Spring 1995 Mission

The brain's disease-buster substance

As far back as 300 B.C., the Greek physicians Herophilus and Erasistratus thought they understood the pineal gland, a part of the brain that resembles a pea-sized pine cone. They said it was the valve that controlled the flow of memory.

By the 17th century, French scientist Rene Descartes had a new explanation. He concluded that the pineal gland was the seat of man's very soul.

None of the ancients knew that the pineal gland produces a hormone called melatonin. Melatonin was only discovered in 1958.

Russel J. Reiter, PhD, professor of cellular and structural biology, has devoted nearly 30 years to pineal research and has become one of the foremost authorities on melatonin. In 1993, his group published what he describes as his most exciting findings.

Melatonin, Dr. Reiter said, is a potent anti-oxidant. Anti-oxidants neutralize "free radicals," renegade molecules implicated in cancer and diseases associated with aging such as Alzheimer's.

What seems most significant is that melatonin levels decline as people age, stripping their defenses against disease. "In short," Dr. Reiter said, "melatonin may control our fate."

Landmark discoveries about melatonin have been coming from Dr. Reiter's laboratory for years. He is credited with earlier findings that helped show how melatonin runs the body's clock for sleep, reproduction and moods. Synthetic melatonin has become a popular diet supplement in health food stores. People take it for insomnia, jet lag and seasonal depression. The U.S. Food and Drug Administration, meanwhile, is examining several prescription applications for melatonin.

Melatonin is named for melanin, or skin pigment, and serotonin, a neurotransmitter found abundantly in the pineal gland. It was discovered by a Yale dermatologist who found that the extract from cow pineal glands lightened the skin of frogs. Melatonin later was identified as a hormone.

Starting in 1992, Dr. Reiter's group produced evidence that melatonin neutralizes the body's most toxic free radical, the hydroxyl radical. He found that melatonin was five times more effective than glutathione, a well-known anti-oxidant.

In another experiment, Dr. Reiter and associates in radiation oncology found that melatonin reduced free-radical damage associated with ionizing radiation such as that from an X-ray. Using groups of human white blood cells, they left one group untreated, then treated a second group with melatonin and a third group with DMSO, dimethyl sulfoxide, a known protectant against radiation damage. Both melatonin and DMSO reduced damage by 70 percent, but DMSO had to be used in a dosage 500 times greater than melatonin, he said.

In a third and most compelling experiment, Dr. Reiter gave a cancer-causing agent called safrole to two sets of laboratory rats. One set of rats also received melatonin; the other did not. Rats with melatonin had 41 to 99 percent less damage to their DNA than those without melatonin. There was lesser damage with higher melatonin doses. Free radicals are known to damage DNA.

Melatonin dictates body cycles and its production is cyclical. The pineal produces melatonin only at night, when blood levels of the substance are 10 to 15 times higher than during the day. This helps explain why people become drowsy at night. It also helps explain why shift work and long-distance air travel disrupt body rhythms. Dr. Reiter himself takes 1 milligram of melatonin at night as a sleep aid.

A second cycle is associated with melatonin. Dr. Reiter said the length of nightfall affects melatonin production and thus behavior in general. For example, he said, long summer days contribute to a primitive instinct to reproduce. Shorter days, such as those in winter, may affect moods and contribute to a form of depression called Seasonal Affective Disorder.

A third cycle makes Dr. Reiter think melatonin is the key to understanding aging.

"As we age, our melatonin rhythm becomes attenuated. Your nighttime peak for melatonin production becomes lower and lower, which may explain why you age faster as you get older. The likelihood of getting a degenerative disease such as Parkinson's or Alzheimer's increases exponentially as you age. Now we think that may in part relate to the loss of the very strong protectant agent in melatonin," said Dr. Reiter, who said additional research will help resolve these important issues.

"The reduction in melatonin output as we age speeds up our rendezvous with death by decreasing our best protection against aging and the oxidants implicated in diseases associated with aging," Dr. Reiter said.

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