Researchers discovered that melatonin, a natural hormone your body makes at night, may help prevent atherosclerosis—a dangerous buildup of plaque in arteries that can lead to heart attacks. In this study, mice given melatonin showed less plaque buildup and less inflammation in their blood vessels. The researchers found that melatonin works by controlling how immune cells called macrophages behave and by fixing problems inside these cells’ power plants (mitochondria). While these results are promising, the research was done in mice and lab cells, so we need human studies before doctors can recommend melatonin as a heart disease treatment.

The Quick Take

  • What they studied: Whether melatonin can slow down or prevent atherosclerosis (clogged arteries) by changing how immune cells work and how their internal power plants function
  • Who participated: Mice genetically designed to develop clogged arteries, plus lab-grown immune cells exposed to damaged cholesterol particles
  • Key finding: Melatonin reduced plaque buildup in arteries, lowered inflammation, and prevented immune cells from becoming overly aggressive—but only when a specific protein called Sirt3 was working properly
  • What it means for you: This suggests melatonin might someday help prevent heart disease, but these are early-stage results from animal and lab studies. Don’t start taking melatonin supplements for heart health yet—talk to your doctor first, and wait for human studies

The Research Details

This research had two main parts. First, scientists gave mice a high-fat diet for 16 weeks to create clogged arteries, then treated some mice with melatonin for another 16 weeks while measuring changes in their blood vessels. Second, they grew immune cells in a lab dish, exposed them to damaged cholesterol particles, and tested how melatonin affected these cells. To understand how melatonin works, they also blocked a specific protein called Sirt3 to see if melatonin still helped. This approach—combining animal studies with lab cell studies—helps researchers understand both whether something works and how it works.

Using both mice and lab cells allowed researchers to see the big picture (does melatonin help prevent clogged arteries?) and the small picture (what’s happening inside the cells?). This combination is stronger than either approach alone because it shows the effect is real at multiple levels. The researchers also used a blocking technique to prove that melatonin’s benefits depend on the Sirt3 protein, which strengthens their conclusion about how melatonin works.

This study has several strengths: it used a well-established mouse model of atherosclerosis, measured multiple related outcomes (plaque size, inflammation, cell behavior), and tested the mechanism by blocking key proteins. However, the study was conducted in animals and lab cells, not humans, so results may not directly apply to people. The sample size for mice wasn’t specified, making it harder to judge statistical reliability. The research is recent (2025) and published in a peer-reviewed journal, which is positive, though the journal’s impact factor wasn’t provided.

What the Results Show

Mice treated with melatonin showed significantly smaller atherosclerotic plaques compared to untreated mice, meaning less buildup of dangerous material in their arteries. The melatonin-treated mice also had lower levels of inflammatory chemicals in their blood vessels—these chemicals normally trigger the immune system to attack artery walls and make atherosclerosis worse. In lab studies, melatonin prevented immune cells from becoming overly aggressive when exposed to damaged cholesterol. Importantly, when scientists blocked the Sirt3 protein, melatonin lost its protective effects, proving that Sirt3 is essential for melatonin to work.

The research revealed that melatonin works by controlling mitochondrial fission—the process where a cell’s power plants break apart into smaller pieces. When these power plants fragment too much, immune cells become more inflammatory and aggressive. Melatonin reduced this fragmentation by increasing Sirt3 levels and decreasing a protein called Drp1 that causes fragmentation. When researchers directly blocked Drp1 using genetic techniques, they saw similar benefits: less cell fragmentation and less aggressive immune cell behavior. This suggests multiple ways to achieve the same protective effect.

Previous research showed that melatonin has anti-inflammatory effects and can influence how mitochondria function, but the specific pathway wasn’t clear. This study fills that gap by identifying the Sirt3-Drp1 pathway as the key mechanism. The findings align with growing evidence that mitochondrial health is important for preventing atherosclerosis and that controlling inflammation is crucial for heart disease prevention. This research adds a new piece to the puzzle of how melatonin might protect the heart.

The biggest limitation is that all experiments were done in mice and lab cells, not humans. Mice don’t always respond the same way people do to treatments. The study didn’t specify how many mice were used, making it impossible to assess whether the results were statistically solid. The research used a specific type of mouse genetically engineered to develop atherosclerosis, which doesn’t perfectly mirror how the disease develops in humans. Additionally, the study only looked at melatonin’s effects; it didn’t compare melatonin to existing heart disease treatments. Finally, the optimal dose of melatonin for humans and potential side effects weren’t explored.

The Bottom Line

Based on this research alone, there is NOT enough evidence to recommend melatonin supplements for preventing heart disease (confidence level: low). This is early-stage research that needs to be followed by human studies. If you’re interested in preventing atherosclerosis, focus on proven strategies: eat a heart-healthy diet, exercise regularly, maintain a healthy weight, don’t smoke, and manage stress. If you’re considering melatonin for any reason, discuss it with your doctor first, especially if you take other medications.

This research is most relevant to cardiovascular researchers and doctors studying new ways to prevent heart disease. People with risk factors for atherosclerosis (high cholesterol, high blood pressure, diabetes, family history of heart disease) might find this interesting, but shouldn’t change their behavior based on this study alone. People currently taking melatonin for sleep should not assume it’s protecting their heart. Anyone considering melatonin supplements should consult their healthcare provider.

If melatonin eventually proves helpful in humans, benefits would likely take weeks to months to appear, since atherosclerosis develops slowly over years. This is not a quick fix. The research suggests melatonin might help prevent disease progression, not reverse existing damage. Realistic expectations would be modest slowing of disease development, not dramatic improvements.

Want to Apply This Research?

  • Track cardiovascular health markers that are modifiable: daily steps (aim for 7,000-10,000), resting heart rate (should be 60-100 bpm), blood pressure readings if you have a home monitor, and weekly servings of heart-healthy foods like fish, nuts, and vegetables. These are proven factors you can control.
  • Use the app to build a heart-healthy routine: set daily reminders for a 30-minute walk, log meals to ensure you’re eating less saturated fat and more fiber, track stress-reduction activities like meditation, and monitor sleep quality. These evidence-based habits are proven to reduce atherosclerosis risk.
  • Create a long-term cardiovascular health dashboard tracking: weekly exercise minutes, monthly blood pressure averages (if available), quarterly cholesterol levels (through your doctor), and overall lifestyle score. Share this data with your healthcare provider at annual checkups to monitor your actual atherosclerosis risk.

This research was conducted in mice and laboratory cells, not humans. The findings are preliminary and do not constitute medical advice. Do not start, stop, or change any medications or supplements based on this study without consulting your healthcare provider. Melatonin supplements are not FDA-approved for treating or preventing heart disease. If you have risk factors for atherosclerosis or heart disease, work with your doctor on proven prevention strategies including diet, exercise, and medication if needed. This article is for educational purposes only and should not replace professional medical guidance.