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High sensitivity and interindividual variability in the response of the human circadian system to evening light
Edited by Diane B. Boivin, Douglas Mental Health University Institute, McGill University, Montreal, Canada, and accepted by Editorial Board Member Michael Rosbash April 20, 2019 (received for review February 3, 2019)

Significance
Electric lighting has fundamentally altered how the human circadian clock synchronizes to the day/night cycle. Exposure to light after dusk is pervasive in the modern world. We examined group-level sensitivity of the circadian system to evening light and the degree to which sensitivity varies between individuals. We found that, on average, humans are highly sensitive to evening light. Specifically, 50% suppression of melatonin occurred at <30 lux, which is comparable to or lower than typical indoor lighting used at night, as well as light produced by electronic devices. Significantly, there was a >50-fold difference in sensitivity to evening light across individuals. Interindividual differences in light sensitivity may explain differential vulnerability to circadian disruption and subsequent impact on human health.
Abstract
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
Footnotes
↵1A.J.K.P. and P.V. contributed equally to this work.
- ↵2To whom correspondence should be addressed. Email: sean.cain{at}monash.edu.
Author contributions: S.W.L. and S.W.C. designed research; P.V., A.C.B., and E.M.M. performed research; A.J.K.P., P.V., A.C.B., E.M.M., S.W.L., and S.W.C. analyzed data; and A.J.K.P., P.V., A.C.B., E.M.M., C.A., S.M.W.R., S.W.L., and S.W.C. wrote the paper.
Conflict of interest statement: C.A. has received a research award/prize from Sanofi-Aventis; contract research support from VicRoads, Rio Tinto Coal Australia, National Transport Commission, and Tontine/Pacific Brands; lecturing fees from Brown Medical School/Rhode Island Hospital, Ausmed, Healthmed, and TEVA Pharmaceuticals; and reimbursements for conference travel expenses from Philips Healthcare. C.A. has served as a consultant to the Rail, Bus, and Tram Union; the Transport Accident Commission; the National Transportation Committee; and Melius Consulting. C.A. has also served as an expert witness and/or consultant in relation to fatigue and drowsy driving. C.A. is a Theme Leader in the Cooperative Research Centre for Alertness, Safety, and Productivity. S.M.W.R. has served as a consultant through his institution to Vanda Pharmaceuticals, Philips Respironics, and Teva Pharma Australia and has, through his institution, received research grants and/or unrestricted educational grants from Vanda Pharmaceuticals, Takeda Pharmaceuticals North America, Philips Lighting, Philips Respironics, Cephalon, and ResMed Foundation, as well as reimbursements for conference travel expenses from Vanda Pharmaceuticals. S.M.W.R. serves as a Program Leader and consultant to the Cooperative Research Centre for Alertness, Safety, and Productivity. S.W.L. has had a number of commercial interests in the last 36 mo (2016–2019). None are directly related to the research reported in this paper but, in the interests of full disclosure, are outlined as follows. S.W.L. has received consulting fees from the Atlanta Falcons, Atlanta Hawks, BHP Billiton, Noble Insights, Slingshot Insights, and Team C Racing; honoraria and/or paid travel from BHP Billiton, DIN, Emory University, IES, Ineos, SLTBR, Solemma, and Teague; has current consulting contracts with Akili Interactive, Apex 2100 Ltd., Consumer Sleep Solutions, Headwaters Inc., Hintsa Performance AG, Light Cognitive, Lighting Science Group Corporation, Mental Workout, PlanLED, Six Senses, Stantec, and Wyle Integrated Science and Engineering; has received unrestricted equipment gifts from Bionetics Corporation and F. Lux Software LLC and royalties from Oxford University Press; and has served as a paid expert in legal proceedings related to light, sleep, and health. He holds a patent through Harvard University and Brigham and Women’s Hospital for “Systems and Methods for Determining and/or Controlling Sleep Quality.”
This article is a PNAS Direct Submission. D.B.B. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1901824116/-/DCSupplemental.
- Copyright © 2019 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
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