The big breakfast study: chrono-nutrition influence on energy expenditure and body weight

During the past three decades, the prevalence of obesity has increased worldwide to epidemic proportions and is considered to be a major health problem because of its association with non-communicable diseases, such as cardiovascular disease, stroke and some cancers. Approaches to manage overweight and obesity are likely to be focused around diet and lifestyle solutions to achieve negative energy balance for weight loss, as clinical pharmaceutical and surgical approaches are targeted for morbid obesity. Current dietary advice for weight management is broadly based on the assumption that a 'calorie is a calorie' and it does not matter when these calories are consumed throughout the day. Recent evidence has challenged this assumption, suggesting that we may utilize or expend calories consumed in the morning more efficiently than in the evening, which is a beneficial strategy for weight control. This would mean in practical terms that you would consume more calories at breakfast time as the main meal of the day, and less during the evening meal. In the UK, the main meal of the day is most often in the evening, which pre-disposes to weight gain. These studies suggest that calories are not metabolized equally at all times during the day, and that the process of digestion, absorption and utilization are influenced by the time of day. Studies have not rigorously investigated how time of eating of the main meal of the day influences energy balance. It may be that eating a larger meal at breakfast time leads to being more physically active, or indeed, a larger meal at the evening leads to inactivity. Or, that the natural biological rhythms in the human body are more responsive to calorie ingestion in the morning. After eating, there is an increase in energy expenditure, this is termed, 'thermic effect of food' (TEF). We will explore the mechanisms and time-course of adaption for enhanced morning (breakfast) TEF response as a means to dissipate extra calories, driven by the natural circadian variation in the human (related to light-dark cycle), which can be maximized in the morning for increased energy utilization. An enhanced morning TEF after breakfast could contribute to increased 24-h energy expenditure and, if food intake remained stable, weight loss would thus ensue over time. Numerous authors have studied 24hr energy expenditure particularly in the context of lean-obese differences, but few have considered circadian rhythms and none have studied the interaction with gastric emptying in overweight/obese subjects.

Our hypothesis is that timing of eating influences energy balance and body weight, because morning energy expenditure is amplified in comparison to evening. The cause of the increased energy expenditure in the morning is unclear, whether this is linked to natural biological circadian rhythm or behavioral adaption. This hypothesis will be addressed through conduct of two controlled dietary intervention studies that will examine,

(i) the impact of the time of the main meal of the day (breakfast Vs evening) on metabolic and behavioral regulation during weight loss to establish the biological mechanisms that drive elevated energy expenditure when eating in the morning, in overweight men and women

(ii) whether time of meal consumption effects on energy balance are modulated though the normal biological circadian rhythm

The proposed work aims to show that our current meal consumption pattern in the UK, of having a small breakfast and large evening meal is working against our internal biological clock and this exacerbates the difficulties in successful weight management. From a public health perspective, this chrono-nutrition study offers an opportunity to provide evidence-based data for translational studies on when to eat to promote weight loss. These studies can potentially support the public health message of the importance of a breakfast meal and offers an alternative strategy to promote body weight control.

Energy balance may be influenced by timing of eating, such that weight loss is greater when consuming a relatively larger morning meal than a comparable evening meal. The mechanisms for this are not understood, but likely to be linked to either behavioral adaption in physical activity in response to time of eating, or, driven by biological circadian rhythms. After eating, a cascade of metabolites and hormones are released, which can influence energy expenditure through thermic effect of food. Neuronal and hormonal systems that are likely involved in driving the circadian rhythm in energy expenditure or TEF are the endocrine hormones (insulin) and metabolites (glucose); with diurnal variation also reported in a gastric emptying. Our hypothesis is that timing of eating influences energy balance, because morning energy expenditure is amplified in comparison to evening. The cause of the increased energy expenditure in the morning is unclear, whether this is linked to natural biological circadian rhythm in response to eating or behavioral adaption. Key objectives will be addressed through a research study program that involves two key experiments in overweight/obese subjects, to explore potential behavioral and circadian influences on energy expenditure and energy balance. Our first diet trial will examine the impact of calorie distribution as morning and evening eating on metabolic and behavioral regulation during weight loss. Finally, we will test whether meal consumption effects on energy balance are modulated though the normal circadian rhythms, by applying a phase delay protocol in a controlled environment. Together, these studies will elucidate how energy balance can be modulated by timing of eating.

The research team have a very strong track record to deliver impact, drawing on existing strengths. This project will provide impact in many key areas identified by the MRC;

Knowledge and knowledge economy. The Food industry will be a main beneficiary from the evidence-basis on the role of breakfast eating on energy balance. Key food ingredient and retail sectors related to breakfast eating can translate these data with immediate effect to influence health and wellbeing with a simple behavioral approach, also creating innovation and wealth creation for these sectors. The Pharmaceutical industry could benefit for innovation and wealth creation by using the data generated to investigate novel approaches for weight management, based on modulation of gastric emptying influencing thermic effect of feeding and energy balance. Additionally, circadian dysregulation in shift workers has a detrimental impact on health and workforce productivity. Our study will provide novel knowledge that has the potential to improve worker performance and therefore produce great economic benefit applied in the Occupation Health arena.

Training and delivering highly skilled people. A postdoctoral researcher will be linked to this application and will spend time in Aberdeen and Surrey labs. The individual will greatly expand their theoretical understanding of dietary approaches influencing energy balance and circadian biology and also learn new practical skills. They will be a highly trained and experienced researcher at the end of the project.

Policy development. The impact of this work will be to provide clear evidence to policy makers that weight management initiatives and policies must take account of the importance of time of day, work patterns (shift work) and lifestyle in tackling the obesity problem. There can be societal gains from the project in the development of new dietary based strategies to manage body weight. These would enhance quality of life, health and wellbeing in the UK population. PJM's role with policy advisors allows opportunity for key messages to be explored with influential stakeholders.

Public engagement, public health and societal issues. It is anticipated that the current application will be of great interest to the media and public, so providing excellent opportunity for public engagement. All of the applicants already have experience of public engagement, ranging from newspaper interviews to television appearances, and are willing to continue this work. As well as providing an interesting scientific story, the research also relates to public health and contemporary societal issues, including nutrition and energy balance. This area of research is of interest to the media and excellent opportunities exist to highlight the research findings.

International development. As many of the issues mentioned above (e.g. energy balance, shift work and scientific advancement) are relevant internationally, the research should have wide-reaching impact both within and outside the UK.