Acute Responses to Dietary Carbohydrate Manipulation

Study Overview
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Brief Summary
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Sugar is perceived negatively, leading to government taxation and targets to reduce consumption. These actions have been taken based on the limited evidence that high-sugar diets are associated with greater total energy intake. However, energy intake comprises just one half of the energy balance equation (e.g. balance = intake - expenditure). Without considering energy expenditure, it is impossible to understand the effects of sugar on health. Sugar, and perhaps total carbohydrate intake, may be important for energy balance - perhaps by stimulating increased energy expenditure. Understanding dietary regulators of energy balance is more important than ever before, because diseases like obesity are a consequence of energy surplus (i.e. energy intake > energy expenditure). No studies have investigated a causal role of dietary sugar or carbohydrate on energy balance. The proposed research will seek to understand the acute (e.g. 24-hour) responses to manipulating dietary carbohydrate and sugar content on energy balance and health. This research will contribute to enabling individuals to make informed dietary choices about carbohydrate and sugar consumption. To achieve this, healthy non-obese adults will be recruited to a randomised crossover study. Measures of energy intake, energy expenditure, metabolic health, appetite, food preference, and gut microbiota will be taken. All laboratory trials will take place at the University of Bath. Three diets will be investigated: Control - reflecting the composition of a typical European diet Low sugar - the same composition of a typical European diet but with <5% energy intake from sugar Low carbohydrate - low carbohydrate diet with <5% energy intake from sugar and <8% energy intake from carbohydrate, replacing carbohydrate energy with fat The study will consist of a 3-day lead-in period with the control diet followed by one trial day with each diet.

Detailed Description
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Dietary sugar is increasingly perceived in a negative way. This has led to taxation by government and guidelines by global public health bodies to reduce sugar intake to <5% of energy intake. All available public health guidelines regarding sugar advocate a reduction in sugar intake, despite a lack of evidence to support these recommendations. These guidelines focus on the association between sugar intake and energy intake, without regard for energy expenditure. This oversimplifies situations in which energy surplus is pathological, for example in diseases like obesity. This complexity is demonstrated by evidence that dietary sugar intake is decreasing in the United Kingdom, whilst rates of obesity have increased in the same timeframe. It is important to consider energy expenditure in the context of health. The most variable component of energy expenditure between individuals is physical activity energy expenditure (PAEE), which varies from  600-2100 kcal per day in men of a similar demographic. Current guidelines do not regard the effect that changing dietary sugar might have on PAEE and therefore total energy expenditure. Carbohydrate availability dictates the capacity to perform physical work. However, the role of carbohydrate in regulating physical activity behaviours has only recently been considered. Ingestion of a carbohydrate-rich breakfast causes a significant increase in 24-hour PAEE compared with no breakfast consumption before midday. The magnitude of this difference is greatest prior to midday, near to when carbohydrate had been ingested and when glucose uptake to peripheral tissue is increased. This points towards a stimulatory role of carbohydrate or sugar on PAEE when carbohydrate is readily available to peripheral tissue. The amount of carbohydrate present in skeletal muscle is dictated by the amount of carbohydrate in the diet. As physical activity is performed by skeletal muscle, dietary carbohydrate intake may regulate physical activity behaviour. Consequently, reducing total carbohydrate intake may result in reduced PAEE. Studies in which carbohydrate has been manipulated and physical activity has been measured have not been sufficient in answering this research question. Often self-report measures of physical activity are used, which are not sensitive enough to discern meaningful differences. Studies which have measured physical activity objectively, i.e. using pedometers or accelerometers, are confounded by a lack of information about actual carbohydrate intake or concurrent prescription of exercise interventions. Furthermore, government targets of reduced sugar intake to <5% of total energy intake are not aimed at overall carbohydrate intake per se. In the breakfast study mentioned, sugar intake was significantly greater amongst individuals who ate breakfast compared with individuals who fasted until midday. Therefore, it is also plausible that a regulatory role of carbohydrate on PAEE may be due to the type of carbohydrate rather than the absolute amount. If the availability of carbohydrate to peripheral tissue plays a regulatory role on PAEE, then theoretically the effects of manipulating the amount or type of carbohydrate will be detectable acutely, within 24 hours.

Official Title
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The Acute Responses to Manipulating Dietary Carbohydrate Content and Type on All Major Aspects of Energy Balance

Conditions
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Nutrition and Energy Balance

Intervention / Treatment
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* Other: Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index 18.5-29.9 kg∙m-2 Age 18-65 years Able and willing to provide informed consent and safely comply with study procedures Females to maintain record of regular menstrual cycle phase or contraceptive use No anticipated changes in diet/physical activity during the study (e.g. holidays or diet plans) Exclusion Criteria: Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes) Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker) Any reported recent (<6 months) change in body mass (± 3%)

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CONTROL<br>Diet consisting of 50% carbohydrate (20% sugar), 15% protein, 35% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|
| Experimental: LOW SUG<br>Diet consisting of 50% carbohydrate (<5% sugar), 15% protein, 35% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|
| Experimental: LOW CHO<br>Diet consisting of <8% carbohydrate (<5% sugar), 15% protein, >77% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour physical activity energy expenditure (kcal/day) | 24-hour physical activity energy expenditure (kcal/day) | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour energy intake (kcal/day) | 24-hour energy intake (kcal/day) | 24 hours | 
| Fasting glucose concentrations | Fasting glucose concentrations in serum samples | 24 hours | 
| Postprandial glucose concentrations | Postprandial glucose concentrations in serum samples | 24 hours | 
| Fasting insulin concentrations | Fasting insulin concentrations in serum samples | 24 hours | 
| Postprandial insulin concentrations | Postprandial insulin concentrations in serum samples | 24 hours | 
| Fasting triglyceride concentrations | Fasting and postprandial triglyceride concentrations determined in plasma samples | 24 hours | 
| Postprandial triglyceride concentrations | Postprandial triglyceride concentrations in serum samples | 24 hours | 
| Fasting non-esterified fatty acid concentrations | Fasting non-esterified fatty acid concentrations in serum samples | 24 hours | 
| Postprandial non-esterified fatty acid concentrations | Postprandial non-esterified fatty acid concentrations in serum samples | 24 hours | 
| Fasting beta-hydroxybutyrate concentrations | Fasting beta-hydroxybutyrate concentrations in serum samples | 24 hours | 
| Postprandial beta-hydroxybutyrate concentrations | Postprandial beta-hydroxybutyrate concentrations in serum samples | 24 hours | 
| Subjective appetite | Measured by 0-100 mm visual analogue scale | 24 hours | 
| Food preference ratings | Food preference ratings determined by bespoke computer software | 24 hours | 
| Resting substrate oxidation | Resting substrate oxidation determined by indirect calorimetry | 24 hours | 
| Postprandial substrate oxidation | Postprandial substrate oxidation determined by indirect calorimetry | 24 hours | 
| Palatability | Measured by 0-100 mm visual analogue scale | 24 hours | 
| Fasting cholesterol, HDL, and LDL concentrations | Fasting cholesterol, HDL, and LDL concentrations in serum samples | 24 hours | 
| Postprandial cholesterol, HDL, and LDL concentrations | Postprandial cholesterol, HDL, and LDL concentrations in serum samples | 24 hours | 
| Fasting leptin concentrations | Fasting leptin concentrations in serum samples | 24 hours | 
| Postprandial leptin concentrations | Postprandial leptin concentrations in serum samples | 24 hours | 
| Macronutrient intake | Macronutrient intake across 24-h | 24 hours | 
| Fasting FGF21 concentrations | Fasting FGF21 concentrations in serum samples | 24 hours | 
| Postprandial FGF21 concentrations | Postprandial FGF21 concentrations in serum samples | 24 hours | 
| Eating rate | Time taken to eat test meals | 24 hours | 
| Body mass | Body mass | 24 hours | 
| Waist and hip circumference | Waist and hip circumference, waist:hip ratio | 24 hours | 
| Fasting haematology profile | Fasting haematology profile including WBC, RBC, HGB, haematocrit, platelet count | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nutrition, Carbohydrates