Does the CYP1A2 (Cytochrome P450 1A2) gene variant, specifically the -163C>A and 5347C>T polymorphisms, cause rapid melatonin metabolism?

From the Guidelines

The CYP1A2 -163C>A and 5347C>T genetic variants can cause more rapid melatonin breakdown, leading to lower circulating melatonin levels and shorter duration of action when taking melatonin supplements. These variants are associated with increased CYP1A2 enzyme activity, which is the primary enzyme responsible for metabolizing melatonin in the liver 1. People with these genetic variants, particularly the -163C>A variant, are considered "fast metabolizers" and may break down melatonin more quickly than those without these variants.

Key Considerations

• The CYP1A2 enzyme plays a crucial role in metabolizing melatonin, and genetic variants can affect its activity 1.
• Individuals with the CYP1A2 -163C>A and 5347C>T genetic variants may experience reduced effectiveness from standard melatonin supplements due to rapid breakdown 1.
• Extended-release formulations or potentially higher doses of melatonin may be necessary to achieve the desired effect, but any dosage adjustments should be discussed with a healthcare provider.

Clinical Implications

• Healthcare providers should consider the potential impact of CYP1A2 genetic variants on melatonin metabolism when prescribing melatonin supplements for sleep disorders.
• Patients with these genetic variants may require closer monitoring and adjustment of their melatonin dosage to achieve optimal therapeutic effects.
• Further research is needed to fully understand the relationship between CYP1A2 genetic variants and melatonin metabolism, as well as to develop personalized treatment strategies for individuals with these variants.

From the Research

CYP1A2 Gene Variant and Melatonin Metabolism

• The CYP1A2 gene variant, specifically the -163C>A and 5347C>T polymorphisms, has been studied in relation to melatonin metabolism 2, 3, 4, 5, 6.
• Research suggests that melatonin is metabolized in the liver by cytochrome P450 (CYP) 1A2, and variations in the CYP1A2 gene may affect melatonin metabolism 3, 5, 6.
• However, the specific polymorphisms -163C>A and 5347C>T are not directly mentioned in the provided studies as causing rapid melatonin metabolism.
• Instead, studies focus on the relationship between CYP1A2 activity and melatonin metabolism, with some suggesting that slow melatonin metabolism may be associated with decreased CYP1A2 activity 2, 3.

CYP1A2 Activity and Melatonin Metabolism

• CYP1A2 activity has been shown to affect melatonin metabolism, with higher CYP1A2 activity resulting in faster melatonin clearance 4, 6.
• The CYP1A21F polymorphism has been found to influence melatonin metabolism, with individuals homozygous for the CYP1A21A allele having higher melatonin concentrations compared to those with the *1F/*1F or *1F/*1A genotypes 4.
• Melatonin has been proposed as a potential probe drug for CYP1A2 phenotyping, with its metabolism reflecting CYP1A2 activity 4, 6.

Melatonin Metabolism and CYP1A2 Polymorphisms

• While the provided studies do not directly address the -163C>A and 5347C>T polymorphisms, they do suggest that CYP1A2 polymorphisms can affect melatonin metabolism 2, 3, 4.
• Further research is needed to determine the specific effects of the -163C>A and 5347C>T polymorphisms on melatonin metabolism 2, 3, 4, 5, 6.