Melatonin is an uncommonly effective antioxidant, so its reduction due to the exposure to light at night may have multiple negative health consequences related to the accumulation of oxidatively damaged molecules.
The drop in melatonin with aging seems to be related to many debilitating changes associated with advanced age, for example, skin deterioration, cataracts, cardiovascular disease, cancer, and neurodegeneration.
In addition to its sleep-aiding effect, melatonin protects our body against free radicals as a potent antioxidant and ensures a quality of life and mental fitness—even in old age. It strengthens our immune system, lowers blood pressure and cholesterol levels, and can help prevent heart disease. Recent studies also demonstrate its excellent effectiveness in the treatment of cancer, diabetes, migraine, chronic pain, eye disease, and infertility, among others. Therefore, melatonin is a true force multiplier for our health.
The choked melatonin production also disrupts processes of cell division and repair, which increases the risk of tumor formation.
Other places in the body where melatonin is produced during the day are the digestive tract, blood platelets, retina, testes or ovaries, spinal cord, lymphocytes, and skin. The melatonin that is also produced in daylight has especially local effects, for example, in its effect as an antioxidant. To what extent and whether the melatonin produced here affects the melatonin production in the pineal gland at night, and thus also functions as a superimposed timer, is still the subject of investigations.
During the day, very little melatonin is produced, and intensive production begins only in the evening. At around 11 p.m., the “sleep” level rises to eight times the daily rate. This is the signal for the command “night operation” to the organs, and the brain then stores important information from the day to long-term memory.
Besides melatonin, the hormone cortisol (produced in the adrenal gland) plays a key role in our circadian rhythm. Between 4 and 5 a.m., it rises continually, reaching its peak at 8:30 a.m. As the day progresses, cortisol levels drop until they reach their lowest level at midnight.
In addition to this receptor-dependent effect, melatonin also acts as a free radical scavenger independent of a receptor and protects the cells against damage resulting from oxidative stress (i.e., stroke or heart attack), UV rays, X-rays, or anemia (Reiter et al. 2014a). Also, the results of the receptor-independent effect of melatonin in animals apply equally in humans.
In addition to the pineal gland, other cells of our body have the ability to produce melatonin, especially in their mitochondria, the so-called power plants of the cell. The melatonin produced in this way is not released into the blood, as from the pineal organ, but acts directly on the spot. This often makes it impossible to prove how much melatonin is produced in these cells. Studies have shown that the mitochondria play an essential role in cell death (e.g., Juszczak and Drewa 2016, Letra-Vilela et al. 2016). Melatonin protects these cell organelles from attack by free radicals,
The protective qualities and positive effects of melatonin extend to all of our cells, regardless of whether the melatonin was formed on the spot, originated from the pineal gland, or was ingested as a supplement. For example, melatonin has the ability to reduce the toxic effects of chemotherapy, while also increasing the effectiveness of such treatment. Ongoing studies also provide the first promising results of melatonin in the fight against cancer. Melatonin, according to a study on its effect on prostate cancer, can positively influence or prevent the spread of tumor cells (Kiss and Ghosh 2016).
Free radicals damage our cells, cause diseases, and accelerate our aging process. As an antioxidant, melatonin acts against the destructive potential of free radicals and protects us from cataracts, stomach ulcers, Alzheimer’s disease, Parkinson’s disease, cancer, and AIDS, among others.
has been shown that melatonin is more potent in controlling free radicals than vitamin C and vitamin E (Reiter et al. 2014a)! The reason is that vitamin C does not reach the brain immediately, while melatonin penetrates very quickly and everywhere in every cell. The importance of this effect cannot be emphasized enough, as more than one hundred diseases of our time are associated with oxidative stress.
Numerous studies demonstrate the high antioxidant activity of melatonin in the fight against free radicals: in the treatment of cancer, cardiovascular diseases (e.g., myocardial infarction and stroke), metabolic diseases (e.g., Diabetes), inflammation, and apoptosis—programmed cell death, which is particularly important in chemotherapy. Furthermore, taken in a sufficient amount, melatonin is a very safe medication without any side effects (Reiter et al. 2016).
Melatonin is the star among the so-called body-specific antioxidants, which can protect you against cataracts, stomach ulcers, and even cancer. Numerous studies have already been carried out with amazing results. Melatonin protects against free radicals, which are released during a stroke and can damage the brain much more than the stroke itself! In addition, it has been demonstrated that melatonin protects against radiation (e.g., X-rays).
However, what is certain is that melatonin can also reduce blood pressure and reduce the risk of diabetes.
If you want to regulate your circadian rhythm by taking melatonin, you will be more likely to succeed by taking it regularly, in low dosage, and one or two hours before sleeping. In this case, it is a chronotherapy.
For example, if you want to use melatonin as an effective free radical scavenger following an acute medical incident such as a stroke, then you should be advised to take it immediately after the incident occurs and not wait for a certain time of day.
Older people with a melatonin deficiency often suffer from high blood pressure, which can lead to a stroke, diseases of the coronary arteries, and high cholesterol. Here, too, melatonin helps maintain healthy blood pressure by its antioxidant effect, not only against harmful cholesterol deposits, but also positively in regard to the cardiovascular system.
Heart attack and stroke are events of acute vessel occlusion. Melatonin has a great vasodilating ability and supports the circulation of blood with its regulating effect. It also protects the heart muscle, as well as the brain, from further damage as a perfect counteragent of free radicals. Recent studies also demonstrate its anti-inflammatory properties, which are particularly effective in the fight against atherosclerosis and associated hereditary diseases (Favero et al. 2014).
Melatonin also plays an important role in the synthesis, secretion, and effects of insulin. As a strong chronobiotic, melatonin is responsible for important metabolic processes. If the melatonin fluctuations are disturbed, this can lead not only to insomnia, but also to insulin resistance, glucose intolerance, and a marked circadian disorganization with further consequences, resulting in obesity and diabetes. This is the result of a study that also concluded that therapy with melatonin benefits the health of the whole body (Cipolla-Neto et al. 2014).
For some time now, researchers have been observing the relationship between sleep disorders and obesity. In people who sleep fewer than four hours, the body secretes the hunger-inducing hormone ghrelin and produces less leptin, a hunger-suppressing hormone. In short, sufficient sleep also leads to balanced eating habits and a healthy body. Evidence that melatonin has a positive effect on body weight and metabolism is increasing.
Studies with shift workers and the elderly have shown that sleep disturbances, melatonin deficiency, and metabolic disorders are related. However, recent studies also demonstrate that melatonin is able to modulate the synthesis and secretion of insulin, to protect the cells producing insulin from overload, thereby counteracting the development of type 2 diabetes (Peschke et al. 2015, Tuomi et al. 2016).
However, if melatonin is produced less—for example, due to the use of sleeping pills, beta-blockers, alcohol, nocturnal light, or increasing age—this leads to long-term insulin resistance and type 2 diabetes. The reason is that melatonin acts on specific receptors on the pancreas, which is responsible for the release of insulin, thus preventing insulin from being released at night. However, if too little melatonin is produced for the reasons mentioned, a vicious cycle is set in motion. Through the release of insulin even at night, the blood glucose level drops, and we get hungry. The nightly walk to the refrigerator is then preprogrammed. A further consequence of melatonin deficiency is that the body accustoms itself to the permanently increased insulin and is resistant, even during the day, which often leads to diabetes with all its accompanying symptoms.
Beta-blockers, which are used as blood pressure agents, are among the handful of drugs that affect melatonin formation. As their name suggests, they block the beta-receptor, which is important in starting melatonin production. Additional drugs that affect sleep are benzodiazepines, or antidepressants. They stimulate sleep but suppress the body’s melatonin release. In other words, by taking a sleeping pill, you block the production of your own sleep regulator.
Studies with aspirin have shown that it can also partly suppress melatonin release (Murphy et al. 1994). Many patients in the studies report problems during and after sleep. Long-term use, especially in the evening, prevents melatonin from protecting you from numerous diseases by acting as a free radical scavenger. Paracetamol, when administered in the evening, has been shown to inhibit melatonin formation to the same extent as ibuprofen and aspirin. If, on the other hand, these products are taken early during the day, they have almost no effect on the production of nocturnal melatonin.
The positive effects of melatonin have been proven many times, not only for healthy sleep and a controlled day-night rhythm, but also for epilepsy, jetlag, diabetes (especially type 2), neuropsychiatric disorders (e.g., Alzheimer’s and Parkinson’s), and even in acute events (e.g., stroke and heart attack). Melatonin relieves stress, pain, and metabolic disturbances, and it increases blood circulation, which has already achieved good success, particularly in the elderly. In cancer treatment, it promotes the efficacy of chemo-and radiation therapy, while simultaneously reducing their negative side effects (Emet et al. 2016).
Inadequate melatonin also affects the liver and the work that is usually done at night. The result is insulin resistance, which can lead to diabetes. In addition, the urge to urinate at night remains as strong as during the day. Because of the lack of melatonin, a special hormone that inhibits urine production (antidiuretic hormone, ADH) is missing.
If melatonin is used as a tablet or capsule, about 30 to 40 percent of the melatonin is absorbed. After about twenty-five minutes, half of the melatonin taken as a pill is already broken down, so there is no longer any significant melatonin after approximately 2.5 hours.
In the case of supporting therapies, such as those for a stroke or myocardial infarction, higher dosages are required. In the earlier studies, quantities of up to 50 mg and more were used successfully as an immediate measure, and specifically as a fast-release form of melatonin. The administration took place immediately after the occurrence of the event, independent of the time of day. It is also advisable to use higher doses for concurrent therapy in tumor patients. Whether these are to be administered in the evening is still controversial but very likely. In the case of radiation therapy, doses of 15 mg need to be administered shortly before the treatment.
Extremely high doses administered in animal experiments show the following: Melatonin is absolutely nontoxic. Melatonin is by no means carcinogenic, but rather has a positive effect in the fight against cancer. Melatonin has no negative effect on the fetus.
How healthy is a short nap during the day? In science, the opinions are divided. There are short “naps,” “power napping,” or a sleep phase of up to 45 minutes at certain times of the day. They do not influence the circadian rhythm, since they have a completely different sleep structure. They are even health promoting, as a recent study has found (Kallistratos 2015).
Nonetheless, it is not recommended to take a nap every day. Some feel even tired after the short sleep and do not even get into gear at all. Others sleep too long and have difficulties with falling asleep in the evening.
Melatonin and Light Even a small, early evening dose of melatonin in a fast-release dosage form improves the consistency of the internal clock and the biological daily rhythm during the winter so that mood improves significantly. Light therapy has also proven to be a useful form of treatment. Used in the morning, the light not only reduces the morning melatonin, but also improves the entire rhythm.
Melatonin as an Effective Painkiller
This leads to the conclusion that a lack of melatonin can lead to nocturnal pain or even pain during the day. In some patients, the frequency of headaches was significantly reduced with the help of melatonin (Srinivasan et al. 2012). There are many mechanisms that may be responsible for the positive effect of melatonin. On one hand, there is an anti-inflammatory effect. On the other hand, it inhibits the excessive release of dopamine, stabilizes the cell membrane, and promotes the release of GABA—the most important neurotransmitter of the brain. In addition, melatonin acts as a protector against free radicals and regulates the vascular nerves and thus the blood flow (Srinivasan et al. 2012).
Melatonin: The Body-Borne Pain Medication Numerous studies deal with the relationship between melatonin and pain. Findings suggest that melatonin is not only the hormone that helps guide our innate circadian rhythm and our biological twenty-four-hour clock, but also serves as a regulator for pain signals. The hormone acts indirectly on the so-called opioid receptors. These are the same receptors on which many painkillers act (Ambriz-Tututi et al. 2009; Danilov and Kurganova 2016).
Melatonin is produced not only in the pineal gland, but also in the retina. Melatonin has many important functions, including the control of the eye pigmentation and thus the regulation of the amount of light that reaches the photoreceptors of the eye. In addition, melatonin protects the outermost leaf of the retina, or retinal pigment epithelium, from oxidative damage.
The British Journal of Ophthalmology recently published an alarming relationship between aging eyes and melatonin production. Measurements show that after the age of 45, fewer sunrays reach the inner eye. This is the result of the slight yellowing of the eyepiece lens and the narrowing of the pupil. For this reason, fewer light particles reach the most important cells in the retina that measure the day-night rhythm to regulate our internal clock. Studies show that changes in the aging eye lead to a series of typical eye diseases in which the cause cannot be found in the eye itself. The consequences of worsening visual power include cognitive deficits (especially memory capacity), insomnia, depression, and prolonged response times. A correlation between this change in the eye and a disturbed melatonin production is therefore always emphasized.
Recently, a study focused on the interplay of circadian rhythm, oxidative stress, and AMD (Fanjul-Moles and López-Riquelme 2016). Even if further studies are required, the results of this study showed that a disturbed circadian rhythm seems to contribute to degenerative processes in the retina that are responsible for the death of cells. Melatonin with its high potency as an antioxidant can help to prevent the destruction of cells by free radicals and thus delay the progress of the disease and to protect the retina. Whether melatonin acts only as a radical scavenger or there are also receptor-mediated effects is still the subject of research.
Research has shown that photoreceptors can also be lost by oxidative stress from glaucoma. Melatonin can be effective by reducing pressure in the eyes as well as protecting the photoreceptors from free radicals.
Melatonin has been shown to be effective in the regulation of blood pressure. Studies in Pechanova et al. 2014 have shown that the oral administration of melatonin reduces both high blood pressure and associated vascular reactivity. This effect results from the fact that the hormone has a relaxing effect on the vessels and acts as a potent free radical scavenger, since these free radicals have a negative influence on blood pressure (Sánchez-Barceló et al. 2010).
In the case of a heart attack, an acute vascular occlusion occurs. The tissue supplied by this vessel suffers from an oxygen deficiency and is damaged. The primary goal of therapy is, therefore, to restore the blood or oxygen supply within a very short amount of time. However, as soon as the oxygen supply necessary for life returns, further oxidative damage occurs to the already-attacked tissue due to the influx of oxygen. This is referred to as a reperfusion injury.
These damages can be significantly mitigated, if not prevented, by administering higher doses of melatonin. Early studies show that melatonin can significantly reduce the extent of cell damage in these situations thanks to its antioxidant and anti-inflammatory effect (Pei et al. 2016, Ozsoy et al. 2016). In order to achieve this effect, though, melatonin must be given immediately after the occlusion of the vessel, irrespective of the time of day.
Numerous studies have shown that melatonin has a positive effect not just in prevention (Pei et al. 2002), but also in acute stroke treatment (Watson et al. 2016). Its antioxidative potency is often documented and could significantly help in the event of stroke in order to alleviate further damage in the brain (Andrabi et al. 2015). In order to prevent a stroke, melatonin should be taken long-term in the evening. When the stroke has occurred, it is important to immediately give higher doses of melatonin, as in myocardial infarction, regardless of the time of day.
The cells in the digestive tract produce four hundred times as much melatonin as the pineal gland. However, this melatonin is not primarily released into the blood, but presumably acts directly on the spot. It, therefore, does not have the characteristic of a timer, as melatonin produced in the pineal gland during the night does. Although the exact function of melatonin in the digestive tract is not yet known, melatonin protects against ulcers of the gastric mucosa thanks to its antioxidant properties. Whether receptor-mediated mechanisms of action play a role here is still the subject of intensive research, but very probable. Scientists have already found out that bacteria in our gut reacts to melatonin. They also follow a circadian rhythm adapted to our natural rhythm. As soon as the bacteria notice that melatonin is multiplied, they begin to heat up and become active. What exactly this behavior means is not yet known. However, what is certain is that the intestinal microbes react to our sleep-wake cycles and thus definitely change their behavior (Paulose et al. 2016)
In the case of gastroesophageal reflux syndrome, in which increased gastric acid is pushed into the esophagus, melatonin significantly reduces the oxidative damage of the mucous membrane and thus also the pain symptoms. Scientists suspect that melatonin serves as universal protection of the stomach lining from the salicylic acid that is contained not only in many foodstuffs, but also in anti-inflammatory and fever-reducing painkillers and for protection against Helicobacter bacteria—which play a superordinate and disease-causing role in gastritis (Vaughn et al. 2014).
The loss of each glycemic control and the increase in glucose in the blood are typical complications that occur in type 2 diabetes and are usually caused by an insulin deficiency, often caused by a lack of function of the beta cells. Melatonin can improve the function of beta cells and support the release of insulin throughout the day. Melatonin supplementation can thus be a hopeful therapy for those affected (Sharma et al. 2015).
Various studies have shown that melatonin may affect the release of insulin and the blood glucose level (Owino et al. 2016). In rats that were diagnosed with type 2 diabetes, melatonin provided protection from hyperlipidemia (an increase in cholesterol) and hyperglycemia. In mice, there was an improvement in insulin resistance and glucose metabolism. In another study with postmenopausal women, it was found that melatonin improves glucose tolerance and insulin sensitivity in older women.
As a natural killer, melatonin plays an important role in the function of cells: it inhibits the uncontrolled proliferation of cells, thus reducing tumor growth, and can even prevent tumor formation by activating the lymphocytes (Zamfir Chiru et al. 2014). Melatonin also protects against common toxic consequences of chemotherapy or radiation, such as nausea and vomiting, low blood pressure, and lack of strength by stimulating the immune system (Seely et al. 2012). Melatonin also relieves inflammation of the oral mucosa, reduces harmful effects on the heart, and helps to reduce blood glucose and insufficient numbers of blood platelets after chemotherapy (Lissoni 2002).
Melatonin plays an important role in the fight against cancer, not only as a potent antioxidant. Many studies have shown that melatonin has a direct influence on various malignant tumors. It can affect tumor growth in some types of breast cancer by directly reducing the cell division rate. In addition, it also affects the activity of estrogens on these cells, which play an important role in breast cancer. Melatonin also reduces the aggressiveness of the tumor and the side effects of radiotherapy and chemotherapy (Sánchez-Barceló et al. 2012). Recently, scientists have shown that melatonin can also prevent cell migration and invasion. This protects our body from the spread of lethal tumor cells into new tissue (Gonçalves et al. 2016b). Melatonin can also positively influence the tumor weight and thus tumor size, a prerequisite required by many therapists before any chemotherapy or surgery is performed (Ma et al. 2015).
Recently, a study showed that melatonin not only inhibits the growth of breast cancer cells, but also the new formation and growth of blood vessels (angiogenesis). This is an important finding, because these vessels provide the tumor with oxygen and nutrients and thus contribute to its growth. Melatonin also reduces uncontrolled cell division, the so-called telomerase activity, and the uncontrolled spread of cancer cells into other tissues. Increased telomerase activity allows the tumor cell to constantly divide and penetrate into other tissues. Melatonin is one of the few substances that can reduce this activity, especially in tumor cells, thus reducing the formation of metastases. What is also underlined in the study is that melatonin supports programmed cell death or apoptosis, alleviates the serious side effects of chemotherapeutic agents, and simultaneously increases the efficacy of chemotherapy and radiation therapy. The authors of the study conclude that its broad spectrum of effects makes melatonin a treatment agent that can achieve very positive effects in breast cancer treatment (Nooshinfar et al. 2017).
As a pretreatment of chemotherapy or radiotherapy, melatonin can significantly sensitize breast cancer cells, according to a recent study. Melatonin reduces the activity and expression of certain proteins by about 50 percent, thereby reducing the amount of bioactive estrogens that promote tumor growth (Alonso-González et al. 2016). Melatonin also demonstrated excellent efficacy after breast cancer surgeries and improved patient sleep quality—an important effect for the regeneration phase and the healing process of women (Madsen et al. 2016b).
The Clinic is recommending full spectrum light:
