Vitamin B12 Deficiency and Restless Legs Syndrome
Yes, restless legs syndrome can result from Vitamin B12 deficiency, though iron deficiency remains the more established and common nutritional cause. 1, 2
Evidence for B12-RLS Association
Vitamin B12 deficiency is independently associated with RLS development and symptom severity. A 2022 case-control study demonstrated that patients with RLS had significantly lower serum B12 levels compared to healthy controls, with B12 deficiency independently associated with RLS occurrence (odds ratio 0.97,95% CI: 0.96-0.98, p<0.05). 2 Importantly, lower B12 levels correlated negatively with both RLS symptom severity (IRLS scores) and depression symptoms in affected patients. 2
The mechanism likely involves neuromuscular dysfunction from demyelination. Vitamin B12 deficiency causes extensive demyelination in both the central and peripheral nervous systems, with axonal degeneration particularly affecting distal afferent fibers of dorsal root ganglion neurons. 3 This produces a range of neuromuscular symptoms including paresthesias, numbness, muscle weakness, abnormal reflexes, and gait disturbances—symptoms that overlap substantially with RLS presentations. 3
Clinical Context and Screening
Screen for B12 deficiency in patients with gastrointestinal disorders, as these populations have higher RLS prevalence. In inflammatory bowel disease patients, 38.7% of those with RLS had vitamin B12, folate, or iron deficiency, with clinically relevant RLS (symptoms ≥twice weekly with moderate distress) occurring in 7.1% of Crohn's disease and 4.8% of ulcerative colitis patients. 4
Secondary RLS typically presents later in life (fifth to seventh decade) without family history. 3 Approximately 80% of patients with only neurological symptoms from B12 deficiency don't present until between ages 50-70 years. 3
Iron Deficiency Remains Primary Nutritional Cause
Iron deficiency is the more established and treatable nutritional cause of RLS. The American Geriatrics Society identifies iron deficiency as the common underlying mechanism in secondary RLS, with serum ferritin <50 ng/mL consistent with RLS diagnosis. 1 For RLS specifically, supplement if ferritin ≤75 ng/mL or transferrin saturation <20%. 5
Iron supplementation shows rapid improvement in RLS symptoms. In IBD patients with RLS and iron deficiency, iron supplementation resulted in significant RLS improvement at week 4 in 7 out of 8 patients (p=0.029). 4
Practical Diagnostic Approach
Obtain comprehensive metabolic screening including both iron studies and B12 levels. Essential workup should include: 5
- Serum ferritin and transferrin saturation (morning draw, avoid iron supplements 24 hours prior)
- Vitamin B12 level
- Electrolytes/renal function (to identify uremic RLS)
- TSH, calcium, HbA1c
- Urine albumin-to-creatinine ratio
Neurological examination is mandatory to distinguish true RLS from mimics. Without proper differential diagnosis, 16% of patients will be misclassified as having RLS if only symptom criteria are assessed. 5 Look for joint abnormalities (arthritis), radiculopathy signs, or peripheral neuropathy findings that suggest alternative diagnoses. 5
Treatment Implications
Correct identified vitamin deficiencies as first-line management in secondary RLS. Treatment of secondary RLS requires management of the underlying condition. 6 Correction of iron deficiency improves symptoms in patients with low ferritin levels. 7
B12 supplementation warrants prospective study but shows promise. While the 2022 study established correlation between B12 deficiency and RLS, prospective treatment studies are needed to confirm efficacy of B12 supplementation specifically for RLS management. 2
Dopaminergic therapy remains effective regardless of etiology. Dopamine agonists are effective for both primary and secondary RLS, though higher doses may be necessary in some secondary cases, particularly uremic RLS. 6, 7
Critical Pitfall
Neurological symptoms from B12 deficiency can present without hematological abnormalities. Approximately one-third of B12 deficiency cases lack macrocytic anemia, and severe neurological symptoms often occur with absent hematological findings. 3 This inverse relationship means you cannot rely on CBC findings alone to exclude B12 deficiency as a contributor to RLS symptoms. 3