Sleep and metabolism are closely interconnected, and emerging evidence suggests that dietary composition may influence both sleep quality and key physiological functions such as glucose regulation, cardiovascular activity, and hormonal signaling. This study aims to investigate how a Western-style unhealthy diet versus a healthier, fiber-rich diet affects objective and subjective sleep measures, 24-hour physiological parameters, and a range of biomarkers related to cardiometabolic, neurodegenerative, and gut microbial function.
Metabolism is tightly regulated by sleep and interacts bidirectionally with diet. While it is well established that insufficient or disrupted sleep can impair glucose regulation, cardiovascular function, and promote unhealthy eating behaviors that promote cardiometabolic disease, less is known about how different dietary patterns impact subjective and objective sleep parameters, as well as related physiological systems. The study will systematically investigate how consumption of an unhealthier "Western" diet, compared to a healthier diet, affects both objective and subjective sleep parameters, as well as 24-hour heart rate and blood pressure profiles, glucose variability, and hormonal and molecular biomarkers. The study will be conducted as a 2-condition, randomized crossover study, with assessments in the field for about a week, followed by a multi-day stay for measurements under standardized laboratory conditions. Participants will be monitored using polysomnography, and wearable devices, including for continuous glucose and heart rate parameters, with multi-compartment sampling to assess diet-mediated responses across cardiometabolic, neurodegenerative, and microbial pathways. In field and in the lab, biological samples will be collected repeatedly across the day to establish diurnal rhythms. Cognitive performance, mood, and subjective appetite will also be evaluated. By identifying diet-driven changes in sleep and related physiological functions, this study aims to provide mechanistic insights into how nutrition impacts sleep, cardiometabolic health parameters and molecular pathways.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
24
Low-fat diet for approximately 1 week, preceding in-lab study period (approximately 2 days) under standardized conditions (total dietary exposure up to 9-10 days).
High-fat diet for approximately 1 week, preceding in-lab study period (approximately 2 days) under standardized conditions (total dietary exposure up to 9-10 days).
Uppsala biomedical center
Uppsala, Sweden
RECRUITINGSleep Architecture and Neurophysiological Features
Objective registration and analysis of sleep, based on polysomnography or validated wearable devices to capture macrosleep, spectral and microsleep features.
Time frame: Up to 9 nights on each diet
Change in 24-Hour Heart Rate Variability (HRV)
Continuous measurement of HRV, using a wearable device, focused on the metric Root Mean Square of the Successive Differences (RMSD); additional metrics (Standard Deviation of NN intervals (SDNN), low frequency to high frequency (LF/HF) ratio) analyzed for exploratory purposes.
Time frame: Up to 9 days on each diet
24-Hour Heart Rate (HR)
Continuous measurement of heart rate using a wearable device
Time frame: Up to 9 days on each diet
Heart Rate Response to Standardized Stair Stepping
ECG-based heart rate measured at baseline, during stepping and repeatedly (up to 5 min) post-stair stepping, to assess recovery, also analyzed in relation to sleep metrics.
Time frame: Baseline and day 7-9 of each diet period
Morning-to-Evening and 24-h blood pressure (BP)
Morning, evening, and 24-h ambulatory measurement of systolic blood pressure, also analyzed in relation to sleep metrics.
Time frame: Up to 9 days on each diet
24 Hour Continuous Glucose Levels
Continuous (24-h) monitoring of interstitial glucose for analysis of mean levels and variability metrics (e.g., SD, coefficient of variation, postprandial changes), also analyzed in relation to sleep metrics.
Time frame: Up to 9 days on each diet
Levels of Blood-based Biomarkers
Changes in levels of molecular factors such as DNA, hormones/proteins and metabolites, due to the preceding dietary intervention, and also in relation to sleep metrics.
Time frame: Up to 9 days on each diet
Levels of CNS biomarkers
Levels of CNS health biomarkers (such as brain-derived neurotrophic factor (BDNF), Tau (e.g. BD-tau) and Amyloid beta (Aβ) species, glial fibrillary acidic protein (GFAP), and Neurofilament light chain (NfL)).
Time frame: Up to 9 days on each diet
Urinary Metabolite Levels
Urine levels of excretion molecules (such as melatonin breakdown metabolites).
Time frame: Up to 9 days on each diet
Change in Metabolic Fuel Utilization
Change in metabolic fuel utilization as measured by respirometry, in response to the dietary interventions.
Time frame: Up to 9 days on each diet
Levels of Fecal Metabolites
Changes in levels of fecal metabolites (such as short chain fatty acids, bile acids) due to each dietary intervention
Time frame: Up to 9 days on each diet
Levels of Fecal Microbiota
Changes in fecal microbiota (metagenomic, compositional) due to each dietary intervention
Time frame: Up to 9 days on each diet
Levels of Salival Biomarkers
Changes in levels of salival molecules (such as cortisol and melatonin), also in relation to sleep-circadian metrics.
Time frame: Up to 9 days on each diet
Levels of Salival Microbiota
Changes in salival microbiota (metagenomic, compositional) due to each dietary intervention
Time frame: Up to 9 days on each diet
Changes in glucose tolerance
Glucometabolic response to a standardized 2-h glucose tolerance test, also analyzed in relation to sleep-circadian metrics.
Time frame: Day 8-9 on each diet
Levels of Immune Cells
Immune cell profile across the day in response to each diet
Time frame: Up to 9 days on each diet
Change in Subjective Sleep Quality
Change in self-reported sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI), supplementing objective sleep data. Total Score (0-21; higher = worse).
Time frame: Up to 9 days on each diet
Subjective Hunger and Appetite Levels
Self-reported hunger and appetite across the day, and prior to and after meals, as assessed via visual analogue scales (VAS, i.e., with scores 0 for the lowest subjective rating, to 100 for the highest rating)
Time frame: Up to 9 days on each diet
Body Temperature
Body temperature measured via wearable sensors to assess effects of dietary interventions on thermoregulation and its relationship to sleep, circadian rhythms and metabolism.
Time frame: Up to 9 days on each diet
Change in Composite Cognitive Performance Score
Composite score from four tasks: 1. Psychomotor Vigilance Task (PVT) - sustained attention; faster reaction times and fewer lapses corresponds to better performance; 2. Go/No-Go Task - inhibitory control; higher accuracy on no-go trials and faster correct go responses corresponds to better performance; 3. Task-Switching Task - cognitive flexibility; smaller switch cost (difference in reaction time between switch and repeat trials) and higher accuracy corresponds to better performance; 4. Memorability Task - episodic memory; higher hit rate (0-100%) and fewer false alarms corresponds to better performance. All scores will be standardized and averaged; higher composite values indicate better cognitive performance.
Time frame: Up to 9 days on each diet
Changes in mental wellbeing
Self-reported assessment of mental wellbeing using validated subjective scales (visual analogue scales going from lowest 0 to highest of 100), to evaluate effects of diet and sleep.
Time frame: Up to 9 days on each diet
Changes in Central Hemodynamics
Morning, evening, and 24-h ambulatory levels of central hemodynamics reflecting central blood pressure and arterial resistance, also analyzed in relation to sleep metrics
Time frame: Up to 9 days on each diet
Effect Modification by Biological Sex
Exploratory subgroup analysis to determine if male vs. female participants differ in response to dietary interventions, for primary and secondary outcomes
Time frame: Based on data collected up to 9 days on each diet
Effect Modification by Cardiorespiratory Fitness
Exploratory analysis to determine whether cardiorespiratory fitness parameters modulates responses to how the diets impact primary and secondary outcomes.
Time frame: Based on data collected up to 9 days on each diet
Change in Dim Light Melatonin Onset
Dim Light Melatonin Onset as assessed via repeatedly measured melatonin levels, measured in the evening under standardized conditions
Time frame: Up to 9 days on each diet
Levels of molecular biomarkers in dried blood spots
Analysis of levels of molecular biomarkers (such as CRP) in dried blood spots from finger samples, and how these correlate with biomarker levels from peripheral venous blood samples
Time frame: Up to 9 days on each diet
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