Coffee Bioequivalence Trial

Coffee has gained interest for its role in the prevention of non-communicable diseases such as heart and liver diseases. Population-based studies have reported that consuming 2-4 cups of coffee per day is associated with lower death rates and, notably reductions in the incidence of heart disease. However, these observational trials do not directly prove causality and carefully designed randomised controlled trials are needed.

This current trial will provide vital information to inform a large-scale randomised controlled trial assessing the effects of coffee consumption on risk markers for developing cardiometabolic disease (such as type 2 diabetes, heart and liver diseases) to test causality. In this follow-up trial to be conducted in 2025, non-coffee consumers will be recruited. To maximise recruitment, retention and adherence in the trial, we are considering providing instant coffee as tablets rather than as a drink. Hence, the current study will help to understand if coffee delivered in a tablet is biologically equivalent to consuming coffee as a drink.

A 3 armed, randomised, controlled crossover trial in healthy participants wil be performed. The primary outcome is the pharmacokinetic profile of coffee bioactives in coffee drink versus the coffee tablet. Secondary outcomes will be assessing the impact of the coffee both as a drink and tablet on cardiovascular and liver health markers (versus a coffee-free control).

Briefly, participants will attend three study phases. Each study phase includes a 480 minute (8-hour) acute postprandial visit and a shorter visit (\~one hour) the following morning. On the first day participants will arrive having fasted overnight and having followed dietary and lifestyle restrictions in the preceding days. They will have baseline anthropometric measures performed and a cannula will be inserted; two baseline blood samples will be collected (14 mL in total). Blood samples will be collected regularly from the cannula, and a clinic blood pressure measurement will be performed at regular intervals following the intervention (a different intervention will be given in a random order at each of the three phases). A breakfast meal and lunch will be provided to the participants during the visit and participants will leave with a standardised meal and snack to consume in the evening. They will return, fasted the following morning to provide a blood samples and have their blood pressure measured. Participants will be asked to collect their urine for 24h following the intervention; this will be returned that morning. There will be a 4-week period between each study phase.

• Fasting concentrations of total cholesterol and high-density lipoprotein cholesterol. [Срок оценки: Acute study days prior to the intervention (0 minutes).]
• Fasting and postprandial lipids concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Fasting and postprandial glucose concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Fasting and postprandial insulin concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Fasting and postprandial liver enzyme concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Fasting and postprandial gut hormone concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to the intervention (0 minutes) and then 30, 60, 120, 180, 240, 300, 360 and 480 minutes.]
• Fasting and postprandial plasma metabolomics after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to the intervention (0 minutes) and then 30, 60, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Fasting and postprandial plasma nitrate and nitrite concentrations after consuming the coffee drink, coffee tablet and control interventions [Срок оценки: Acute study days, blood taken prior to the intervention (0 minutes) and then 15, 30, 45, 60, 120, 180, 240, 300, 360, 420 and 480 minutes.]
• Urinary metabolomics [Срок оценки: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.]
• Urinary creatinine [Срок оценки: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.]
• Urinary osmolality and pH [Срок оценки: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.]
• Urinary sodium and potassium [Срок оценки: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.]