News on The Use of Melatonin: It Preps Your Metabolism and Circadian Rhythm


News on The Use of Melatonin: It Preps Your Metabolism and Circadian Rhythm

Sixty years after melatonin was isolated and with more than 23,000 published studies showing the many functions of this hormone secreted by the pineal gland, it’s time for us to talk about the safest guidelines for us.

In an article published in the journal Endocrine Reviews, Dec 2018, Cipolla Neto, the principal investigator for a project supported by São Paulo Research Foundation — FAPESP on the role of melatonin in energy metabolism regulation. According to the research team, melatonin not only adapts us to rest at night but also prepares us metabolically for the next day, when it will need to be sufficiently sensitive to absorb food.  

“If the nocturnal production of melatonin is blocked by light during the night, especially by the blue light from smartphones, this can contribute to diseases, such as sleep disorders and hypertension, and metabolic disturbances, including obesity and diabetes. This potentially pathogenic situation is due not only to insufficient melatonin production but also to one of its more immediate consequences, which is a condition known as chronodisruption, a temporal disorganization of the circadian rhythm of biological functions.

The use of melatonin has been studied greatly over time. For example, between 1996 and July 2017, over 195 systematic reviews were published on the effects of the clinical use of melatonin, among which 96 addressed the use of melatonin to treat psychiatric diseases and neurological disturbances, including sleep disorders, while 43 focused on the association between melatonin and cancer.

Patent applications relating to therapeutic uses of melatonin and analogs filed worldwide between 2012 and September 2014 focused predominantly on the central nervous system — including sleep disorders, the disruption of the circadian cycle and neuroprotection — as well as cancer and immunological issues.

New Benefits of Melatonin

  • Melatonin — which derives from tryptophan, an essential amino acid found in proteins — is highly efficient at eliminating free radicals and has remarkable antioxidant properties. It interacts directly with free radicals and stimulates antioxidant enzymes in different tissues.
  • In recent years, researchers have discovered that owing to its special properties, it is an exceptionally important molecule that acts through several mechanisms at almost all physiological levels, including components of the cardiovascular, reproductive, immune, respiratory and endocrine systems as well as energy metabolism.
  • Melatonin synchronizes our temporal order, meaning a property relating to time. chronological sequence and chronological succession,  both daily and on the seasonal time scale. Its effects depend not just on the route of administration and concentration but also on the time of administration, among other factors.

Individual Dosing

  • Onset of melatonin production vary from person to person. Early birds (people who wake early) start their daily melatonin production before night owls (people who stay up late), and people who sleep for longer periods of time produce melatonin over a longer time than those who sleep for shorter periods.
  • A given dose of melatonin may result in different plasma levels in different patients owing to individual differences in absorbing, distributing, metabolizing and eliminating melatonin. These differences are associated with age, clinical condition, the existence of pathologies, and the functional integrity of physiological systems such as the gastrointestinal tract, liver and kidneys. A proper chronic melatonin hormonal replacement therapy is only achieved when dosage and formulation are carefully chosen and individually tailored and controlled to accomplish the desired clinical effect.
  • A more practical approach is to take the time at which the patient usually goes to sleep at night as a reference for the timing of melatonin administration. An oral lozenge formula like Clear ZZZ’s should be taken 45 to 60 minutes before bedtime to be bioavailable. Also, given that melatonin is a powerful timer of the organism’s physiology, it should be taken strictly at the same time every day. I explain to patients that feeling groggy in the morning means you have taken the melatonin at too high of a dose or too late.
  • Dose is another key point to be discussed. There is no consensus in the literature on this matter. On average, plasma levels in young people who take 0.1-0.3 milligrams will reach 100-200 picograms per milliliter (pg/ml), equivalent to the expected normal physiological range, while 1 gram will probably result in plasma levels of 500-600 pg/ml, which is much higher than the physiological range. I usually recommend 1 to 3 lozenges of theClear zzz’s, professional strength, pharmaceutical grade melatonin.


José Cipolla-Neto, Fernanda Gaspar do Amaral. MELATONIN AS A HORMONE: NEW PHYSIOLOGICAL AND CLINICAL INSIGHTSEndocrine Reviews, 2018; DOI: 10.1210/er.2018-00084

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