Melatonin not only for sleep

Published: 11-02-2020

Last modified: 29-03-2020

Melatonin is known as the “sleep hormone”, but its importance for the body is much broader. It influences, among others the immune system, it is a powerful antioxidant, and newer studies indicate that it can be helpful in the treatment of obesity, osteoporosis and other common diseases in the elderly.

Melatonin is a hormone which levels fluctuate significantly throughout the day. It is produced mainly at night, in the pineal gland, in cells called pinealocytes. A signal to pinealocytes ordering them to produce melatonin comes from the suprachiasmatic nuclei in hypothalamus. The activity of these nuclei provokes the release of noradrenaline, thanks to which serotonin is converted into melatonin.

In addition to the pineal gland, melatonin also produces in smaller quantities, among others retina, digestive system, bone marrow, leukocytes.

In the largest amounts, melatonin is secreted between 4 and 10 years of age. During puberty, its secretion decreases, and then remains relatively stable until around 45 years of age. After this age, there is a clear decrease in the secretion of melatonin again, and in people over 60 – 70 years of age only small amounts of this hormone are observed in the blood. Its circadian rhythm of secretion also disappears.

Melatonin and biological rhythms

The best known function of melatonin is to regulate biological rhythms – seasonal and circadian. Seasonal rhythms are more pronounced in animals, circadian rhythms are more important in humans, including sleep-wake cycle. Melatonin is responsible for the feeling of drowsiness, but also for lowering the temperature and blood pressure at night. Thanks to its ability to shift the sleep phase, it is recommended to regulate the rhythm for shift workers and people with jet lag. It also helps blind people whose circadian rhythms are often disturbed and people with advanced or delayed sleep phase syndrome.

Melatonin as an antioxidant

During cellular respiration in mitochondria, some free radicals always form. These are mainly oxygen atoms with an unpaired electron, which in large quantities cause oxidative stress and contribute to the destruction of cell DNA.

Melatonin reduces oxidative stress and thus prevents cell death, which is particularly important in the nervous system, because all the most common neurodegenerative diseases are characterized by extinction of nerve cells.

Studies have shown that melatonin is more effective in removing free radicals than vitamins C and E, often indicated as an example of antioxidants.

In addition to removing free radicals, melatonin also prevents their formation due to its effect on thyroid hormones. The pineal gland regulates the production of the TRH hormone, which stimulates the production of another hormone – TSH, which stimulates the thyroid gland. Thanks to TSH, the thyroid secretes the hormone triiodothyronine (T3) and thyroxine (T4). Melatonin is involved in the conversion of T4 to T3, which is a more active hormone than T4. One of the functions of triiodothyronine is to provide mitochondria with energy to carry out the process of cellular respiration. If the energy is too low, excess unused oxygen remains, which leads to the formation of free radicals. By regulating thyroid hormones, melatonin prevents the formation of free radicals.

Melatonin in the prevention and treatment of cancer

By neutralizing free radicals, melatonin protects DNA from damage that can result in cancer. In addition, it can also help fight cancer. It has the ability to inhibit the proliferation of tumor cells, accelerate the apoptosis (death) of cancer cells, also prevents metastasis and is involved in the differentiation of cancer cells (transforming into other, less capable of division).

It can be particularly helpful in the prevention and treatment of hormone-dependent cancers (estrogen-dependent breast cancer and testosterone-dependent prostate cancer). Melatonin secretion cycle disorders, which have the ability to regulate estrogen and testosterone levels, have been observed in people with breast and prostate cancer.

It is possible that the reason for the increased number of cancer cases in recent decades is the melatonin deficiency that occurs in modern society due to artificial lighting. In the past, when the sun was setting, the pineal gland began producing melatonin. We are currently stopping this process and adjusting the natural circadian rhythm while staying in lit rooms. The hypothesis of the effect of melatonin deficiency on cancer formation is also supported by the fact that cancers are more common in older people who also have lower melatonin levels than in young people.

Melatonin and the immune system

Melatonin can be effective in preventing cancer also by strengthening the immune system.

The activity of the immune system decreases with age. NK cell activity, which plays an important role in preventing cancer and metastasis, as well as macrophages and granulocytes that destroy pathogenic organisms, is lowered. The lymphocyte profile also changes. The number of helper T lymphocytes, which are responsible for stimulating the immune response, is reduced, and the number of cytotoxic T lymphocytes, which are involved in the fight against viruses and tumors, and which may also be responsible for transplant rejection, is increased.

Melatonin stimulates the production of macrophages, granulocytes, NK cells and T helper cells and inhibits the production of cytotoxic T cells. It also increases the activity of NK cells and helper T cells. In this way, it contributes to the “rejuvenation” of the immune system.

Another beneficial feature of melatonin is the prevention of damage to the immune system by corticosteroids secreted during stress.

In animals and humans, seasonal changes in the functioning of the immune system have also been observed which may be due to changes in the amount of melatonin produced.

Melatonin and the circulatory system

Melatonin also has a beneficial effect on the circulatory system. Lowers blood cholesterol if it gets too high and has the ability to regulate blood pressure.

Melatonin in the digestive system

In the digestive system, melatonin’s function is to slow down digestive processes, which increases the absorption of needed vitamins and microelements contained in food. It is particularly beneficial to increase the absorption of zinc, which deficiency often occurs in older people, and which has a beneficial effect on the immune system.

Melatonin in the treatment of neurodegenerative diseases

Recently, the possibility of using melatonin in the treatment of neurodegenerative diseases is being investigated.

Lower levels of melatonin have been demonstrated in Alzheimer’s patients, including those in preclinical conditions when there are no visible symptoms yet. People with Alzheimer’s disease often have a disturbed sleep-wake cycle, which can be regulated by melatonin intake. Although there is not much research on the effects of melatonin on people with this disease, some of them indicate that melatonin can have a positive effect not only on sleep but also can slow down cognitive decline.

Research is also underway to introduce melatonin for the treatment of Huntington’s disease and amyotrophic lateral sclerosis. Although little research is available yet, the first one are promising.

Contradictory results were obtained in the case of Parkinson’s disease. Some studies have shown a reduction in the severity of symptoms after melatonin, while the opposite, an increase.

Melatonin in the treatment of obesity

Adipose tissue is divided into white and brown, which function is to generate heat. Until recently, it was thought that brown adipose tissue only occurs in newborns and young children, but recent studies show that it also occurs in quite significant amounts in adults. This tissue burns large amounts of calories to produce heat, thus consuming glucose and fatty acids, reducing fat build-up. Melatonin controls the size and activity of brown fat and the conversion of white tissue to brown. There are no studies yet on the effects of melatonin on obesity in humans, but animal studies have shown that it contributes to weight reduction, even without changing diet.

Animal studies have also shown that melatonin deprivation causes glucose intolerance and insulin resistance. The same symptoms are seen in people with reduced levels of melatonin in the blood (e.g. night workers, people with diabetes, older people).

Melatonin’s function is also to increase leptin synthesis, which is responsible for suppressing appetite.

Melatonin in bone diseases

It is thought that melatonin may play a role in osteoporosis and idiopathic scoliosis (lateral curvature of the spine).

Animal studies have shown that deprivation of melatonin causes calcium deficiency, while in vitro studies have shown the stimulating effect of melatonin on osteoblast differentiation (osteogenic cells) and their activity. It is possible that with age, a decrease in melatonin levels causes a shift in the differentiation of bone marrow cells, from osteoblasts to adipose tissue cells.

The hypothesis of the effect of melatonin deficiency on osteoporosis is supported by an analysis of 38,000 postmenopausal women which showed that women who worked 20 years or more at night had a greater risk of wrist or hip fractures than women who never worked at night.

Some data also indicate the possible role of melatonin deficiency in the development of scoliosis. Many studies have shown that depleting melatonin causes scoliosis in animals. Some studies also show lower levels of melatonin in people with scoliosis. There is currently little research into the role of melatonin in scoliosis, but many scientists agree that it may be important in the development and prevention of this disease.

References:

1. Cipolla-Neto, J., Amaral, F. G., Afeche, S. C., Tan, D. X., Reiter, R. J. (2014). Melatonin, energy metabolism, and obesity: a review Journal of Pineal Research, 56(4), 371-381
2. Karasek, M. (2007). Znaczenie kliniczne melatoniny Postępy Nauk Medycznych 10, 395-398
3. Pandi-Perumal, S. R., BaHamman, A. S., Spence, D. W., Brown, G. M., Bharti, V. K., Kaur, C., Hardeland, R., Cardinali, D. P. (2012). Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotoxicity Research, 23(3), 267-300 (pdf on uca.edu.ar)
4. Pierpaoli, W., Regelson, W., Colman, C. Cud melatoniny, Wydawnictwo Amber, 1996
5. Reiter, R. J., Tan, D. X., Fuentes-Broto, L. (2010). Melatonin: a multitasking molecule. Progress in Brain Research, 181, 127-151 (pdf on drvitaminsolutions.com)
6. S´anchez-Barcel, E. J., Mediavilla, M. D., Tan, D. X., Reiter, R. J. (2010). Scientific Basis for the Potential Use of Melatonin in Bone Diseases: Osteoporosis and Adolescent Idiopathic Scoliosis, Journal of Osteoporosis, 2010, 1-10 (pdf on hindawi.com)
7. Srinivasan, V., Maestroni, G. J., Cardinali, D. P., Esquifino, A. I., Pandi-Perumal, S. R., Miller, S. C. (2005). Melatonin, immune function and aging Immunity & Ageing, 2(17)

Author: Maja Kochanowska