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Objective: Down's syndrome (DS) is the most frequent genetic cause of Alzheimer-type dementia. Its metabolic phenotype involves an increased trans-sulphuration of homocysteine. The aim of the present study was to investigate the influence of homocysteinaemia (t-Hcys), folate, vitamin B12, and related polymorphisms on intelligence quotient (IQ) in DS. Methods: The IQ of 131 patients with trisomy 21 from a specialist centre in Sicily was determined and classified according to DMS-IV. The effects of age, folate, vitamin B12, t-Hcys, and genetic polymorphisms on IQ were evaluated separately and in combination using regression analyses. Results: IQ was significantly lower in DS patients with t-Hcys >7.5 µmol/l (median) and in those who were carriers of methylenetetrahydrofolate reductase (MTHFR) 677 T allele and of methylenetetrahydrofolate reductase 677 T and transcobalamin 776 G combined alleles (p = 0.0013, p = 0.0165, and p = 0.0074, respectively). The IQ correlated significantly with t-Hcys and folate in single and multiple regression analyses, independently of age. In addition, t-Hcys >9.6 µmol/l (upper quartile) was found to be associated with low IQ (

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.

The binding of vitamin B12 by serum proteins was studied by separating Co57B12-enriched serum by Sephadex gel filtration, column chromatography with DEAE-cellulose, and paper electrophoresis. Each method of separation yielded two discrete B12-binding fractions. However, the analysis of each serum by all three separation technics indicated that one of the fractions was, in each case, bipartite. The "high" molecular weight B12-binding fraction defined by Sephadex gel filtration consisted of transcobalamin I and just part of the transcobalamin II fraction. The remaining portion of transcobalamin II was eluted from Sephadex gel in a "low" molecular weight fraction. Thus, transcobalamin II, equivalent to the β-globulin B12-binder, consisted of both "high" and "low" molecular weight components. This suggests that there are at least three serum proteins that can bind vitamin B12: two β-globulins, together comprising the transcobalamin II fraction and differing in molecular weight; and transcobalamin I.