Clinical trial NCT03509610: Acute Responses to Dietary Carbohydrate Manipulation
Official title: The Acute Responses to Manipulating Dietary Carbohydrate Content and Type on All Major Aspects of Energy Balance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nutrition and Energy Balance
Keywords: Nutrition
Carbohydrates
Lead sponsor: University of Bath
Sponsor class: OTHER
First posted: 2018-04-26
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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:

1. Control - reflecting the composition of a typical European diet
2. Low sugar - the same composition of a typical European diet but with \<5% energy intake from sugar
3. 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: 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.

Eligibility criteria: 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%)

Primary outcomes:
measure: 24-hour physical activity energy expenditure (kcal/day)
timeFrame: 24 hours
Secondary outcomes:
measure: 24-hour energy intake (kcal/day)
timeFrame: 24 hours
measure: Fasting glucose concentrations
timeFrame: 24 hours
measure: Postprandial glucose concentrations
timeFrame: 24 hours
measure: Fasting insulin concentrations
timeFrame: 24 hours
measure: Postprandial insulin concentrations
timeFrame: 24 hours
measure: Fasting triglyceride concentrations
timeFrame: 24 hours
measure: Postprandial triglyceride concentrations
timeFrame: 24 hours
measure: Fasting non-esterified fatty acid concentrations
timeFrame: 24 hours
measure: Postprandial non-esterified fatty acid concentrations
timeFrame: 24 hours
measure: Fasting beta-hydroxybutyrate concentrations
timeFrame: 24 hours
measure: Postprandial beta-hydroxybutyrate concentrations
timeFrame: 24 hours
measure: Subjective appetite
timeFrame: 24 hours
measure: Food preference ratings
timeFrame: 24 hours
measure: Resting substrate oxidation
timeFrame: 24 hours
measure: Postprandial substrate oxidation
timeFrame: 24 hours
measure: Palatability
timeFrame: 24 hours
measure: Fasting cholesterol, HDL, and LDL concentrations
timeFrame: 24 hours
measure: Postprandial cholesterol, HDL, and LDL concentrations
timeFrame: 24 hours
measure: Fasting leptin concentrations
timeFrame: 24 hours
measure: Postprandial leptin concentrations
timeFrame: 24 hours
measure: Macronutrient intake
timeFrame: 24 hours
measure: Fasting FGF21 concentrations
timeFrame: 24 hours
measure: Postprandial FGF21 concentrations
timeFrame: 24 hours
measure: Eating rate
timeFrame: 24 hours
measure: Body mass
timeFrame: 24 hours
measure: Waist and hip circumference
timeFrame: 24 hours
measure: Fasting haematology profile
timeFrame: 24 hours
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Department for Health, University of Bath
Study officials:
References:
citation: Smith HA, Gonzalez JT, Thompson D, Betts JA. Dietary carbohydrates, components of energy balance, and associated health outcomes. Nutr Rev. 2017 Oct 1;75(10):783-797. doi: 10.1093/nutrit/nux045.
citation: Betts JA, Richardson JD, Chowdhury EA, Holman GD, Tsintzas K, Thompson D. The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults. Am J Clin Nutr. 2014 Aug;100(2):539-47. doi: 10.3945/ajcn.114.083402. Epub 2014 Jun 4.
citation: Erickson J, Sadeghirad B, Lytvyn L, Slavin J, Johnston BC. The Scientific Basis of Guideline Recommendations on Sugar Intake: A Systematic Review. Ann Intern Med. 2017 Feb 21;166(4):257-267. doi: 10.7326/M16-2020. Epub 2016 Dec 20.
citation: Hengist A, Davies RG, Rogers PJ, Brunstrom JM, van Loon LJC, Walhin JP, Thompson D, Koumanov F, Betts JA, Gonzalez JT. Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women. Eur J Nutr. 2023 Mar;62(2):921-940. doi: 10.1007/s00394-022-03048-x. Epub 2022 Nov 3.