased dietary intake, confer cardiometabolic benefits beyond lipid-lowering effects, improving insulin sensitivity and reducing cardiovascular risk in individuals with cardiometabolic risk conditions.

Objectives

The primary objective is to evaluate the effect of a short-term intervention with an LA-enriched oil on insulin sensitivity and glucose homeostasis in adults with insulin resistance.

Secondary objectives include assessing the impact of the intervention on lipid profile, circulating fatty acid composition, inflammatory status, hepatic enzymes, oxidative stress markers, and estimated cardiovascular risk in Chilean adults with insulin resistance and cardiometabolic risk conditions.

Experimental Design

This study is a randomized, single-blind, controlled, parallel-group clinical trial conducted at the Clinical Research Center (CICUC) of the Pontifical Catholic University of Chile. Eligible adults with insulin resistance will be randomly assigned in a 1:1 ratio to receive either a linoleic acid-rich oil or a blend oil for 8 weeks at a dose of 0.4 mL per kilogram of body weight per day. Fasting blood samples will be collected at baseline and at 8 weeks to assess insulin resistance (HOMA-IR), lipid profile, circulating fatty acid composition, inflammatory and oxidative stress markers (AOPP, oxidized LDL), and hepatic enzymes. Anthropometric and clinical parameters will also be recorded following standardized protocols.

Inclusion criteria

• Men and women aged 20 to 60 years.
• Insulin resistance (HOMA-IR > 2.6).
• At least one cardiometabolic risk factor: abdominal obesity (waist circumference > 90 cm in men or > 80 cm in women); low HDL-cholesterol (< 40 mg/dL in men or < 50 mg/dL in women); elevated LDL-cholesterol (> 70 / 100 / 130 mg/dL, according to estimated cardiovascular risk); or elevated blood pressure (≥ 130/85 mmHg).

Exclusion criteria

• Diabetes diagnosis.
• Severe psychiatric illness.
• Malabsorption disorders or previous bariatric surgery.
• Pregnancy or lactation.
• Previous clinical cardiovascular disease.
• Regular use of medications that could influence study outcomes, including:

lipid-lowering agents insulin sensitizers antihypertensive drugs anticoagulants antiretroviral therapy thyroid hormones oral corticosteroids immunosuppressants polyunsaturated fatty acid (PUFA) supplements.

• Fasting serum triglycerides ≥ 500 mg/dL or LDL-cholesterol ≥ 190 mg/dL.
• Body mass index (BMI) ≥ 35 kg/m².
• Very high blood pressure.
• Any additional condition that may limit adherence to the study.