Anti-Oxidation and Mitochondrial Damage 2 of 2

doc_ahof_group4_cropped_small_145By Duane Graveline MD, MPH

Statins and Mitochondrial Damage Part 10 of 11

Melatonin is sometimes called the suicide antioxidant because once reduced it cannot be recycled.  Once oxidized, melatonin cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals.  It is a powerful antioxidant that ordinarily is reliably synthesized in sufficient amounts by the body.

Only in 1993 was the importance of melatonin established as a powerful antioxidant.  In addition, it has a long established role in the functioning of our biologic clock of day/night cycling.  Melatonin  crosses the blood-brain barrier giving it free access to our brains. Melatonin is a direct scavenger of nitric oxide, the hydroxyl radical and the oxygen ion.

Since the first metabolite of melatonin in the melatonin antioxidant pathway appears to be AFMK (acetyl-formyl-methoxy- kynuramine) it has unusually potent antioxidant effects, leading to a biochemical process known as the free radical scavenging cascade.  This capacity is limited only to melatonin, marking it as an unusually capable antioxidant.

For the past 75 years when someone ordered or consumed vitamin E, they were using the tocopheral form.  In the past decade the other form of vitamin E, the tocotreinol form with antioxidation effectiveness some 50 times greater than tocopherol, has been identified and developed. 

The Annatto source, a South American plant, yields almost pure tocotreinol and in addition to its antioxidation role, appears to have other very interesting metabolic actions.  Like tocopherol its action is primarily that of inhibiting lipid peroxidation but the full scope of activity regarding reactive oxygen species neutralization remains to be determined.

The enzyme superoxide dismutase (SOD) converts the oxidant, superoxide, into hydrogen peroxide, which is further converted to water. The various catalases and peroxidases involved in converting superoxide have complex interactions, difficult to separate. Our cells are well supplied with SOD enzymes most of which are combined with metallic co-factors. Manganese SOD is the combination most often present in our mitochondria.

The observation that our body is heavily supplied with a complex system of potentially interacting anti-oxidants documents the adverse effect of oxidation in our body. Yet numerous studies have been done by supplementing with vitamin C or E or both and failing to show a consistent effect.

For every study done documenting a positive contribution another will appear in the literature refuting the results.  Obviously, antioxidants are critical to health and even life, yet we seem unable at this point to prove it, at least for these two antioxidants.  We need to know much more about the various actions and interactions of the antioxidants.

The importance of our innate antioxidant system in serving to minimize the production of reactive oxygen species is well established.  Because a substance is an antioxidant, even a powerful antioxidant such as vitamin C or tocotreinol, does not necessarily mean that substance is vital to our mitochondria's antioxidant requirements.
Those antioxidants that are vital are the ones that our biochemists have thoroughly documented to be intimately involved in the chemistry underlying mitochondrial maintenance.  No one can challenge the effectiveness of superoxide dismutases or glutathione and the necessity of their metallic co-factors. 

The  enzyme superoxide dismutase converts the oxidant, superoxide, into hydrogen peroxide, which is further converted to water.  Our mitochondria are well supplied with SOD enzymes and their manganese cofactor.  Glutathiones in the firm of glutathione peroxidases with their selenium co-factors, have a major role in hydrogen peroxide breakdown. 

Additionally, melatonin appears to be very important, especially with its unique ability to trigger our "free radical scavenging cascade" and can anyone dispute CoQ10's critical role, especially with its placement in our mitochondria's complex one and two?

What of vitamin C and vitamin E?  A number of large scale studies have failed to show significant benefit of these common anti-oxidant vitamins prompting the question, "Does the established antioxidant chemical effect of a substance such as these vitamins automatically establish them as legitimate and vital members of our mitochondrial antioxidant complex?" 

Other vital anti-oxidant roles within the human body, such as scurvy prevention and treatment with vitamin C, and a general antioxidant role for vitamin E - yes, but my question as to protectant role for our mitochondria remains as yet unanswered.  I am completely convinced, however, of the vital roles of superoxide dismutase, glutathione peroxidases, CoQ10 and melatonin in mitochondrial maintenance.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Updated September 2013

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