Single arm phase II study of oral vitamin B12 for the treatment of musculoskeletal symptoms associated with aromatase inhibitors in women with early stage breast cancer

Abstract

Breast cancer patients receiving endocrine therapy with aromatase Inhibitors (AIs) often experience musculoskeletal and joint-related side effects. The purpose of this study was to evaluate the effect of Vitamin B12 supplements on musculoskeletal symptoms such as pain and arthralgias induced by AIs and to correlate response with serum and inflammatory biomarkers. Upon receiving approval by the Institutional Review Board (IRB), the majority of the patients consented into the study were treated at the Texas Tech Breast Care Center. Included were patients who had a diagnosis of invasive breast cancer (Stages I-III), and were experiencing significant musculoskeletal symptoms associated to AIs. Only patients with an average pain score ≥ 4, as assessed by the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, were included in the study. Participants received 2500 mcg of sublingual vitamin B12 daily for 90 days. Assessments at baseline and at 3 months included: BPI-SF pain scores, the impact on quality of life determined by Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), and correlative serum markers relative to baseline (a pre-post study). A total of forty-one patients were enrolled. Average pain scores were improved by 34% (P < .0001) at 3 months compared to baseline. In addition, a 23% improvement in worst pain was noted (P = .0003). Analysis of the results for the FACT-ES scoring showed improvement on all scales. No significant adverse events were observed. Decrease in pain score was correlated with increased serum B12 levels. This study suggests that Vitamin B12 reduces pain and improves quality of life for patients taking AIs who experienced AI-related musculoskeletal symptoms. If confirmed in large randomized prospective trials, Vitamin B12 would be a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms.

Aromatase inhibitor–associated musculoskeletal pain: An overview of pathophysiology and treatment modalities

“…Supplementation with daily over-the-counter glucosamine sulfate (1500 mg/day) and chondroitin sulfate (1200 mg/day) for 24 weeks lead to a significant decrease in joint stiffness, Range of Motion (ROM), and improved grip strength in 46% of patients. 23 Supplementation with 2500 µg of sublingual vitamin B12 for 90 days leads to improvement in pain severity scores in 34% of women in a study by Campbell et al 24 …”

Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

“…Another promising option in AIA's symptoms management is vitamin B12. Administered orally at the dosage of 2500 mcg daily for 90 days, as a dietary supplementation, it was shown to reduce pain, as evaluated by BPI, and improve quality of life, as determined by FACT-ES TOI in a single arm phase II study [98]. Obviously, large controlled trials, based on formal medical prescription schedules, are necessary to validate these suggestive results.…”

Effect of vitamin B12 on the symptom severity and psychological profile of fibromyalgia patients; a prospective pre-post study

“…The other effects of vitamin B12 on neuroplasticity and pain neurobiology may include the moderation of neurotransmitter imbalance toward decreased glutamatergic and increased GABAergic activity, interactions with prostaglandin synthesis such as cyclooxygenase (COX) enzymes, and some other complex interaction [ 9 , 10 ]. Furthermore, accumulating clinical data supports the pain-relieving role of vitamin B12 in various nociceptor or neuropathic pain conditions such as low back pain, diabetic neuropathy, chemotherapy-induced pain in breast cancer patients, and postherpetic neuralgia [ 7 , 11 , 12 ]. However, despite numerous positive data on pain reliving effect of vitamin B12, there are scarce interventional studies about the effect of vitamin B12 on nociplastic pain.…”