Melatonin: Correcting Circadian Rhythm

When most people hear the term ‘circadian rhythm,’ they think about sleep cycles. Humans that operate on a diurnal pattern and need sleep for brain development, physical and mental health, and cognitive function maintenance. After a good night's sleep, most people wake with a sense of well-being and the ability to work and play. After a bad night’s sleep, the world can look unnecessarily grim.

The British Journal of Pharmacology has published a review article that deals with circadian rhythm and specifically with melatonin's role in metabolism and health. The authors cover the physiology of diurnal rhythm thoroughly and discuss melatonin's emerging roles in diseases of aging.

The researchers began with a discussion of melatonin's use for circadian rhythm and sleep disorders. They discussed non 24-hour sleep-wake disorders and the FDA’s recent approval of tasimelteon, a melatonin receptor agonist.

They also discussed delayed sleep phase syndrome and advanced sleep phase syndrome, conditions in which circadian rhythm of sleep and wakefulness is out of sync. Compelling evidence indicates that melatonin can advance sleep onset and wake times, a process called phase shifting, the authors noted. Many people use melatonin to deal with phase shifting problems like jet lag.

Next, the researchers discussed insomnia in adults, which is very common. Melatonin production often decreases or shifts with age. Poor sleep quality has been associated with cardiovascular, metabolic, and cognitive disease, and melatonin replacement therapy may be helpful. It has advantages over the benzodiazepines and non-benzodiazepine hypnotics because it preserves psychological sleep structure and architecture. Supplementation with melatonin seems to help patients to fall asleep, although it does not appear to have any effect on other sleep qualities. They suggested that sustained release formulations may have advantages in terms of helping patients who fall asleep stay asleep.

The researchers also devoted some attention to Alzheimer's disease (AD). Patients who have AD are more than 3 times more likely to have insomnia than others. They noted that early nerve pathological changes in preclinical AD often occur concurrent with decreasing melatonin levels. Currently, research findings about melatonin's use in AD are conflicted.

Of note, melatonin has also been used in patients who have nocturnal hypertension. Blood pressure tends to drop at night, but in patients who have melatonin insufficiency or deficits, blood pressure may remain elevated throughout the night. A few studies have demonstrated that melatonin has significantly lowered blood pressure between 2 AM and 6 AM, averaging 6 mmHg.

Reference

Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. 2018 Jan 10. doi: 10.1111/bph.14116. [Epub ahead of print]