Millions of people work through the night, including nurses, factory workers, security staff, and emergency responders. More and more research shows that this can disrupt a key biological process that helps protect us from cancer. Now, a new clinical trial has found a possible way to counteract this risk.
If you regularly work night shifts, your body is constantly struggling to keep up with its biological clock. The human circadian system evolved over millions of years to match our body’s functions with light and dark, regulating sleep, metabolism, immune function, and most importantly, the system that repairs damaged DNA. Working through the night disrupts all of these processes.
One of the most serious consequences is a much higher risk of cancer. The International Agency for Research on Cancer even classifies night shift work as a probable carcinogen. However, the exact biological links between disrupted sleep and cancer have not been fully understood, and until recently, no clinical trial had tested if a simple, affordable supplement could help undo the damage.
A landmark study published in Occupational & Environmental Medicine by researchers at BC Cancer Research Institute and the University of British Columbia has changed that. It is the first randomized, placebo-controlled trial to test whether melatonin supplements can help repair oxidative DNA damage in night shift workers, and the early results are promising.
The Hidden Biological Cost of Night Shifts
When you work at night and sleep during the day, one of the first things affected is your melatonin levels. This hormone is produced by your brain in the dark to signal to your body that it’s nighttime. For night-shift workers, melatonin production is disrupted and reduced at the times they need it most: when they sleep during the day and work at night.
This is important for cancer risk because melatonin does much more than just regulate sleep. It is a strong antioxidant that directly neutralizes reactive oxygen species (ROS), which are unstable molecules produced naturally by our cells. If ROS are not controlled, they can damage DNA, and this damage must be found and removed before it leads to mutations and, eventually, cancer.
The most common type of this oxidative DNA damage involves a molecule called 8-hydroxy-2′-deoxyguanosine (8-OH-dG). When the body’s DNA repair system removes these damaged parts, 8-OH-dG is released in urine. Measuring its level in urine shows how well the body is repairing its DNA. Higher amounts in urine indicate better repair, while lower amounts indicate that damage is building up.
In earlier observational studies, the same research team found that night-shift workers excreted much less 8-OH-dG in their urine during daytime sleep and night work than during normal night sleep on days off. This suggested that working nights weakens the body’s ability to repair DNA damage, likely because of lower melatonin levels. Melatonin is known to activate the nucleotide excision repair pathway, which detects and removes 8-oxo-7,8-dihydro-2′-deoxyguanosine.
The next logical question was whether taking melatonin supplements to restore its levels could also bring back the body’s ability to repair DNA.
The Trial: What They Did
The researchers recruited 40 night shift workers from the Greater Vancouver area, most of whom worked in healthcare, through the British Columbia Federation of Labour. All participants worked at least 2 consecutive night shifts each week and had been sleeping during the day for at least 6 months. None were currently taking melatonin supplements.
The trial was randomized and placebo-controlled: 20 participants received a 3mg melatonin capsule, and 20 received a lookalike placebo. Neither the participants nor the staff knew who got which. Importantly, participants took the supplement after finishing their night shift, 1 hour before their planned daytime sleep, as Health Canada recommends for people with altered sleep schedules. The study lasted four weeks.
The researchers collected all urine produced during two different daytime sleep periods and two following night work periods, once before the four-week study started and once near the end. They used high-precision mass spectrometry to measure both 8-OH-dG (a marker for DNA repair) and 6-sulfatoxymelatonin (a marker for melatonin levels) in the samples. Participants also wore wrist devices to track how long and how well they slept, and rated their sleepiness during night shifts using a standard scale.
The Results: A Meaningful Signal
The main finding was that, compared with the placebo group, people taking melatonin had a 1.8-fold higher level of 8-OH-dG in their urine during daytime sleep, indicating much better DNA repair activity. This result was right at the edge of what is usually considered statistically significant (p=0.06), which the researchers describe as borderline meaningful but not conclusive because of the small sample size.
The biological effect was even clearer when the researchers considered differences in how people absorb melatonin. Melatonin levels in the body can vary a lot from person to person, since some people absorb and process it more easily than others. When the analysis focused on those with the highest melatonin levels during the study, the improvement in DNA repair was even greater and statistically significant: a twofold increase (p=0.04).
The melatonin supplement worked as intended, raising melatonin levels: participants who took melatonin had about 60 times as many melatonin markers in their urine during daytime sleep as those in the placebo group. By the next night shift, these levels had returned to normal, which explains why there was no significant difference in DNA repair during the night shift itself. The benefit for DNA repair seems to happen mainly during sleep, when melatonin levels are highest.
Regarding sleep quality, there was a hint that people taking melatonin woke up less during sleep, but this was not a significant finding. There was also no real difference in how sleepy people felt during the night shift between the two groups.
Why This Matters: Connecting Melatonin, DNA, and Cancer
The process being tested in this trial is well understood and supported by growing evidence. When oxidative DNA damage accumulates and goes unrepaired, it can cause mutations, which are the basis of cancer. Large studies have shown that night shift workers have higher risks of breast, prostate, colorectal, and other cancers. The World Health Organization’s cancer agency has even put night shift work in the same probable carcinogen category as diesel exhaust fumes and acrylamide.
What makes this trial particularly significant is that it moves the field from observation to intervention. Prior research has established that night shift work suppresses melatonin, and that melatonin suppression correlates with reduced DNA repair. This trial is the first to test whether restoring melatonin with a readily available, inexpensive over-the-counter supplement can reverse that impairment.
In this early trial, the answer seems to be yes, at least during daytime sleep, when the supplement has the biggest effect on melatonin levels.
Important Limitations to Keep in Mind
The researchers are appropriately cautious about what this trial can and cannot prove. With only 40 participants, the study was designed as a proof-of-concept large enough to detect a meaningful signal, but not large enough to provide definitive answers. The wide confidence intervals around the primary result reflect this uncertainty.
The trial also ran for only four weeks. Night shift workers often maintain their schedules for years or decades, and whether melatonin’s protective effects on DNA repair persist over that timescale and whether they translate into actual reductions in cancer incidence remains completely unknown. A supplement that improves a biological marker over a month may or may not confer long-term protection.
There is also the issue of dose and the extent of melatonin absorption by the body. The 3mg dose used in the trial led to melatonin levels much higher than the body normally produces. It is not yet clear whether lower doses would work as well or whether very high doses could cause side effects. Since people absorb melatonin differently, a single approach may not work for everyone.
Participants were also predominantly from one occupational sector (healthcare), limiting the extent to which the results can be applied.
What Comes Next
The researchers call for larger trials that examine multiple doses, account for the wide individual variation in melatonin bioavailability, and follow participants over longer periods to understand the long-term effects. Ideally, future studies would also include diverse occupational groups and track not just biological markers but actual health outcomes.
For the tens of millions of people worldwide who work night shifts, including hospital nurses, warehouse staff, and long-haul truckers, the potential public health impact is huge. If a simple, affordable supplement taken before daytime sleep could really lower cancer risk by helping the body repair DNA, it would be one of the easiest and most accessible health interventions available.
The lead researcher puts it simply: melatonin supplements “may prove to be a viable intervention strategy to reduce the burden of cancer among night shift workers.” The early results support this hope, and larger trials to confirm it are urgently needed.
Reference:
Zanif U, Lai AS, Parks J, Roenningen A, McLeod CB, Ayas N, Wang X, Lin Y, Zhang J, Bhatti P. (2025). Melatonin supplementation and oxidative DNA damage repair capacity among night shift workers: a randomised placebo-controlled trial. Occupational and Environmental Medicine, 82: 1–6. https://doi.org/10.1136/oemed-2024-109824