Natural Medicines Newsletter

Volume 1, Issue 24, 07/02/2009

Question

What is the mechanism by which melatonin supplementation works as an antioxidant and prevents free radical damage?

Answer

Melatonin is a neurohormone that is produced by the pineal gland in the brain and normally is derived through a series of steps from the metabolism of tryptophan, but is also available as an oral supplement over-the-counter (see figure 1).(1-3)  It is recognized for its use primarily as a sleep aid.(4)  However, it is also known to be a potent antioxidant and prevent free radical damage of tissue in the brain.(5)  This is the basis for why melatonin has also been used to prevent or treat antipsychotic induced oxidative neurotoxicity or tardive dyskinesia as well as other neurodegenerative diseases.(6-11)  Regardless of its indication, it is clear that melatonin is an antioxidant that can prevent the damage associated with free radical formation to the DNA, proteins, lipid membranes and even mitochondrial physiology.  What are free radicals and why are they so damaging?

Simply stated, during the partial reduction of oxygen the formation of reactive oxygen species can occur and if they end up having an unpaired electron they are called oxygen free radicals (such as superoxide anion radical and hydroxyl radical).  Free radicals are unstable due to their unpaired electron.  Thus, they will find another electron by taking it from normal surrounding cellular structures such as DNA, proteins, and/or lipid membranes.  If free radicals act too much, they will damage the cell and its function eventually resulting in its death.  This process can also take place where oxygen utilization is high, such as in the electron transport chain within mitochondria and result in the activation of apoptotic pathways.  How does melatonin inactivate free radicals and protect mitochondrial physiology? 

A number of mechanisms are known to take place with melatonin therapy (see figure 1).  As it relates to the direct antioxidant effects, melatonin is known to....

There is a figure with this newsletter that shows where melatonin works to protect cells from free radical damage.

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