Low Vitamin B12 Linked to Longer-Lasting Wheals in Patients with CSU

Vitamin B12 deficiency may be associated with longer-lasting wheals and greater symptom burden in patients with chronic spontaneous urticaria (CSU), according to findings from a cross-sectional study evaluating vitamin B12 status, disease severity, and markers of autoimmunity.¹ Because immune dysregulation and autoimmunity play important roles in many cases, the investigators explored whether vitamin B12, a nutrient involved in immune regulation and neurologic function, might be associated with disease activity.

Study Population and Baseline Levels

The study included 57 adults with CSU who were recruited from a dermatology department between September 2023 and August 2024. Participants had a mean age of approximately 35 years, and women slightly outnumbered men (33 versus 24). Clinical assessments included urticaria activity scores (UAS), wheal and pruritus duration, angioedema history, laboratory testing, serum vitamin B12 levels, and autologous serum skin testing (ASST) to evaluate autoimmune involvement.

Most patients had moderate to severe disease. The median disease duration was 12 months, while wheals and pruritus typically lasted a median of 60 minutes. Nearly 60% of participants reported diurnal variation, with the majority experiencing worsening symptoms at night. Angioedema occurred in approximately one-third of patients. Overall, mean serum vitamin B12 levels were within the normal range at 422.12 pg/mL. However, vitamin B12 deficiency, defined as levels below 200 pg/mL, was identified in 15.7% of participants, while nearly 79% had normal vitamin B12 concentrations.

Key Findings and Statistical Correlations

The primary finding was a statistically significant negative correlation between vitamin B12 levels and wheal duration. Lower vitamin B12 levels were associated with longer-lasting wheals and flares (p=0.04). When patients were grouped according to vitamin B12 status, those with deficiency experienced significantly longer wheal episodes, with a median duration of 120 minutes compared with 60 minutes among patients with normal vitamin B12 levels (p=0.02).

Patients with vitamin B12 deficiency also demonstrated a trend toward longer-lasting pruritus, although this difference did not reach statistical significance (p=0.06). No significant associations were identified between vitamin B12 levels and overall disease duration, urticaria activity scores, angioedema, ASST positivity, or serum IgE levels.

The investigators noted that previous studies have reported lower vitamin B12 levels in patients with CSU compared with healthy controls, but evidence has remained limited.² Their findings add support to the possibility that vitamin B12 status may influence specific aspects of disease severity, particularly symptom duration, rather than overall disease activity.

Autoimmune Evaluation and Potential Biological Mechanisms

Autoimmune features were also evaluated. ASST positivity was observed in 21.1% of participants, suggesting an autoimmune component in approximately one-fifth of cases. Patients with positive ASST generally exhibited more severe symptoms, consistent with prior reports linking autoimmune CSU to greater disease burden and reduced responses to conventional antihistamine therapy.

According to the authors, there are several potential mechanisms through which vitamin B12 could influence CSU. Vitamin B12 contributes to immune regulation, methionine metabolism, and neurotransmitter synthesis. Deficiency may promote inflammation through elevated homocysteine levels or altered immune function, while also potentially affecting mast cell-mediated inflammatory pathways central to CSU pathogenesis. However, these mechanisms were not directly evaluated in the study.

Clinical Implications and Future Directions

Several limitations should be considered when interpreting the findings. The study was conducted at a single center with a relatively small sample size, limiting generalizability. Its cross-sectional design also precludes conclusions regarding causality. Information on dietary habits, vitamin supplementation, smoking, alcohol use, and other potential confounding factors was not collected.

Despite these limitations, the authors believe the findings have practical implications. They suggest that measuring vitamin B12 levels in patients with severe, prolonged, or refractory CSU may provide clinically useful information as part of a broader evaluation. Further prospective studies are needed to determine whether correcting vitamin B12 deficiency can improve clinical outcomes or reduce symptom burden. Future research should also investigate how vitamin B12 interacts with other micronutrients, immune biomarkers, and autoimmune mechanisms in CSU. Such studies may help clarify whether nutritional interventions could serve as useful adjunctive therapies alongside established treatments for CSU.

References

1. Mali KR, Konda D, Thota SS, et al. Evaluation of Vitamin B12 Levels in Chronic Spontaneous Urticaria Patients and Correlation with Severity of Disease. Maedica (Bucur). 2026;21(2):406-413. doi:10.26574/maedica.2026.21.2.406

2. Abadeh A, Herman SM, Abdalian R. The prevalence of gastrointestinal symptoms and cobalamin deficiency in patients with chronic urticaria. Allergy Asthma Clin Immunol. 2023;19(1):14. Published 2023 Feb 24. doi:10.1186/s13223-023-00771-w