Blood Lipid Responses to Diet

Study Overview
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Brief Summary
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The macronutrient composition of our diet (proportions of carbohydrates, fats and proteins) strongly influences the way our body stores and utilises substrates (e.g., fats and sugars), which in turn influences our 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, we will also examine the interaction between macronutrient content and an individual's genes on blood lipid responses and liver metabolism.

Detailed Description
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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. We will also examine if an individual's genotype affects the metabolic response to a shift in dietary macronutrient content. 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.

Official Title
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Investigating Blood Lipid Responses to Dietary Macronutrient Content

Conditions
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Nutritional and Metabolic Diseases

Intervention / Treatment
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* Other: Diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High carbohydrate, low fat diet<br>65% of energy is derived from carbohydrates, 20% from fat, and 15% from protein. | Other: Diet<br>* Eucaloric diet enriched in either carbohydrates or fat (both contributing to 65% total energy intake)<br>|
| Experimental: High fat, low carbohydrate diet<br>65% of energy is derived from fat, 20% from carbohydrates, and 15% from protein. | Other: Diet<br>* Eucaloric diet enriched in either carbohydrates or fat (both contributing to 65% total energy intake)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma triglyceride concentrations [mmol/L] | 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. | Pre- and post-diet [21-28 days] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver fat content [%] | Liver fat content (intra-hepatic triglyceride) will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy | Pre- and post-diet [21-28 days] | 
| Change in cardiac fat content [%] | Cardiac fat content will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy | Pre- and post-diet [21-28 days] | 
| Change in the contribution of dietary and adipose tissue derived fatty acids to very low density lipoprotein-triglyceride (VLDL-TG) palmitate | Through measuring the incorporation of [13C]palmitate and [2H2]palmitate in isolated plasma VLDL during a mixed-macronutrient feeding test. | Pre- and post-diet [21-28 days] | 
| Change in hepatic fatty acid synthesis | Measured by incorporation of [2H2] palmitate from 2H2O into VLDL-triglyceride | Pre- and post-diet [21-28 days] | 
| Influence of genotype on the change in plasma lipid content [mmol/L] | 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. | Pre- and post-diet [21-28 days] |