A prospective clinical study¹⁰ was conducted to assess the value of the uMMA test for the diagnosis of Vitamin B12 deficiency in hospital patients being evaluated for anemia and neurologic disorders. All subjects (N=27) with uMMA > 20 micrograms per mL were verified B12 deficient by the serum B12 assay, Schilling test, and blood counts. A second similar study 9 showed all patients (N=27) with uMMA levels > 14 micrograms per milligram creatinine as being B12 deficient. Analysis of data from the 54 verified B12 deficient patients showed 20% had no anemia, 28 % exhibited mental changes, 52% had a neurologic disability at diagnosis and many had neurologic manifestation attributable to B12 deficiency years prior to diagnosis.⁹ In addition, it was stated that "Although a systematic study has not been made to determine the sensitivity of the uMMA test, from physician feedback after studying over 1600 patients over a five year period we have not encountered an untreated pernicious anemia patient, as identified with a positive Schilling test, with normal uMMA".¹³ Because of the high incidence of neurologic disease in non anemic hospital patients independently living seniors were screened using the uMMA test to detect untreated B12 deficiency. Although finding 1% B12 deficient was considered significant, a surprising 7% were confirmed B12 deficient but actually 22% by the current standard.^9,13 See previous discussion of the uMMA test.

     Matchar et. al. ¹⁷ further defined the uMMA test in a prospective double blinded clinical study of less obvious B12 deficient hospital patients with uMMA levels between 5 and 15 micrograms per mg creatinine and determined the uMMA assay to have a sensitivity and specificity of 100%/99%. Following the above studies, Lindenbaum et. al. ²² reported a retrospective study using SMMA confirming the previously reported high prevalence of neurologic disease in non anemic B12 deficient hospital patients.²³

     The uMMA assay has been validated as a screening test identifying B12 deficiency in non anemic elderly populations.¹⁴ During this work, it was discovered that the serum B12 test was less sensitive than the uMMA test and was not identifying B12 deficient individuals with tissue/cellular B12 deficiency. This finding created considerable interest when presented at a poster session at the 1989 American Society of Hematology convention. The poster handout was subsequently published in The Vitamin B12 Report.^16,45 A vegetarian population without signs of B12 deficiency was studied using the uMMA test.⁵ Of individual identified with cellular B12 deficiency through high uMMA (normal < 4.0) levels, 83% exhibited a normal serum B12 test. Subsequent treatment with various means of B12 therapy demonstrated the high accuracy, simplicity and reliability of the uMMA assay which has not been shown by any other B12 deficiency test to date.

     Aspects of measuring of SMMA and Hcys by GC/MS are under patent protection as noted in reference 53: "The authors and the University of Colorado and Colombia University hold patents relating to the use of methylmalonic acid, homocysteine, cystathionine, and methylcitrate in the diagnosis and follow-up of vitamin B-12 and folate deficiency. A company has been formed at the University of Colorado to perform the assays."⁵³ There are no patent restrictions for measurement of uMMA.

     NCL established in 1985 was the first commercial laboratory to provide the uMMA test. NCL introduced the Mayo Clinic to the uMMA assay and Mayo Clinic has also provided the uMMA test for years. Now other laboratories around the world are offering the uMMA test which has benefited thousands.