The role of Epithalon in the processes of restoring the proper circadian rhythm and better sleep quality

Effect restoring balance of the circadian rhythm and improving sleep quality and duration. Peptide therapy for insomnia and disturbances of melatonin production.

Summary: Epithalon is a synthetic peptide, created based on a natural peptide present in the pineal gland; it is a peptide used as a sleep regulator improving its quality. Additionally, peptide therapy using Epithalon allows elimination of insomnia problems and disturbances in melatonin production.

Keywords: epithalon; circadian rhythm; sleep; sleep quality; melatonin; balance; insomnia; sleep phases; metabolism; synthesis; release; sleep disorders; melatonin receptors; telomere shortening; stimulation List of abbreviations: SCN- SPZ- NREM; ALA; ASP; GLU

Introduction

Recent studies have shown that NL Epithalon stimulates the pineal gland to produce melatonin – sleep hormone. These observations are supported by experiments in both animals and humans, where a positive effect on nighttime melatonin production was observed in both cases. This mechanism also contributes to circadian rhythm regulation and anti-aging effects, as with advancing age the ability to produce melatonin declines and sleep quality deteriorates, which in turn may negatively affect other aspects of health.

WHAT IS SLEEP

Sleep is a functional state of the central nervous system, cyclically occurring and recurring in a circadian rhythm, during which consciousness and movement are suppressed. Physiological sleep is characterized by full reversibility under external stimuli.

SLEEP PHASES

MELATONIN

Considering its chemical nature, melatonin is a low-molecular-weight compound that is well soluble in both water and fats. Melatonin, as a hormone produced by the pineal gland in the brain, is regulated in a circadian cycle and even in seasonal patterns, and participates in the regulation of many behavioral and physiological processes. Melatonin levels fluctuate across different phases of the cycle. The substance itself is not stored in the body, and the rate of its synthesis is proportional to the rate of its release into the bloodstream.

MELATONIN SYNTHESIS

In the body, melatonin synthesis occurs thanks to its precursor, tryptophan, which is taken up from the blood. The main enzyme involved in melatonin synthesis is N-acetyltransferase. The site of synthesis is the aforementioned pineal gland; in small amounts melatonin is also produced in the retina and lens of the eye, the epithelial lining of the gastrointestinal tract, and blood cells. Information about environmental light conditions reaches the pineal gland via a complex neuronal pathway starting in the retina: retina → retinohypothalamic tract → SCN → paraventricular nucleus → medial forebrain bundle → midbrain roof → intermediolateral cell column of the spinal cord → superior cervical ganglion → postganglionic sympathetic fibers → pinealocytes of the pineal gland.

MELATONIN METABOLISM

Circulating melatonin in the blood undergoes rapid metabolic transformation in the liver, first by hydroxylation at position 6, followed by conjugation of 6-hydroxymelatonin with sulfuric or glucuronic acid. The resulting inactive metabolites are excreted from the body via urine. The biological half-life of exogenous melatonin in humans is short and ranges from 10 to 60 minutes.

MELATONIN RELEASE

Postsynaptic receptors located in the superior cervical ganglion regulating the pituitary control melatonin release. The suprachiasmatic nuclei of the hypothalamus receive signals from the retina, giving them the character of an anatomical biological clock linked to the light cycle. At night, signals are sent from the suprachiasmatic nuclei to receptors in the superior cervical ganglion and the pineal gland, leading to melatonin secretion. Synthesized melatonin is rapidly and pulsatilely released into the bloodstream and cerebrospinal fluid, from where it is distributed throughout the body.

MELATONIN RECEPTORS

Activation of melatonin receptors determines subsequent biological effects. The main melatonin receptors are membrane receptors MT1 and MT2, which are coupled with regulatory proteins binding guanine nucleotides (G proteins). The second group of melatonin receptors, called nuclear receptors, belongs to the ROR/RZR family. Melatonin action via membrane receptors and G proteins leads to a decrease in intracellular cAMP with a simultaneous increase in calcium ion concentration and activation of phospholipase C. Membrane receptors are also involved in regulating ion channel activity and cellular detoxification. ROR/RZR receptors participate in the regulation of immune processes, differentiation of the central nervous system, and maturation of T lymphocytes.

MELATONIN SECRETION DEPENDING ON AGE

Melatonin secretion in humans during the circadian rhythm begins after the sixth week of life. With age, a significant increase in nocturnal hormone secretion is observed. During puberty, melatonin secretion decreases, and then gradually declines further with age. After reaching 65–70 years of age, the circadian rhythm of melatonin secretion almost completely disappears.

MELATONIN IN SLEEP DISORDERS

Melatonin, as a hormone regulating the day–night circadian rhythm and seasonal biorhythms, is also involved in mood and sleep quality. It has been shown that administration of an analogue of this hormone in tablet form induces drowsiness or sleepiness and improves sleep quality to allow faster and more effective recovery and rest. Observations in humans have shown that daily and seasonal changes in melatonin levels lead to sleep disturbances, insomnia, and affective disorders described as depressive states, most often occurring in winter. In humans, melatonin accelerates sleep onset, reduces nighttime awakenings, increases total sleep duration, and improves its quality.

SLEEP REGULATION PROCESSES

Two processes are involved in sleep regulation: homeostatic and circadian. The first depends on sleep duration, while the second regulates transitions between sleep and wakefulness. All stages of NREM sleep, which constitute over 80% of total sleep, are controlled by the homeostatic process. The suprachiasmatic nucleus interacts with regulatory mechanisms and is likely responsible for disturbances in the functioning of the main circadian clock, playing an important role in sleep–wake disorders. Circadian sleep–wake cycles also require neurons in the ventral subparaventricular zone of the hypothalamus, which project to the dorsomedial hypothalamus. The sleep–wake rhythm is therefore controlled by a circuit with two relays: one from the suprachiasmatic nucleus to the ventral subparaventricular zone (SPZ), and the second connecting it to the dorsomedial hypothalamus.

CIRCADIAN RHYTHM

The circadian rhythm is the fundamental mechanism influencing sleep duration, quality, and timing. Technological progress, widespread exposure to artificial light in the evening and at night combined with low exposure to sunlight during the day, lack of physical activity, long periods of mental activity during the day and often immediately before sleep, irregular meal times, shift work and/or irregular work schedules contribute to circadian rhythm disturbances of sleep and wakefulness, manifesting as poor sleep quality and reduced psychophysical performance during the day, which are common health problems in developed societies. It should be remembered that the circadian rhythm determines proper functioning of the organism. Unfortunately, with age it is often disrupted. A clear decline in melatonin production and deterioration of sleep quality accompany this process.

NL EPITHALON

NL Epithalon is a synthetic tetrapeptide with the amino acid sequence Ala-Glu-Asp-Gly, molecular formula C14H22N4O9, and molecular weight 390.35 g/mol. NL Epithalon is derived from epithalamin, a naturally occurring polypeptide produced in the pineal gland. The main property of NL Epithalon is its ability to increase telomerase activity in somatic cells. This helps cells restore telomeres, which are essential protective parts of our DNA, resulting in regulatory effects on circadian rhythm and sleep disturbances through normalization of melatonin levels, promotion of deeper sleep, and strong antioxidant properties.

SLEEP ACTION OF NL EPITHALON

Available data indicate a beneficial effect of NL Epithalon as a therapy for sleep disorders, causing, among others, earlier evening fatigue and sleepiness, reduced sleep latency, faster sleep onset and awakening, faster resynchronization of biological rhythms to a new time zone, and reduced sleep disturbances.

TELOMERE SHORTENING

A telomere is an important region of repetitive nucleotide sequences at each end of a chromosome that protects the chromosome ends from degradation or fusion with neighboring chromosomes. With each cell division, telomeres shorten because DNA polymerase cannot fully replicate chromosome ends, resulting in progressive shortening at each replication cycle. After many divisions, telomeres reach a critical length, after which the cell loses its ability to divide further to replace worn-out or damaged cells. Further division becomes impossible, and the cell undergoes aging. At this point, the cell has reached the so-called Hayflick limit.

EXPERIMENT ON TELOMERE SHORTENING

Mothers who slept less than 7 hours per day had significantly shorter telomeres in white blood cells. Telomeres are small DNA fragments located at the ends of each chromosome. They act as protective caps, shielding it from damage during replication. Shortened telomeres have long been associated with higher risk of cancer, cardiovascular disease, and other conditions, as well as earlier death.

NL EPITHALON SUPPORTING BETTER SLEEP QUALITY THROUGH PREVENTION OF TELOMERE SHORTENING

NL Epithalon is used to increase natural telomerase production, an enzyme that helps cells restore telomeres, the protective parts of our DNA. This ultimately slows cellular aging. Through these mechanisms, NL Epithalon can be used to restore and normalize melatonin levels or to protect cells from oxidative stress. It has also been shown to help restore and normalize melatonin production in the pineal gland and to restore the normal circadian rhythm of cortisol production, ensuring better night sleep.

STIMULATION OF MELATONIN BY NL EPITHALON

With aging, a reduced nocturnal plasma melatonin level and reduced amplitude of the hormonal circadian rhythm are observed, indicating impaired pineal melatonin release. The peptide preparation NL Epithalon restores nocturnal endogenous melatonin secretion and normalizes the hormonal circadian rhythm in blood plasma. In elderly individuals, NL Epithalon modulates pineal function: functional insufficiency of the pineal gland is accompanied by an increase in nighttime melatonin levels. Additionally, NL Epithalon effectively increases melatonin concentration without causing side effects.

EXPERIMENT ON MELATONIN STIMULATION BY NL EPITHALON

NL Epithalon tetrapeptide (Ala-Glu-Asp-Gly) was synthesized based on the amino acid composition of Epithalamin. The effect of NL Epithalon on melatonin and cortisol secretion in individuals of different ages was studied.

EXPERIMENT RESULTS:

The experiment clearly showed that NL Epithalon increased melatonin levels in the evening hours. Melatonin levels in subjects treated with NL Epithalon were more than 3 times higher than in the control group. NL Epithalon not only stimulated melatonin synthesis but also normalized circadian rhythms of cortisol concentration in peripheral blood.

RESTORATION OF NORMAL CIRCADIAN RHYTHM BY NL EPITHALON

A study of the effect of NL Epithalon on circadian rhythms disrupted by the neurotoxin DMH showed restoration of daily NE dynamics in the MPA. This peptide prevents xenobiotic-induced disturbances in DA circadian rhythm, maintaining low metabolite levels at 5 o'clock (CT) and increasing them at 11 o'clock (CT). The obtained data suggest that the pineal gland is important for normalization of the circadian signal required for gonadotropin-releasing hormone secretion.

EXPERIMENT ON RESTORATION OF NORMAL CIRCADIAN RHYTHM BY NL EPITHALON

A small study involving 14 individuals of different ages showed that NL Epithalon improved melatonin production in all participants.

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