Laboratory Evaluation for Vitamin B₁₂ Deficiency: The Case for Cascade Testing

Objective Potential vitamin B₁₂ deficiency is a common clinical diagnostic problem, and many providers have a low threshold for initiating therapy. The goal of this study was to systematically evaluate current practice patterns regarding the laboratory evaluation of suspected vitamin B₁₂ deficiency.

Methods This retrospective study reviewed the electronic medical records of 192 patients initiated on intramuscular vitamin B₁₂ injections.

Results Only 12 patients had objectively documented hematologic responses: decrease of mean corpuscular volume by ≥5 fL with stable or improved hemoglobin. Another 5 patients had equivocal hematologic responses. There was one plausible neurologic response. Thus, only 18 (9.4%) of 192 patients had data supportive of a clinical response. In these 18 patients, the baseline serum B₁₂ level was ≤107 pg/mL; only 3 also had a baseline serum methylmalonic acid level, which was ≥1.29 umole/L in all 3.

Conclusions Currently, only a small minority of patients initiated on intramuscular vitamin B₁₂ supplementation derive any meaningful clinical benefit. Furthermore, current testing recommendations for vitamin B₁₂ deficiency are usually not followed. Up-front ordering of a diagnostic testing cascade is recommended to improve compliance; an example is presented with decision points chosen to improve specificity for clinically evident vitamin B₁₂ deficiency without loss of sensitivity. Ultimately, a better understanding of vitamin B₁₂ physiology is needed to develop and evaluate laboratory tests that more accurately reflect true intracellular vitamin B₁₂ status.