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

NCT ID: NCT07287514

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-13

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Insulin Resistance Metabolic Disease

Keywords

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linoleic acid Insulin Resistance omega-6 fatty acid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups:

1. an intervention group receiving a linoleic acid-rich oil, or
2. a control group receiving a blended oil. The study follows a single-blind, parallel-group design lasting 8 weeks.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
Participants are blinded; both oils are provided in identical coded bottles to maintain masking

Study Groups

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Linoleic Acid-Rich Oil

Participants in this group will receive a daily supplement of a linoleic acid (LA)-rich oil at a dose of 0.4 mL per kilogram of body weight per day for 8 weeks.

Group Type EXPERIMENTAL

Linoleic Acid-Rich Oil

Intervention Type DIETARY_SUPPLEMENT

Participants in the experimental group will receive a daily supplement of a linoleic acid (LA)-rich oil at a dose of 0.4 mL per kilogram of body weight per day, taken orally for 8 weeks. The oil is characterized by a high content of omega-6 polyunsaturated fatty acids, primarily linoleic acid (\~60%).

To facilitate adherence and appropriate use, participants will receive a recipe booklet encouraging the use of the oil in cold or minimally cooked preparations, or as a topping over foods. They will be instructed to avoid prolonged heating and to store the oil protected from light and at room temperature.

The supplement will be provided in identical coded bottles to maintain single-blind conditions. Participants will be asked to maintain their usual diet and lifestyle throughout the intervention.

Blend Oil

Participants in this group will receive a daily supplement of a blend oil at 0.4 mL per kilogram of body weight per day for 8 weeks.

Group Type ACTIVE_COMPARATOR

Blend Oil

Intervention Type DIETARY_SUPPLEMENT

Participants in the control group will receive a daily supplement of a blend oil at a dose of 0.4 mL per kilogram of body weight per day, taken orally for 8 weeks. The blend was formulated to contain approximately equal proportions of saturated, monounsaturated, and polyunsaturated fatty acids, with less than half the linoleic acid content of the LA-rich oil.

Participants will receive a recipe booklet promoting the use of the oil in cold dishes or lightly cooked preparations, or as a dressing or drizzle over meals. They will also be instructed on proper storage away from heat and direct light.

The supplement will be supplied in identical coded bottles to ensure blinding. Participants will maintain their usual diet and lifestyle during the intervention.

Interventions

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Linoleic Acid-Rich Oil

Participants in the experimental group will receive a daily supplement of a linoleic acid (LA)-rich oil at a dose of 0.4 mL per kilogram of body weight per day, taken orally for 8 weeks. The oil is characterized by a high content of omega-6 polyunsaturated fatty acids, primarily linoleic acid (\~60%).

To facilitate adherence and appropriate use, participants will receive a recipe booklet encouraging the use of the oil in cold or minimally cooked preparations, or as a topping over foods. They will be instructed to avoid prolonged heating and to store the oil protected from light and at room temperature.

The supplement will be provided in identical coded bottles to maintain single-blind conditions. Participants will be asked to maintain their usual diet and lifestyle throughout the intervention.

Intervention Type DIETARY_SUPPLEMENT

Blend Oil

Participants in the control group will receive a daily supplement of a blend oil at a dose of 0.4 mL per kilogram of body weight per day, taken orally for 8 weeks. The blend was formulated to contain approximately equal proportions of saturated, monounsaturated, and polyunsaturated fatty acids, with less than half the linoleic acid content of the LA-rich oil.

Participants will receive a recipe booklet promoting the use of the oil in cold dishes or lightly cooked preparations, or as a dressing or drizzle over meals. They will also be instructed on proper storage away from heat and direct light.

The supplement will be supplied in identical coded bottles to ensure blinding. Participants will maintain their usual diet and lifestyle during the intervention.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role lead

Responsible Party

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Loni Berkowitz Fiebich

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Loni Berkowitz, PhD

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Locations

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Centro de Investigaciones Clínicas UC (CICUC) - Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, Chile

Site Status RECRUITING

Countries

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Chile

Central Contacts

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Loni Berkowitz, PhD

Role: CONTACT

Phone: 23543862

Email: [email protected]

Facility Contacts

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Loni Berkowitz, PhD

Role: primary

References

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Berkowitz L, Echeverria G, Salazar C, Faundez C, Coe CL, Ryff C, Rigotti A. Lipidomic Signature of Healthy Diet Adherence and Its Association with Cardiometabolic Risk in American Adults. Nutrients. 2024 Nov 22;16(23):3995. doi: 10.3390/nu16233995.

Reference Type BACKGROUND
PMID: 39683389 (View on PubMed)

Berkowitz L, Razquin C, Salazar C, Biancardi F, Estruch R, Ros E, Fito M, Corella D, Coe CL, Ryff CD, Ruiz-Canela M, Salas-Salvado J, Wang D, Hu FB, Deik A, Martinez-Gonzalez MA, Rigotti A. Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies. Cardiovasc Diabetol. 2024 Dec 18;23(1):446. doi: 10.1186/s12933-024-02505-7.

Reference Type BACKGROUND
PMID: 39695759 (View on PubMed)

Berkowitz L, Mateo C, Salazar C, Samith B, Sara D, Pinto V, Martinez X, Calzada M, von Schultzendorff A, Pedrals N, Bitran M, Echeverria G, Ruini C, Ryff C, Rigotti A. Healthy Eating as Potential Mediator of Inverse Association between Purpose in Life and Waist Circumference: Emerging Evidence from US and Chilean Cohorts. Int J Environ Res Public Health. 2023 Nov 23;20(23):7099. doi: 10.3390/ijerph20237099.

Reference Type BACKGROUND
PMID: 38063529 (View on PubMed)

Calderon M, Plaza G, Gomez M, Samith B, Pinto V, Martinez X, Sara D, Echeverria G, Calzada M, Berkowitz L, von Schultzendorff A, Pedrals N, Bitran M, Rigotti AG. [Limitations and opportunities for the appropriation of the Mediterranean diet in Chilean adults with diagnostic elements of metabolic syndrome]. Nutr Hosp. 2024 Feb 15;41(1):86-95. doi: 10.20960/nh.04652. Spanish.

Reference Type BACKGROUND
PMID: 38047416 (View on PubMed)

Echeverria G, Samith B, von Schultzendorf A, Pinto V, Martinez X, Sara D, Calzada M, Pacheco J, Plaza G, Scott F, Romero J, Mateo C, Julio MV, Utreras-Mendoza Y, Binder MV, Gutierrez F, Riquelme ME, Cuevas M, Willatt R, Sanchez O, Keilendt A, Butron P, Jarufe A, Huete I, Tobar J, Martin S, Alfaro V, Olivos M, Pedrals N, Bitran M, Avalos I, Ruini C, Ryff C, Perez D, Berkowitz L, Rigotti A. Mediterranean diet and psychological well-being intervention to reverse metabolic syndrome in Chile (CHILEMED trial). Contemp Clin Trials Commun. 2023 Jun 26;35:101167. doi: 10.1016/j.conctc.2023.101167. eCollection 2023 Oct.

Reference Type BACKGROUND
PMID: 37538196 (View on PubMed)

Other Identifiers

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230330018

Identifier Type: -

Identifier Source: org_study_id

11240454

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id