Melatonin in Humans

By Dr Ananya Mandal, MD

Melatonin is purported to play a myriad of roles in humans. The most important of these is maintaining the sleep-wake cycle or the circadian rhythm. The roles of melatonin in humans can be summarized as:

Melatonin in circadian rhythm and sleep

Melatonin is secreted by the pineal gland within the brain. Although melatonin produces a signal that regulates the sleep-wake cycle by causing drowsiness and lowering the body temperature, the actual sleep is regulated by the central nervous system. The suprachiasmatic nuclei, or SCN actually controls the daily cycle rather than melatonin alone.

Melatonin and response to light and dark cycles however is vital for sleep. For example, after birth it takes around three months for the melatonin levels to become normal. In infants of three months, the peak levels are recorded between midnight and 08:00 (8 AM). The sleep cycle regularizes in an infant beyond this age. As children become adolescents melatonin release is delayed, leading to later sleeping and waking times similar to adults.

The secretion of melatonin is inhibited by light. For this reason, melatonin has been called "the hormone of darkness." Every evening the secretion begins to rise till it reaches its peak before bed time. Its onset each evening is called the Dim-Light Melatonin Onset (DLMO). It is principally blue light, around 460 to 480nm, that suppresses melatonin, increasingly with increased light intensity and length of exposure. 

Melatonin as an antioxidant

Melatonin has been found to have free radical scavenging actions that makes it an endogenous antioxidant. The discovery of melatonin as an antioxidant was made in 1993. 

Melatonin can easily cross cell membranes and the blood-brain barrier. It acts as a direct scavenger of OH, O2−, and NO. Unlike other antioxidants, melatonin does not undergo redox cycling. This means it does not undergo reduction and oxidation repeatedly and is not available for reuse.

In addition, those like Vitamin C that undergo redox cycling may also become pro-oxidants. Melatonin once oxidized, cannot be reduced to its former state. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.

Melatonin protects against various oxidative injuries including brain injury caused by ROS (Reactive oxygen species) release in experimental hypoxic brain damage. As an antioxidant, melatonin may also help in brain disorders like Parkinson’s disease, heart diseases like arrhythmias etc.

It is possible that the antioxidant effects of melatonin help it act against cancer. Melatonin may be useful against breast cancer, non-small-cell lung cancer, metastatic renal cell carcinoma or kidney cancer, hepatocellular carcinoma (liver cancer), and brain metastases from solid tumors (spread of primary cancers to the brain).

Melatonin on the immune system

Melatonin interacts with the immune system. The effects may be mediated by the high affinity melatonin receptors (MT1 and MT2) expressed in immunocompetent cells. Melatonin enhances cytokine formation and may be useful fighting infectious diseases. Endogenous melatonin in human lymphocytes has been related to interleukin-2 (IL-2) production and to the expression of IL-2 receptor.

Melatonin and disease

Some diseases have been shown to be associated with low levels of melatonin. These include coronary heart disease, multiple sclerosis, epilepsy, and postmenopausal osteoporosis.

Melatonin and aging

Research has supported the anti-aging properties of melatonin. Normally the peak melatonin production occurs at night. As a person ages this peak occurs later. This may explain why older adults go to bed earlier, wake up earlier and may suffer from insomnia more commonly than children.

Melatonin and skin color

Melatonin controls pigmentation changes by aggregation of melanin into the melanocytes within the skin, causing the skin to change color. This interaction is also responsible for the paler skin color of elderly people and those with insomnia.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Sources

  1. http://www.thorne.com/altmedrev/.fulltext/10/4/326.pdf
  2. http://www.sleephealthfoundation.org.au/pdfs/melatonin.pdf
  3. http://www.tocris.com/pdfs/pdf_downloads/melatonin_receptors_review.pdf
  4. http://www.actabp.pl/pdf/1_2007/1.pdf
  5. http://www.alsearsmd.com/pdf/melatonin.pdf
  6. http://www.emfields.org/news/downloads/melatonin.pdf
  7. https://www.medcertinc.com/Download/What%20is%20Melatonin.pdf
  8. http://www.tga.gov.au/pdf/auspar/auspar-circadin.pdf
  9. http://vas.web.arizona.edu/478/melatonin.pdf

Further Reading

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