Article by Dr Manasa S, B.A.M.S
AIAPGET Points
– Melatonin is synthesized from tryptophan → serotonin → melatonin in pinealocytes of the pineal gland.
– Secretion of melatonin is inversely proportional to light exposure and is mediated via the retino-hypothalamic-pineal pathway.
– Light information reaches the pineal gland through the sequence:
Retina → Suprachiasmatic nucleus (SCN) → Sympathetic fibers → Pineal gland.
– Suprachiasmatic nucleus (SCN) of hypothalamus is the master circadian pacemaker controlling melatonin secretion.
– Melatonin secretion shows a circadian rhythm with nocturnal peak (2–4 AM).
– Melatonin does not induce sleep directly, but facilitates sleep by lowering core body temperature and reducing alertness.
– Exposure to blue light (screens) suppresses melatonin secretion — a frequent exam distractor.
– Longer nights → prolonged melatonin secretion (basis of winter sleepiness and SAD).
– Melatonin is absent in neonates; circadian rhythm develops by 3–4 months of age.
– Melatonin levels are highest before puberty and decline after puberty.
– Progressive decline occurs after 40 years, contributing to sleep disturbance in elderly.
– Melatonin has an inhibitory effect on GnRH → ↓ LH & FSH secretion.
– Excess melatonin is associated with delayed puberty and hypogonadotropic hypogonadism.
– Pineal tumors in children may present with precocious puberty due to loss of melatonin inhibition.
– Melatonin is a potent free-radical scavenger, especially within the CNS.
– It protects neurons from oxidative stress, nitric oxide, and hydrogen peroxide.
– Reduced melatonin is linked with neurodegenerative disorders (Alzheimer’s, Parkinson’s)
– Hypomelatoninemia → circadian rhythm disorders, insomnia, SAD.
– Hypermelatoninemia is most commonly due to excess supplementation, not pineal overproduction.
– Beta-blockers reduce melatonin secretion → beta-blocker–induced insomnia.
Melatonin
Melatonin is a naturally occurring hormone that is primarily produced by the pineal gland in the brain. It plays a central role in regulating the sleep–wake cycle and maintaining the body’s circadian rhythm.
Endogenous melatonin (melatonin produced within the body) helps synchronize internal biological rhythms with the external light–dark cycle. Its secretion increases during the evening and night, promoting sleepiness, and decreases during daylight hours, supporting wakefulness. Through this rhythmic secretion, melatonin helps the body recognize when to rest and when to be alert.
Melatonin is therefore an essential hormonal signal for sleep initiation and sleep timing, rather than a sedative itself. It supports the natural process of falling asleep and waking after adequate rest.
In addition to natural production, melatonin can also be synthesized in laboratories and is available as a dietary supplement. This form is known as exogenous melatonin and is commonly used to manage sleep-related disorders and circadian rhythm disturbances.
Function of Melatonin
Melatonin plays a key role in regulating the body’s circadian rhythm.
The circadian rhythm is the natural sleep–wake cycle that follows a 24-hour pattern.
– Melatonin prepares the body for sleep.
It does not directly cause sleep, but it signals the body that it is time to slow down and rest.
– The pineal gland secretes melatonin in response to darkness.
Melatonin levels are highest at night and lowest during daylight hours.
– Exposure to light suppresses melatonin secretion.
This is why melatonin levels fall in the morning and rise after sunset.
– The duration of melatonin secretion depends on the length of darkness.
Longer nights result in prolonged melatonin release.
– During winter months, reduced daylight leads to increased melatonin secretion.
This explains why people may feel sleepy earlier or experience increased sleepiness in winter.
Mechanism of Action of Melatonin
Melatonin acts as a chemical messenger that signals the body to enter a state of rest.
The pineal gland releases melatonin at roughly the same time every evening, usually after sunset.
Melatonin primarily acts on the hypothalamus.
It signals the hypothalamus to reduce daily physiological activity.
In response, the hypothalamus slows down functions such as:
– Body temperature
– Blood pressure
– Emotional alertness
These changes help prepare the body for sleep.
Melatonin also acts on the retina of the eyes.
It reduces retinal sensitivity to light, promoting relaxation and reduced alertness.
With morning light exposure, retinal activity increases.
This suppresses melatonin secretion and promotes wakefulness.
Ayurveda Viewpoint
The pineal gland which secretes the hormone melatonin is located in the brain (head) which is also the chief seat of Prana Vayu. The functions of these are directly related to those of Prana Vayu to a greater extent and also to those rendered by Sadhaka Pitta and Tarpaka Kapha and also Udana Vayu. The functions of the mentioned dosha subtypes can thus be attributed to the neuro-endocrine functions of pineal gland and those of Melatonin. The circadian rhythm is a resultant of balance and coordinated functioning of these dosha subtypes.
The detachment of manas i.e. mind from its senses (indriyas) is very much essential for the person to withdraw from the worldly objects and slip into a pleasant sleep while its indulgence with the indriyas brings about alertness.
The physiology of sleep, its benefits and harmful effects as explained in Ayurveda reflects the entire game of Melatonin.
The functions of pineal gland and melatonin represent the synchronized functional axis of Prana Vata and other Vata Subtypes. They grossly and subtly represent the functions of the entire orchestra of the endocrinal / hormonal system. The pineal gland too serves as the key link between the nervous system and hormonal regulation.
Related Reading – Ayurveda Understanding of Circadian Rhythm, Pineal Gland and Functions and Dysfunctions of Melatonin
Benefits of Melatonin
Melatonin plays a central role in maintaining the body’s internal biological rhythm. Its primary function is to regulate the sleep–wake cycle, but its influence extends to several physiological systems.
Regulation of Sleep and Circadian Rhythm
Melatonin acts as the body’s natural signal for sleep onset. It helps prepare the body for rest by synchronizing the circadian rhythm with the light–dark cycle. Adequate melatonin secretion supports restorative sleep, which is essential for overall health, including the maintenance of:
– Mental and emotional well-being
– Skin health
– Hair health
– Optimal function of internal organs
Because of this role, melatonin is often referred to as the “sleep hormone” and is commonly used as a natural aid in certain sleep disorders.
Seasonal Affective Disorder (SAD)
Seasonal affective disorder is associated with changes in daylight exposure across seasons.
– Winter-pattern SAD may be linked to increased melatonin secretion due to prolonged darkness.
– Summer-pattern SAD, which accounts for a smaller proportion of cases, may involve relatively lower melatonin levels.
The exact role of melatonin in SAD is still under investigation, and further research is needed to clarify its therapeutic significance.
Reproductive and Hormonal Balance
Melatonin contributes to the regulation of reproductive hormones and is believed to help maintain regular menstrual cycles by interacting with the hypothalamic–pituitary–gonadal axis.
Neuroprotective Effects
Melatonin exhibits neuroprotective properties. It may help protect brain cells from oxidative damage and degeneration, processes that are associated with neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease. While experimental and observational studies are promising, definitive clinical evidence is still evolving.
Antioxidant and Cellular Protection
Melatonin is a potent antioxidant. It helps neutralize free radicals, thereby reducing cellular damage. This antioxidant action may support eye health and overall cellular integrity, though long-term effects of supplemental melatonin require further human studies.
Gastrointestinal Benefits
Melatonin has been shown to influence gastrointestinal function. It may:
– Reduce gastric acid secretion
– Decrease nitric oxide production, thereby preventing excessive relaxation of the lower esophageal sphincter
Through these mechanisms, melatonin may help alleviate symptoms of gastroesophageal reflux disease (GERD), such as heartburn and acid reflux.
Therapeutic Uses of Melatonin (Based on Evidence)
Likely Effective
– Delayed sleep phase syndrome: Helps reduce sleep-onset latency in children and young adults
– Non-24-hour sleep–wake disorder: Improves sleep patterns in blind children and adults
Possibly Effective
– Beta-blocker–induced insomnia
– Adjunctive use in certain cancers (under medical supervision)
– Reduction of postoperative confusion and agitation in children
– Controlled-release melatonin for hypertension
– Short-term management of insomnia, particularly in older adults
– Jet lag symptom relief
– Migraine prevention
– Pre-procedure anxiety and sedation reduction
– Sunburn prevention (topical use)
– Temporomandibular joint disorders (TMD)
– Cancer-related thrombocytopenia
Possibly Ineffective
– Athletic performance enhancement
– Cancer-related fatigue and pain
– Cachexia in chronic illness
– Critical illness recovery
– Dementia symptom improvement (except possible reduction of sundowning)
– Infertility
– Shift-work sleep disorder
Likely Ineffective
– Benzodiazepine withdrawal symptoms
– Depression (may worsen symptoms in some individuals)
Melatonin and Aging
Experimental observations suggest that removal of the pineal gland accelerates aging processes. This has led to the hypothesis that endogenous melatonin may possess anti-aging properties, though this concept remains under active research.
What are normal melatonin levels?
Normal melatonin levels vary based on age and sex recorded at birth. In general, females tend to have slightly higher melatonin levels than males.
Melatonin production also changes significantly across the lifespan:
– Before birth: A fetus does not produce its own melatonin. Instead, melatonin is supplied through the placenta from the mother.
– After birth: Newborns initially do not synthesize melatonin. They may receive small amounts through breast milk or formula.
– Infancy: A regular melatonin rhythm begins to develop around 3 to 4 months of age, when infants start establishing a sleep–wake cycle.
– Childhood and adolescence: Melatonin levels are highest during childhood and early teenage years, peaking just before the onset of puberty.
– Post-puberty: After puberty, melatonin secretion gradually decreases and stabilizes by the late teenage years.
– Adulthood: Levels generally remain steady until around 40 years of age, after which there is a slow, natural decline for the rest of life.
Most people are unaware of their melatonin levels unless they experience sleep disturbances or related symptoms. When testing is required, a healthcare provider can assess whether melatonin levels fall within the expected normal range for that age group.
Conditions and Disorders Related to Melatonin
Disorders related to melatonin mainly arise due to imbalances in its secretion. These conditions are broadly classified into two types:
– Hypomelatoninemia – lower-than-normal melatonin levels
– Hypermelatoninemia – higher-than-normal melatonin levels
Hypomelatoninemia
Hypomelatoninemia refers to reduced nighttime melatonin levels or a total melatonin output lower than expected for a person’s age.
This condition is commonly associated with circadian rhythm sleep disorders, where the body’s natural sleep–wake cycle is disrupted.
These disturbances may affect:
– The timing of sleep and waking
– Quality of sleep
– Daytime alertness, mood, and overall functioning
Low melatonin levels can make it difficult to fall asleep, stay asleep, or feel refreshed after sleep.
Hypermelatoninemia
Hypermelatoninemia occurs when there is an excess of melatonin in the blood.
– The most common cause is excessive intake of synthetic (supplemental) melatonin.
– Rarely, it may result from overproduction by the pineal gland.
Elevated melatonin levels have been linked to an increased risk of certain conditions, including:
– Anorexia nervosa and other eating disorders
– Hypogonadotropic hypogonadism, where reduced estrogen or testosterone production occurs due to hypothalamic or pituitary dysfunction
– Polycystic ovary syndrome (PCOS), characterized by hormonal imbalance, irregular menstruation, and possible infertility
– Rabson–Mendenhall syndrome, a rare genetic disorder associated with severe insulin resistance and hyperglycemia
– Spontaneous hypothermia with hyperhidrosis, marked by sudden episodes of low body temperature accompanied by excessive sweating
Dosage of Melatonin
Melatonin is commonly taken in doses ranging from 0.5 mg to 10 mg per day.
Since the strength and formulation of melatonin supplements can vary, it is advisable to follow the dosage recommended on the product label to avoid adverse effects. Starting with a lower dose and gradually increasing, if required, is generally recommended to determine individual tolerance and effectiveness.
– For improving sleep quality, melatonin is best taken about 30 minutes before bedtime.
– For correcting circadian rhythm disorders or establishing a regular sleep–wake cycle, melatonin may be taken 2–3 hours before the intended bedtime.
Safety of Melatonin
Research indicates that melatonin is generally safe and non-addictive when used for short-term and long-term purposes in adults.
However, long-term safety data in children and adolescents is limited. Therefore, routine use of melatonin in these age groups is not currently recommended without medical supervision.
Side Effects of Melatonin
Melatonin is usually well tolerated. The most commonly reported side effects include:
– Nausea
– Headache
– Dizziness
– Daytime sleepiness
These effects are typically mild and dose-dependent.
Drug Interactions
Melatonin may interact with certain medications, including:
– Antidepressants
– Blood thinners
– Antihypertensive medications
Caution is advised when melatonin is used alongside these drugs, and medical guidance is recommended.
Melatonin – Quick Revision Points
– Melatonin is a natural hormone mainly secreted by the pineal gland.
– It is also known as the “sleep hormone” due to its role in regulating the sleep–wake cycle.
– Melatonin regulates the circadian rhythm, which follows a 24-hour biological cycle.
– Endogenous melatonin refers to melatonin produced naturally by the body.
– Exogenous melatonin refers to synthetic melatonin used as a dietary supplement.
– Melatonin secretion increases in darkness and decreases with light exposure.
– Peak melatonin levels occur at night, while levels are low during daylight.
– Longer nights (e.g., winter) lead to prolonged melatonin secretion.
– Melatonin acts on the hypothalamus to reduce body temperature, blood pressure, and alertness.
– It helps prepare the body for sleep but does not directly induce sleep.
– Normal melatonin production begins in infants at 3–4 months of age.
– Melatonin levels are highest before puberty and decline after puberty.
– After the age of 40 years, melatonin levels show a gradual physiological decline.
– Females generally have higher melatonin levels than males.
– Melatonin has antioxidant properties and may protect neurons from oxidative stress.
– It plays a role in menstrual cycle regulation.
– Hypomelatoninemia is associated with circadian rhythm sleep disorders.
– Hypermelatoninemia is most commonly caused by excess melatonin supplementation.
– Recommended oral dose of melatonin ranges from 0.5 – 10 mg/day.
– Melatonin is generally safe and non-addictive in adults, with common side effects being headache, dizziness, nausea, and sleepiness.
For Further Reading:
Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement – ScienceDirect
Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials – PubMed
Status of research on the application of melatonin in insomnia based on bibliometric visualization analysis and development trends
Melatonin supplementation: new insights into health and disease – PubMed
Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders | PLOS One
Melatonin: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
10 Melatonin Mistakes That Could Be Ruining Your Sleep
Melatonin for Sleep: Does It Work? | Johns Hopkins Medicine
Foods High in Melatonin
Melatonin as a Hormone: New Physiological and Clinical Insights | Endocrine Reviews | Oxford Academic
Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action – PMC
