Association of Vitamin B12 and Ferritin Levels With Neuropathic Pain and Disease Severity in Fibromyalgia Syndrome.

BACKGROUND

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain, often accompanied by fatigue, sleep disturbance, and cognitive impairment. Neuropathic pain is an important but underrecognized component of FMS, which significantly worsens disease burden. Micronutrient deficiencies, particularly serum vitamin B12 and ferritin, are suggested to influence pain perception and neuronal function, yet their role in FMS remains unclear, especially in Pakistan.

OBJECTIVES

To determine the association of serum vitamin B12 and ferritin levels with neuropathic pain and disease severity in patients with fibromyalgia.

STUDY DESIGN AND

SETTING

A cross-sectional analytical study conducted at the Department of Medicine, Shaikh Zayed Hospital, Lahore, Pakistan, from January to June 2025.

METHODOLOGY: A total of 241 patients fulfilling the American College of Rheumatology (ACR 2016) criteria for FMS were enrolled. Demographic data, Fibromyalgia Impact Questionnaire-Revised (FIQR) scores, and Douleur Neuropathique en 4 Questions (DN4) scores were recorded. Serum vitamin B12 and ferritin levels were measured. Independent sample t-test and chi-square test were applied for comparisons, and multivariable logistic regression was performed to identify predictors of neuropathic pain, with p < 0.05 considered significant.

RESULTS

Mean age of participants was 46.0 ± 15.6 years, with female predominance (77.6%). Neuropathic pain was present in 58.5% of cases. Patients with neuropathic pain had significantly higher FIQR (52.7 ± 9.5 vs. 41.0 ± 8.9, p < 0.001) and DN4 scores (5.8 ± 1.4 vs. 2.8 ± 1.0, p < 0.001). Serum vitamin B12 and ferritin levels were lower in neuropathic patients (p = 0.001 and p = 0.005, respectively). Multivariable regression identified FIQR score as the strongest predictor of neuropathic pain (OR = 1.159, 95% CI: 1.112-1.208, p < 0.001).

CONCLUSION

Neuropathic pain is highly prevalent in FMS and is strongly associated with disease severity. Although vitamin B12 and ferritin showed lower levels in affected patients, only disease severity independently predicted neuropathic pain. Larger longitudinal studies are warranted to clarify causal pathways and therapeutic implications.