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. 2025 Jul 4;15(7):450.
doi: 10.3390/metabo15070450.

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

Laura Claudia Popa  1   2 , Ahmed Abu-Awwad  3   4   5 , Simona Sorina Farcas  2 , Simona-Alina Abu-Awwad  3   6 , Nicoleta Ioana Andreescu  2   7
Affiliations

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

Laura Claudia Popa et al. Metabolites. .

Abstract

Background/Objectives: 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. Methods: 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. Results: 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). Conclusions: 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.

Keywords: caffeine metabolism; cytochrome P-450 CYP1A2; folic acid; metabolic syndrome; personalized medicine; vitamin B12.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Relationship between serum folate levels and BMI stratified by CYP1A2 genotype (AA vs. AC + CC) and coffee consumption (moderate vs. high).
Figure 2
Figure 2
Relationship between serum vitamin B12 levels and BMI stratified by CYP1A2 genotype (AA vs. AC + CC) and coffee consumption (moderate vs. high).
See this image and copyright information in PMC

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