Biochemical markers of vitamin B12 deficiency combined in one diagnostic parameter: The age-dependence and association with 'cognitive function and blood hemoglobin

Background: Vitamin B-12 deficiency is diagnosed by measurements of total B-12, holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (Hcy) in blood. Results of the individual biochemical tests are often contradictory. Here the four markers are combined to achieve a more reliable indication of the B-12 status. The results are aligned with hemoglobin and cognitive score. Methods: Databases from the literature were plotted in coordinates x = (holoTC center dot B-12)(1/2), y = 1/2 . log(10) (MMA center dot Hcy), where distribution of points revealed the subgroups characterized by logarithmic ratios lr = log(10) [(holoTC center dot B-12)/(MMA center dot Hcy)]. Distance between the subgroups w = lr(Test) - lr(Normal) was taken as a robust biochemical indicator of B-12 status ("wellness parameter"). Results: The dependence of lr(Normal) vs. age was described by a mathematical function to correct parameter w. The B-12 status was defined as "excellent" (w approximate to +0.4), "normal" (w approximate to 0), "transitional" (w approximate to -0.5), "deficient" (w approximate to -1.7) and "pernicious" (w approximate to -3.0). The groups of individuals with either w >= 0 or w <= -1 exhibited the statistically significant differences in both hemoglobin and cognitive score. Analogous assessment of B-12 status by the individual markers agreed with only one out of two physiological characteristics. Conclusion: Combined parameter w is a reliable diagnostic tool. (c) 2013 Elsevier B.V. All rights reserved.