title: Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial.
abstract: OBJECTIVE
  To determine whether a combination of L-methylfolate, methylcobalamin, and pyridoxal-5'-phosphate (LMF-MC-PLP [Metanx; Pamlab LLC, Covington, La]) improves sensory neuropathy.
  
  
  METHODS
  This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5'-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B(6) and B(12), methylmalonic acid (MMA), and homocysteine.
  
  
  RESULTS
  There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P=.013 vs placebo) and week 24 (P=.033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7±3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5±2.4 μmol/L with placebo (P=.0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects.
  
  
  CONCLUSIONS
  LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration may have been too short to show an effect on VPT. In addition, further research on the effects in patients with cobalamin deficiency would be useful.
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA 70112, USA. vfonseca@tulane.edu
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Lavery
authors.forename: Tina K
authors.initials: TK
authors.lastname: Thethi
authors.forename: Yahya
authors.initials: Y
authors.lastname: Daoud
authors.forename: Cyrus
authors.initials: C
authors.lastname: DeSouza
authors.forename: Fernando
authors.initials: F
authors.lastname: Ovalle
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Denham
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.forename: Peter
authors.initials: P
authors.lastname: Sheehan
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C575384:metanx; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D014805:Vitamin B 12