Is Melatonin Killing Our Hearts?
Observation is not causation
This is fresh from the American Heart Association meeting In New Orleans and making waves on the internet, so I decided to provide clarity for our community in a quick post.
In a research abstract at the meeting, investigators reported that an OBSERVATION derived from hundreds of medical records that habitual use of melatonin for insomnia (defined as use for at least a year) significantly increases the risk of heart failure including hospitalization and death.
Since there is no publication, just a poster presentation, it is impossible to know all the biases, strengths and weaknesses of the study but some are glaring.
Key Findings
In a large study looking at medical records, those who used melatonin for at least a year were almost twice (2x) as likely to have new onset heart failure diagnosis over the 5 years, and 3.5 times more likely to have heart failure hospitalization.
Study is observational, not cause and effect. Patients did not have history of heart failure.
Significant study limitations include underreporting by patients, inaccuracies int he EHR data, and the use of melatonin as over the counter supplement except for the UK.
Limiting data to the UK and looking at prescriptions data, the risk was still significant at 82%.
Is it really melatonin or the insomnia itself? Cases and controls were matched but it is unclear if they were matched for the degree of insomnia or inflammation.
Insomnia, and associated circadian sleep disruption impact multiple health domains.
Insomnia is an inflammation multiplier, and inflammation is at the core of heart failure, atrial fibrillation and CAD.
Taking Melatonin? Lets figure out why you need it, and what actually is happening with your circadian rhythm, sleep and stress.
Here is the study design and the findings with my comments in italics.
Is This A Signal or A Red Herring? See Problems.
The study data was from TriNetX, established in 2013, a growing global network of real-world, de-identified patient data available for research. The study included 130,828 adults (average age of 55.7 years; 61.4% women) diagnosed with insomnia.
65,414 participants had been prescribed melatonin at least once and reported taking it for at least a year. Problem: attribution bias. Patients often underreport supplement use, and we all know that medical records are often erroneous, mentioning same medications or supplements even if a patient stopped those.
A second group of people were examined for comparison (control group) — those who had never been prescribed melatonin and were matched to the group taking melatonin on 40 factors including demographic information, health conditions and medications. Same problem as above: reliance on patient reporting and EHR data is open to inaccuracies as patients often do not consider over the counter supplements important enough to report. Also, in many countries melatonin is over the counter and would not be dispensed by prescription.
The main analysis found:
Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) had about a 90% higher chance of incident heart failure over 5 years compared with matched non-users (4.6% vs. 2.7%, respectively). Problem: is this melatonin or the insomnia itself? It is entirely possible, even likely that chronic use of melatonin was for severe insomnia which leads to multiple metabolic disturbances and is an inflammation amplifier. It is unknown if these patients were evaluated for sleep apnea, a condition commonly associated with incident heart failure. So the study is akin to seeing ambulances at the scene of an accident and concluding that ambulances cause accidents.
There was a similar result (82% higher) when researchers analyzed people who had at least 2 melatonin prescriptions filled at least 90 days apart. (Melatonin is only available by prescription in the United Kingdom.) This is better, but having one region substantially lowers the strengths of these findings. While it is by RX in the UK, patients can still get it over the counter including the internet.
A secondary analysis found:
Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure when compared to those not taking melatonin (19.0% vs. 6.6%, respectively). Problem: again, is it melatonin or the inflammation due to severe insomnia resulting in chronic use?
Participants in the melatonin group were nearly twice as likely to die from any cause than those in the non-melatonin group (7.8% vs. 4.3%, respectively) over the 5-year period. Now we really have a problem but again, it is not clear if this was melatonin or the insomnia itself. Likely the latter.
What Should You Do if You Are Taking Melatonin
Speak to a trained integrative or functional medicine physician and engage in collaborative conversation.
Find the root causes of your sleep disturbance such as sleep apnea: get home-based sleep study! I am testing a home-based device from Empower Sleep, and will report on it later.
Address inflammation, oxidative stress, hormonal imbalances, environmental exposures, sleep apnea, excess weight.
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