title: Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain.
abstract: Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered.
  
  
  
  A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed.
  
  
  
  B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 μmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested.
  
  
  
  Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population.
authors.affiliation: Section of Palliative Care, Department of Medicine, Yale University School of Medicine and Smilow Cancer Hospital, 333 Cedar Street WWW-403, P.O. Box 208021, New Haven, CT, 06520-8021, USA. lawrence.solomon@yale.edu.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Solomon
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000209:etiology*
chemical_list: D008764:Methylmalonic Acid; D014805:Vitamin B 12
keywords: Homocysteine; Malignancy; Methylmalonic acid; Neuropathic pain; Neuropathy; Oxidative stress; Vitamin B12