Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials

Objectives: This systematic review aimed to evaluate the efficacy of B vitamins and vitamin D therapy in improving the standard treatment of depression and anxiety disorders. We also aimed to gather the evidence supporting the recommendations for supplementation in clinical practice. Methods: Performed between March 2020 and September 2021, the main inclusion criteria were randomized controlled trials (RCTs), with patients >= 18 years old, both sexes, fulfilling target diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), or mild to severe depressive and anxiety symptoms. In addition, the RCTs were included if the scales to assess the severity of the symptoms were standardized rating scales in psychiatric. Trials that reported diagnoses of schizophrenia, perinatal depression, bipolar depression, sleep disorders, eating disorders, cancer, and multiple sclerosis in association with any of the mentioned diagnoses were excluded. Results: We identified 20 RCTs that matched all eligibility criteria, totaling 2,256 subjects, diagnosed with MDD, GAD, and depressive or anxiety symptoms. Supplementation with folic acid or L-methylfolate, B1, B12 or methylcobalamin, and vitamin D (in different doses and study duration) significantly decreased depression and anxiety score scales by increasing response to standard pharmacological treatment or as monotherapy, including partial or complete remission. Discussion: B vitamins and vitamin D associated with other compounds also showed significant results, so the improvement in symptoms cannot be attributed strictly to those. Our results suggest that intervention with B vitamins and/or vitamin D may be an effective and well-tolerated adjuvant strategy for improving the symptoms of depression and anxiety, according to the patient's clinical status and nutritional biomarkers.