International Health News

Melatonin and Cancer

by Hans R. Larsen, MSc ChE

Hans Larsen Melatonin is a hormone secreted by the pineal gland and is important in synchronizing the production and excretion of other hormones according to the time of day (circadian rhythm). Melatonin production is low during daylight hours and peaks between 1 and 3 AM when it is darkest. In 1985 Christian Bartsch and colleagues at the University of Tubingen discovered that prostate cancer patients had an abnormal melatonin secretion pattern and concluded that melatonin secretion may be related to the development and growth of prostate cancer.[1] In 1992 the same group of researchers reported that prostate cancer patients had abnormally low levels of melatonin.[2] These findings prompted other German researchers to investigate whether people living north of the Arctic circle (many dark nights) had a lower incidence of hormone-dependent cancers, such as breast and prostate cancer. They found that this was indeed the case.[3] Moretti, et al at the Center for Endocrinological Oncology in Milan, Italy followed up in the laboratory and found that very small amounts of melatonin inhibited the growth of androgen-dependent prostate cancer cells in culture.[4] The same researchers later discovered that melatonin also very significantly inhibits the growth of androgen-independent cells.[5] Chinese researchers, treating a patient with terminal, metastatic prostate cancer and rising PSA levels with 5 mg a day of melatonin (given at 8 PM), found that this therapy stabilized his disease for 6 weeks as indicated by stable PSA levels.[6] Finally, in April 2005 researchers at the University of Texas concluded that treatment of both androgen-dependent and androgen-independent prostate cancer cells with pharmaceutical doses of melatonin dramatically reduced the number of cancer cells and essentially stopped the production of new cancer cells.[7]

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While it is thus clear that low melatonin levels are associated with prostate cancer and that melatonin kills both androgen-dependent and androgen-independent prostate cancer cells, it is not clear what causes low levels in the first place. Fortunately, breast cancer research provides several intriguing clues. In 1995 Molis, et al at Tulane University discovered that melatonin prevents the growth of breast cancer cells.[8] In October 2001 Scott Davis and colleagues at the Fred Hutchinson Cancer Research Institute reported that exposure to magnetic fields created by house wiring during the night significantly decreased melatonin production.[9] Norwegian researchers later linked exposure to magnetic fields created by residential wiring to a 58% increased risk of developing breast cancer.[10] In a controlled experiment just reported, a team of researchers from three American universities found that women exposed to relatively low magnetic fields (EMFs) of 5 and 10 mG during the night produced significantly less melatonin than women not exposed to EMFs.[11] As is common in cancer research, one recent study found no association between overall exposure to EMFs and breast cancer.[12] However, it is likely that only exposure to EMFs during the night would be detrimental.

Another important clue is the finding by Danish researchers that women who predominantly work at night have a 50% increased risk of developing breast cancer. The researchers conclude that exposure to light during the night suppresses melatonin production and hence increases the risk of cancer.[13] Jasser et al at Thomas Jefferson University in Philadelphia believe that the higher risk of breast cancer in industrialized countries is partly due to increased exposure to light at night.[14] Researchers at the University of Connecticut concur with this and further suggest that exposure to bright light during the day and total darkness at night is optimum.[15] Very recently the Bartsch team at the University of Tubingen in Germany concluded that, "melatonin controls not only the growth of well-differentiated cancers, but also possesses anti-carcinogenic properties". They suggest that short-term melatonin supplementation may be justified to optimize control over cancerous growth and development.[16]

There is credible evidence that a low level of melatonin is associated with an increased risk of prostate and breast cancer. It has also been demonstrated that pharmacological doses of melatonin will dramatically slow cancer progression and reintroduce appropriate cell differentiation. There is also evidence that exposure to low level electromagnetic fields created by normal (60 Hz) household electrical wiring may increase the risk of breast cancer and, by inference, prostate cancer. Finally, there is growing evidence that exposure to light during the night reduces melatonin production and thus increases cancer risk.

Hence, an inappropriately low melatonin level is a risk factor for prostate (and breast) cancer. There is evidence that a low level can be avoided by sleeping in a completely dark room at night and by ensuring that the ambient EMF level is low. Although the officially sanctioned safe continuous exposure level in the United States is 1000 mG [17], there is evidence that an exposure level of only 5 mG significantly reduces melatonin levels.[11] An obvious question is, "If low melatonin levels are detrimental, would it not make sense to supplement?" The medical literature does not contain an answer to this question. In view of the fact that melatonin is a hormone whose many and varied effects are not fully understood, continuous supplementation would probably not be wise until more information on its overall effect becomes available.[16] It has also been suggested that supplementing with melatonin prior to a long airline flight will not only help prevent jet lag, but will also afford some protection against the ionizing radiation experienced at high altitudes.[16] However, sleeping in a completely dark room with an EMF level of 1 mG or less is certainly safe and may be effective in preventing hormone-related cancers like breast and prostate cancer.

REFERENCES
  1. Bartsch, C, et al. Evidence for modulation of melatonin secretion in men with benign and malignant tumors of the prostate: relationship with the pituitary hormones. J Pineal Res, Vol. 2, No. 2, 1985, pp. 121-32
  2. Bartsch, C, et al. Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: evidence for reduced pineal activity and relevance of urinary determinations. Clin Chim Acta, Vol. 209, August 31, 1992, pp. 153-67
  3. Erren, TC and Piekarski, C. Does winter darkness in the Arctic protect against cancer? The melatonin hypothesis revisited. Med Hypotheses, Vol. 53, July 1999, pp. 1-5
  4. Moretti, RM, et al. Antiproliferative action of melatonin on human prostate cancer LNCaP cells. Oncol Rep, Vol. 7, March-April 2000, pp. 347-51
  5. Marelli, MM, et al. Growth-inhibitory activity of melatonin on human androgen-independent DU 145 prostate cancer cells. Prostate, Vol. 45, No. 3, November 1, 2000, pp. 238-44
  6. Shiu, SY, et al. Melatonin slowed the early biochemical progression of hormone-refractory prostate cancer in a patient whose prostate tumor tissue expressed MT1 receptor subtype. J Pineal Res, Vol. 35, October 2003, pp. 177-82
  7. Sainz, RM, et al. Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate, Vol. 63, No. 1 April 1, 2005, pp. 29-43
  8. Molis, TM, et al. Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer. J Pineal Res, Vol.18, March 1995, pp. 93-103
  9. Davis, S, et al. Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. American Journal of Epidemiology, Vol. 154, October 1, 2001, pp. 591-600
  10. Kliukiene, J, et al. Residential and occupational exposures to 50-Hz magnetic fields and breast cancer in women: a population-based study. American Journal of Epidemiology, Vol. 159, May 1, 2004, pp. 852-61
  11. Davis, S, et al. Effects of 60-Hz magnetic field exposure on nocturnal 6-sulfatoxymelatonin, estrogens, luteinizing hormone, and follicle-stimulating hormone in healthy reproductive-age women: results of a crossover trial. Ann Epidemiol, January 31, 2006
  12. Feychting, M and Forssen, U. Electromagnetic fields and female breast cancer. Cancer Causes Control, Vol. 17, No. 4, May 2006, pp. 553-8
  13. Hansen, J. Increased breast cancer risk among women who work predominantly at night. Epidemiology, Vol. 12, January 2001, pp. 74-77
  14. Jasser, SA, et al. Light during darkness and cancer: relationships in circadian photoreception and tumor biology. Cancer Causes Control, Vol. 17, No. 4, May 2006, pp. 515-23
  15. Stevens, RG. Artificial lighting in the industrialized world: circadian disruption and breast cancer. Cancer Causes Control, Vol. 17, No. 4, May 2006, pp. 501-07
  16. Bartsch, C and Bartsch, H. The anti-tumor activity of pineal melatonin and cancer enhancing life styles in industrialized societies. Cancer Causes Control, Vol. 17, No. 4, May 2006, pp. 559-71
  17. U.S. Department of Energy. Environment, Safety, and Health Manual. Document 20.07 Nonionizing Radiation and Fields (Electromagnetic Fields and Radiation with Frequencies Below 300 GHz), April 5, 2005, Appendix A http://www.llnl.gov/es_and_h/hsm/doc_20.07/doc20-07.pdf

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