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A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis
  1. D T Wade1,
  2. C A Young2,
  3. K R Chaudhuri3,
  4. D L W Davidson4
  1. 1Oxford Centre for Enablement, Oxford, UK
  2. 2The Walton Centre for Neurology and Neurosurgery, Liverpool, UK
  3. 3Department of Neurology, Lewisham and King's College Hospitals, London SE13, UK
  4. 4Department of Neurology, Ninewells Hospital, Dundee, UK
  1. Correspondence to:
 Professor D T Wade, Oxford Centre for Enablement, Windmill Road, Oxford OX3 7LD, UK;


Objective: To determine whether combination therapy with lofepramine, L-phenylalanine, and intramuscular vitamin B-12 (the “Cari Loder regime”) reduces disability in patients with multiple sclerosis.

Methods: A placebo controlled, double blind, randomised study carried out in five United Kingdom centres on outpatients with clinically definite multiple sclerosis, measurable disability on Guy's neurological disability scale (GNDS), no relapse in the preceding six months, and not on antidepressant drugs. Over 24 weeks all patients received vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily, or matching placebo tablets. Outcome was assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck depression inventory, the Chalder fatigue scale, and the Gulick MS specific symptom scale.

Results: 138 patients were entered, and two were lost from each group. There was no statistically significant difference between the groups at entry or at follow up. Analysis of covariance suggested that treated patients had better outcomes on four of the five scales used. Both groups showed a reduction of 2 GNDS points within the first two weeks, and when data from all time points were considered, the treated group had a significant improvement of 0.6 GNDS points from two weeks onwards.

Conclusions: Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections. The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit. More research is needed to confirm and explore the significance of this clinically small difference.

  • Cari Loder regime
  • multiple sclerosis
  • vitamin B-12
  • lofepramine
  • L-phenylalanine

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  • Contributors: CY and DW both took an active part in all aspects of the study including helping with the design and execution of the study, recommending the measures, and undertaking some of the data analysis. CY and DW are the guarantors. RC and DD took part in discussions about the design of the trial and in data interpretation, and checked the manuscript.

  • Competing interests: All investigating centres received some financial support to carry out the study, and investigators had expenses reimbursed.