Melatonin is a hormone produced by the brain in response to darkness, playing a key role in regulating circadian rhythms and sleep patterns. Its production and release are closely tied to the time of day, increasing in the dark and decreasing in light, and tend to decline with age. Melatonin supplements, commonly used for sleep disorders like insomnia and jet lag, are usually manufactured in laboratories.

Historical and Evolutionary Perspective

• Melatonin is an ancient molecule, dating back to the origin of life, initially functioning as a free radical scavenger in bacteria.
• Its evolution is linked to the endosymbiotic theory, where ingested bacteria evolved into mitochondria and chloroplasts in eukaryotes, retaining their ability to produce melatonin. Thus, it's found in all living organisms, including bacteria, yeasts, fungi, animals, and plants​​.
• Throughout evolution, melatonin has retained its chemical structure and diversified its functions beyond being an antioxidant, including regulating sleep and circadian rhythms, enhancing immunity, and acting as a multifunctional oncostatic agent in animals. In plants, it plays roles in growth, stress resistance, and seed germination​​.

Synthesis and Regulation

• Melatonin synthesis begins with the amino acid tryptophan. In animals, tryptophan converts to serotonin, which then forms melatonin. In plants, tryptophan first converts to tryptamine, then to serotonin, and finally to melatonin​​.
• The molecule's synthesis is regulated by various factors, including stress, where transcription factors like activator protein-1 up-regulate melatonin synthesis genes under stress conditions​​.

Medical Uses and Research

• Research indicates melatonin's effectiveness in treating circadian rhythm sleep disorders, delayed sleep phase disorder, insomnia, jet lag, and shift work disorder. It also shows potential in managing sleep disorders in children with certain conditions like ADHD or autism spectrum disorder​​​​​​.
• Additionally, melatonin might reduce evening confusion and restlessness in people with Alzheimer's disease, though it doesn’t seem to improve cognition​​.
• Studies are exploring its potential benefits in reducing anxiety before surgery, but its efficacy in post-surgery anxiety and in cancer symptoms is still unclear​​.
• Current research on melatonin's effects on COVID-19 is in early stages, with no conclusive results yet​​.

Safety and Side Effects

• Generally, melatonin is considered safe for short-term use, but long-term safety is not well-established. Common side effects include headache, dizziness, nausea, and drowsiness. There are also concerns about its interaction with various medications, particularly in people with epilepsy or those on blood thinners​​​​​​.
• Special caution is advised for pregnant or breastfeeding women, older people (especially those with dementia), and children due to limited research on its long-term effects and safety in these groups​​​​​​​​.

Regulation and Quality Concerns

• In the United States, melatonin is regulated as a dietary supplement, meaning it's subject to less strict regulation by the FDA compared to prescription or over-the-counter drugs. This can lead to inconsistencies in product quality, as some supplements may not contain the listed amounts of melatonin or may have contaminants like serotonin​​.

In conclusion, melatonin, a vital hormone for regulating sleep and circadian rhythms, has an ancient evolutionary history and a wide range of biological functions. While beneficial for certain sleep-related conditions and possibly other health issues, its use should be approached with caution, particularly regarding dosage, long-term effects, and potential interactions with other medications.