From the Guidelines
The genetic variants rs762551 and rs2470890 may affect how your body metabolizes melatonin, potentially influencing its effectiveness as a sleep aid. These variants are found in the CYP1A2 gene, which produces an enzyme responsible for breaking down various substances in the body, including melatonin. If you have certain variations of these genes, you might metabolize melatonin either faster or slower than average. For those who metabolize melatonin quickly (fast metabolizers), a standard dose may not last long enough to help with sleep throughout the night, and you might benefit from a time-released formulation or a slightly higher dose (typically 3-5mg instead of 1-2mg) 1. Conversely, if you're a slow metabolizer, standard doses might remain active longer in your system, potentially causing morning grogginess, and you might do better with a lower dose (0.5-1mg). These genetic variations don't necessarily mean you have a problem with your natural melatonin production; they simply affect how quickly your body processes supplemental melatonin. Before making any changes to melatonin supplementation based on genetic information, it's advisable to consult with a healthcare provider who can interpret your specific genetic profile in the context of your overall health and sleep patterns. Some key points to consider when using melatonin include:
- The optimal dosing of melatonin for circadian effects remains unclear, and studies suggest that timing is more important than dose 1
- Melatonin is associated with a lack of reported serious adverse effects, but caution is advised when prescribing to patients taking warfarin and to patients with epilepsy 1
- Long-term effects of melatonin are scarce, and studies that specifically involve pediatric/adolescent populations are limited 1 It's essential to weigh the benefits and risks of melatonin supplementation and consult with a healthcare provider to determine the best course of treatment for your specific situation.
From the Research
Melatonin Metabolism and Genetic Variants
The question of how rs762551 and rs2470890 affect melatonin metabolism can be addressed by examining the role of these genetic variants in the context of melatonin and its analogues.
- rs762551 and rs2470890 are single nucleotide polymorphisms (SNPs) associated with the CYP1A2 gene, which encodes an enzyme involved in the metabolism of various substances, including melatonin and its analogues like agomelatine 2.
- The CYP1A2 enzyme plays a crucial role in the hepatic metabolism of melatonin, influencing its plasma concentrations and, consequently, its physiological effects 3.
- Studies have shown that certain polymorphisms in the CYP1A2 gene, such as rs762551 and rs2470890, can affect the pharmacokinetics of melatonin analogues. For instance, the rs762551 A allele and the rs2470890 T allele have been associated with lower exposure to agomelatine, suggesting altered melatonin metabolism in individuals carrying these variants 2.
- Furthermore, the rs2470890 polymorphism has been linked to increased side effects in patients treated with clozapine, another substance metabolized by CYP1A2, indicating the potential impact of this variant on drug metabolism and response 4.
Implications for Melatonin Metabolism
Given the association of rs762551 and rs2470890 with altered metabolism of melatonin analogues, it is reasonable to infer that these genetic variants could influence melatonin metabolism as well.
- Individuals carrying the rs762551 A allele or the rs2470890 T allele may exhibit differences in melatonin plasma concentrations, which could affect the hormone's physiological functions, such as sleep-wake cycle regulation and antioxidant defenses 3, 5.
- However, the direct impact of these polymorphisms on melatonin metabolism and its consequences for human health requires further investigation, as the current evidence is primarily based on studies of melatonin analogues and other substances metabolized by CYP1A2 6, 2, 4.