Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis

<b>Background/Objectives</b>: The prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, driven by complex genetic, nutritional, and environmental factors. Caffeine metabolism, primarily mediated by CYP1A2 (though other enzymes such as CYP1A1 may also be involved), and...

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Main Authors: Laura Claudia Popa, Ahmed Abu-Awwad, Simona Sorina Farcas, Simona-Alina Abu-Awwad, Nicoleta Ioana Andreescu
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/7/450
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author Laura Claudia Popa
Ahmed Abu-Awwad
Simona Sorina Farcas
Simona-Alina Abu-Awwad
Nicoleta Ioana Andreescu
author_facet Laura Claudia Popa
Ahmed Abu-Awwad
Simona Sorina Farcas
Simona-Alina Abu-Awwad
Nicoleta Ioana Andreescu
author_sort Laura Claudia Popa
collection DOAJ
description <b>Background/Objectives</b>: The prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, driven by complex genetic, nutritional, and environmental factors. Caffeine metabolism, primarily mediated by CYP1A2 (though other enzymes such as CYP1A1 may also be involved), and the status of micronutrients such as vitamin B12 and folate have each been linked to MetS components. This study investigates the interaction between CYP1A2 genetic variants and vitamin B12/folate levels in patients with MetS, aiming to identify a novel biomarker axis with potential implications for personalized interventions. <b>Methods</b>: This cross-sectional observational study included 356 adults diagnosed with MetS, recruited from Western Romania. Genotyping for CYP1A2 rs762551 was performed using TaqMan PCR assays. Daily caffeine intake was assessed via validated dietary questionnaires. Serum levels of folate and vitamin B12 were measured using chemiluminescence immunoassays. <b>Results</b>: AA genotype patients with a moderate coffee intake (1–2 cups/day) had significantly higher folate and B12 levels than AC or CC carriers. These nutritional advantages were associated with more favorable BMI and triglyceride profiles. The interaction between CYP1A2 genotype and coffee intake was significant for both micronutrient levels and metabolic parameters, particularly in the AA group. No significant associations were found in high-coffee-intake subgroups (≥3 cups/day). <b>Conclusions</b>: The interplay between CYP1A2 polymorphisms and B-vitamin status may represent a clinically relevant biomarker axis in MetS. Moderate caffeine intake in slow metabolizers (AA genotype) may boost micronutrient status and metabolic health, supporting personalized nutrition.
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spelling doaj-art-e797f3c8a54145d8b2393209e0d7c77e2025-08-20T02:47:17ZengMDPI AGMetabolites2218-19892025-07-0115745010.3390/metabo15070450Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker AxisLaura Claudia Popa0Ahmed Abu-Awwad1Simona Sorina Farcas2Simona-Alina Abu-Awwad3Nicoleta Ioana Andreescu4Doctoral School, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania“Pius Brinzeu” Emergency Clinical County Hospital, Bld Liviu Rebreanu, No. 156, 300723 Timisoara, RomaniaDepartment of Microscopic Morphology, Discipline of Genetics, Genomic Medicine Centre “Victor Babes”, University of Medicine and Pharmacy, 300041 Timisoara, Romania“Pius Brinzeu” Emergency Clinical County Hospital, Bld Liviu Rebreanu, No. 156, 300723 Timisoara, RomaniaDepartment of Microscopic Morphology, Discipline of Genetics, Genomic Medicine Centre “Victor Babes”, University of Medicine and Pharmacy, 300041 Timisoara, Romania<b>Background/Objectives</b>: The prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, driven by complex genetic, nutritional, and environmental factors. Caffeine metabolism, primarily mediated by CYP1A2 (though other enzymes such as CYP1A1 may also be involved), and the status of micronutrients such as vitamin B12 and folate have each been linked to MetS components. This study investigates the interaction between CYP1A2 genetic variants and vitamin B12/folate levels in patients with MetS, aiming to identify a novel biomarker axis with potential implications for personalized interventions. <b>Methods</b>: This cross-sectional observational study included 356 adults diagnosed with MetS, recruited from Western Romania. Genotyping for CYP1A2 rs762551 was performed using TaqMan PCR assays. Daily caffeine intake was assessed via validated dietary questionnaires. Serum levels of folate and vitamin B12 were measured using chemiluminescence immunoassays. <b>Results</b>: AA genotype patients with a moderate coffee intake (1–2 cups/day) had significantly higher folate and B12 levels than AC or CC carriers. These nutritional advantages were associated with more favorable BMI and triglyceride profiles. The interaction between CYP1A2 genotype and coffee intake was significant for both micronutrient levels and metabolic parameters, particularly in the AA group. No significant associations were found in high-coffee-intake subgroups (≥3 cups/day). <b>Conclusions</b>: The interplay between CYP1A2 polymorphisms and B-vitamin status may represent a clinically relevant biomarker axis in MetS. Moderate caffeine intake in slow metabolizers (AA genotype) may boost micronutrient status and metabolic health, supporting personalized nutrition.https://www.mdpi.com/2218-1989/15/7/450metabolic syndromecaffeine metabolismcytochrome P-450 CYP1A2vitamin B12folic acidpersonalized medicine
spellingShingle Laura Claudia Popa
Ahmed Abu-Awwad
Simona Sorina Farcas
Simona-Alina Abu-Awwad
Nicoleta Ioana Andreescu
Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
Metabolites
metabolic syndrome
caffeine metabolism
cytochrome P-450 CYP1A2
vitamin B12
folic acid
personalized medicine
title Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
title_full Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
title_fullStr Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
title_full_unstemmed Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
title_short Interaction Between CYP1A2-Related Caffeine Metabolism and Vitamin B12/Folate Status in Patients with Metabolic Syndrome: A Novel Biomarker Axis
title_sort interaction between cyp1a2 related caffeine metabolism and vitamin b12 folate status in patients with metabolic syndrome a novel biomarker axis
topic metabolic syndrome
caffeine metabolism
cytochrome P-450 CYP1A2
vitamin B12
folic acid
personalized medicine
url https://www.mdpi.com/2218-1989/15/7/450
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