Artificial Light and Melatonin Secretion - Edoardo Favale e Alessio Corradi
Environmental Physical Agents

Author: Alessio Corradi
Date: 20/02/2013


How Artificial Light is related to a wide spread of diseases

What's Melatonin

Melatonin is an hormone secreted by the pineal gland in the brain that maintains the body's circadian rhythm. The circadian rhythm is an internal 24-hour time-keeping system that plays a critical role in determining when we fall asleep and when we wake up. Darkness stimulates the production of melatonin while light suppresses its activity. Exposure to too little light during the day or excessive light in the evening can disrupt the body’s normal melatonin cycles.
The light influences activity of ipRGCs (intrinsecal photosensible Retinal Ganglion Cells), wich contain the photopygment melanopsin: these cells project to the SCN (SopraChiasmatic Nucleus) via the retinotalamic tract. From the SCN the signal, through variuos intermediate stations, reaches the epiphysis, where inhibits the activity of the HIOMT, the last enzyme of the pathway responsible of the synthesis of melatonin by tryptophan.

Melatonin Functions

Besides its function as synchronizer of the biological clock, melatonin was found to have a lot of different functions in our body:

  • ANTIOXIDANT and ONCOSTATIC ACTION: Melatonin is an antioxidant that can easily cross cell membranes and the blood–brain barrier. This antioxidant is a direct scavenger of radical oxygen and nitrogen species including: OH, O2−, and NO. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.
    In animal models, melatonin has been demonstrated to prevent the damage to DNA by some carcinogens, stopping the mechanism by which they cause cancer. Moreover melatonin plays a significant role in controlling the immune system mediated by its stimulatory effect on the lymphocytes the secretion of some cytokines and its effect on the maturation and activity of NK cells. For this reason, melatonin may play a significant role in the promotion of immune system interactions with neoplastic cells.
    Also in human melatonin seems to have some effect in preventing cancer: for example, although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women.

Women with shorter sleep-time seems to have major RR to gain breast cancer.
Sleep duration, melatonin and breast cancer among Chinese women in Singapore, 2008.

  • IMMUNOSTIMULATORY FUNCTION: In vivo studies show that melatonin exerts immunoenhancing properties. Thus, pinealectomy on newborn rats causes disorganization of thymic structure and suppression of pineal functions, whereas constant light diminished antibody responses to T-cell activity, whereas melatonin treatment enhances antibody dependent cellular citotoxicity and INF-gamma. Production by murine-splenocytes. Furthermore, in vitro studies show that melatonin acts on immune cells by regulation cytokine production. Moreover, the existence of specific melatonin binding sites in lymphoid cells provides evidence for a direct effect on the regulation of the immune system.
    Recently, the pineal gland has been implicated in the pathogenesis and clinical course of Multiple Sclerosis (MS). When melatonin levels decline, an exacerbation of MS symptoms is seen. Remission effects in MS are thought to be related to the stimulatory influence of melatonin on the immune system.
  • EFFECTS ON CARDIOVASCULAR SYSTEM: The recent data indicated that impaired melatonin production is involved in several cardiovascular pathologies including ipertension and ischemic heart diseases. In fact melatonin influences blood pressure, myocardial contractility and increases the antioxidant reserve.
    A decrease in melatonin causes increased nighttime sympathetic activity, which in turn appears to increase the risk for coronary disease. Investigators surmised that lower levels of melatonin may act to increase circulating epinephrine and norepinephrine, which have been implicated in damage to blood vessel walls.
    Therefore, decreased melatonin levels were reported in various pathological conditions including ipertension with non dipper pattern, impairment of heart failure, ischemic diseases or in patients after acute myocardial infarction.
  • ROLE OF MELATONIN IN GASTRO-INTESTINAL TRACT: Gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin suggests that this hormone is involved in digestive pathophysiology. Here melatonin is released from entero-endocrin cells (EE) of GIT wall, where this indole may act via endocrine, paracrine and luminal pathway through G-protein cupled receptors. Melatonin in GIT is generated in about 500 times larger amounts then it is produced in pineal gland. Different study has focalized attention on the role of melatonin in upper portion of GIT, including oral cavity, esophagus, stomach and duodenum, where this indole is generated and released into the GIT lumen and into the portal circulation to be uptaken, metabolized by liver and realized with bile into duodenum. In the upper portion of GIT, melatonin exhibits a wide spectrum of activities such as circadian entrainment, free radical scavenging lesions such as stomatities, esophagities, gasrtities and peptic ulcer. There is a relationship between melatonin and food intake: abundant melatonin production in GIT, occurs mainly after good intake and maintains the indole concentration in peripheral blood, expecially following the intake of high dietary protein rich in tryptophan, wich serves as this indoleamine precursor.
  • BEHAVIORAL DISORDERS: Abnormalities of melatonin circadian function have been closely linked to a variety of behavioral changes and mood disorders. In general, studies have reported decreased nocturnal melatonin levels in patients suffering from depression and in patients with panic disorder.
    In Seasonal Affective Disorder (SAD) melatonin secretion tends to be elevated. Since full spectrum light reduces the rate of melatonin secretion, light therapy can be very effective in treating patients with SAD.
    Low levels of melatonin are also involved in insomnia and unrefreshing sleep, considering the role that the hormone has in the regulation of the circadian clock.

The Role of Artificial Lights

Light at night has become an important environmental exposure after 1870, when the light-bulb was invented. Before that discovery, humans were exposed only to low-intensity lights such as candels and petroleum lamps.
Industrialization brought a need for longer days and electric light made possible to achieve this need: as a result, a whole bunch of activities were pushed further and further into the night.
Today population experiences exposure to light at night, both as occupational exposure during night work and as a personal choice or lifestyle. We have numerous night-active members in our society.
Howewer we do not appear to be well adapted to this new lifestyle: shift workers, for instance, suffer from a variety of health problems (The effect of shift work on gastrointestinal (GI) function: a review, 1989 ; The problem: shiftwork, 1997 ; Shift work, risk factors and cardiovascular disease, 1999 ).
Light falling on the retinas at night leads to a rapid depression in the production and secretion of melatonin by the pineal gland. The magnitude of the drop in circulating melatonin due to light exposure at night is related to the brightness (intensity) as well as the wavelength (color) of light to which humans are exposed: of the visible wavelengths, those in the blue range (approximately 500-520 nm) seem most effective in suppressing melatonin production.

The circadian rythm is coupled with the day-night cycle, in wich at nightime there is no light. Therefore, melatonin secretion is maximal during lightless night, while almost absent during lighfully day.

Technological developments have led to bigger and brighter self-luminous electronic devices, such as televisions, computer screens, and cell phones. Light coming at night from these electronic devices can suppress nocturnal melatonin, which may disrupt sleep or pose a health risk. To produce white light, these electronic devices must emit light at short wavelengths, which makes them potential sources for suppressing melatonin at night or for delaying the onset of melatonin in the evening, thereby possibly reducing sleep duration and disrupting sleep. This is particularly worrisome in populations such a young adults and adolescents, who already tend to be more “night owls”.
Since a large portion of population spends most of their waking hours in front of a self-luminous display, it is important that manufactures and users have a tool to increase or to decrease circadian stimulation delivered by their self-luminous displays, maybe regulating the different wavelenghts coming to our retina, in order to avoid short-wave lenght like blue light (<520nm) and use longer wavelenghts.
As an example, we point out a study (Light level and duration of exposure determine the impact of self-luminous tablets on melatonin suppression, 2013 ) in which the partecipants were divided in 3 groups:

  1. tablets-only set to the highest brightness,
  2. tablets viewed through clear-lens goggles equipped with blue light-emitting diodes that provided 40 lux of 470-nm light at the cornea, and
  3. tablets viewed through orange-tinted glasses (dark control; optical radiation <525 nm ≈ 0).

The study highlighted that only blue-glasses users suffered a major suppression of melatonin levels, while orange-glasses users presented normal melatonin levels.
Based on these results, display manufacturers can determine how their products will affect melatonin levels and use model predictions to tune the spectral power distribution of self-luminous devices to increase or to decrease stimulation to the circadian system.

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