# Uncovering the Impact of Diet on the Human Circadian Timing System

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $610,322

## Abstract

Summary/Abstract
Synchronization of biological processes and behaviors with the 24-hour light-dark cycle is fundamental to
optimal physiology, cognitive function, and health. Because humans have, on average, a longer than 24-hour
internal clock, most people must perform this synchronization process on a daily basis. An inability to
adequately entrain internal circadian rhythms to the external environment, even a small misalignment, can
have severe consequences including poor cardiometabolic outcomes (i.e., cardiovascular disease, diabetes,
obesity) and impaired sleep, cognitive function, and learning. Entrainment is believed to be entirely
orchestrated by exposure to morning light, as it has been assumed that non-photic exogenous stimuli have
little influence on circadian entrainment in humans. However, emerging evidence from animal models indicates
that circadian entrainment to light could be hampered by dietary composition. Specifically, mice fed a high-fat
diet have a 20% slower rate of entrainment to light and a longer circadian period. If these findings hold true in
humans, this would challenge current theory within the field of human circadian physiology and would have
vast public health implications as so many Americans consume high-fat diets. Thus, quantifying the interaction
between typical dietary choices and circadian entrainment has great importance. The goal of this project is to
determine if these diet-related circadian effects in rodents translate to humans. Our specific aims are to
establish the impact of a high-fat diet on the: 1) rate of entrainment of the circadian system to light; 2) circadian
period and the resultant circadian timing of daily behaviors i.e., phase angle of entrainment (time difference
between melatonin and sleep onsets); and 3) how the combination of eating a high-fat diet and circadian phase
(i.e., circadian alignment vs misalignment) and the rate of re-entrainment impacts cardiometabolic health,
cognitive function, and learning. To accomplish our aims, we have designed a randomized cross-over
mechanistic study in controlled laboratory settings. We hypothesize that when individuals that habitually eat a
low-fat diet are provided an isocaloric high-fat diet (versus when provided an isocaloric low-fat diet), they will
take longer to entrain to a shift in the light-dark cycle, have a narrower phase angle of entrainment, and have
increased circadian misalignment and associated impairments in cardiometabolic health, cognitive function,
and learning. These data will provide a fundamental understanding of how common dietary patterns alter the
way humans synchronize to the environment. Importantly, these data will have far-reaching implications for the
large portions of society that endure: 1) travel across multiple time zones (jet-lag); 2) a need to readjust
sleep/wake timing on workdays (social jet-lag); and 3) work and school start times that are too early for the
circadian clock of most young adults and teens. T...

## Key facts

- **NIH application ID:** 10904648
- **Project number:** 5R01HL156948-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrew William McHill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $610,322
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904648

## Citation

> US National Institutes of Health, RePORTER application 10904648, Uncovering the Impact of Diet on the Human Circadian Timing System (5R01HL156948-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10904648. Licensed CC0.

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