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NCT Number: NCT05973539

Blood Lipid Responses to Diet Macronutrients

The macronutrient composition of a diet (proportions of carbohydrates, fats and proteins) strongly influences the way the body stores and utilises substrates (e.g., fats and sugars), which in turn influences the risk of developing cardiometabolic diseases (e.g., coronary artery disease or insulin resistance). The optimal dietary composition to lower the risk of cardiometabolic disease is unknown.

In a randomized, parallel design, this study will investigate how the overconsumption of carbohydrates and fats affects blood lipid responses and liver metabolism in adults free from metabolic disease. By genotyping participants, the interaction between macronutrient content and an individual's genes on blood lipid responses and liver metabolism will be examined.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom

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About this study

Dietary and lifestyle interventions are central to lowering the risk and preventing the development of metabolic disease, including non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. There is, however, no one fits all dietary approach, and in the context of diets where an individual is not gaining or losing weight (known as eucaloric), the optimal macronutrient composition associated with a reduced risk of metabolic disease and dyslipidemia is highly debated. For instance, eating less of one macronutrient implies eating more of another; a reduction in the intake of dietary carbohydrates is met by an increase in dietary fats. How this affects one's metabolic health in the setting when someone is not gaining or losing body weight is unclear.

Therefore, this study aims to provide an understanding of the effect that the quantity of specific dietary macronutrients (e.g., carbohydrates, fats) have on plasma triglyceride concentrations in both the fasting and postprandial state, liver fat content and metabolism, and cardiac fat content and function. An individual's genotype affects the metabolic response to a shift in dietary macronutrient content and this will be examined in this study.

Sixty volunteers free from metabolic disease will be recruited into a randomized, parallel-armed dietary intervention study. Participants will consume either a low carbohydrate, high-fat diet or a high carbohydrate, low-fat diet for up to 28 days. Diets will be eucaloric (i.e., designed to meet the individual participant's energy requirements). Comprehensive in vivo metabolic and physiological testing will be performed before and after the experimental diet to document the effects of the overconsumption of specific macronutrients (i.e., fats or carbohydrates) on liver and lipid metabolism.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant is willing and able to give informed consent for participation in the study.
  • Male or Female, aged ≥18 to ≤65 years
  • Body mass index (BMI) ≥19 to ≤35 kg/m2
  • No medical condition or relevant drug therapy that is known to affect the liver, adipose tissue, or cardiac metabolism.
  • Weight stable for the previous 3 months

Exclusion criteria

  • Aged <18 or >65 years
  • BMI <19 or >35 kg/m2
  • A blood haemoglobin <135 mg/dL for men and <120 mg/dL for women
  • Donated (or lost) ≥250 mL of blood in the previous two months
  • On a weight loss diet or decreased their body weight by >5% in the previous 3 months
  • Currently adhering to or have consumed in the previous 3 months a diet with a notably altered macro-nutrient content (e.g. high-fat - low-carbohydrate diet)
  • Have increased their body weight by >5% in the previous 3 months
  • Any metabolic condition or relevant drug therapy
  • Current smoker
  • History of alcoholism or a greater than recommended alcohol intake (>30 g of alcohol daily for men and >20 g of alcohol daily for women)
  • History of albumin allergy.
  • Pregnant or nursing mothers
  • History of severe claustrophobia

Treatment and study plan

Diet

Other

Eucaloric diet enriched in either carbohydrates or fat (both contributing to 65% total energy intake)

Primary outcomes

  1. Change in plasma triglyceride concentrations [mmol/L]

    Time frame: Pre- and post-diet [21-28 days]

    Change in plasma triglyceride concentrations in response to consumption of macronutrient meal will be measured by basic clinical chemistry before and at the end of the dietary intervention.

Secondary outcomes

  1. Change in liver fat content [%]

    Time frame: Pre- and post-diet [21-28 days]

    Liver fat content (intra-hepatic triglyceride) will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy

  2. Change in cardiac fat content [%]

    Time frame: Pre- and post-diet [21-28 days]

    Cardiac fat content will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy

  3. Change in the contribution of dietary and adipose tissue derived fatty acids to very low density lipoprotein-triglyceride (VLDL-TG) palmitate

    Time frame: Pre- and post-diet [21-28 days]

    Through measuring the incorporation of [13C]palmitate and [2H2]palmitate in isolated plasma VLDL during a mixed-macronutrient feeding test.

  4. Change in hepatic fatty acid synthesis

    Time frame: Pre- and post-diet [21-28 days]

    Measured by incorporation of [2H2] palmitate from 2H2O into VLDL-triglyceride

  5. Influence of genotype on the change in plasma lipid content [mmol/L]

    Time frame: Pre- and post-diet [21-28 days]

    Change in plasma lipid concentrations in the fasting state and in response to consumption of macronutrient meal will be measured by basic clinical chemistry before and at the end of the dietary intervention.

Study contacts

Contact information is provided by the study sponsor or research team.

David J Dearlove

CONTACT

[email protected]

07739460623

Leane Hodson

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Registry information

Official study title

Investigating Blood Lipid Responses to Dietary Macronutrient Content

Acronym: BoLD

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Aug 3, 2023
Registry last updated
May 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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