Researchers emphasize that the study was observational - correlation is not the same as causation
American Heart Association
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The findings do not prove that melatonin itself caused the
increased risks. However, they raise new questions about the long-term safety
of a supplement that many people view as a harmless or "natural" way
to improve sleep.
Why Melatonin Is So Widely Used
Melatonin is a hormone made naturally by the pineal gland in
the brain. It helps control the body's sleep and wake cycle, also known as the
circadian rhythm. Levels of the hormone typically rise when it gets dark and
fall during daylight.
Synthetic melatonin is chemically identical to the hormone
produced by the body. It is commonly used for insomnia (difficulty falling
and/or staying asleep) and jet lag.
Melatonin supplements are available over the counter in many
countries, including the U.S. In the U.S., over-the-counter supplements are not
regulated, so each brand of supplement can vary in strength, purity, etc.
For the new study, researchers divided participants
according to their documented melatonin use. People with at least one year of
melatonin use recorded in their electronic medical records were placed in the
"melatonin group." Those with no record of melatonin use anywhere in
their medical records were assigned to the "non-melatonin group."
"Melatonin supplements may not be as harmless as
commonly assumed. If our study is confirmed, this could affect how doctors
counsel patients about sleep aids," said Ekenedilichukwu Nnadi, M.D., lead
author of the study and chief resident in internal medicine at SUNY
Downstate/Kings County Primary Care in Brooklyn, New York.
Researchers Looked for Long-Term Heart Risks
Melatonin is often promoted as a safe sleep aid, but
researchers say there is limited evidence about its cardiovascular safety when
taken for extended periods.
That uncertainty led the team to investigate whether
long-term melatonin use might be associated with heart failure among people who
already had chronic insomnia.
Heart failure does not mean that the heart has completely
stopped working. It develops when the heart cannot pump enough oxygen-rich
blood to meet the body's needs. According to the American Heart Association's
2025 Heart Disease and Stroke Statistics, the condition affects about 6.7
million adults in the U.S.
Researchers used data from the TriNetX Global Research
Network, a large international database containing de-identified electronic
health records.
They examined five years of medical records for adults with
chronic insomnia whose records showed melatonin use for more than a year. Those
participants were matched with other people who also had insomnia but had no
documented melatonin use.
Anyone who had already been diagnosed with heart failure or
who had been prescribed other sleep medications was excluded.
Heart Failure Risk Was About 90% Higher
The main analysis found a substantial difference between the
two groups.
Among adults with insomnia, people with documented long-term
melatonin use (12 months or more) had about a 90% higher chance of developing
heart failure during the following five years compared with matched nonusers.
Heart failure occurred in 4.6% of the melatonin group compared with 2.7% of the
comparison group.
Researchers then performed another analysis designed to
strengthen confidence that participants had actually been using melatonin over
an extended period.
When they limited the analysis to people who had filled at
least two melatonin prescriptions at least 90 days apart, the association
remained. That group had an 82% higher risk of heart failure. (Melatonin is
only available by prescription in the United Kingdom.)
Hospitalization and Death Were Also Higher
A secondary analysis found even larger differences in some
outcomes.
People in the melatonin group were nearly 3.5 times as
likely to be hospitalized for heart failure as those in the comparison group.
The hospitalization rates were 19.0% and 6.6%, respectively.
Deaths from any cause were also more common among people
with documented melatonin use. During the five-year period, 7.8% of
participants in the melatonin group died compared with 4.3% of those in the
non-melatonin group, making the risk nearly twice as high.
"Melatonin supplements are widely thought of as a safe
and 'natural' option to support better sleep, so it was striking to see such
consistent and significant increases in serious health outcomes, even after
balancing for many other risk factors," Nnadi said.
The results also drew concern from sleep researcher
Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, who was not involved in the study.
"I'm surprised that physicians would prescribe
melatonin for insomnia and have patients use it for more than 365 days, since
melatonin, at least in the U.S., is not indicated for the treatment of
insomnia. In the U.S., melatonin can be taken as an over-the-counter supplement
and people should be aware that it should not be taken chronically without a
proper indication," said Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA,
chair of the writing group for the American Heart Association's 2025 scientific
statement, Multidimensional Sleep Health: Definitions and Implications for
Cardiometabolic Health.
St-Onge is a professor of nutritional medicine in the
division of general medicine and director of the Center of Excellence for Sleep
& Circadian Research in the department of medicine at Columbia University
Irving Medical Center in New York City.
Important Limitations Complicate the Findings
The study comes with several significant limitations,
particularly because melatonin is handled differently from one country to
another.
Some countries, such as the United Kingdom, require a
prescription for melatonin, while others, including the United States, allow
people to buy it over the counter. Researchers did not have access to
participants' locations because the medical data had been de-identified.
Melatonin use was identified only when it appeared in
electronic medical records. That means people in the U.S. or other countries
who bought melatonin over the counter without having it entered into their
medical records could have been incorrectly classified as nonusers.
As a result, the melatonin and nonmelatonin groups may not
perfectly reflect who was actually taking the supplement.
There was another complication involving hospitalizations.
The number of heart failure-related hospitalizations was higher than the number
of newly diagnosed heart failure cases because hospitals may enter a variety of
related diagnostic codes. Those records do not always include a code
specifically identifying a new heart failure diagnosis.
Researchers also did not have information about how severe
each participant's insomnia was or whether participants had other psychiatric
disorders.
Those missing factors are important because people with more
severe insomnia, depression, anxiety, or other conditions may be more likely to
use melatonin and could independently have a different cardiovascular risk.
"Worse insomnia, depression/anxiety, or the use of
other sleep-enhancing medicines might be linked to both melatonin use and heart
risk," Nnadi said. "Also, while the association we found raises
safety concerns about the widely used supplement, our study cannot prove a
direct cause-and-effect relationship. This means more research is needed to
test melatonin's safety for the heart."
What the Study Included
- The
analysis included 130,828 adults (average age of 55.7 years; 61.4% women)
who had been diagnosed with insomnia.
- The
data came from TriNetX, established in 2013, a growing global network of
real-world, de-identified patient information used for medical research.
- Of the
participants, 65,414 had been prescribed melatonin at least once and
reported using it for at least one year.
- Researchers
also created a comparison group (control group) made up of people who had
never been prescribed melatonin. These participants were matched to the
melatonin group using 40 factors, including demographic characteristics,
existing health conditions, and medications.
- Anyone
who had already been diagnosed with heart failure was excluded, as were
people who had been prescribed other kinds of sleeping pills such as
benzodiazepines.
- The
melatonin and comparison groups were matched for age, sex, race/ethnicity,
heart and nervous system diseases, medications for heart and nervous
system diseases, blood pressure, and body mass index.
- Researchers
then examined electronic medical records covering the five years after the
groups were matched.
- For
the primary analysis, they searched for medical codes indicating an
initial diagnosis of heart failure. Secondary outcomes included codes
associated with hospitalization for heart failure or death.
- The
researchers also carried out what is known as a sensitivity analysis, a
method used to check whether results remain similar when the study
criteria are changed slightly.
- For
this additional test, participants in the melatonin group had to have
filled at least two melatonin prescriptions at least 90 days apart. The
association with higher heart failure risk remained, providing an
additional check on the original findings.
- Even
so, the researchers emphasize that the study was observational. It
identified an association between long-term documented melatonin use and
serious health outcomes, but it cannot establish that melatonin directly
caused those outcomes. Further research will be needed to determine
whether long-term melatonin use itself affects cardiovascular health and,
if so, why.
American Heart Association. "Long-term melatonin use linked to 90% higher heart failure risk." ScienceDaily. ScienceDaily, 29 August 2026. <www.sciencedaily.com/releases/2026/08/260829035228.htm>.
