Melatonin - all about the sleep hormone!

What is melatonin?

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone that is excreted by the pineal gland in the brain. The pineal gland is located just above the middle of the brain and is the size of a pea.

The synthesis and release of melatonin is stimulated by darkness and suppressed by light. The sleep hormone melatonin is also produced by many other organs in the body, especially in the stomach.

Melatonin is responsible for maintaining the biorhythm of the body. The biorhythm is the modern term for the internal clock, which also has a 24-hour rhythm, just like the day. This internal clock plays a crucial role in when we fall asleep and when we wake up.

Melatonin effect

When it's dark, more melatonin is released through the pineal gland. When it is light outside, the production of melatonin decreases. Because of this, blind people or people who work at night may have problems with their melatonin levels. However, for everyone, a lack of light exposure during the day or bright light in the evening can disrupt the body's normal melatonin cycles.

Exposure to light stimulates a nerve that runs from the retina in the eye to an area in the brain called the hypothalamus. This is where the suprachiasmatic nucleus is located and this activates the pineal gland.

The melatonin is released according to the circadian rhythm in response to the day and night cycle. In fact, the enzymes that synthesize melatonin in the body are activated by darkness or suppressed by light. This timed property means that melatonin is classified as a chronobiotic compound.

As soon as the suprachiasmatic nucleus activates the pineal gland, melatonin is released into the bloodstream. The precursor of melatonin is serotonin, a neurotransmitter that is derived from the amino acid tryptophan. Serotonin is processed into melatonin in the pineal gland.

The melatonin formation is closely related to the light sensors in the eye. The pineal gland usually begins producing melatonin at around 9:00 PM;. This increases the melatonin level and you start to feel tired. When the body is functioning normally, the melatonin level remains elevated for about 12 hours while sleeping. The melatonin level drops at around 9:00 AM to an undetectable level that is maintained throughout the day.

The melatonin concentration peaks between 2:00 and 4:00 AM and drops again in the morning. At the same time, the cortisol level in the blood increases, which ensures that you wake up in the morning. In the evening, the cortisol level drops again and the melatonin level rises.

On cloudy winter days, when there is little light, melatonin production is not completely stopped during the day, which can make you feel tired and even depressed during the day.

Physical activity during the day and exposure to light promote the normal biorhythm of melatonin and ensure a higher melatonin level during the night.

Small children have the highest level of melatonin at night. Many researchers are convinced that melatonin levels decrease with age. If that's true, it could explain why older people don't sleep as well as younger people.

Melatonin is a neurotransmitter-like compound that is a derivative of serotonin and is mainly produced in the pineal gland in the brain. The role of melatonin is the normalization of the biological rhythm and the temporal adaptation of the body to different biological processes.

Melatonin receptors

Melatonin interacts with two receptor proteins, MT1 and MT2.

MT1 and MT2 receptors control different phases of sleep: MT1 controls deep sleep/REM sleep, and MT2 controls the sleep phase before dreaming.

These receptors are present in a variety of organs and immune cells, suggesting that melatonin also controls the functioning of the immune system and other systems in the body.

Melatonin benefits for our health

Everyone knows that good sleep is important for maintaining health and is particularly important for preventing acute and chronic health problems. According to a new study by the Center for Disease Control and Prevention, one in three American adults often lack enough sleep.

Melatonin affects sleep and the circadian rhythm. This is like the body clock. It is a built-in function that controls biological processes in an approximately 24-hour cycle.

This central clock is located in the SCN (suprachiasmatic nucleus) of the anterior hypothalamus in the brain. It controls the circadian rhythm of the body. The circadian rhythm helps control the sleep-wake cycle, body temperature and hormone production.

Ambient light affects the signals sent by the SCN. Under the control of the circadian rhythm, the pineal gland produces and secretes melatonin. Under normal conditions, melatonin is excreted during the night. In daylight there are undetectable amounts in the blood.

While most scientists believe that melatonin can change the circadian rhythm phase and include the circadian rhythm, this property of melatonin is controversial.

In addition to the sleep and circadian rhythms, melatonin has many important health benefits as it is a powerful antioxidant and anti-inflammatory hormone. Furthermore, it has many advantages for the health of the brain, the intestine and for fertility.

Melatonin is also vital for the healthy female reproductive function, as it plays an important role in controlling the timing and release of female reproductive hormones. It decides when a woman's menstruation begins, the frequency and length of the menstrual cycles and the time at which menstruation completely stops (menopause).

Melatonin has many important functions in the body, including:

• influences the circadian rhythm
• supports the immune system
• supports eye function
• reduces oxidative stress
• promotes sleep
• affects female reproductive hormones
• controls many cellular metabolic functions, including the synthesis of important molecules

Melatonin deficiency - Why?

Various reasons can contribute to the fact that the melatonin release at night is not high enough, which can lead to a disturbance of the wake-/sleep rhythm and sleep problems.

• With age, the body produces less melatonin because the pineal gland calcifies over time. Due to the lack of melatonin, sleep duration and sleep quality decreases, which is why around 40% of older people often complain about insomnia. These sleep problems can range from falling asleep to staying asleep and reduced sleep quality.
• Electric light as well as blue light from screens (TV, computer, telephone etc.) can reduce the release of melatonin. Therefore, you should make sure to avoid all light sources in the bedroom, including light points from various electrical devices that are on stand-by.
• People who work at night often have sleep problems during the day because the pineal gland does not release enough melatonin in the morning for a restful sleep due to the bio-rhythm.
• In people who spend the day in a dark environment or sleep, the circadian rhythm and therefore the melatonin release can be disturbed.
• Persistent stress and intense exercise in the evening also reduces the release of melatonin.
• Consuming caffeine, alcohol and nicotine can also decrease the melatonin release.
• Taking medication can reduce melatonin release. These include beta blockers, cortisone preparations or ASA.
• Melatonin levels can also be reduced in people with certain diseases (e.g. Addison's disease, autism) and for blind people.
• Serotonin deficiency can also lead to a decreased melatonin formation.

Melatonin as a dietary supplement

Melatonin is available in different forms: as melatonin capsules, melatonin tablets, melatonin drops and melatonin lozenges (which dissolve under the tongue).

Can you overdose on melatonin?

As with any dietary supplement or medication, it is definitely possible to take too much melatonin. Most doctors and researchers recommend not taking more than 5 milligrams a day but recommendations can vary from person to person and depending on the indication.

Melatonin tablets are particularly popular, especially the sublingual melatonin lozenges, which cause the melatonin to be quickly absorbed into the body.

There is currently no recommended dose for melatonin as a dietary supplement. It is important to know that people react differently to taking melatonin. Lower doses seem to work better in people who are very sensitive.

Melatonin and sleep disorders

The melatonin intake has the potential to correct sleep-wake cycles and other sleep disorders.

Studies have shown that there is a connection between melatonin levels and sleep. With increasing age, the melatonin level drops significantly, which has a negative impact on the quality and duration of sleep.

The sleep-promoting property of melatonin is controlled by the suprachiasmatic nucleus in the hypothalamus, which is the control center for regulating the body's sleep-wake rhythm. The suprachiasmatic nucleus activates or restricts the release of melatonin via the pineal gland due to light stimuli from the retina.

This is mainly done by the neurotransmitter GABA, which exerts an inhibitory control over the activation systems during sleep. Activating neurotransmitters such as noradrenaline and acetylcholine are released after sleep to counteract sleep and force the patient to wake up.

Clinical tests show that melatonin as a chronobiotic - a substance that determines the biological temporal rhythm - can help to improve the quality of sleep. In addition, taking melatonin can significantly reduce the time between waking and sleeping and also improve the quality of sleep.

Melatonin can be beneficial for a variety of sleep disorders, including the following:

• Melatonin can help with primary sleep disorders or other sleep disorders caused by beta blockers or other medication.
• Melatonin can help with cases of narcolepsy, a chronic neurological disorder with pronounced daytime sleepiness.

Melatonin as a natural sleeping aid

The use of melatonin as a natural sleep aid is by far the best known use. Conventional medical treatment for sleep problems usually includes drugs, but these drugs often lead to long-term dependency and are associated with a long list of possible side effects. For this reason, many are looking for a more natural product that will help you have a good night's sleep.

Research suggests that the sleep hormone melatonin can help people with disturbed biorhythms, such as those who work the night shift and people who suffer from jet lag. Melatonin supplementation can also help people sleep better if they have chronically low melatonin levels, such as people with schizophrenia who suffer from poor sleep quality.

A 2012 study in Drugs & Aging analyzed the effects of prolonged release of melatonin in the treatment of insomnia in patients aged 55 years and older.

In the European Union, a dosage of 2 milligrams of melatonin is approved for the treatment of primary insomnia, which is characterized by poor sleep quality.

The randomized double-blind study found that two milligrams of melatonin one to two hours before bedtime compared to a placebo resulted in significant improvements in sleep quality and duration, better morning alertness and better health-related quality of life.

The study also found that whether the melatonin dose (2 milligrams) was taken in the short or long term, there were no symptoms of addiction, tolerance issues, or withdrawal symptoms.

How you can optimize your melatonin level

If you expose yourself to artificial light at night, the body switches off the own production of the hormone melatonin.

Melatonin plays a role in cancer screening, strengthening your immune system and can even slow cellular aging; in fact, it is the subject of preclinical research on over 100 different disease applications. It is the 'superhero at night' for your body and light is its preferred nemesis.

For the past century or so, the industrialized nations have conducted an open experiment by lengthening the days and shortening their nights to create a 24/7 productive society.

However, the light pollution generated by modern technologies has a serious biological impact on humans.

Two factors that can make sleep difficult are light pollution and temperature. The following suggestions can improve your sleep hygiene and help optimize your melatonin production:

1. Avoid watching TV or using the computer in the evening, at least an hour before going to bed. These devices emit blue light that trick your brain into thinking it is still day. Usually, your brain begins to secrete melatonin between 9:00 and 10:00 PM and these devices emit light that can suffocate this process.
2. Make sure you are regularly exposed to bright sunlight. Your pineal gland produces melatonin by focusing on the contrast of bright sunlight during the day and complete darkness at night. If you are in the dark all day, she cannot orient herself and optimize her melatonin production.
3. Sleep in complete darkness or as dark as possible. Even the slightest light in your bedroom can disrupt your biological clock and melatonin production in your pineal gland. Even the tiniest glow from the clock radio could affect your sleep. Cover your radio or alarm clock at night or banish it completely from the room. Place all electrical equipment at least three meters from your bed. It would also be beneficial to have curtains or blackout curtains on your windows.
4. Install a low watt, orange or red light bulb with a low wattage if you need a light source at night. Light in this range does not lower melatonin production as much as white and blue light. Salt lamps are practical for this purpose.
5. Keep the temperature in your bedroom no higher than 21° C. Many people keep their houses too warm (especially the bedrooms that are upstairs). Studies show that the optimal room temperature for sleep is between 15° and 20° C.
6. Take a hot bath 90 to 120 minutes before going to bed. This increases your core body temperature, and when you come out of the bath it suddenly drops and signals your body that you are ready to sleep.
7. Avoid loud alarm clocks. Getting ripped out of your sleep every morning can be very stressful. If you get enough sleep on a regular basis, you may no longer need an alarm clock.
8. Soak up the sun in the morning as early as possible. Your circadian system needs bright light to reset. 10-15 minutes of morning sunlight sends a strong message to your internal clock that the day has started and is less likely to be confused by the weaker light signals during the night. The older you get, the more sunlight you need. To make the most of it, leave the sunglasses at home and avoid artificial light in the early morning.
9. Pay attention to electromagnetic fields in your bedroom. EMFs can disrupt your pineal gland and melatonin production and have other negative biological effects. A gaussmeter is required if you want to measure EMF values in different areas of your home.
10. Take melatonin supplements. We recommend about 0.5 mg per day. But choose the right variety, because if you take melatonin orally, it breaks down in the liver. Most of it will never reach your bloodstream. It is therefore important to use a sublingual tablet. They are easier to absorb and act faster. This is the most effective way to take melatonin.

Melatonin - A powerful antioxidant

Several health benefits of melatonin derive from its powerful antioxidant properties, both directly and indirectly. The administration of melatonin increases the cellular production of antioxidative enzymes (superoxide dismutase, glutathione peroxidase and gamma-glutamyl cysteine synthase), which in turn can increase antioxidants such as glutathione.

These enzymes help cleanse the cells, mitochondria and bloodstream from harmful reactive oxygen species.

Furthermore, the melatonin molecule can bind itself to reactive oxygen species (ROS) and reactive nitrogen species (RNS), making them less harmful. Melatonin can thus protect several tissues and organ systems from oxidative damage. Tissues that produce melatonin and rely on melatonin for this purpose are the intestine, ovaries, testicles, lens, bone marrow and the brain.

Most of the molecules (metabolites) into which melatonin is transformed also retain the ability to bind harmful oxygen and nitrogen species, making melatonin and its products highly effective in protecting.

A single melatonin molecule can neutralize up to 10 ROS and RNS molecules. It also blocks an enzyme called nitric oxide synthase, which produces reactive nitrogen species and causes inflammation.

Melatonin protects the mitochondria

Mitochondria are part of the energy-producing cell. They have their own DNA. As energy factories, they are crucial for survival. The nucleus and mitochondria are the areas that contain the most melatonin.

Mitochondrial energy production leads to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS damage mitochondrial DNA and proteins, which means that they can no longer generate energy. This damage can also cause the mitochondria to leak, which can lead to cell death (apoptosis).

Melatonin therefore supports the organs that are most dependent on mitochondria, including the nervous system and heart.

Melatonin and jet lag

Jet lag is a temporary sleep disorder for people who travel quickly by plane across multiple time zones. This arises as a result of the slow adaptation of the body's internal clock to the time of the destination. As a result, the rhythm of sleep and wake is out of sync with the new environment.

Jet lag can have a negative impact on our wellbeing, as well as our mental and physical performance. The signs of jet lag are extreme tiredness, difficulty orienting, difficulty concentrating, balance problems and loss of appetite.

Studies have shown that melatonin is not only exceptionally effective in reducing the severity of jet lag at the destination, but can even prevent jet lag if taken before the flight. Melatonin can help reset the sleep-wake cycle.

A scientific assessment of a large number of trials and studies on melatonin and jet lag found that melatonin 'is remarkably effective in preventing or reducing jet lag and that occasional short-term use appears to be safe'.

The research revealed that in nine out of ten studies, if melatonin was taken at the destination close to bedtime (10:00 PM to midnight), jet lag decreased when crossing five or more time zones.

The researchers also observed that daily doses of melatonin between 0.5 and five milligrams worked similarly well, but the subjects fell asleep faster and also slept better after taking five milligrams compared to 0.5 milligrams.

When melatonin doses above 5 mg were administered, the results were not better. Another important conclusion is that the timing of a dose of melatonin is crucial, because if it is taken too early, it may delay the adjustment to the new time zone. There were few other side effects of the melatonin dosage.

The following guidelines can help you to optimally use melatonin preparations to avoid or reduce jet lag:

• Melatonin works better the more time zones you cross.
• Melatonin appears to be more effective when traveling in the east than when traveling in the west.
• Melatonin is only successful if it is taken at the destination in the evening.

Melatonin and sleep for elderly persons

Melatonin based sleeping pills have also been extensively studied in the elderly. They have a strong tendency to benefit from melatonin for insomnia because the production of melatonin hormones gradually decreases as they age. This fact has led to melatonin also being studied as an anti-aging supplement.

Older people suffer more from side effects such as morning sleepiness, although they are more likely to benefit from melatonin administration. Therefore, a low dose, such as 0.1 to 0.3 milligrams, should always be taken at the beginning instead of higher doses. It has been shown that these small amounts are usually as effective as higher dosages and cause fewer problems.

Melatonin for sleep is a well-researched area. While the long-term effects of melatonin are not yet fully known, melatonin has been safely used in high doses for up to 3 years with almost no problems.

Melatonin for sleep disorders, anxiety, depression and bipolar disorders

Melatonin can help treat sleep disorders associated with anxiety and depression. Depression and other mood disorders are often linked to sleep disorders and require agents that have both a sedative and a calming effect. Drugs that activate and bind MT2 receptors are potential therapeutic agents for such diseases.

Abnormal day and night concentrations of melatonin are markers of severe depression.

Melatonin helps regulate sleep and depression in patients with delayed sleep phase syndrome.

In rats, melatonin relieves chronic stress-induced depression and significantly changes the brain dynamics of these animals.

Treatment with melatonin in breast cancer patients reduces the risk of depression.

Melatonin synthesis is also impaired in patients with bipolar disorder. Melatonin and drugs that target melatonin receptors such as Ramelteon and Tasimelteon can also be beneficial therapy for bipolar disorder. Because bipolar disorder is also associated with sleep and mood deregulation, melatonin improves the condition in patients with this problem.

Melatonin protects the stomach

Melatonin has a remarkable healing and gastric protective effect on gastric ulcers caused by aspirin or helicobacter pylori.

The mechanism of the gastric protective effect of melatonin can be attributed to the improvement of gastric blood flow, as well as its anti-inflammatory properties.

Studies have shown that taking melatonin daily can help heal gastric ulcers caused by aspirin or helicobacter pylori. In one study, the healing rate of ulcers infected with helicobacter pylori increased significantly compared to standard treatment (omeprazole) alone.

Melatonin has also been shown to be gastric protective when taken with aspirin. This indicates that it can prevent aspirin-induced gastric ulcers from developing.

Melatonin has a healing effect on stomach ulcers

The melatonin concentration in the stomach tissue is 10 to 100 times higher than in the blood. The concentrations in the intestine are 400 times higher than in the brain.

The melatonin produced in the stomach is controlled differently than the melatonin produced in the brain. This concentration is highest at noon, not at night. In the stomach, it mostly reacts to ingested food. The melatonin produced in the stomach also controls the behavior of intestinal bacteria.

Melatonin and its precursor, L-tryptophan, can help heal stomach ulcers in humans. They protect against lesions caused by taking aspirin and H. pylori infections. Melatonin administration also accelerates ulcer healing.

In studies, the sleep hormone melatonin strengthened the intestinal barrier by reducing oxidative stress by up to 88%. The prevention of stress-induced gastric damage is dose-dependent and increases the efficiency of medications used in gastric ulcers, such as ranitidine and omeprazole.

The antioxidant properties can help stop inflammation in the stomach. This could reduce disorders such as colitis and irritable bowel syndrome.

Melatonin also helps prevent the death of mucous membrane cells in the stomach due to poisoning.

Melatonin also relieved the stomach pain of patients with irritable bowel syndrome.

Melatonin and mental disorders

The main effect of melatonin is to maintain the biological rhythm by promoting the synchronization and stabilization of various processes.

There is growing evidence that disorders in these biological rhythms play an important role in the development of mental disorders such as depression, bipolar disorder and seasonal depression.

Studies are currently underway examining light therapy as a treatment to restore the sleep-wake cycle in patients with serious mental disorders.

Light therapy aims to increase melatonin production and could improve circadian rhythm and overall brain function in people with mental disorders.

In summary, melatonin theoretically offers a new method for the treatment of these disorders, based on the regulation of the sleep-wake rhythm. Therefore melatonin is tested for its possible antidepressant effect.

Melatonin and anti-aging

As people get older, the melatonin level drops. Oxidative stress and its damage contribute to the aging process. The antioxidant properties of melatonin can help reduce oxidative damage. Melatonin can help reduce the signs of aging due to its antioxidant properties.

Melatonin can neutralize reactive oxygen species (ROS) that play a role in the free radical theory of aging. These harmful ROS, which are highly reactive compounds, can directly damage a number of important biological structures in the body's cells.

The aging process is associated with the development of cancer, arthritis, neurodegeneration and diabetes, all of which are related to oxidative stress and the resulting oxidative damage.

With its ROS neutralizing properties, melatonin can directly counteract the damage that these free radicals can potentially cause. Melatonin also has indirect antioxidant properties due to its ability to increase the activity of various antioxidant enzymes, such as superoxide dismutase.

Superoxide dismutase plays a vital role in defending cells against the harmful effects of oxygen radicals, and their activation helps to suppress cell damage.

Melatonin and the immune system

Research shows that melatonin has strong antioxidant properties and can help boost the immune system. In a scientific assessment from 2013, melatonin is referred to as an 'immune buffer' because it appears to act as a stimulant in immunosuppressive diseases. It also acts as an anti-inflammatory compound when there is an increased immune response, such as in the case of acute inflammation.

Melatonin reduces inflammation and promotes healthy immune function

Melatonin receptors are found in a variety of immune cells. It is immunomodulatory, which means that it reduces excessive immune function during inflammatory conditions and enhances immune function in immunocompromised people.

Melatonin can reduce the production of inflammatory cytokines including IL-6, IL-8 and TNF-alpha.

Furthermore, by reducing free radicals in the microglia (immune cells that are specific to the brain), melatonin can minimize brain inflammation by reducing NF-kB.

Melatonin, fibromyalgia and chronic pain relief

Symptoms of fibromyalgia include long-term and widespread pain in muscles and connective tissue with no specific cause. A randomized, placebo-controlled study in 101 patients with fibromyalgia investigated the effectiveness of melatonin in reducing symptoms.

Patients were found to experience a significant reduction in their symptoms when taking a dose of melatonin alone or in conjunction with the antidepressant fluoxetine (Prozac).

The group that only took melatonin received a daily dose of 5 mg melatonin, while the other group took 3 milligrams of melatonin and 20 milligrams of the antidepressant.

Other studies suggest that melatonin may be able to help with other chronic pain conditions, such as migraines.

Melatonin protects the heart

Several studies indicate that melatonin has a protective effect on the heart. Specifically, the research shows that melatonin has an anti-inflammatory and antioxidant effect in cardiovascular problems.

It can also lower blood pressure and help with high cholesterol. As a direct radical scavenger, it appears to have heart-protecting properties. Overall, the protective effects of melatonin can help to reduce cardiovascular diseases such as stroke and heart attack.

Melatonin lowers the blood pressure

Melatonin plays an important role in regulating blood pressure. The activation of its receptors MT1 and MT2 expand the blood vessels, which lowers blood pressure.

Like sleep, blood pressure has a circadian rhythm. It rises in the morning and sinks at night. Melatonin rises at night and drops in the morning. This suggests that there may be a link between melatonin and blood pressure. Certain types of hypertension (high blood pressure) indicate an undersupply of melatonin.

In patients with type 2 diabetes, blood pressure levels were reduced with 5 mg melatonin. However, there is insufficient information on how melatonin lowers blood pressure to determine if it could be effective as a blood pressure lowering therapy. However, it can be used as a supportive therapy in hypertensive patients.

Melatonin and tinnitus

Tinnitus is an inexplicable sound in the ears that affects many people, such as the elderly, people with hearing impairments or as a result of taking certain medications.

Melatonin was 150 times more effective compared to other drugs that treat tinnitus with decreasing tinnitus symptoms.

Melatonin levels are very low in elderly patients with tinnitus. This may indicate that normal melatonin levels are closely related to normal ear activity.

Melatonin and the eyes

The cells of the eye, especially the retina, produce melatonin. Light affects melatonin production by producing cells that respond to light. The more light there is, the less melatonin is produced in the cells located in the eyes.

The disruption of the MT receptors leads to the death of cone cells, which help the eye to recognize colors.

Melatonin is also important for normal eye development. For example, mice lacking one of the melatonin receptors, MT1, showed a decrease in the specific visual cells that are critical to vision.

In addition, it was shown that the human cells that produce eye pigments are protected from cell death.

Melatonin protects the nerve cells in the eyes

Melatonin also prevented the death of nerve cells in an experimental model of optic nerve inflammation in rats. Optic neuritis is a disease that causes the death of optic nerve cells that are responsible for vision.

Melatonin is also beneficial for refractory central serous chorioretinopathy, a disease affecting the eyes of diabetics.

Melatonin supplementation, especially in the elderly, is potentially beneficial for eye protection.

Melatonin and glaucoma

Melatonin also reduced the increased pressure in the human eye. In addition, the removal of MT1 in mice leads to an increase in pressure in the eye and to the death of nerve cells.

Melatonin function disorders can be one of the causes of glaucoma. Melatonin and 5-MCA-NAT (a molecule similar to melatonin) are promising agents for the treatment of glaucoma, an eye disease caused by increased pressure.

Melatonin and Parkinson's

The development of Parkinson's disease disrupts sleep. There are several studies showing that melatonin improves sleep in patients with this condition, but it does not improve the other symptoms associated with it.

The study carried out in the Parkinson animal model showed that melatonin can prevent cell death and the associated brain damage.

Melatonin and Alzheimer's

Melatonin helps alleviate symptoms similar to Alzheimer's and Parkinson's disease in mice and rats. The use of synthetic melatonin analogs or molecules related to melatonin to block nitric oxide synthase is being evaluated for the treatment of neural diseases ranging from stroke to Alzheimer's and Parkinson's disease.

In humans, both MT1 and MT2 levels are low in the elderly with Alzheimer's.

In mouse neurons, melatonin prevents cell death caused by amyloid beta25-35, a substance that causes an Alzheimer's-like condition.

The decrease in melatonin activity and synthesis can partly explain the disturbance of sleep and the problems with processing information that has been observed in Alzheimer's patients.

Treating elderly patients with Alzheimer's disease (AD) with bright light in the morning and melatonin at night improved their sleep and overall rest.

Treating elderly patients with Alzheimer's disease (AD) with bright light in the morning and melatonin at night improved their sleep and overall rest.

Melatonin's antioxidant effects were more efficient than vitamin C in treating the animal model of Alzheimer's disease. It reduced oxidative stress better than vitamin E.

Melatonin could protect against diabetes

Melatonin acts as a clock and changes insulin levels according to the time of day. Melatonin is very important for the balance of insulin, since a disturbance in this system can make the cells' response to insulin and glucose ineffective.

In patients and rats with type 2 diabetes, the concentrations of melatonin, both during the day and at night, are lower compared to healthy volunteers.

Even a sleepless night can cause insulin resistance. It can also disrupt your metabolism. Disrupting the balance of melatonin can cause all of these problems.

In rats with diabetes, long-term treatment with melatonin improves diabetic effects on muscle, liver and adipose tissue.

In a cell-based study, melatonin protected muscle cells from a poison that causes insulin resistance and improved the transport of glucose into the cell.

Melatonin also helped improve the condition of the liver and its activity in diabetic obese rats. It also protects insulin-producing cells in the pancreas from cell death. It also restores their function.

Medication that correct melatonin (epifamine and melaxen) can improve diabetes in rats.

Agomelatine, an antidepressant that targets the melatonin receptors, improves the chronic pain associated with diabetes. Agomelatine also acts against depression in patients with diabetes and is used to control blood sugar levels.

Study combines type 2 diabetes with low melatonin levels

Low nighttime secretion levels of melatonin are associated with an increased risk of developing type 2 diabetes. Recent research from Brigham and the Women's Clinic (BWH) has found that the amount of melatonin that a person excretes during sleep can predict the risk of developing type 2 diabetes.

'This is the first time that an independent association between nighttime melatonin secretion and type 2 diabetes risk has been confirmed,' said Dr. Ciaran McMullan, a researcher in the renal department and the clinical institute for kidney research at the BWH. 'Hopefully, this study will stimulate future research and examine what affects a person's melatonin secretion and what role melatonin plays in changing a person's glucose metabolism and risk of diabetes.'

For this study, researchers identified 370 women who developed diabetes while participating in the Nurses Health Study and 370 controls of the same age and race. When the two groups were compared, researchers found that the subjects with low levels of nighttime melatonin secretion were about twice as likely to develop type 2 diabetes as those with high levels of nighttime melatonin secretion.

After excluding already established risk factors for diabetics, such as body mass index, family background of diabetes and lifestyle factors such as diet, exercise, smoking and sleep duration, it turned out that a low melatonin level still persisted as a significant risk factor.

Melatonin protects the brain

Melatonin not only helps reduce oxidative stress and inflammation in the brain, but also increases BDNF (brain-derived neurotrophic factor) and strengthens the blood-brain barrier. It has been suggested as a treatment for several brain and neurological disorders.

Melatonin has an antioxidant effect in the brain, spinal cord, optic nerve and white matter of the spinal cord and additionally protects the nerve cells.

Melatonin helps with brain regeneration and neuroplasticity

Melatonin activates the brain-derived neurotropic growth factors (BDNF), a protein that is responsible for the well-being and regeneration of nerve cells.

Melatonin strengthens the blood-brain barrier

Melatonin strengthens the barrier between the brain and blood. [75] A leaky blood-brain barrier can cause cognitive dysfunction (brain fog), Alzheimer's, and can also contribute to psychiatric disorders such as anxiety and depression.

Melatonin and traumatic brain injuries

Melatonin helps with brain trauma. Treatment of rats with melatonin after brain injuries can reduce the subsequent swelling of different brain regions.

Melatonin in menopause

Melatonin supplements have been shown to improve sleep disorders during menopause. In a study with peri-menopausal and menopausal women aged 42 to 62 years and a daily dose of melatonin over a period of six months, most women reported on a general improvement in their mood and a significant decrease in depression. The results of this study indicate that melatonin supplements in peri-menopausal and menopausal women can lead to a resumption of the function of the pituitary and thyroid glands and adolescent hormone regulation.

This is a positive result because it shows that melatonin can reduce both peri-menopause and menopause symptoms, such as sleep problems.

Melatonin relaxes the smooth muscles

Melatonin supplements benefit some people with the ability to relax with 'smooth' muscles. This differs from most muscle relaxants, which often help to relax skeletal muscles - such as back muscles or shoulder muscles - which you can consciously control. Smooth muscles, on the other hand, are muscles that you have little or no control over in most circumstances.

'Unexpected improvements were seen in connection with esophageal reflux, gastrointestinal symptoms of ulcerative colitis, cystic fibrosis and chronic diarrhea. It therefore appears that melatonin has some unclear function in the gastrointestinal tract. '

One of the lesser known benefits of melatonin are its effects on the digestive tract smooth muscles. It can help relax these muscles to the extent that it has been shown to be beneficial for irritable bowel syndrome, esophageal reflux and other irritable digestion problems.

This makes sense since melatonin is not only produced in the pineal gland but also in the gastrointestinal tract. It is possible that this is an adaptive mechanism to avoid irritability and inflammation due to stress.

Melatonin and cancer

Some scientists believe that prolonged exposure to artificial light (light pollution) could be a possible reason for the dramatic increase in cancer rates in the western world.

It is believed that artificial light interferes with the day-night rhythm and other biological processes that are naturally controlled by the internal biological clock. This is supported by studies that have shown that night shift workers are more likely to develop cancer than people who have a regular daily rhythm.

Night shift workers are exposed to artificial light at night for long periods and then to natural sunlight during the day.

The increased exposure to light results in a melatonin release profile that can't adapt properly. This leads to an overall reduced release of melatonin, which could probably be the reason for the increased spread of cancer.

Current research on the effect of melatonin against tumors shows that it can limit the triggering and progression of tumors. Melatonin has also been shown to act against the metastasis of various cancers, melanoma and leukemia.

Although more research is needed on the effectiveness and safety of melatonin as a therapeutic cancer inhibitor, the effects appear to be promising.

The current cancer research in the melatonin therapy field is currently dealing with the following topics:

• Clinical studies on the effects of melatonin for the prevention and treatment of breast cancer.
• Melatonin plays a role in prostate and colon cancer by avoiding the growth and differentiation of carcinomas.
• The effect and termination of melatonin injections in tumor treatment is currently being investigated.
• Melatonin appears to help cancer patients tolerate chemotherapy better.

Melatonin can help prevent and treat cancer

Melatonin can play a role in the prevention and treatment of various types of cancer. Breast, prostate and colon cancer patients had low melatonin levels as compared to healthy patients.

The addition of melatonin blocked cancer-like tumors in artificial spheres which were taken from breast and cancer cells. This was because melatonin blocked the estrogen receptors that caused the cancer.

The treatment of the cells with melatonin increased the production of the cancer-suppressing protein E-cadherin. It also reduced the levels of OCT4 and N-cadherin, which help tumor cells survive and spread to other organs.

It also works against cancer stem cells, the type of cells that divide uncontrollably and make cancer more resistant to treatment. Melatonin reduces the aggressiveness and viability of cancer cells.

Melatonin's anti-cancer effect is due to its ability to improve the immune function (R). It stimulates various types of immune cells, such as TH2 cells and natural killers.

A constant melatonin treatment reduced the amount and size of breast tumors in patients.

A melatonin supplementation stabilized the health of patients with lung and colon cancer. It reduced the spread of tumors and increased cancer cell death.

Melatonin interferes with the energy processes of cancer cells in cell cultures. This effect blocks cancer cell growth and limits their ability to infiltrate.

However, melatonin injections can stimulate tumor growth if given in the morning. You need to be careful when timing your melatonin administration.

Melatonin for breast and prostate cancer

Several studies suggest that low melatonin levels can be associated with breast cancer risk. Scientific research has shown that it can also benefit cancer patients, especially those diagnosed with breast or prostate cancer.

To determine the effectiveness of melatonin in preventing tumor growth, a group of researchers examined the effect of melatonin dosing on breast tumor growth in vitro (using human cancer cells) and in vivo (using mice). So it makes sense that a hormone like melatonin can play a crucial role in their treatment.

The researchers found that melatonin can inhibit tumor growth and cell production, as well as the formation of new blood vessels in estrogen receptor-negative breast cancer. This 2014 study shows the potential of melatonin as a therapeutic agent in breast cancer.

Another study dealt with women taking the chemotherapy drug Tamoxifen against breast cancer, with no improvements. By adding melatonin to their therapy, researchers found that the tumors slightly shrunk in more than 28 percent of the women.

Studies also show that men with prostate cancer have lower melatonin levels than healthy men. A study published in Oncology Reports aimed to assess whether melatonin can change the growth of androgen-dependent prostate tumor cells. The results showed that melatonin is able to significantly inhibit the spread of prostate cancer cells.

Together, these studies show the promising potential of melatonin for a complementary natural treatment of cancer.

Melatonin dosage for adults

Melatonin is available in tablet, capsule, drop or sublingual tablet forms. Depending on the age and the intended benefits, melatonin can be dosed between 0.5 to 10 mg per day.

The benefits of melatonin have been extensively researched and the results showed that it does not pose much of a problem as an aid to insomnia in almost all age groups, from children to the elderly. However, it seems that it works differently in different dosages and that a higher dosage doesn't necessarily help better with insomnia.

The dosage of melatonin does not appear to be different for adults or for the elderly. Melatonin as a sleep aid in a dosage of 0.1 to 20 mg has effectively restored sleep pattern problems.

A study found that doses of 0.1 mg achieved a very good improvement in sleep problems and therefore compared this level of melatonin in the blood with that of healthy people without sleep problems. It has been shown that such a low dose was not only effective for sleep, but also increased the level of melatonin in the blood, up to the same range as that of healthy people without sleep problems.

In fact, when melatonin was first discovered by MIT (Massachusetts Institute of Technology) scientists, the university patented dosages between 0.3 mg and 1 mg because they never thought that people would take a dose three times higher than the 'physiological dose' of 0.3 mg. To avoid these patents, ironically, other companies started creating higher doses. This does not mean, that higher doses are better, the higher dosed product just got around the patent.

Remember - melatonin is a hormone. If hormones are ingested instead of using the hormones produced by the body itself, the body uses a feedback loop and often stops making these hormones itself. That is why it is often not a good idea to take more than the smallest effective dose when it comes to hormones like melatonin.

In a study in older people with sleep disorders, a dose of 0.3 mg melatonin (equivalent to 300 mcg) significantly improved sleep, but a dose of 3 mg, which was 10 times higher, was in fact not very effective.

In another study, a blind man with difficulty falling asleep was unable to improve his sleep by 10 mg, although the remaining members of a group with the same problem had no difficulty. They increased his dose to 20 mg with no improvement. But when they reduced his melatonin dose to 0.5 mg, his sleep improved significantly.

This means that a small dose of melatonin of 0.1 mg to 3 mg is usually as effective, and sometimes more effective, than a higher dose.

Melatonin against jet lag: An oral administration of 0.5 to five milligrams of melatonin one hour before bedtime at the final destination has been used in several studies. Another option is to take 1 to 5 milligrams an hour before bedtime, two days before departure and two to three days after arriving at your destination.

Melatonin for bio-rhythmic sleep disorders in people with and without visual disturbances: Melatonin for bio-rhythmic sleep disorders in people with and without visual disturbances

Melatonin in delayed sleep phase syndrome:0.3 to 6 milligrams orally (5 milligrams are most often used) a day before bedtime for two weeks to three months.

There are many other suggestions for dosing melatonin for various health problems based on scientific research, traditional use and expert advice.

When should you take melatonin?

Because melatonin is a hormone that is naturally produced by the body at night to promote sleep, without exception it should only be taken in the evening about half an hour before bed.

Melatonin makes you tired because that's exactly what it's supposed to do. So this is not a 'side effect of melatonin' as some people think, but an effect. If you are taking melatonin, please prepare to fall asleep and only take it before going to bed if you are able to sleep a full 8 hours.

Avoid the following mistakes when taking melatonin:

- When taking melatonin for a good night's sleep, people often take one tablet too early before going to bed, then notice that it doesn't work quickly enough and take another tablet.

- Some also wake up during the night and take another dose of melatonin. Although this may not cause serious problems, it is not the right way or safest way to use melatonin. The more you take, the more likely you are to experience undesirable side effects, such as morning tiredness.

Note:If you have cancer, you should always consult your doctor before taking melatonin.

Do massive doses of melatonin have side effects?

Different doses of melatonin have different effects. An investigation in which melatonin was administered in very high doses of up to 300 mg per day for several months and doses of 75 mg for 3 years showed no problems.

Lower melatonin doses show better effects

It is advisable to use the lowest possible dose of melatonin with an immediate release formulation for older adults, from 0.3 mg (which is already effective) to a maximum of 1 or 2 mg, preferably 1 hour before bed. This best mimics the physiological circadian rhythm of melatonin and avoids long-lasting blood levels above the physiological level.

It has also been shown that higher doses of orally ingested melatonin cause a prolonged increase in melatonin levels. Gooneratne et al. [5] showed that a higher dose in a 75% sustained release formulation (4 mg) compared to a lower dose (0.4 mg) caused a substantial prolongation of the elevated melatonin levels during the morning and during the day.

Zhdanova et al. also found that melatonin levels in the high dose group (3 mg) were maintained above a set threshold for longer than in the low dose groups (0.1 and 0.3 mg). This means that a higher dose carries the risk of prolonging the supra-physiological levels in older adults during the next day. This could lead to problems with side effects such as dizziness, drowsiness or a restless feeling when waking up, despite the low toxicity of melatonin.

Studies also looked at additional effects of melatonin administration on other outcomes, such as sleep and core body temperature. Oral melatonin had a positive effect on sleep parameters. Some studies showed that with higher doses and prolongation of the supra-physiological levels, melatonin loses its effectiveness on sleep parameters and with lower doses regains its effectiveness.

Melatonin for children - Is that a good idea?

Melatonin is a hormone that is produced in the pineal gland and digestive tract when you are exposed to the dark so that you can sleep. While naturally produced melatonin is absolutely safe, is taking melatonin a good idea for children too?

Most children produce enough melatonin themselves and do not normally need additional melatonin. However, there are some children who can't produce enough melatonin themselves and studies show that children with certain diseases can benefit from melatonin.

While there are only a few 'double-blind placebo-controlled' studies, there are many 'open' and 'cross-over' studies of children with

• developmental disorders
• autism
• neurological problems
• ADHD
• Asperger syndrome
• severe sleep disorders
• blindness
• cerebral palsy

It has not been studied for use in fibromyalgia in children, but since one of the defining symptoms of fibromyalgia is an altered sleep/wake cycle, it may also be effective for children.

There has been a significant number of studies with melatonin and children. Almost every study found that melatonin was effective in treating these children's sleep disorders with little to no side effects. It is so safe, that even high doses have been administered. It turned out to also show improvements for critically ill newborn babies who needed ventilation. This shows how safe melatonin is for children.

Melatonin dosage for children

Most melatonin studies in children were given a melatonin dose of 1 to 6 mg in the evening. But some adult studies and reports of melatonin for children show that as little as 0.1 mg (1/10 of a milligram) can be just as effective and may cause fewer problems with morning sleepiness or nightmares.

While it doesn't sound like much, there have been case studies from adults showing that higher doses were ineffective while lower doses were more effective. Although it is almost impossible to overdose on melatonin, it is always wise to give melatonin to children with the lowest dose, late in the evening or right before bed.

Overall, melatonin appears to be an effective and amazingly safe therapy for sleep disorders in children. In addition to this, children with digestive problems have shown improvements in the effects of melatonin as a relaxant for smooth muscles.

Melatonin side effects for children

Among the few side effects, most were associated with morning sleepiness. A very small number suffered from temporary headaches, nightmares and some others suffered from bed-wetting.

Otherwise, there have been very few reports of problems over the past decade of melatonin supplementation. Because the Defeat Autism Now protocol also recommends melatonin in children with sleep problems, thousands of autistic children have been taking melatonin as a safe sleep aid for a long time with few reported problems.

Is melatonin safe for children with seizures?

In at least one study, there was a report of a child with developmental disabilities who had a first attack after starting the melatonin study. So doctors are more likely to advise against giving melatonin to a child.

But there are actually many reports of seizures that have improved after the children were given melatonin. There is at least one study that has used melatonin effectively as a treatment for seizures in children who have had such severe seizures that no other medication has worked.

Despite a report in a child who had the seizure after starting the treatment, my reports and studies suggest that melatonin can be really beneficial for children with seizures.

In any case, there doesn't seem to be any reason not to give a child melatonin for sleep disorders just because they have a seizure disorder or are worried that melatonin could cause an attack. There seems to be little to no justification for this warning if it is used safely by thousands of children with autism and developmental disorders each year.

However, higher doses of melatonin can cause seizures in young people. It also disrupts puberty development because of the potential effects on hormones. Before you give melatonin to a child, you should always consult an experienced doctor in advance.

Melatonin and children with autism

Research has shown that melatonin can help children with developmental problems like autism. This is especially important as autism is on the rise.

A 2011 scientific review published in Developmental Medicine and Child Neurology evaluated 35 studies with melatonin-related insights into autism spectrum disorders, including autistic disorder, Asperger's Syndrome, Rett Syndrome and other common ones Developmental disorders.

After reviewing the numerous studies, the researchers came to the conclusion that melatonin supplementation for disorders in the autistic spectrum is associated with better sleep parameters, improved behavior during the day, and minimal side effects.

Does melatonin have side effects?

Very few people have problems with melatonin. Despite the large number of people taking melatonin in the United States, only a few side effects have been reported to the FDA.

Melatonin is very safe when taken for a short time. It can also be safe for some people to take it long term. Melatonin was taken without problems over a period of up to two years.

Melatonin has low toxicity and is generally well tolerated. However, sensitive people can experience the following side effects:

• vivid dreams or nightmares
• a headache
• dizziness
• drowsiness during the day
• short-term feelings of depression
• stomach cramps
• irritability
• decreased libido

Pregnant or breastfeeding women should not take melatonin. Melatonin is a hormone; So if you have or have had hormonal health problems, you should only use melatonin under the supervision of a doctor.

No motor vehicles or machines should be operated up to five hours after taking melatonin.

If you intentionally or accidentally take an overdose of melatonin, you should see a doctor immediately.

• Morning sleepiness

Morning fatigue is probably one of the most common side effects of melatonin and can be more pronounced with higher doses. It is not a symptom of an overdose as it is extremely difficult to cause an overdose of melatonin. In fact, those who have tried to overdose on melatonin have failed. In studies, up to 6 grams of melatonin have been administered every day for 30 days without noticing symptoms of an overdose.

If you are excessively sleepy after taking melatonin, there are two things to keep in mind the next time you take it:

1) Make sure that you can sleep a full 8 hours: The vast majority of people who complain of fatigue the next morning simply haven't had 8 hours of sleep. Of course, you are tired in the morning if you take melatonin as a sleep aid and do not allow yourself to sleep through the night.

2) Take a lower dose of melatonin: Some studies actually showed that a lower dose of melatonin could work better than higher doses. The average melatonin dosage is between 1 and 3 milligrams. But as little as 1/10 of a milligram was effective in studies to help people fall asleep. For some people, the lower dosage was even more helpful for sleep and they were less tired in the morning.

• Sleepiness and exhaustion

Since melatonin is a sleep enhancer, most of the reported side effects of melatonin are drowsiness. While this is more of an effect than a side effect, some people complain about it and often experience it as exhaustion rather than sleepiness.

It should be noted that melatonin should be taken in the evening, because that is the time when it is normally produced in the body. And since it helps users fall asleep, some people feel battered and tired in the morning, even throughout the day.

This is especially true for those with chronic sleep deprivation who have finally been able to sleep well again. When you can finally sleep again, but feel extremely tired during the day, no matter how much sleep you have got, this is called a state of 'hypersomnolence'. It's not a problem, it's a signal that things are changing for you.

If you experience hypersomnolence, stop taking melatonin until you have a few days off and take it just before going to bed on the weekend. Just plan on sleeping most of the weekend.

If you don't feel better at the end of the weekend, stop taking melatonin and repeat it the next weekend.

Your body 'catches up' due to long-term sleep deprivation and it can take up to a month or two weekends to remedy this.

If you see this as a cure, not a side effect of melatonin, it will be easier for you. Hypersomnolence is not a problem if you know what it is and how you can control it. It is actually a necessary part of a good night's sleep for those who have suffered from chronic insomnia.

• Sexual side effects

A very small percentage of people have complained of decreased sex drive and, interestingly, infertility. The reason for the low sex drive could very well be connected with the intake of melatonin at the wrong time of the day, with hypersomnolence or an excessive dosage of melatonin.

It can just be exhaustion and sleepiness instead a real problem with libido and if hypersomnolence resolves, the low libido is probably as good as gone.

However, one of the more interesting side effects of melatonin is the change in hormonal balance, which can lead to infertility in women and men when taken in massive doses.

Therefore, couples trying to conceive or women who are pregnant or breastfeeding should avoid melatonin for this reason.

Is melatonin safe?

The safety of melatonin is well documented. In the past decade that melatonin has been used as a supplement, there has been an astonishingly small amount of reports of melatonin side effects - even at high and even extremely high doses.

It has been shown that an overdose of melatonin is extremely difficult to produce. Indeed, it is extremely difficult to poison someone with melatonin, so scientists who attempted to produce toxicity in mice failed.

Scientists who are conducting preliminary studies on substances to find out the level of toxicity have developed a number called LD 50. The LD 50 is the dose that consistently kills half of the mice given the substance.

The scientists who were looking for Melatonins LD 50 could not produce a concentration that was strong enough to kill a mouse. This means that melatonin does not have an LD 50, regardless of the dosage.

And when scientists gave test subjects 6 grams (6,000 mg) of melatonin every night for a month, stomach problems and some remaining sleepiness were the only reported side effects.

In one study, people received 1 gram (1000 milligrams) of melatonin every day for a month without any problems. Another study gave the test subjects 6 grams (6000 milligrams) a day for a month, which was associated with a little sleepiness in the morning.

Does melatonin cause interactions?

Although the interactions between melatonin and medication have not been fully researched, people who take the following medications should consult their doctor before taking melatonin.

• Antidepressants
• Antipsychotic drugs
• Medicines for ADSH
• Birth control pills
• Medication against diabetes
• Medication that suppress the body's immune response
• Anticoagulants and anti-platelet drugs
• Sedatives
• Blood pressure medication
• Corticosteroids
• Gastric acid inhibitors such as omeprazole