Cobalamin Status (Holo-Transcobalamin, Methylmalonic Acid) and Folate as Determinants of Homocysteine Concentration

Concern has emerged in America about subtle cobalamin (Cbl; vitamin B12) deficiency, especially in at-risk population groups such as the elderly and vegetarians (1). An optimal test to diagnose vitamin B12 deficiency is still not available (2)(3)(4). The determination of total serum vitamin B12 has a low diagnostic accuracy (2)(5). Measurements of homocysteine (HCY) and methylmalonic acid (MMA) have shown more specificity and sensitivity for subnormal Cbl status, but have disadvantages. HCY, for example, is also increased in folate and vitamin B6 deficiencies, as well as in renal insufficiency (4); in addition, MMA is expensive to measure, and it, too, increases in renal insufficiency (2)(4)(5). To improve specificity and sensitivity in diagnosis of vitamin B12 deficiency, holo-transcobalamin (holoTC) assays have been introduced (6). Because only transcobalamin II promotes the specific cellular uptake of Cbl, the Cbl subfraction attached to transcobalamin II represents the biologically active vitamin B12 fraction (6)(7)(8). Our previous observations in Syrian individuals revealed a high prevalence of Cbl deficiency (≈49%) when we used MMA as a metabolic marker for Cbl status (9). The present work was undertaken to further investigate the role of Cbl and folate status as determinants of hyperhomocysteinemia in Syrians.