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Saturday, December 1, 2007

Melatonin and Cancer: Risk and Treatment

Health and disease are two great differences between ancient civilizations and industrialized cultures. Changes in lifestyle are often blamed for the rise of modern illnesses and there is no doubt that manufactured toxic compounds in air, water and food play a part. Scientists now believe that light may have important implications as well. The effects of light on melatonin production in the body are being studied for their role in cancer risk and treatment. Can something as subtle as circadian rhythm have such a serious impact?

Physiological Functions

Melatonin, a hormone produced and secreted primarily by the pineal gland in the brain, regulates our circadian rhythm of natural sleep and wake cycles. Patterns of melatonin secretion vary by time of day and also by season. Levels are lowest during daylight hours and begin to rise in the evening. They remain high for most of the night, promoting sleep. Melatonin levels abate in early morning hours, promoting wakefulness. Young children have the highest levels of nighttime melatonin and production declines gradually with age.

Melatonin has other essential functions in the body. It has antioxidant actions and plays a part in controlling the timing and release of female sex hormones such as estrogen. It also has an important role in immunity because it helps to regulate the development and function of white blood cells, specifically helper T-cells and natural killer cells that destroy cancer cells.

Light suppresses melatonin secretion and darkness stimulates it. When people are exposed to excessive light during the night or too little light during the day, natural cycles of melatonin are disrupted. The most dramatic effects occur in people who work night shifts, such as hospital employees and commercial flight crews.

Cancer Risk

Researchers at Brigham and Women’s Hospital and Harvard Medical School have conducted several studies on melatonin, night shift work and breast cancer. Examining Nurses’ Health Study data from women with invasive breast cancer and cancer-free women, they found that those who worked rotating night shifts experienced increased levels of estrogen and decreased levels of melatonin.

The researchers also concluded that lower melatonin levels were associated with an elevated risk for developing breast cancer. Women who worked rotating night shifts for one year or more, including at least 3 night shifts in addition to day and evening shifts during the same month, had a moderately increased risk of breast cancer. Those who worked rotating night shifts for 30 years or more had an even higher breast cancer risk.

Although the protective effect of melatonin has been most studied in relation to breast cancer, researchers have found that women who work rotating night shifts also have an increased risk of colorectal cancer. Other preliminary studies have found that melatonin may play a protective role in prostate cancer as well.

Cancer Treatment

Studies show that melatonin is a critical component in the treatment of cancer. Scientists in Spain found that melatonin reduces circulating levels of estrogens by inhibiting their production and interfering with estrogen receptors in the body. At breast tumor sites, melatonin acts as a selective estrogen receptor modulator (SERM) much like pharmaceutical drugs by the same name that are used to treat breast cancer.

In a more general cancer study, researchers in Italy followed more than 1,600 patients with advanced, untreatable tumors. Some patients were only given chemotherapy treatment and others received 20 milligrams of melatonin daily during darkness hours in addition to chemotherapy. Weakness, wasting, low platelet levels and low white blood cell counts were less common in those who received the adjunct melatonin treatment compared to the patients who were given chemotherapy alone. Those treated with melatonin also experienced greater benefits from the chemotherapy, measured by tumor response rate and stabilization of tumor growth, and significantly fewer side effects, including mouth inflammation, cardiotoxicity and neurotoxicity (harmful effects on heart and nerve tissues). Additionally, the one-year survival rates were significantly higher in the patients given melatonin.

A study in Germany demonstrated that melatonin induces apoptosis, or programmed cell death, in colorectal cancer cells. Researchers in Texas found that melatonin reduced prostate cancer cell multiplication by a mechanism that involved sex hormone receptors. Research studies on melatonin and the treatment of various types of cancer continue.

The Bottom Line

Artificial light has become an essential element of life in industrialized societies, especially during hours of darkness. However, spending time outdoors during daylight hours and dimming lights indoors during evening hours can minimize disruption in melatonin secretion. Avoiding night shift work also helps maintain a healthy circadian rhythm and reduces the risk of cancer, particularly breast cancer.

Melatonin has great potential for treating cancer and reducing side effects of conventional chemotherapy treatment. Melatonin has very low toxicity and overall adverse effects are not significantly more common with melatonin than with placebo. However, people interested in supplementing melatonin should consult with their doctor.