A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population

Abstract

Vitamin B 12 deficit is one of the most common vitamin deficiencies. However, there is no consensus on the cut-off points for vitamin B 12 and its co-markers, such as folate, holotranscobalamin, methylmalonic acid and homocysteine. In order to establish the state of the art about cut-off points used to determine vitamin B 12 deficiency in the last decades, the database MEDLINE was used for searching studies published in adults between December 1992 and May 2014 (69 articles), using search terms like 'vitamin B 12 ', 'cobalamin', 'cut-off', 'deficiency' alone or in combinations. Broad ranges of cut-off points for vitamin B 12 and its biomarkers were identified: vitamin B 12 ranged between 100 pmol/L and 350 pmol/L, holotranscobalamin 20-50 pmol/L, methylmalonic acid 0.210-0.470 μmol/L, homocysteine 10-21.6 μmol/L, serum folate 3.7-15.9 nmol/L and red blood cell 124-397 nmol/L. For the majority of studies, the potential influence of age, analytical methods, gender and fortified food consumption was not taken in account when choosing cut-off values. This could explain the discrepancies between studies on vitamin B 12 and folate deficiency prevalences. We conclude that there is inconsistency in the literature regarding vitamin B 12 cut-offs. It would be necessary to establish different reference cut-offs according to age, considering the analytical methods used.

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study,

“…There is uncertainty about the most appropriate measures or cutoffs for assessing vitamin B-12 status. It has been suggested that age-and sex-specific reference cutoffs may be needed (27).…”

A Prospective Study on Serum Methylmalonic Acid and Homocysteine in Pregnant Women

“…Vitamin B12 deficiency is an important nutritional problem worldwide as subclinical deficiency affects well-defined risk groups [2]. The recognition and treatment of vitamin B12 deficiency is critical since it is a reversible cause of bone marrow failure and demyelinating nervous system disease in the general population [3].…”

“…In order to reliably diagnose vitamin B12 deficiency, a combination of several markers associated with vitamin B12 metabolism could be used in place of a single vitamin B12 measurement [2]. Because of the limitations of assays that directly measure vitamin B12 such as poor standardization between different laboratories, different methods or platforms, low sensitivity and specificity, etc., measurement of methylmalonic acid (MMA), homocysteine, or both is used to confirm vitamin B12 deficiency in untreated patients.…”

“…Various techniques are used for MMA and homocysteine analyses; these include high performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (GC-MS), liquid chromatography–mass spectrometry (LC-MS), and LC–tandem mass spectrometry (LC-MS/MS) for MMA and enzyme-linked immunosorbent assay, fluorescence polarization immunoassay, chemiluminescent immunometric assay, enzyme-linked immunosorbent assay, radioimmunoassay, HPLC, GC-MS, LC-MS, and LC-MS/MS for homocysteine [2]. Different analytical detection methods have different sensitivities and specificities which could affect the measurement of MMA and homocysteine [2].…”

“…Different analytical detection methods have different sensitivities and specificities which could affect the measurement of MMA and homocysteine [2]. …”