Repairing DNA Damage: A Surprising New Benefit of Melatonin?

Key takeaways

• A small trial in night‑shift workers found that taking 3 mg melatonin before daytime sleep increased a marker of oxidative DNA repair by about 80% compared with placebo.

• The effect showed up during daytime sleep after a night shift, but not during the following night of work, and the study was too small and short to test long‑term outcomes.

• The findings hint that melatonin may help restore part of the body’s nighttime repair signal in people who sleep during the day, but it is far from proof of long‑term protection.

Melatonin rises in darkness and helps coordinate sleep‑wake timing with internal repair processes. For people who regularly work overnight, this rhythm can be flipped: bright light at night and sleep during the day can suppress natural melatonin at the very time cells expect it.

Researchers are particularly interested in how this disruption affects oxidative DNA damage—a routine kind of molecular wear‑and‑tear that needs constant repair. If repair capacity lags behind damage for years, errors can accumulate in dividing cells. That possibility is one reason long‑term night work and light at night have been treated as important public‑health concerns.

What this trial actually tested

To see whether restoring melatonin might improve repair, investigators ran a randomized, placebo‑controlled trial in 40 night‑shift workers. Everyone had been working at least two night shifts per week for six months or more, with each shift lasting seven hours or longer. None reported major sleep disorders or chronic conditions.

For four weeks, half the participants took 3 mg melatonin once a day, with food, about an hour before going to sleep during the day. The other half took a matching placebo on the same schedule. The team collected urine samples during daytime sleep after a night shift and again during the next night shift, both before and near the end of the intervention, and they used activity trackers to confirm sleep timing and duration.

A DNA repair marker rose with melatonin

The main outcome was urinary 8‑hydroxy‑2′‑deoxyguanosine (8‑OHdG), commonly used as a readout of oxidative DNA damage and repair. In this study, higher levels of 8‑OHdG excreted during sleep were interpreted as evidence that more repair work was being done.

After four weeks, workers taking melatonin had about 80% higher urinary 8‑OHdG during daytime sleep than those on placebo. That suggests melatonin may have enhanced DNA repair while they were resting after night work. However, during the subsequent night shift, 8‑OHdG levels did not differ meaningfully between the groups, implying that any repair boost was tied to the sleep period rather than extending into the work period itself.

How to interpret the findings

The trial provides mechanistic support for an idea scientists have discussed for years: melatonin might act as more than a sleep hormone, also nudging antioxidant defenses and DNA repair pathways. For people who must sleep in daylight after overnight work, a supplemental dose could partially restore part of the “night” signal the body expects when it runs heavy repair routines.

At the same time, the study has important limits. It was small, lasted only four weeks, and focused on a single biomarker in urine rather than on health outcomes. Most participants worked in healthcare, so the results may not apply to all types of night work. The researchers also could not fully control for natural light exposure, which influences melatonin production and circadian timing.

What this does—and doesn’t—mean for night‑shift workers

For now, the trial should be seen as an early proof‑of‑concept, not a prescription. It strengthens the scientific rationale for larger, longer studies that test different doses, follow people for years, and track real‑world outcomes, not just lab markers. Those trials would also need to carefully weigh benefits against any risks of long‑term, nightly supplementation.

The most practical, cautious takeaway is that melatonin may play a broader role in nighttime repair than sleep alone, and that restoring its signal during day‑sleep could support DNA maintenance in people working through the night. But the core pillars for night‑shift workers still look familiar: protecting sleep duration and quality, managing light exposure (especially bright light at night and early‑morning light on the way home), supporting nutrition and movement, and working with clinicians before adding any regular supplement.

References:

1. Umaimah Zanif, Agnes S Lai, Jaclyn Parks, Aina Roenningen, Christopher B McLeod, Najib Ayas, Xiangtian Wang, Yan Lin, Junfeng (Jim) Zhang, Parveen Bhatti. Melatonin supplementation and oxidative DNA damage repair capacity among night shift workers: a randomised placebo-controlled trial. Occupational and Environmental Medicine, 2025; 82 (1): 1 DOI: 10.1136/oemed-2024-109824