What is the metabolism duration of melatonin (N-acetyl-5-methoxytryptamine) in a healthy individual?

From the Guidelines

Melatonin is fully metabolized within 8 hours in a healthy individual, with levels decreasing to 0% of maximum by 08:00 hours. The metabolism duration of melatonin can be understood by examining its plasma levels over time, as shown in a study published in the Journal of Clinical Sleep Medicine 1. According to this study, melatonin levels peak at 16:00 hours and then gradually decrease, with levels at 75% of maximum by 20:00 hours, 50% by 24:00 hours, and 25% by 04:00 hours.

Key Points

• Melatonin has a relatively short half-life, but its complete clearance from the body takes longer, typically within 4-8 hours after ingestion.
• The liver plays a crucial role in breaking down melatonin through hydroxylation, followed by conjugation with sulfate or glucuronic acid before elimination through urine, as described in the context of melatonin metabolism 1.
• Individual factors such as age, liver function, genetics, and medication use can influence melatonin metabolism rates, with older adults often metabolizing melatonin more slowly 1.
• The timing of melatonin supplementation is critical, as taking it 30-60 minutes before bedtime can support sleep, but taking it at high doses or too late at night may lead to prolonged effects and morning grogginess.

Metabolism Timeline

• 16:00 hours: Melatonin levels peak at 100% of maximum.
• 20:00 hours: Melatonin levels decrease to 75% of maximum.
• 24:00 hours: Melatonin levels decrease to 50% of maximum.
• 04:00 hours: Melatonin levels decrease to 25% of maximum.
• 08:00 hours: Melatonin levels decrease to 0% of maximum, indicating full metabolism.

From the Research

Metabolism Duration of Melatonin

• The metabolism duration of melatonin in a healthy individual is not directly stated in the provided studies.
• However, it is mentioned that melatonin displays a short blood half-life and undergoes a high first-pass hepatic metabolism 2.
• More than 80% of melatonin is excreted exclusively in the urine as 6-sulfatoxymelatonin 2.
• The primary metabolism of melatonin in humans occurs through various pathways, including indolic, kynuric, and cytochrome P450 (CYP) mediated hydroxylations and O-demethylation or non-enzymatic processes 3, 4.
• The metabolism of melatonin in the central nervous system involves several concurrent pathways, leading to different products, including N-acetylserotonin, 6-hydroxymelatonin, and 5-methoxytryptamine 4.

Melatonin Metabolism Pathways

• The indolic pathway is one of the primary metabolism pathways of melatonin, resulting in the formation of 6-hydroxymelatonin and other metabolites 3.
• The kynuric pathway is another significant metabolism pathway, leading to the formation of N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) 3, 4.
• Cytochrome P450 (CYP) mediated hydroxylations and O-demethylation are also involved in the metabolism of melatonin, resulting in the formation of various metabolites 3, 4.

Factors Influencing Melatonin Metabolism

• The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress, and brain levels of melatonin 4.
• The metabolism of melatonin can be affected by various factors, including age, light exposure, and individual differences in melatonin production and metabolism 5, 2.