New Insights on Melatonin’s Role in Sleep and Circadian Regulation

The scientific paper New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation by Zisapel et al. provides a comprehensive review of how melatonin, a hormone produced by the pineal gland, influences human sleep patterns, internal biological clocks (circadian rhythms), and overall health. The study highlights the natural rise and fall of melatonin levels in response to light and dark, and how disruptions to this rhythm—due to aging, disease, or environmental factors—can lead to sleep problems and increase the risk of neurodegenerative and cardiovascular diseases. The authors explore both basic science and clinical research, emphasizing the therapeutic potential of prolonged-release melatonin in treating insomnia, especially in older adults, and its possible role in preventing conditions like Alzheimer’s disease by improving sleep quality and restoring circadian balance.

Melatonin is a natural hormone made by the brain’s pineal gland. It helps control the body’s internal clock, also known as the circadian rhythm. This rhythm tells us when to sleep, wake up, and eat. Melatonin production rises in the evening and signals the body that it's time to rest.

As people get older or develop certain health problems like Alzheimer’s disease or high blood pressure, their melatonin levels often drop. This can lead to poor sleep and other problems. Researchers have been studying how melatonin can be used as a treatment to help people sleep better and support brain and heart health.

This scientific paper gives new insight into how melatonin affects the brain, especially in the elderly and those with sleep or memory problems.

This is a scientific review paper written by Dr. Nava Zisapel, a neurobiology expert at Tel Aviv University and Neurim Pharmaceuticals. The paper collects and discusses findings from many clinical studies and lab research. It looks at how melatonin is made in the body, how it works in the brain, and how it helps with different medical conditions. The studies include both healthy individuals and people with sleep disorders, Alzheimer's disease, and other issues.

The research includes clinical trials using melatonin pills, especially prolonged-release melatonin (PRM), which slowly releases melatonin through the night to mimic the body’s natural rhythm.

Melatonin is released at night and helps the body feel sleepy. The study describes it as “a message of darkness to the clock,” helping the brain know when it’s time to rest. It doesn't work like a sedative. Instead, it helps your body prepare for sleep in a natural way.

Melatonin’s effects are strongest when taken at times when the body isn’t already producing it, like in the late afternoon or early evening. That’s when it helps most with sleep problems.

People who are totally blind often struggle with Non-24-Hour Sleep-Wake Disorder (N24HSWD) because they can’t detect light, which usually helps reset the body’s clock. Melatonin has been shown to help them get on a regular sleep schedule. In one part of the study, taking melatonin every evening helped blind people “entrain endogenous melatonin and cortisol rhythms to the 24 h cycle.”

It also helps people with Delayed Sleep Phase Syndrome (DSPS) fall asleep earlier. Although not yet officially approved for jet lag, many people use melatonin to adjust after flying across time zones.

As we age, our melatonin levels naturally drop. This can lead to insomnia, especially poor sleep quality, where people wake up feeling tired even if they slept for several hours.

The study explains that in people over 55, taking prolonged-release melatonin (PRM) improves sleep quality, shortens the time it takes to fall asleep, and makes people feel more alert in the morning. PRM has been shown to be safe for long-term use and doesn’t cause the problems often linked to sleeping pills, like memory issues or falls.

Many children with autism spectrum disorder (ASD) and related conditions have trouble sleeping. This is often due to abnormal melatonin rhythms. Studies reviewed in the paper show that melatonin can help these children fall asleep faster and stay asleep longer. Better sleep also helps reduce daytime behavior problems and stress in families.

The paper mentions that melatonin “could become a standard treatment of insomnia in neurodevelopmentally-challenged children,” once approved by health authorities.

Good sleep helps lower blood pressure at night, which is important for heart health. But in many older people or those with insomnia, this drop doesn't happen. These people are called "non-dippers."

Melatonin, especially PRM, has been shown to help reduce nighttime blood pressure in people with hypertension . The study says, “A 6 mmHg reduction in mean systolic BP overnight... is clinically meaningful,” suggesting it could help prevent heart attacks or strokes.

Sleep plays a big role in cleaning waste from the brain, including a harmful protein called amyloid-β (Aβ), which builds up in Alzheimer’s disease. Poor sleep may increase this buildup.

This study shows that melatonin helps improve sleep quality and may slow down memory loss in people with mild to moderate Alzheimer’s disease. In a six-month clinical trial, people who took PRM showed better memory, daily function, and sleep. One reason may be that melatonin reduces brain activity in areas where Aβ usually builds up, like the precuneus in the default mode network (DMN).

“Exogenously administered melatonin may... improve the restorative value of sleep,” the study says, which may help clear out Aβ and support brain health.

This study shows that melatonin does more than just help people fall asleep. It may support healthy aging, lower the risk of heart problems, and even slow memory decline. It’s especially helpful for people who naturally produce less melatonin, like older adults or children with autism.

Melatonin is safe, especially when used in the prolonged-release form. It mimics the body’s own nighttime pattern, which may be more effective and natural than traditional sleeping pills.

As we learn more about how sleep affects our overall health, melatonin could become an important tool, not just for fixing sleep problems, but for protecting the brain and heart as we age.

The science behind melatonin is clearer than ever. This study shows that melatonin, especially in prolonged-release form, helps regulate sleep, align our internal clock, and support both brain and heart health. It’s safe, well-tolerated, and particularly helpful for older adults, children with autism, and people with circadian rhythm disorders.

As the link between poor sleep and diseases like Alzheimer’s and high blood pressure grows stronger, using melatonin to restore healthy sleep rhythms may become a key part of future healthcare. If improving sleep can help prevent or slow down these diseases, melatonin may be one of the most promising, natural tools we have to age well, both in body and mind.