The relationship between cobalamin and folate below the cutoff values on anxiety and insomnia symptoms: Findings from the 8-year longitudinal EPISONO study.

INTRODUCTION

Cobalamin and folate are critical for central nervous system function through their roles in one‑carbon metabolism, which supports neurotransmitter synthesis and methylation reactions. Deficiencies in these vitamins have been linked to mood disorders and may influence sleep patterns and circadian rhythms.

OBJECTIVE

To investigate whether cobalamin and folate levels below established cutoff values are associated with the incidence and/or predict the development and severity of insomnia and anxiety symptoms, as well as their relationship with diurnal preferences using a longitudinal approach.

METHODS

Data from the EPISONO 3rd edition cohort and its follow-up (2007 and 2015; n = 1042 and n = 712, respectively) were analyzed. Vitamin levels were quantified via chemiluminescence assays. Insomnia and anxiety were assessed using validated questionnaires (The Insomnia Severity Index and Beck Anxiety Inventory), while diurnal preferences were assessed with the Morningness-Eveningness Questionnaire. Mixed models and logistic regressions were applied to investigate the longitudinal trajectories between vitamin levels, insomnia, and anxiety.

RESULTS

Cobalamin and folate below the cutoff values were more prevalent in 2015 than in 2007 (cobalamin: 11 % vs. 2 %; folate: 7 % vs. 3 %). There was a significant association between cobalamin below the cutoff value and more severe symptoms of insomnia and anxiety, and between folate below the cutoff value and increased anxiety over the 8 years. Greater preference for morningness was associated with less severe symptoms in respect of both outcomes.

CONCLUSION

Cobalamin and folate below the cutoff value were associated with increased insomnia and anxiety severity, respectively. Furthermore, diurnal preferences influenced these outcomes.