Can B12 (Vitamin B12) supplements help with chemotherapy-induced neuropathy?

Vitamin B12 for Chemotherapy-Induced Peripheral Neuropathy

Vitamin B12 supplements are not recommended as a primary treatment for chemotherapy-induced peripheral neuropathy (CIPN) as there is insufficient evidence supporting their effectiveness. 1, 2

Evidence on B12 for CIPN

• The American Society of Clinical Oncology (ASCO) guidelines do not recommend vitamin B12 or other B vitamins for the prevention or treatment of chemotherapy-induced peripheral neuropathy 1

• A randomized, open-label, crossover study comparing duloxetine to vitamin B12 found that duloxetine was significantly more effective than vitamin B12 in reducing numbness (p=0.03) and pain (p=0.04) associated with CIPN 3

• A placebo-controlled trial evaluating an oral vitamin B complex in patients receiving neurotoxic chemotherapy found no significant reduction in the incidence of CIPN compared to placebo (p=0.73) 3, 4

• A systematic review of B-vitamin therapy in cancer patients concluded that evidence for B-vitamins in managing CIPN is low, and supplementation cannot be recommended 2

Functional B12 Deficiency and CIPN

• Some research suggests that functional vitamin B12 deficiency (normal B12 levels but elevated methylmalonic acid and homocysteine) is common in patients with advanced malignancy 5

• A 2025 study found that increases in serum methylmalonic acid levels (indicating functional B12 deficiency) significantly predicted increases in CIPN severity (p=0.001) 6

• This suggests that monitoring B12 metabolites rather than just B12 levels might be valuable in cancer patients at risk for CIPN 5, 6

Current Recommended Approaches for CIPN

• Duloxetine is the only agent with adequate evidence to support its use in patients with established painful CIPN 1

• In a direct comparison between duloxetine and vitamin B12, duloxetine showed superior efficacy for both numbness and pain associated with CIPN 3

• When comparing duloxetine to pregabalin in a 2020 trial, pregabalin showed greater improvement in visual analog scores (93% vs 38%, p<0.001) 3

• Acupuncture combined with methylcobalamin (B12) showed better pain reduction than methylcobalamin alone, suggesting B12 might have a role as an adjunctive therapy rather than monotherapy 3

Clinical Implications and Pitfalls

• Pitfall to avoid: Relying solely on serum B12 levels without measuring metabolites (methylmalonic acid and homocysteine) may miss functional B12 deficiency in cancer patients 5, 6

• Pitfall to avoid: Using vitamin B12 as a first-line treatment for CIPN when more evidence-based options like duloxetine are available 3, 1

• The evidence for vitamin B12 in CIPN is primarily from small studies with methodological limitations, making it difficult to draw definitive conclusions 2, 7

• If considering B12 supplementation, it should be used as an adjunctive therapy rather than monotherapy, particularly in patients with documented functional B12 deficiency 5, 6

Treatment Algorithm for CIPN

1. First-line: Duloxetine (20mg/day orally for first week, then 40mg/day) 3
2. Alternative: Pregabalin (if duloxetine is not tolerated or ineffective) 3
3. Consider acupuncture as an adjunctive non-pharmacological approach 3
4. Check for functional B12 deficiency (elevated methylmalonic acid and homocysteine) in patients with CIPN 5, 6
5. If functional B12 deficiency is present, consider B12 supplementation as an adjunctive therapy 5, 6