Night shift work has been classified by the International Agency for Research on Cancer as a probable human carcinogen, largely because disrupted circadian rhythms suppress the body's natural melatonin production — and with it, the overnight DNA repair processes that protect against cancer. A new randomized trial now offers the first clinical evidence that a simple melatonin supplement can partially restore that protection.
The study, published in Occupational & Environmental Medicine, found that night shift workers who took 3 mg of melatonin before daytime sleep had 80% higher urinary levels of 8-OH-dG — a validated biomarker of oxidative DNA repair — compared to those taking a placebo. The finding suggests that melatonin supplementation may help the body repair the kind of DNA damage linked to cancer development.
The Trial Design
Researchers at the BC Cancer Research Institute and the University of British Columbia, led by Umaimah Zanif and Dr. Parveen Bhatti, enrolled 40 participants between the ages of 18 and 50. All worked at least two consecutive night shifts per week, each lasting at least seven hours, and had maintained this schedule for a minimum of six months. None had diagnosed sleep disorders or chronic health conditions.
Half the participants were randomly assigned to take a 3 mg melatonin tablet with food approximately one hour before their daytime sleep following a night shift. The other half took an identical placebo on the same schedule. The trial lasted four weeks.
What the Biomarker Reveals
The key measurement — urinary 8-OH-dG — reflects how actively the body is repairing oxidative damage to DNA. When cells fix damaged DNA, they excrete the damaged nucleoside fragments in urine. Higher levels of 8-OH-dG therefore indicate more active repair, not more damage.
During daytime sleep periods, the melatonin group showed a 1.8-fold increase in 8-OH-dG excretion compared to the placebo group — an 80% boost in this repair marker. The result was borderline statistically significant, which the researchers attributed to the small sample size, and they called for larger confirmatory trials.
Why This Matters for Shift Workers
Roughly 16% of the U.S. workforce — more than 25 million people — regularly works evening, night, or rotating shifts. Epidemiological studies have consistently linked long-term night shift work to elevated rates of breast, prostate, and colorectal cancer. The suspected mechanism centers on melatonin suppression: exposure to light during normal sleep hours blunts melatonin production, which in turn reduces the hormone's antioxidant and DNA-protective effects.
Until now, the evidence connecting melatonin supplementation to DNA repair in shift workers came only from observational studies, which could not establish causation. This trial is the first to use a randomized, placebo-controlled design — the gold standard for clinical evidence — to test the relationship directly.
Melatonin's Dual Role
Melatonin is best known as a sleep-onset aid, but its biological functions extend well beyond drowsiness. The hormone is a potent antioxidant that scavenges free radicals and stimulates the activity of other antioxidant enzymes. It also directly enhances DNA repair pathways, particularly those involved in fixing oxidative damage — the type of genetic injury most strongly associated with cancer initiation.
The trial's findings suggest that even a modest dose of supplemental melatonin — 3 mg, roughly what is found in many over-the-counter sleep aids — can measurably amplify these protective mechanisms during the vulnerable daytime sleep window when the body's endogenous melatonin production is naturally suppressed.
Limitations
The trial was small (40 participants) and the statistical significance of the primary finding was borderline. The four-week duration also means the study cannot speak to whether the DNA repair benefit persists over months or years, or whether it translates into lower cancer incidence. The researchers emphasized that their results are preliminary and require replication in larger, longer trials.
What This Means for Patients
For the millions of people who work night shifts, this study introduces a potentially actionable finding: an inexpensive, widely available supplement may help offset one of the biological costs of working against the body's circadian clock. While the evidence is not yet strong enough to constitute a clinical recommendation, the trial provides the first controlled evidence that melatonin does what observational studies have long suggested it might — enhancing the body's ability to repair the DNA damage that accumulates when darkness and sleep fall out of sync.
The study was published in Occupational & Environmental Medicine (PMID: 39993913).
