Melatonin – hormone
Melatonin – hormone with antioxidant effect Photo © : AdobeStock/JEGAS_RA Melatonin – a versatile substance not only for sleep disorders Philipp Gebhardt Melatonin is a hormone synthesized and released by cells in the pineal gland. It controls the day-night rhythm of the human body and promotes sleep. The European Food Safety Authority (EFSA) considers it scientifically proven that melatonin helps to alleviate the subjective sensation of jet lag and to reduce the time it takes to fall asleep. Melatonin also has endocrine effects and affects the functioning of the immune system. Current scientific studies have shown positive effects on various diseases. The endogenous hormone melatonin is formed from serotonin by the pineal cells of the epiphysis (Fig. 1). Melatonin synchronizes the organism to the 24-hour rhythm of day and night. The synthesis and release of the hormone are stimulated by darkness. The blood concentration increases during the night, the maximum is reached around three o'clock in the morning (Fig. 2). In children, values can be measured about twelve times higher at night than during the day. With increasing age, less melatonin is formed (Fig. 3). Melatonin is a natural antagonist of the stress hormone cortisol. Reduced melatonin formation is associated with sleep disorders or disorders of the sleep-wake cycle. (1) Pituitary gland Pons Pineal gland Cerebellum Spinal cord Fig. 1: Melatonin is formed from serotonin in the epiphysis located in the diencephalon. The activity of certain enzymes involved in melatonin synthesis is indirectly dependent on daylight. Melatonin in insomnia Sleep is vital for the regeneration of body and mind. A good and restful sleep is important for our daytime well-being and our perfor- 12 No. 2 August/September 2022
Melatonin – hormone with antioxidant effect 100 Melatonin [pg/ml] plasma saliva 80 60 40 20 darkness 0 08:00 12:00 16:00 20:00 24:00 04:00 08:00 Fig. 2: The synthesis of melatonin is inhibited by light and stimulated by darkness. The highest concentrations are reached around midnight. During the second half of the night, the concentrations fall off. (2) 140 Melatonin [pg/ml] 120 100 80 60 40 20 Age (years) 0 0 10 20 30 40 50 60 70 Fig. 3: The formation of melatonin varies with age. The highest concentrations are reached during early childhood. With increasing age, less melatonin is produced. From the age of about 55 years, only low levels can be measured. (2) mance, both mentally and physically. Sleep is also very important for learning. During sleep, processes take place that consolidate what has been learned. Sleep disorders lead to reduced performance and tiredness during the day, irritable mood and disturbances in attention and concentration. According to this, about 10 % of adults in industrialized countries suffer from chronic insomnia symptoms, which are characterized by difficulty falling asleep, sleeping through the night or only superficial and non-restorative sleep. (3) It has been proven that sleep disorders impair the function of the immune system and increase the risk of heart attacks, heart failure and high blood pressure in the long term. Due to its chronobiological effect, melatonin is being studied for the treatment of sleep disorders and as a natural sleep aid. According to a review that evaluated the data of 1,683 participants, melatonin can contribute significantly to reducing the time it takes to fall asleep as well as increasing sleep time. Longer use and a higher dosage were associated with greater effects. The use of melatonin also led to a significant improvement in sleep quality. (4) It has also been shown that melatonin can reduce disturbances in the sleep-wake cycle after long-haul flights (jet lag). (5) In clinical practice, melatonin has also proven itself as a suitable substance for inducing sleep in children with psychomotor disorders. Significant improvements in terms of sleep duration and sleep quality could be demonstrated. (6) Melatonin as an antioxidant As highly reactive intermediate products of the metabolism, free radicals damage the body's own tissues. It is assumed that corresponding damage to the DNA can also lead to degenerative diseases or cancer. Melatonin forms a direct radical scavenger for oxygen and nitrogen radicals, which is charac terized by the fact that the resulting metabolites can also neutralize radicals. This property is called a cascade reaction and makes melatonin a particularly potent antioxidant. In addition, melatonin seems to significantly improve the body's antioxi dant capacity, as it positively influences both the cellular formation and the activity of antioxidant enzymes. (7) Effect on the mitochondria Mitochondria are cell organelles in which the oxidative phosphorylation, the generation of energy with oxygen consumption, takes place. The number of mitochondria per cell is typically in the order of 1000 to 2000, with a volume fraction of about 25 %. While 2 moles H + H + H + H + I e e e Q10 e II Cyt.C III e e IV V Inner mitochondrial membrane Mitochondrion ADP of adenosine triphosphate (ATP) per mole of glucose can be obtained through anaerobic fermentation, aerobic energy generation via the respiratory chain located in the mitochondria enables 36 moles of ATP per mole of glucose. Due to the high efficiency of oxidative phosphorylation, more than 90 % of the organism's energy is formed in the mitochondria. Since ATP cannot be stored in significant amounts, it has to be constantly regenerated from ADP in the cells. The daily conversion of ATP is in the range of a person's body weight. Mitochondria are believed to have been incorporated into more developed cells during evolution as bacterial symbionts. Mitochondria have their own genome, which is sensitive to oxidative damage due to its simple structure. Damage to the mitochondrial genome results in reduced energy production and is associated with the increased occurrence of chronic diseases in old age. Melatonin concentrations are about 100 times higher in mitochondria than in plasma. (8) Melatonin plays a special role in the mitochondria because it protects a special phospholipid, cardiolipin, from reactive oxygen radicals. (9) Cardiolipin is the only phospholipid synthesized exclusively in the mitochondria. It is stored in the inner mitochondrial membrane and serves to stabilize the respiratory chain complexes. According to recent findings, cardiolipin helps to give the membrane a specific shape, which is also required for the efficient functioning of a transport protein called Aac2. Aac2 transports ADP into the mitochondria and ATP out of the mitochondria (Fig. 4). (10) Fig. 4: Mitochondria are cell organelles enclosed by a double membrane. The inner membrane carries the respiratory chain complexes. These are proteins that catalyse oxidative phosphorylation, the production of energy while consuming oxygen. The transport protein Aac2, which transports ADP into the mitochondria and transports ATP out of the mitochondria, is also stored in the inner membrane. ATP Aac2 ADP ATP ATP Aac2 ADP ADP No. 2 August/September 2022 13
