Role of Linoleic Acid in Cardiometabolic Health Beyond Its Lipid-lowering Effects, and Its Dietary and Pathophysiological Implications
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Change in insulin resistance (HOMA-IR)
Study Overview
Brief Summary
Linoleic acid (LA), the predominant omega-6 polyunsaturated fatty acid in human diets, has been associated with improved lipid metabolism and insulin sensitivity compared with saturated fats. However, its role in metabolic health remains debated due to the limited number of well-controlled intervention studies.
This randomized controlled trial aims to evaluate the metabolic effects of an LA-rich oil compared with a blended oil in adults with insulin resistance. Participants will be randomly assigned to receive either a daily supplement of LA-rich oil or a control blend oil for 8 weeks, while maintaining their usual diet and lifestyle. The primary outcome is the change in insulin resistance, assessed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes include changes in fasting glucose, insulin, lipid profile, inflammatory and oxidative stress markers, and body composition.
The study is designed as a single-blind, parallel-group intervention conducted at the Pontifical Catholic University of Chile. The results are expected to clarify the effects of increased dietary linoleic acid intake on insulin sensitivity and metabolic risk factors, contributing to the ongoing debate about the role of omega-6 fatty acids in cardiometabolic health.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Masking Description
Participants are blinded; both oils are provided in identical coded bottles to maintain masking
Eligibility Criteria
- Ages
- 20 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
Change in insulin resistance (HOMA-IR)
Time Frame: Baseline and 8 weeks after the start of the intervention.
Insulin resistance will be assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting glucose and fasting insulin concentrations. The primary outcome is the change in HOMA-IR from baseline to week 8 between the two study groups.
Secondary Outcomes
- Change in plasma fatty acid profile(Baseline and week 8)
- 24-hour dietary recall(Baseline and week 8)
- Glycated hemoglobin (HbA1c)(Baseline and week 8)
- Fasting glucose(Baseline and week 8)
- Fasting insulin(Baseline and week 8)
- Lipid profile(Baseline and week 8)
- Liver enzymes(Baseline and week 8)
- Body Weight(Baseline and week 8)
- Body mass index (BMI)(Baseline and week 8)
- Waist circumference(Baseline and week 8)
- Inflammatory markers(Baseline and week 8)
- Oxidative stress markers(Baseline and week 8)
- Diet quality (Chilean MDI)(Baseline and week 8)
- Sleep quality (PSQI)(Baseline and week 8)
- Physical activity (GPAQ)(Baseline and week 8)
Investigators
Loni Berkowitz Fiebich
Assistant Professor
Pontificia Universidad Catolica de Chile