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

> **NIH NIH R56** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $569,728

## 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),
impaired sleep, reduced cognitive performance, and even economic disadvantage. 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 because 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) impacts cardiometabolic health and cognitive
function. 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 and cognitive function. These data will provide a
fundamental understanding of how common dietary patterns alter the way humans synchronize to the
environment. Importantly, these data would 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 natural internal clock timing of most young
adults and teens. This stu...

## Key facts

- **NIH application ID:** 10475344
- **Project number:** 1R56HL156948-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrew William McHill
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $569,728
- **Award type:** 1
- **Project period:** 2021-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475344

## Citation

> US National Institutes of Health, RePORTER application 10475344, Uncovering the Impact of Diet on the Human Circadian Timing System (1R56HL156948-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10475344. Licensed CC0.

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