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Melatonin FAQs

Why did the HPA request the AGNIR to produce a report on power frequency electromagnetic fields, melatonin and the risk of breast cancer?


There have been concerns that exposure to electromagnetic fields (EMFs) might increase the risk of breast cancer. In particular, the “melatonin hypothesis” attempts to link long-term exposure to EMFs (and to light at night) with increased risk of breast cancer via a reduction in the hormone melatonin. The report considers the relevant scientific evidence for the melatonin hypothesis in relation to breast cancer.

Breast cancer development is influenced by various hormonal factors and these could be influenced by exposure to EMFs. This disease was viewed as providing valuable information on the mechanisms that could give rise to cancer induction in organs and tissues following exposure to power frequency EMFs.

A variety of factors are believed to affect the production of melatonin in humans, including alcohol and oral contraceptives, as well as various drugs and medicines. Changes in the timing or extent of melatonin production may affect the risk of other diseases, in addition to breast cancer. However, all such considerations were outside of the remit of the AGNIR report.

Information on the independent Advisory Group on Non-Ionising Radiation (AGNIR) is available.

 

What is the scope and coverage of the AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer?


The report considered papers that had been published in scientific journals up to August 2005. It covered both experimental studies using cells, animals and volunteers, as well as the evidence from human health studies (epidemiology) and data from clinical trials.

 

What are EMFs?


EMFs (electromagnetic fields) are associated with the use or supply of electricity. Electric fields are produced by differences in voltage, and magnetic fields are produced by the flow of electrical currents. Every wire and cable carrying electricity, and all electrical devices and appliances will produce EMFs to some extent. However EMFs rapidly decrease with distance from the source, which can make assessing personal exposures very difficult. A comprehensive set of frequently asked questions specifically about EMFs is available.

What is melatonin?


Melatonin is a hormone primarily produced by the pineal gland in the brain. It is produced in a distinctive, daily rhythm that is governed by day length. In humans and animals, levels of melatonin are very low during the day and become elevated at night, showing a distinct peak. Melatonin levels are very sensitive to light, and can be much reduced or even completely suppressed by exposure to light at night. Moderately low intensities of light may partially suppress and shift the time of the melatonin peak in humans. Melatonin secretion is related to the length of the night: the longer the night, the longer the duration of secretion. Individuals show very stable melatonin rhythms over time, although there are great variations between individuals.

 

What effects does melatonin have?


Melatonin has wide-ranging effects in people, conveying information about the light-dark cycle and so influencing rhythmic functions such as the sleep-wake cycle and core body temperature. Melatonin also controls seasonal reproductive rhythms in various animals. The timing and duration of melatonin secretion are its critical features with regard to its physiological functions. Melatonin may also be associated with preventing cancer in a number of ways. For example, changes in the expression of the genes controlling rhythmic functions are known to influence cancer development, and this process may involve melatonin. In addition, administering melatonin can help to reduce the toxicity of existing cancer chemotherapy treatments, and so improve their effectiveness. Melatonin can also act as an antioxidant, helping to prevent free radicals (produced as a part of normal metabolic processes) from causing damage to DNA and which could lead to malignancy.

 

What causes melatonin levels to change?

 

Melatonin is part of a sensitive, finely balanced physiological system that is programmed to be responsive to changes in the environment. Therefore melatonin rhythms can be changed by many factors, but exposure to light at night, many drugs and medicines, and changes to normal sleep habits can have dramatic effects on melatonin (which may persist beyond that night). It is therefore very important to appreciate and control for these factors when investigating possible influences on melatonin.

Can exposure to EMFs affect melatonin?


The report concludes that the exposure of humans to EMFs at levels likely to be found at work or at home does not appear to be associated with changes in melatonin. Most experimental studies have found that melatonin was not affected by short-term exposures. The results of epidemiological studies are more difficult to interpret, and although many studies have found some changes, no consistent effects have been observed. This lack of consistency raises strong doubts about these results being caused by EMFs alone.

Does melatonin affect the risk of breast cancer?


After reviewing the evidence, the AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer concludes that melatonin can reduce the growth and development of cancers in some types of cancer cells and in animals, although it is not clear that this occurs in humans. Studies investigating whether melatonin levels are different in women who develop breast cancer and those who do not have so far produced inconclusive results. It is not clear that decreases in melatonin production are associated with increased breast cancer risk. Thus the report calls for more research on this topic.

Recent publications
The results of a large, prospective study by Schernhammer and Hankinson (2005) which examined the association between melatonin and the development of breast cancer in a cohort of female nurses was mentioned only briefly in the AGNIR report: a paper has now been published. In this nested case control study, the concentration of 6-sulfatoxymelatonin (aMT6s) the major metabolite of melatonin, was measured in a morning urine sample of each participant as an indication of the melatonin level in the blood.

It was found that aMT6s levels were significantly lower in women who subsequently developed invasive breast cancer (10.8 versus 12.7 ng/mg creatinine, p=0.03 after adjustment for other breast cancer risk factors) and that aMT6s levels in urine were inversely associated with the risk of breast cancer (this trend was of borderline statistical significance, p=0.06). However morning urine samples only provide an estimate of overall production of melatonin but not of timing or duration of secretion. Thus, changes in the timing of the melatonin peak (phase shifts) could help to explain these results. Potential limitations of the study, noted by the authors, included a modest follow-up period of only four years. Further studies are needed to investigate whether the timing of the melatonin peak is important in the development of breast cancer.

In addition, a laboratory study by Blask and colleagues (2005) was published too late to be included in the AGNIR report. This experiment used rats bearing MCF-7 human breast cancer xenografts or rat hepatomas. Among other results, it found that perfusing the tumours for one hour with nocturnal blood containing melatonin from healthy women inhibited the growth of the tumours (assessed using molecular and biochemical assays), whereas this suppression was absent following perfusion with blood containing reduced levels of melatonin (induced by exposing the women to a bright light for 90 minutes at night). A previous study from this group using this xenograft model was highlighted in the AGNIR report, and further studies on this topic were recommended.

Taken together, the results of these two studies strengthen the likelihood that changes in the timing or extent of melatonin production may play a role in modulating the risk of breast cancer in humans, and additional studies are needed to explore this possibility further.

Does exposure to EMFs affect the risk of breast cancer?


The AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer found no compelling evidence to suggest that exposure of people to EMFs increased the risk of breast cancer. Similarly, there was no convincing evidence that EMFs had a direct effect on breast cancer cells or on the growth and development of tumours in animals. There were some uncertainties with the animal studies, with regard to different sensitivity between strains, and the report called for further research to examine this further.

Recent publication< p/> A study by Davis and colleagues published in 2006 has suggested that exposure of healthy women to elevated levels of magnetic fields at night may marginally affect melatonin levels. In this study 115 women were exposed to 60 Hz fields for five consecutive nights using a charging base of an electric toothbrush placed under their beds. This produced a field at the pillow of about 0.8 µT, approximately ten times the average background value. Exposure decreased the level of 6-sulfatoxymelatonin (aMT6s, the major metabolite of melatonin) in the overnight urine by a small amount (1.2-2.2 ng/mg creatinine, against a background value of about 18-52 ng/mg creatinine); this was adjusted for many factors that are known to affect melatonin. No effects of exposure was seen on levels of sex hormones measured in the urine, perhaps suggesting that these small changes in melatonin may not have been biologically significant.

Although it was reported that magnetic field exposure was associated with decreased aMT6s levels, it should be pointed out that the result became marginally significant only when seven participants whose body mass index was out of range of the eligibility criteria were included in the analysis. The paper also reported that the volunteers using prescription medications and anovulatory participants had more pronounced decreases in aMT6s levels with magnetic field exposure. However, these results were based on subgroup analysis of 14 and 16 participants respectively and chance findings could not be ruled out due to the small number of participants involved.

Overall, the relatively large value of the standard deviation in the aMT6s levels and the small sample size suggest that the study might not have sufficient statistical power to detect a small association between the magnetic field exposure and aMT6s. Thus the results of this study should be interpreted with caution.


Can exposure to light at night affect the risk of breast cancer?


The report concludes that there was some very suggestive evidence that shift work and airline cabin work appear to increase the risk of breast cancer, possibly as result of exposure to light at night. Conversely, the risk of breast cancer appeared to be reduced in blind women. However, there was no direct evidence that these results involved changes in melatonin.

Recent publication A recent study by Schernhammer and colleagues published in 2006 investigated whether the risk of breast cancer in female nurses was affected by the duration of working on rotating night shifts (defined as working at least three nights per month in addition to days or evenings in that month). Compared to women who never worked on rotating night shifts, the risk of breast cancer was found to be unaffected by working on shifts for up to 20 years, but a significantly raised risk of 1.79 (1.06-3.01) was observed for those women who worked on rotating night shifts for more than 20 years. However, this result was based on only 15 cases in the subgroup analysis. The trend analysis showed no significant increase of relative risk over the duration of rotating night shifts (p=0.65). Due to small number of cases in the subgroup analysis, the present results should be interpreted with caution, and further studies with larger numbers of women are needed to confirm this result.

Some further evidence in support of light at night being able to affect the risk of breast cancer has come from a study by Blask and colleagues using rats bearing human breast cancer xenografts (see the recent publication discussed in Does melatonin affect the risk of breast cancer?). This study was not included in the AGNIR report.

Why did the AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer call for more research?


Although the AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer found that exposure to EMFs does not appear to affect melatonin, nor to increase the risk of breast cancer, there is little information about the risk of long-term exposure to EMFs and especially if very small and presently undetectable, short-term changes might result in significant biological effects over time. Thus the report recommended that further research was necessary in order to improve the health risk assessment. The report contains a detailed list of research recommendations.

What do more recent studies show?


Research into the physiology of melatonin is very active on many fronts, and new studies are being published all the time. Results from a few studies that were published after the AGNIR report on power frequency electromagnetic fields, melatonin and the risk of breast cancer have been considered above in this set of frequently asked questions. These studies provide further intriguing data especially concerning the possible association between change in melatonin and the risk of breast cancer. Nevertheless, the balance of evidence would appear not to have shifted sufficiently to challenge the overall conclusions of the AGNIR report.


Should I try and reduce my exposure to EMFs, especially at night?


The report on power frequency electromagnetic fields, melatonin and the risk of breast cancer concluded that there was no compelling evidence to indicate that typical exposures to EMFs, especially at night, could have a substantial detrimental effect on melatonin, so it should not be necessary to try and reduce exposures further. However, should anyone be particularly concerned then perhaps moving an electrical device away from the bed, a clock radio for example, is a simple, no-cost measure that can reduce exposure, and this might provide additional peace of mind.

Such simple, precautionary approaches to reduce exposure to EMFs are the subject of much interest at the moment, and further discussion about this policy can be found at the World Health Organization (WHO) website at www.who.int/topics/electromagnetic_fields/en/ and on the website of the Stakeholder Advisory Group on Extremely Low Frequency EMFs (SAGE) at www.sagedialogue.org.uk/. SAGE has been specifically set up by the Department of Health to explore the implications and make practical recommendations for a precautionary approach to EMFs.

Should I turn off all lights in the bedroom at night?


The report on power frequency electromagnetic fields, melatonin and the risk of breast cancer did not address this issue directly. However, it found that the evidence was not sufficient to conclude that altered exposure to light (either through shift working, airline cabin work, or blindness) can alter breast cancer risk in women. The report acknowledged that some interaction may exist between light and breast cancer, however, and called for more study on this topic. The inclusion of a more recent study investigating the effects of shift working in nurses does not alter this overall assessment, although it does add weight to the possibility that working rotating shifts for many years may increase the risk of beast cancer.

There would appear to be no studies addressing whether sleeping in a light room is capable of suppressing melatonin in humans, or data describing the effects of a brief exposure to a low intensity light at night. However it is known that melatonin production is affected by the intensity, duration and quality of the light, so exposure to a dim light for a few minutes would not have the same result as exposure to a very bright light for the entire night. In addition, the eyelid is a very effective attenuator of light, so closing the eyes during sleep will very much reduce the subjective intensity of light. Whether or not a short-term, partial suppression of melatonin, as may occur following a brief period of illumination at night, is harmful largely remains an open question.

Should melatonin be used to treat breast cancer, or other illnesses?


The use of melatonin as a potential treatment for breast cancer and other illnesses was outside the remit of the report on power frequency electromagnetic fields, melatonin and the risk of breast cancer, and so it does not make any recommendations regarding the possible clinical uses of melatonin.

Do other opinions exist concerning EMFs, melatonin and cancer induction?


The possible effects of EMFs on melatonin (and on issues of health in general) are controversial, and while the conclusions in the AGNIR report would appear to be consistent with the views of many scientists and expert groups, others place a different interpretation on the experimental data and arrive at different conclusions. In short, they suggest that exposure to power frequency EMFs may disrupt melatonin and so increase the risk of cancer or other diseases.

For example, it has recently been suggested that magnetic fields may increase the risk of childhood leukemia via melatonin disruption (Henshaw and Reiter, 2005). It remains to be seen whether the increased risk in childhood leukaemia that has been found following long-term exposure in the home to magnetic fields (above about 0.4 µT) can be explained by changes in the timing or extent of melatonin production. As yet no direct evidence is available to support the hypothesis.

The issue of childhood leukaemia was outside the remit of the 2005 AGNIR report because it looked specifically at power frequency EMFs, melatonin and the risk of breast cancer. However, it has been considered in other AGNIR reports, published in 1992 and 2001, dealing with the risk of cancer from exposure to extremely low frequency EMFs.

Even if exposure to elevated levels of magnetic fields in the home could increase the risk of childhood leukaemia (via changes in melatonin, or by another route) magnetic fields are unlikely to be a major risk factor for that disease. It has been estimated by AGNIR that magnetic fields could be responsible for contributing an increased incidence of no more than about two extra cases of childhood leukaemia to the total burden in the UK of about 500 cases per year. One of these might be fatal. Research is continuing on many fronts to discover the major cause(s) of childhood leukaemia.