Light + Health, Research

Rethink Circadian Metrics? REV-ERBα Biomarker for Daytime!

BIll Chan

By Bill Chan, President at LiteController Inc.

We know how nighttime light affects Melatonin production – but do we truly understand how light exposure during the day influences our circadian system?  Current circadian lighting metrics do not fully capture the biological effects or circadian entrainment of daytime light exposure.

The two circadian lighting metrics (CS and EML) illustrated in UL 24480 have limitations.

  • CS is based on Melatonin suppression, which may not fully apply to daytime light exposure.
  • EML is based on in vitro cell experiments and lacks validation using human biomarkers.
  • Neither metric directly measures how light affects human physiology during the daytime.

Why Do We Need a New Circadian Metric for Daytime?

 A recent study by Gubin et al. (2025), suggests REV-ERBα could be the missing biomarker to bridge this gap. This newly published paper titled “Light Exposure, Physical Activity, and Indigeneity Modulate Seasonal Variation in NR1D1 (REV-ERBα) Expression” may be the first to use REV-ERBα (NR1D1) as a biomarker to investigate how light exposure affects humans during daytime. Its web link is https://www.mdpi.com/2079-7737/14/3/231. This is significant because current circadian lighting metrics do not effectively measure how daytime light exposure influences circadian health.

 The Shortcomings of Current Circadian Lighting Metrics (UL 24480)

 UL 24480 illustrates two widely used circadian lighting metrics:

  • The Circadian Stimulus (CS) Model

How It Works:

CS is based on Melatonin suppression experiments conducted at night. It assumes that nighttime results apply equally during the day—but this has never been validated.

The Problem:

Melatonin levels are minimal during the day, making it difficult to study how light affects circadian rhythms outside of nighttime conditions. CS may not accurately reflect daytime circadian entrainment.

  • The Equivalent Melanopic Lux (EML) Model

How It Works:

EML is based on the Melanopic sensitivity function (MSF) and so as Melanopic EDI illustrated in CIE S 028. MSF was derived from in vitro retinal cell experiments using genetically modified HEK 293 (Human Embryonic Kidney) cells. Researchers measured calcium responses in these modified Melanopsin cell tissues after 1-minute of light exposure. It does not measure any actual human biomarker response.

The Problem:

EML estimates how light activates Melanopsin but does not measure actual biological effects in humans. It does not provide direct insights into how light affects metabolism, alertness, or daytime circadian health.

Could REV-ERBα Be the Key to a New Daytime Circadian Metric?

Unlike Melatonin, REV-ERBα may be the missing biomarker for understanding how daytime light exposure influences circadian rhythms. Gubin et al. (2025) precisely identified its biphasic peak pattern – a minor peak at 07:18 AM and a major peak at 19:31 PM. This is a crucial finding because it provides direct experimental evidence validating REV-ERBα’s role as a circadian biomarker.

REV-ERBα’s distinct morning and evening peaks suggest it plays a dual role – helping regulate alertness and metabolism during the day while preparing the body for nighttime recovery. Unlike Melatonin, which primarily signals sleep, REV-ERBα is influenced by light exposure and directly interacts with the body’s internal clock. It also connects light exposure to metabolism, physical activity, and cognitive function, making it a more dynamic biomarker for circadian health. These characteristics highlight its potential as a key biomarker for understanding how light shapes our biological rhythms. Additionally, studies have demonstrated that REV-ERBα dynamically controls circadian gene transcription, reinforcing its importance in regulating biological rhythms. These findings further validate its potential as a biomarker for assessing how light exposure influences human physiology.

Several factors reinforce its importance in circadian entrainment:

  • It regulates BMAL1, the master circadian clock gene.
  • It is influenced by light exposure and plays a role in circadian rhythm regulation.
  • Recent animal studies suggest that blue light (~442 nm) may enhance REV-ERBα expression.
  • It connects light exposure to metabolism, physical activity, and cognitive function.

The Future of Daytime Circadian Lighting Metrics

It’s time to develop a circadian lighting metric that accurately reflects human responses to light during daytime. We need a new metric that moves beyond Melatonin and reflects how light influences human biology during the day. REV-ERBα could be the key to bridging the gap between light exposure, metabolism, and circadian health. Its distinct biphasic oscillatory pattern – validated by Gubin et al. (2025), with a minor peak at 07:18 AM and a major peak at 19:31 PM – further highlights its role as a critical biomarker for understanding how light influences circadian entrainment.

More research is needed to explore how different light spectra and intensities influence REV-ERBα expression – helping us design better lighting for health and well-being.

REFERENCES

Ikeda R. et al. REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output. Scientific Reports volume 9, Article number: 10171 (2019)

Kim Y.H. et al. Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription. SCIENCE, 8 Feb 2018, Vol 359, Issue 6381

About The Author

Bill Chan is the President of LiteController Inc., a manufacturer of Circadian Lighting LED fixtures and modules. Bill has also been an Honorary Professor of Electrical Engineering at Tongji University for 32 years. Bill lives and works in Markham, Ontario, Canada.

Image: Bill Chan

 

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David Shiller
David Shiller is the Publisher of LightNOW, and President of Lighting Solution Development, a North American consulting firm providing business development services to advanced lighting manufacturers. The ALA awarded David the Pillar of the Industry Award. David has co-chaired ALA’s Engineering Committee since 2010. David established MaxLite’s OEM component sales into a multi-million dollar division. He invented GU24 lamps while leading ENERGY STAR lighting programs for the US EPA. David has been published in leading lighting publications, including LD+A, enLIGHTenment Magazine, LEDs Magazine, and more.

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