|Sleep, Dreams, Youth, and Melatonin|
|Tuesday, 02 October 2007 14:10|
Melatonin is not a vitamin, it is a hormone particularly active in the hypothalamus and pituitary gland, and its major function is to coordinate some of the internal systems of the body, especially brain, immune and reproductive systems, in relation to the light-dark cycles of the day and the changes in length of day and night from season to season in the course of the year.
Melatonin is produced by the pineal gland, a pea-sized gland, shaped like a pinecone, and located smack in the middle of the brain. An active pineal gland contains about 3 mg of melatonin, which is about the average daily dose for sleep effects. Melatonin is also found in the retina of the eye, in the brain and in the intestinal tract. In fact, the intestinal epithelium produces an amount even greater than the pineal gland! The function of intestinal melatonin is unknown but there are indications that it acts as a “tranquilizer” for the intestine, to slow bowel transit and increase the efficiency of absorption of vital nutrients.
Melatonin is made from the essential amino acid, tryptophan, by way of serotonin, and its chemical name is: 5-methoxy-acetyl serotonin. Melatonin synthesis is stimulated by light and its release is provoked by darkness. Light suppresses melatonin[i] and electromagnetic radiation has a similar, though lesser effect.[ii] Geopathic zones’, areas of strong electromagnetic energies, occur at areas of intersecting earth magnetic fields. Even these low level exposures seem to be sufficient to cause illnesses, for chronic fatigue, insomnia, and anxiety are increased there, presumably due to the inhibition of melatonin secretion by geomagnetic fields. There is great interest in the possibility that background electromagnetic fields, as are found in some homes, due to 60 cycle alternating current fields in the wiring, might interfere with melatonin.
Melatonin is enjoying enormous popularity with the American public, who have learned of its benefits for sleep disorders, jet lag and as an anti-aging pill. Some of these benefits have been substantiated in clinical trials with humans. In one study, sleep latency, the time to fall asleep was reduced by 14 minutes and the sleep efficiency, ie. time asleep as percent of time in bed) increased from 75% to 83% in a group of 12 elderly patients with insomnia.[iii] They were given only 2 mg of melatonin two hours before bedtime. Other studies show a decrease in sleep latency in healthy subjects, i.e. normal sleep gets better with and without adverse effects.
Jet lag, due to irregular bedtime or travel beyond three time zones, has been studied after melatonin doses between 5 and 8 mg. The studies confirm the practical value of the hormone in overcoming the fatigue, depression, insomnia and irritability that can otherwise disrupt an otherwise perfect business or holiday trip. In a study of 52 airline crew members, a 5 mg dose of melatonin for 5 days after arrival decreased sleep disturbances and fatigue.[iv] There was less benefit from a similar dose begun three days before and continued for 5 days after and it appears that the strategy of taking melatonin at bedtime upon arrival at one’s destination works best.
An increased life span in rats was reported in 1987 by Dr. Vladimir Dilman at the Institute of Experimental Medicine in Moscow. Melatonin-treated rats lived 25 percent longer and were visibly more youthful in appearance than the matched control rats not treated with melatonin. This led Dr. Walter Pierpaoli, author, with Dr. William Regelson, of the recent book, The Melatonin Miracle, to perform a dramatic experiment in cross-transplantation: old animals received the pineal glands of young animals and vice versa. The results were convincing: the old mice with young pineal transplants lived twice as long as the younger animals with old glands.![v] Dr. Pierpaoli concludes from this that melatonin controls aging.
If so, we might also ask: “what controls melatonin?” Melatonin synthesis is affected not only by age but also by diet. Inadequate protein can curtail synthesis, which begins with the essential amino acid, tryptophan, as a substrate, and which also requires adequate essential amino acid, methionine, to provide the methylating enzyme, SAM (S-adenosyl methionine), which in turn depends on vitamins folic acid, B12, B6 and magnesium, all commonly deficient in the American diet. Vitamin A deficiency has also been proved to cause decreased melatonin in rat studies.[vi] And the amino acid, taurine is known to be the most protective molecule against damage to the pineal gland.
As we get older, especially past age 40, the amount of the hormone usually drops by almost 40 percent.[vii] But the drop in blood levels of melatonin is actually much more dramatic in childhood. Nighttime plasma melatonin averages 250 pg per ml in children age 1 to 3, but drops by 50 percent between 8 and 15 years old and continues to drop to an average of only 20 pg per ml by age 50. The effect of these changes is strongest on the sex system: puberty coincides with a 50 percent drop and menopause coincides with an additional 40 percent drop. Notice the opposite direction of effects: turning on sexual development at puberty; turning it off at menopause.
Melatonin research has been complicated by such contradictions and by technical difficulties. For example it was not until sleep research established 24 hour observation studies that research was set-up to study melatonin levels at night. Daytime levels average 4 - 10 pg per ml for all age groups. But serotonin levels are increased relative to intensity of light exposure. Melatonin synthesis and release are triggered by darkness.
Melatonin levels are also influenced by the fact that the pineal gland has no blood-barrier; thus other molecules, including toxins and viruses, can enter the gland and alter concentrations and conditions there. This may be why calcification, involution and non-function of the gland, is common at early age. Therefore, measurement of melatonin output in a 24-hour urine would be a practical test.
There have been over 4000 scientific papers published on the physiology and effects of melatonin in the past 20 years. The mechanisms of action have not been entirely worked out. Here are some of the actions and interactions.
1. regulates sleep-waking cycles and thus entrains or synchronizes all 3 types of sleep: a) Pituitary-adrenal sleep: melatonin inhibits release of pituitary ACTH, which otherwise would keep the adrenal glands turned on. b) Slow wave sleep: melatonin’s inhibition of the adrenal hormones further rests the cerebral cortex and thalamus, thus permitting hippocampal and cortical nerve cells to synthesize DNA and consolidate memory signals into the structure of the brain cells. c) REM or Rapid Eye-Movement sleep, in which acetylcholine neurons are active, while amines and serotonin are not, thus releasing individual neurons in the PGO (pontine-geniculate-occipital) tracts, which are experienced as dreams.
(Note: the foregoing explanation of REM is hypothetical but based on research observations; my own thinking is contrary, based on the fact of increased dreaming sleep after intake of zinc and B6, which are known to increase brain serotonin, which generates PGO activity. Assuming a shift of serotonin N-acetyltransferase activity for melatonin synthesis, there might be a reciprocal decreased activity of choline acetyltransferase for acetylcholine synthesis, which would manifest as reduced muscle tone, which is characteristic of REM sleep).
2. regulates the circadian stress hormone-immune cycle by inhibiting pituitary secretion of ACTH, the adrenal cortex stimulating hormone; thus putting the pituitary and adrenal cortex at rest, lowering cortisone output, and thus preparing lymphocytes to conquer allergy, infection, and cancer.
3. lowers pituitary ACTH, which also interrupts cholesterol synthesis, lowering cholesterol and LDL, and allowing HDL to remove tissue deposits.
4. regulates synapses in the hippocampal formations: excitable by day, when melatonin is low; resting at night when melatonin is high. This protects hippocampal cells and preserves normal memory function.[viii]
5. regulates sexual development by delaying puberty, which comes on after the adolescent drop in melatonin secretion occurs; regulates menopause by a drop in melatonin in the 5th decade; regulates fecundity by inhibiting libido in the dark months of winter...
6. regulates monthly estrus and fertility cycles, with peak melatonin at menses (which inhibits pituitary gonadotrophins and sex steroids). The low point of melatonin activity is at ovulation, coincident with sex hormone peak.
Melatonin therapy can protect against sex hormone tumor promotion.
7. increases dreaming and enhances sexuality via erotic dreams which occur in REM sleep.[ix]
8. regulates seasonal mood-energy cycles (pro-hibernation) because during longer winter nights the duration of melatonin secretion is greater than in shorter summer nights. Melatonin increases deposits of brown fat, which contains thermogenin, a protein that shunts fat cell chemistry into water and temperature production, which creates warmth at the expense of weight. This offers a promising adjunct for weight loss.
9. blocks the action of melanocyte stimulating hormone, thus causing a lightening of skin color and inhibiting melanoma and other cancer cells.
10. lowers beta-endorphin release, thus controlling these internal opiates, which otherwise stimulate melatonin release; this is an incompletely worked-out feed-back cycle of pain and mood control.[x] Pierpaoli is convinced that there is also a synergism effect, such that melatonin enhances the pain relief and mood elevating effect of endorphins and opiates.
11. entrains TSH, thyroid stimulating hormone, to the circadian rhythm. When thyroid T3 is active, it increases melatonin and thus accounts for the paradox that thyroid supplements often improve sleep.
12. interacts with an unknown circadian factor to regulate stress response; eg. at night-time melatonin enhances antibody response to antigen; in the morning no such effect is seen.[xi]
[i] Lewy AJ, Wehr TA, Goodwin FK et al. Light suppresses melatonin secretion in humans. Science 1980; 210: 1267-1269.
[ii] Cremer-Bartels G, et al. Magnetic field of the eart as additional zeitgeber for endogenous rhythms. Naturwissenschaften, 1984; 71:567-574.
[iii] Garfinkel D et al. Melatonin enhanced sleep in elderly insomniacs. Lancet,1995; 346:541.
[iv] Petrie K et al. Melatonin overcomes jet lag. 1993. Biol Psych 33:526.
[v] Drs. Lesnikov VA Pierpaoli W; Pineal cross-transplantation (old-to-young and vice versa as evidence for an endogenous aging clock. 1994, Ann NY Acad Sci; 719:456-460.
[vi] Herbert D et al. Changes in pineal indoleamine metabolism in vitamin A deficient rats. Life Sciences, 1985; 37:2515-2522.
[vii] Aguchi H, Kato KI, Ibayashi H, Age dependent reductions in serum melatonin concentration in healthy human subjects. 1982, J Clin Endocrinol Metab 55:27-29. Nair NPV, Hariharasubramanian H, et al: Plasma melatonin—an index of brain aging in humans? 1986, Biol Psychiat 21:141-50.
[viii] Sapolsky, R, et al. Prolonged glucocorticoid exposure reduces hippocampal neuron number. Implications for aging. J Neuroscience, 1985; 5(5):1222-1227
[ix] Pierpaoli and Regelson. Melatonin Miracle. Simon and Schuster. NY 1995.
[x] Lissoni P, et al. A clinical study of the relationship between the pineal gland and the opioid system. J Neural Transmission, 1986; 65: 63-73.
[xi] Maestroni GJM, Conti A, Pierpaoli W; Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effects of corticosterone. 1986, J Neuroimmun 13:19-30.
[xii] Hattori A, Migitaka H, Iigo M et al: Identification of melatonin in plants. Biochem Mol Biol Int; 35:627-634. 1995
©2007 Richard A. Kunin, M.D.