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

Background: Vitamin B12 deficiency is diagnosed by measurements of total B12, 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 B12 status. The results are aligned with hemoglobin and cognitive score.

Methods: Databases from the literature were plotted in coordinates x=(holoTC·B12)(1∕2), y=1∕2·log10(MMA·Hcy), where distribution of points revealed the subgroups characterized by logarithmic ratios lr=log10[(holoTC·B12)/(MMA·Hcy)]. Distance between the subgroups w=lr(Test)-lr(Normal) was taken as a robust biochemical indicator of B12 status ("wellness parameter").

Results: The dependence of lr(Normal) vs. age was described by a mathematical function to correct parameter w. The B12 status was defined as "excellent" (w≈+0.4), "normal" (w≈0), "transitional" (w≈-0.5), "deficient" (w≈-1.7) and "pernicious" (w≈-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 B12 status by the individual markers agreed with only one out of two physiological characteristics.

Conclusion: Combined parameter w is a reliable diagnostic tool.