Melatonin as an Antioxidant: Implications for Aging and Age-Related Diseases

Author of eight scientific books on his melatonin research and now Melatonin: Your Body's Natural Wonder Drug for public consumption, Dr. Reiter has been researching the pineal gland and melatonin for 32 years.

His first message was words of caution to not abuse the use of light because light interferes with our biological rhythms and depresses melatonin levels. The pineal gland, located just about at the anatomical center of the brain, is most active at night. Unknowingly, many of us abuse our environment, like shift workers, who can't avoid light at night. And there is a price to pay for altering your biological clock.

The Pineal Gland

The pineal gland is, in most people, about the size of a pea. It is an end organ of the visual system. The production of melatonin is regulated by the eye's perception of light and dark. In non-mammalian vertebrates the pineal gland is the so-called "third eye." In birds and reptiles, fish and amphibians, it is directly photosensitive, organized like a retina. But in humans it is the eyes that do the light perception and the information is transferred to the pineal gland over a series of neurons.

The Melatonin Rhythm

Describing the melatonin rhythm, he noted that a person's melatonin would be low at, say, 11:00 in the morning. With the onset of darkness, the melatonin levels increase, although with variations from individual to individual. Individuals tend to remain in patterns so that a person who does not produce much melatonin at flight will tend to remain in that pattern and produce less melatonin over a lifetime. The pattern is genetically determined. It appears thin people who produce more are generally in a better position than those who do not.

Melatonin, once released into the blood, goes where R wants to go. It is measurable in al1 body fluids. It goes into every part of every cell in the body. This is very important once we consider the antioxidant value of melatonin.

Circadian Rhythms

All organs function differently day from night. These are our circadian rhythms. Over eons of time when the sun was up it was light; when it went down it was dark. These were no exceptions. By creating artificial sources of light to be used at night, we have altered our circadian-rhythms. Simply, light at night is bad. The liver, for example, does not have eyes so its night/day function is regulated by melatonin. If you get up in the melatonin production -- your liver basically gets the message, "It has to be day." It can't make any other interpretation and so it responds by changing its function. We evoked from specks that had no access to artificial light. Dr. Reiter cautioned you will have a price to pay if, once you go to bed and turn out the lights, you turn on a bright light again.

If you want to improve your sleep and reestablish your circadian rhythm, stay in the dark once you turn out the lights.

We also abuse our melatonin cycle with light in the evening and morning. In this day and age most of us are not exposed to darkness other than when we sleep. And as melatonin production is initiated not by sleep but by darkness, we are curtailing our production of it by extending light beyond natural daylight hours.

Traveling Across Time Zones

Dr. Reiter described how travel across time zones affects melatonin production. He noted that migrating species like birds travel wast distances, but only noah and south, not east and west across time zones. Our tendency to do things in a rhythm is demonstrated by the fact that biological events tend to be more or less common at specific times of day. An extreme is that heart attacks occur most often between 8:00 and 10:00 a.m. But normal body functions operate on a 24-hour cycle.

He cautioned that many pharmaceuticals impair our ability to produce melatonin. Propranonal calcium channel blockers, benzodiazapine and many anti-depressants and caffeine especially, as well as aspirin and ibuprofen, obstruct somewhat your ability to produce melatonin. We were meant to have our melatonin and we abuse it on a regular basis.

Supplementing with Melatonin

If you take melatonin -- and Dr. Reiter points out he is a researcher and did not come to speak as an advocate of melatonin supplemendations:

- Consult you heath care practitioner.

- Don't take melatonin indiscriminately. It's fashionable right now, which is not a good reason to take a supplement.

- Take it at night.

- Maintain a regular sleep cycle and adhere to your customary bedtime.

- If you take melatonin, take it every night at the same time.

- Take it in small amounts, generally one milligram or less.

Melatonin has been widely tested as a sleep aid. Clinical studies have shown it to be an effective aid both in getting to sleep initially and enjoying more adequate sleep. It is widely used for jet lag as it helps reestablish biological rhythms. Melatonin has many other possible applications. For example, it is also a powerful antioxidant. In the Netherlands, melatonin is being studied as a contraceptive in high doses of 75 mg in combination with progesterone. It is also an anti-epileptic. There is also research supporting melatonin for its anti-carcinogenic effects.

Melatonin serves as a powerful antioxidant. The free radicals thin are primarily derived from the oxygen you breathe are very damaging to your cells. You accumulate free radical damage over a lifetime, and the rate at which you accumulate this damage may determine your longevity and the development of age-related diseases. So protection from free radical damage may enable you to live longer.

As you age, the accumulation of free radicals from, say, environmental toxins, smoking, etc., overwhelms your defenses to protect against them. Melatonin is a very good neutralizer for free radicals, as is vitamin C and the other antioxidants. But melatonin has some unique advantages over the others. Vitamin E, although a terrific antioxidant, is limited because it only gets into the lipid rich parts of cells. Melatonin however, goes wherever melatonin wants to go. Vitamin C, like E, is limited as to where in the call it can go, namely, in an aqueous portion of the cell. andoxidants are segregated within the cell, except for melatonin. Melatonin also positively interacts with the other andoxidants to increase their efficiency, so it potentates the Vitamin E or C, when taken in combination. It is measurable in every body fluid.

If you were to take melatonin as an andoxidant, the same rules apply as for Rs use as a sleeping aid: take R in the evening. Dosages have not yet been worked out, but a starting place would be 250 mcg and up.

Dr. Reiter gave examples of when we are producing free radicals. During vigorous exercise you produce a lot of free radicals because you are breathing a lot of oxygen. And when you exercise excessively, you use lots more oxygen and generate more free radicals. So sustained mild exercise may be much better than intense workouts -- the issue is still being debated.

Over a lifetime, we experience a lot of diseases. As we age we become more debilitated with such problems as retinal degeneration, Alzheimer's Parkinsonism, cancel etc. What these diseases have in common is free radical damage. That is why there is so much interest in andoxidants. Clinical studies on melatonin are showing benefit in the prevention of these free radical mediated processes.

Possible Contraindications

Some people should not take melatonin. People with very severe allergies may not be good candidates for using melatonin. And while there is not be harmful to the severely allergic, Dr. Reiter recommended being conservative. "When in doubt, take the conservative approach." It is theorized that those with auto-immune disease and with immune system cancers like lymphoma should not take melatonin. Melatonin stimulates immune function and may exacerbate these conditions. On the other hand, a recent study published in the British medical journal Lancet shows melatonin to be very effective in the treatment of sarcoidosis, an autoimmune disease. Nevertheless, as a scientist and researcher, Dr. Reiter remains very conservative in his recommendations about who should or should not use melatonin. Similarly, although there are clinical studies suporting the use of melatonin in children's conditions, he does not yet recommendits use by children. There is one published study that indicates melatonin may not be appropriate for people on steroids. Neither does he racommend that pregnant and lactating women use melatonin. And people with severe mental illness are not recommended to take it. He noted, however, that people who are depressed have been shown to be producing less than normal amounts of melatonin.

Regarding toxicity, no LD 50 (lethal dose in 50% of animals tested) has been established. All drugs, including aspirin, have LD 50s. It has been bund thin you cannot give enough to an animal or human to make them sick. Even if you took a solid cup of melatonin, there would be no known adverse effects. He noted people have taken as much as a gram daily with no adverse effects noted. No toxicity in animals has been described.

Melatonin is already present in all humans so any drags being developed are automatically tested in the presence of melatonin. He noted, however, that there has been little in the way of controlled studies on interactions.

Forms of Melatonin

Melatonin is available in many forms: oral quick and slow release, capsules and liquid time release tablets. It comes in sublingual caa be patches and nasal spray. All of them should be taken at night. And different delivery systems create different patterns of blood levels of melatonin. Remaining in his role as conservative scientist, however, he noted that it is best to preserve your own melatonin rhythm by avoiding light at night.

Your melatonin level wanes as you age, which he feels is very important to age-related disease involving to free radicals and disturbances of your biological clock. We know the elderly sleep much less efficiently, perhaps a reset of reduced melatonin levels. Them is also a possibility that those who, over time, produce less than optimal amounts of melatonin are more prone to the free radical disease like cancer, Alzheimer's and Parkinsonism. It is highly individual. Many octogenarians who are in good heath show a higher measure of melatonin than those who are frai1. This, of course, proves no causal relationship; R is simply his observation.

Ancient Presence of Melatonin

Demonstrating the ancient presence of melatonin, Dr. Reiter noted the melatonin rhythm of a single celled organism, algae. It appears that every organism between algae and human found having a melatonin rhythm to be advantageous. So melatonin has been with us since roughly 2.5 billion years ago. He believes the early organisms developed this for the express purpose of neutralizing oxygen-based free radicals. Prior to this, oxygen was not used by organisms on earth. Around twos time, oxygen in the environment increased to 20% and the organisms had to protect themselves against the free radicals. So melatonin evolved in a rhythm to give clock information and to scavenge. This has been in place for 2.5 billion years. That is unusual in nature. A molecule will normally evolve and change its structure somewhat. But melatonin in single-celled algae is 100% identical to the melatonin in us. It has never changed.

Melatonin is also found in some plants. No plants have been identified that provide melatonin in signifixant amounts.

FAIM.

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By Russel J. Reiter

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