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Tuesday, August 11, 2009

Melatonin Update Breaking Research on the Body's Master Hormone

By Linda Fugate, PhD

If the body has a master hormone, melatonin may be it. The pineal gland, located in the brain, produces melatonin on a daily schedule. Most melatonin is secreted at night, less in the daytime. This hormone regulates the sleep-wake cycle, (1) as well as the eating cycle (2) and the production of other hormones. (3) Some plants contain melatonin, including several herbs used in Chinese medicine. (4,5,6) Melatonin is well known as a beneficial agent for jet lag and general sleep disturbances, sometimes called delayed sleep phase syndrome. (1) Older people are especially at risk. Approximately 30 percent of people over the age of 50 exhibit insomnia to a greater or lesser degree. However, doses of melatonin as small as 0.3 mg taken at bedtime improves sleep quality. (16) Melatonin provides numerous benefits for both healthy individuals and patients with specific medical conditions. Melatonin production decreases dramatically and predictably with age (Fig. 1).

Melatonin Use in Serious Diseases
Melatonin has been used in the treatment of serious illnesses such as cancer, conditions requiring surgery, schizophrenia with tardive dyskinesia, and blindness with circadian rhythmic disturbances. In addition, daytime sleepiness caused by nighttime sleep disturbances is the greatest identifiable cause of accidents in all modes of transportation. (8)

ICU Psychosis and Melatonin
Surgical patients commonly have their sleep cycle disrupted. (9) The hospital environment may include 24-hour light, noise, unusual activity, needles, tubes, and other disruptions to the patients normal routine. In severe cases, postoperative sleep-wake cycle disruption may result in delirium, which is associated with increased complications and death. The reported incidence of post-operative delirium or confusion is up to 78 percent. Sleep deprivation may even lead to psychosis. Melatonin prevented these postoperative complications in two patients in a preliminary research study at the Albert Einstein College of Medicine in New York. Further research is expected to show benefits for a significant number of patients. (1)

In another study of the effect of premedication with melatonin prior to anesthesia, patients receiving melatonin were found to have less anxiety, better response to anesthesia, and less impairment of cognitive and psychomotor skills. The melatonin doses were administered 100 minutes before standard surgical anesthesia. The optimum dose of melatonin was found to be 0.05 mg per kilogram of body weight. This treatment made the patients feel better while awaiting surgery, and did not impair their recovery. (11) Many other conditions respond to melatonin treatment as well.

Melatonin Aids Cancer Patients Fighting Cachexia
About half of all cancer patients suffer from cachexia, a condition associated with weight loss, psychological distress, and a lower quality of life. Cachexia includes complicated changes in the bodys normal biochemistry. The appetite is suppressed, and the bodys tissues break down in a process called wasting. The wasting process includes increased cytokine production. Cytokines, such as interleukin-1 (IL1), tumor necrosis factor (TNF), and interferons (IFN) can suppress appetite and disturb normal metabolic activity. Other alterations in interwww.y metabolism, including the release of lipid-mobilizing and proteolysis-inducing factors, speed up the loss of body mass.

Appetite is strongly related to the sleep-wake cycle. I discovered this from personal experience on a trip to Germany. My first meal after the flight occurred at approximately 3:00 am in my hometown. I found it difficult to eat when my body thought it was time to sleep. Cancer patients are subject to surgery, sedating drugs, and other medical intervention, sometimes in the middle of the night. Without a normal sleep pattern, they may never feel that its time to wake up and eat. Melatonin treatment can normalize the eating cycle. Additionally, a recent paper reported that melatonin inhibits tumor-derived catabolic factors that produce the wasting effect (cachexia). (2)

Melatonin and Schizophrenia
Schizophrenics also benefit from melatonin. The drugs used to treat schizophrenia may cause tardive dyskinesia, a disabling movement defect. Up to 50 percent of patients hospitalized with schizophrenia suffer from this problem. Tardive dyskinesia is believed to be caused by increased sensitivity of dopamine receptors, plus neurotoxicity caused by oxidative stress. Melatonin has been shown to effectively alleviate these patients symptoms. Researchers in Israel showed that 10 mg per day of melatonin for 6 weeks significantly improved movement control of tardive dyskinesia patients. They attributed these benefits to melatonins antioxidant effects. Melatonin also tends to normalize dopamine release in schizophrenic patients. (12)

Melatonin Improves Quality of Life for Blind People
The quality of life for totally blind people is also improved by melatonin. Most blind people have free-running circadian rhythms that drift away from the normal 24-hour day. Recurrent insomnia and daytime sleepiness may cause significant problems to blind people who already have a difficult life. Melatonin administration can correct the problem in most totally blind people. In a recent study, seven blind people received 10 mg per day of melatonin, one hour before their preferred bedtime. At the beginning of the study, the circadian rhythms of these subjects ranged from 24.2 to 24.9 hours. After three to nine weeks, six of the seven subjects were sleeping on a 24-hour cycle. The dose of melatonin was then reduced to 0.5 mg per day over a period of three months. Once established, the 24-hour cycle persisted even at the much lower dose. (13)

Melatonin and Aging
Aging commonly causes an increase in abdominal fat, plasma insulin, and lipids such as cholesterol. Researchers at the University of Washington showed that melatonin supplements in elderly rats could prevent or even reverse these effects of aging. The melatonin-treated rats also returned to youthful behavior patterns, including response to novelty. (7) In one animal model, melatonin supplements increased the lifespan. Older people are more susceptible to death from infection. Melatonin deficiency is related to decreased immune system function.16 One study showed that melatonin can rejuvenate the degenerative thymus (part of the immune system) in aging animals. (17)

Melatonin plays a direct role in regulating ovarian function. Progesterone production and hormone receptor function were both improved by melatonin. (3) In another study, 2 mg per day of melatonin was useful in balancing the hormones of women 64 to 80 years of age. (18) A decrease in melatonin is also associated with male menopause, also called andropause or androgen decline in the aging male (ADAM). (18)

Melatonin is a Powerful Antioxidant
One important mechanism for melatonins anti-aging effects is its role as an antioxidant. Many researchers believe that antioxidants can prevent and delay the onset of chronic degenerative diseases, and possibly extend the lifespan. Unlike other antioxidants, melatonin reacts with oxidative molecules to produce other molecules which are also antioxidants. This phenomenon is called the free radical scavenging cascade reaction of melatonin. Because of this cascade, one melatonin molecule has the potential to neutralize approximately four reactive oxygenating species. This indicates that melatonin is several times more potent than Vitamin C or Vitamin E as an antioxidant. (19)

Melatonin and Immune System
Melatonin is also a potent stimulator of immune cells, but it should not be taken in combination with Echinacea. Many people take melatonin for sleep disturbances and Echinacea for virus infections, especially in the winter. Canadian researchers tested the effects of the combination of these two products on mice. They found that this combination inhibits the production of granular leukocytes from their precursors, called myeloid cells. Granular leukocytes are important elements of the immune system. Both melatonin and Echinacea stimulate the production of T, B, natural killer cells, and myeloid cells in the immune system, either separately or together. However, melatonin and Echinacea together appear to inhibit the maturation of myeloid cells into granular leukocytes. The exact mechanism for this action is not yet known, but it is not desirable to reduce the granular leukocyte count. (20) Since individual responses to any health product vary, those who respond poorly to Echinacea may want to consider melatonin as an alternative. Melatonin should always be taken near bedtime, even when it is used for purposes other than sleep regulation.

Other Uses for Melatonin
Preliminary research indicates other possible uses. Melatonin has shown some promise as a treatment for migraine headaches. (21) Cluster headaches have also been treated successfully with melatonin. At the Thomas Jefferson University in Philadelphia, two patients were given 9 mg of melatonin daily at bedtime, along with their usual headache medication. Both remained free of headaches during their six to eight month follow-ups. One patient required only two days of melatonin treatment to rid himself of the cluster headaches. (22)

For cancers that are treated with Interleukin-2 immune therapy, the addition of melatonin may prolong survival time and increase the efficiency of Interleukin-2. This strategy appears to be superior to the use of high-dose Interleukin-2 alone. (23)

Agomelatine, which makes melatonin more effective, has been shown to be beneficial in patients with major depression. (25) This result suggests that melatonin itself may be useful in treating depression.

Melatonin is an important hormone that declines with age. People over 50 benefit most from supplemental melatonin, but there are numerous uses for melatonin in people of all ages. The benefits of melatonin include:

Sleep regulation for jet lag, shift work, or general insomnia
Regulation of other hormone cycles
Anti-aging and antioxidant protection
Enhancement of immune function
Better recovery from surgery
Enhancement of cancer therapies
Potential treatment of other diseases, such as tardive dyskinesia and migraine headache

Because of its safety and numerous benefits on health and lifespan, (7,24) I think melatonin may be one of the most effective anti-aging substances currently available.

1. Melatonin Q & A,

2. Inui A, Cancer anorexia-cachexia syndrome: current issues in research and management, CA Cancer J Clin 2002 Mar-Apr;52(2):72-91.

3. Woo MM, et al. J Clin Endocrinol Metab 2001 Oct;86(10):4789-97.

4. Reiter RJ, Tan DX, Melatonin: an antioxidant in edible plants, Ann N Y Acad Sci 2002 May;957:341-4.

5. Burkhardt S, et al. J Agric Food Chem 2001 Oct;49(10):4898-902.

6. Watanabe H, et al. Am J Chin Med 2002;30(1):65-71.

7. Zhdanova IV, Wurtman RJ, Regan MM, et al, J Clin Endocrinol Metab 2001 Oct;86(10):4727-30.

8. Rasmussen DD, Mitton DR, Larsen SA, Yellon SM. J Pineal Res 2001 Aug;31(1):89-94.

9. Rajaratnam SM, Arendt J, Health in a 24-hour society, Lancet 2001 Sep 22;358(9286):999-1005.

10. Cronin AJ, et al. Lancet 2000 Oct 7;356(9237): 1244-5.

11. Hanania M, Kitain E, Melatonin for treatment and prevention of postoperative delirium, Anesth Analg 2002 Feb;94(2):338-9.

12. Naguib M, Samarkandi AH. Anesth Analg 2000 Aug;92(2):473-9.

13. Atkinson G, Buckley P, Edwards B, Reilly T, Waterhouse J. Int J Sports Med 2001 Apr;22(3):232-4.

14. Shamir E, et al. Arch Gen Psychiatry 2001 Nov;58(11):1054-5.

15. Sack RL, Brandes RW, Kendall AR, Lewy AJ, Entrainment of free-running circadian rhythms by melatonin in blind people, N Engl J Med 2000 Oct12;343(15):1114-6.

16. Karasek M, Reiter RJ, Melatonin and Aging, Neuroendorocrinology Letters 2002;23(Suppl. 1):14-16.

17. Tian YM, et al. J. Pineal Research 2001;31(3):214-221.

18. Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. Neuroendocrinology Letters 2002;23(Suppl. 1):17-19.

19. Morales A, Heaton JP, Carson CC 3rd, Andropause: a misnomer for a true clinical entity, J Urol 2000 Mar;163(3):705-12.

20. Tan DX, et al. Curr Top Med Chem 2002 Feb;2(2):181-97.

21. Currier NL, Sicotte M, Miller SC. J Leukoc Biol 2001 Aug;70(2):274-6.

22. Gagnier JJ. Altern Med Rev 2001 Aug;6(4):383-9.

23. Melatonin: New Relief from Cluster Headaches?

24. Lissoni P, Bolis S, Brivio F, Fumagalli L. Anticancer Res 2000 May-Jun;20(3B):2103-5.

25. Skolnick A, Int Clin Psychopharmacol 2002;17:239-247.

26. Medline abstract search,

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