Melatonin and Heart Disease: Is There a Connection and What Does It Mean? 

Recent research presented at the American Heart Association’s Scientific Sessions has everyone in the medical and health fields talking about melatonin and whether it can increase risk of heart failure. 

There’s a lot of nuance to consider when looking at this research, and I’ll start by saying that if you take or have taken melatonin, there’s no need to panic. The study shows an association (not causation), and there are a number of other important limitations and caveats to be aware of. 

But the research does bring up some important considerations about how and why we use melatonin, and the safety of long-term use of these supplements overall. 

Let’s unpack this new research, what it means, and what else we know about melatonin and heart disease, and I’ll also share my own observations and perspective on the use of melatonin as a functional medicine practitioner (and what I recommend for sleep). 

An Overview of Melatonin 

Melatonin is a hormone that is naturally produced primarily by the pineal gland, the endocrine gland found in our brains. It’s primarily involved in regulating the sleep-wake cycle (circadian rhythm), along with other hormones including (most prominently) cortisol. 

A healthy circadian rhythm, which is largely determined by light exposure, involves low levels of melatonin and higher levels of cortisol in the morning to energize us for the day ahead, and higher levels of melatonin at night to prepare us for sleep. 

Melatonin is also available as a supplement. Most melatonin supplements are synthetic and designed to be chemically identical to the natural hormone. They’re most commonly used for those who are experiencing difficulty sleeping. 

Those who struggle to fall or stay asleep may have disrupted circadian rhythms, which can occur as a result of insufficient sunlight in the morning, the use of bright lights or screens and blue light at night, chronic stress, and other factors. Supplemental melatonin is used in these cases to mimic the natural effects of the hormone and promote sleep. 

In some countries, melatonin is only available with a prescription. But in many countries, including the US, it’s widely available over-the-counter and is a very popular sleep aid. 

Melatonin is generally considered safe for short-term use and can be helpful in specific situations, like to help reset your rhythm when traveling to a different time zone. But there are a lot of questions around longer term use, which we’ll explore below, and it’s not FDA-approved for chronic insomnia. 

The New Research on Melatonin and Heart Disease 

Let’s talk about the study that’s making headlines. This research was presented at the American Heart Association’s 2025 Scientific Sessions, and hasn’t yet been published in a peer-reviewed journal. (1) 

The study was a retrospective analysis, meaning that researchers analyzed data that had already been collected (in this case, 5 years worth of electronic health records).  They looked at the records of more than 130,000 adults with chronic insomnia, some of whom were taking melatonin and some of whom were not.

The researchers found that those who were using melatonin for at least 12 months had around a 90% higher risk of developing heart failure over 5 years compared to non-users. They were nearly 3.5 times more likely to be hospitalized for heart failure, and almost twice as likely to die from any cause. 

In order to minimize bias, participants in the melatonin and non-melatonin group were matched according to 40 different factors (including age, sex, and comorbidities). Individuals with a history of heart failure, as well as those who were taking other sleep medications, were excluded. 

Breaking Down the Nuances and Limitations of the Study 

The findings of this study are very compelling, and should definitely make anyone think twice about long-term melatonin use. However, there are also a lot of things we don’t know, and some limitations of the study to be aware of. Here are some of the important nuances to understand. 

• Retrospective studies by nature can’t demonstrate causation. This study tells us that there’s an association between long-term melatonin use and heart failure, but it can’t tell us whether or not melatonin actually causes heart failure. 
• The data relies on prescriptions and likely misses over-the-counter users. This was a multinational study that included data from participants in countries requiring a prescription for melatonin as well as those that don’t. But researchers were only able to account for prescribed melatonin. This means OTC users in countries like the US may have been counted as “non-users”. 
• Dosage wasn’t documented or analyzed. The study looked at long-term usage of melatonin, but some people may have been taking much larger doses than others, and we don’t know how this might affect the association. 
• Hospitalization codes and records vary. Because documents from many different healthcare facilities in different countries were analyzed, there are inherently going to be differences in record keeping practices and hospitalization codes related to heart failure that may skew some of the results. 
• The abstract lacks full clinical nuance. So far, only a brief summary of the study has been presented. This tells us about the key findings, but we’ll understand more about the details and nuances when the full study is published in a peer-reviewed journal. 
• Melatonin may be a red flag for underlying factors. The severity of insomnia, an underlying condition or imbalance leading to insomnia, or another confounder could explain the findings (in other words, is it the melatonin or is it something else about the group of people taking the melatonin that’s most associated with the increase?). 
• The findings relate specifically to long-term use. I just want to drive this point home for anyone who is panicking over the occasional use of melatonin when traveling or otherwise; we don’t know if these findings are relevant for short-term use.

Ultimately, this is a preliminary study. The results of this study are definitely compelling enough to warrant future research, and that future research is necessary before we can draw any real conclusions. But, it’s certainly time to start paying attention.

Future studies will ideally look more closely at dosage, duration, and other factors, and determine using more controlled study designs whether there is a direct causal relationship. 

What Else Do We Know About the Connection? 

One of the reasons why this study has been so talked about is that past research on melatonin and cardiovascular health has actually suggested potential benefits and protective effects, including antioxidant effects and the reduction of oxidative stress, improvement of medication-induced insomnia for those taking beta-blockers, and protection against hypertrophy of the heart muscle (which would in theory reduce the risk of heart failure). All of these potential benefits also require much more research. (2-4)  

A small 2019 randomized controlled trial also found that 8 weeks of melatonin supplementation improved fatigue, appetite, and quality of life for patients with heart failure and cachexia (wasting syndrome). In this case we’re talking about short-term use for a very specific population, but it’s still notable. (5) 

Taking a step back from melatonin specifically, we do know that sleep difficulties and cardiovascular disease often go hand-in-hand. And while we’ve long known that disrupted sleep can increase the risk of heart disease, a growing body of research suggests that the connection goes both ways and that heart disease can increase the risk of sleep disorders. (2) 

Especially given this connection, there is a concern in light of the new evidence that insomnia could be masking the signs of early heart failure for some people—in these cases, melatonin wouldn’t be directly causing heart failure, but the use of melatonin potentially in place of properly investigating insomnia could make it harder to catch early stage heart failure. 

General Cautions Around Melatonin Supplements

In general, I don’t recommend long term use of melatonin to my functional medicine telehealth patients. I think on the surface melatonin can seem very harmless because we think, “my body makes this naturally anyways”. 

But this is actually a big part of the problem and my concern: melatonin is a hormone that we make naturally. And when we rely on external melatonin, it can confuse the body and disrupt its ability to regulate natural melatonin production, which can have a cascading effect on hormonal balance. 

There’s a balancing act here, because sleep is so essential for our health, and if melatonin helps someone sleep, that’s a good thing on the surface—but especially over the long term, this reliance can cause more harm than good. I always try to find different holistic ways to improve sleep without leaning on melatonin supplements. 

I do think melatonin is helpful for short-term adjustments, like when traveling to a different time zone which disrupts your circadian rhythm; this is a very different use of melatonin supplements and is much more in line with what associations like the American Academy of Sleep Medicine recommend. 

As a number of clinicians and researchers have pointed out following the presentation of this new research, it’s somewhat surprising that so many doctors were prescribing long-term melatonin for insomnia in the first place, as it’s not an indicated treatment for this in most places including the United States and the United Kingdom. 

Boosting Melatonin Naturally 

There are several ways to both encourage natural circadian rhythm regulation and melatonin production, and to support sleep holistically without melatonin supplements. 

Our central circadian rhythm is predominantly influenced by light, and a lot of people notice huge changes when adjusting their light diets. Ideally, you want a good dose of natural, bright light in the morning, and as much darkness as possible at night. 

If you can get outside for a walk in the morning within an hour of waking, this is great. In the evening, power down screens at least a couple of hours before bed if you can. If you do need to use screens in the evening, I highly recommend wearing blue light blocking glasses. Avoid bright and overhead lighting in the evening, and aim for complete darkness in the bedroom when you go to sleep. 

Other practices that can help with sleep include intentionally winding down with meditation, gentle yoga, or a hot bath or sauna before bed; avoiding caffeine for 6-8 hours before bed; and keeping your bedroom cooler at night. A consistent sleep-wake schedule is also ideal for circadian rhythm regulation. In terms of supplements, one of the simplest, most effective, and safest options for sleep support without disrupting hormones is magnesium. 

Of course, if your doctor has recommended melatonin or if you’re currently taking it consistently, speak with your practitioner before making any changes to your protocol. 

A Mindful Approach to Melatonin 

One of the biggest takeaways from this research for me is that clinicians need to be really thoughtful about when, why, and how they’re recommending melatonin. Whether melatonin is itself causing heart failure or whether it’s masking an underlying problem, or there’s something else entirely going on, our work when it comes to insomnia shouldn’t stop at prescribing a synthetic hormone replacement. It’s so important to understand what’s at the root of someone’s sleep challenges, and to support the body in natural circadian rhythm regulation. 

If you’re looking for a holistic and mindful approach to improving your sleep, please consider reaching out to schedule a health consultation. We’d be happy to help you. 

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe. 

Photo: Unsplash.com

Sources

• Nnadi, E., Masara, M., Offor, R., Unal, S., Rebah, R., Atere, M., … & Graham-Hill, S. (2025). Effect of Long-term Melatonin Supplementation on Incidence of Heart Failure in Patients with Insomnia. Circulation, 152(Suppl_3), A4371606-A4371606.
• Covassin, N., & Somers, V. K. (2023). Sleep, melatonin, and cardiovascular disease. The Lancet Neurology, 22(11), 979-981.
• Shechter, A., Lespérance, P., Kin, N. N. Y., & Boivin, D. B. (2012). Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder. Sleep medicine, 13(8), 1071-1078.
• Tobeiha, M., Jafari, A., Fadaei, S., Mirazimi, S. M. A., Dashti, F., Amiri, A., … & Mirzaei, H. (2022). Evidence for the benefits of melatonin in cardiovascular disease. Frontiers in cardiovascular medicine, 9, 888319.
• Jafari-Vayghan, H., Moludi, J., Saleh-Ghadimi, S., Enamzadeh, E., Seyed-Mohammadzad, M. H., &
• Alizadeh, M. (2022). Impact of melatonin and branched-chain amino acids cosupplementation on quality of life, fatigue, and nutritional status in cachectic heart failure patients: a randomized controlled trial. American Journal of Lifestyle Medicine, 16(1), 130-140.