Are U.S. Lower  Normal B12 Limits Too Low?


Are U.S. Lower Normal B12 Limits Too Low?

To the Editors.
     Reported is a single case study of a dementia in an 85-year old white male with "normal" B12 values reversed with intramuscular B12 injections. A.S., an 85-year-old, left-hand dominant, white male with a 10-year history of controlled hypertension, presented with memory slippages and lethargy that developed gradually for 2 years. The patient appeared to be independent, active, and ambulatory and was able to drive to and from work. Past medical history was positive only for remote prostatectomy and a successful percutaneous transluminal coronary angioplasty. Mr. S. was a semi-retired masonry contractor and denied anorexia, weight loss, history of tobacco, alcohol, or any medication other than nifedipine. Physical examination revealed a well nourished and developed man, oriented in all three spheres, who appeared younger than stated age. Neurological examination was nonfocal, except for absent vibratory sensation bilaterally at the ankles.
     Laboratory data showed a normal CBC with normal RBC and WBC morphology. Toxicology screening was negative, as was RPR. The serum vitamin B12 level was 368 (pg/mL), which is well within normal range, and was found reliable on repeated analyses.
     An extensive neurocognitive assessment (NCA) was performed and displayed evidence of cognitive slowing and mild anomias, without aphasias, paraphasic errors, or thought disorder. An initial Mini-Mental Status Examination (MMSE) score was 21/30, with mild acalculia. Immediate, short- and long-term visuoconstructional memory were grossly intact. Tactile recognition of familiar objects without visual aid was grossly intact; however, tactile short-term memory was moderately-severely impaired. Auditory-verbal short-term memory (three words from MMSE) was nonexistent on spontaneous recall although cueing (providing hints) resulted in correct short-term recall of 2 of 3 words. Frontal lobe/executive functioning/mental abstraction abilities were grossly intact and without evidence of perseveration. Psychomotor visual-spatial coordination was also grossly intact. These patterns of findings were inconsistent with an Alzheimer's dementia because of the intact frontal lobe functioning, but rather they were suggestive of a global/metabolically induced dementia. In addition, our previous NCA's have demonstrated a similar pattern of results and deficits in four other geriatric patients treated successfully and reversed with intramuscular B12 despite "normal" serum vitamin B12 levels.
     With a working diagnosis of B12 deficiency, the patient received intramuscular supplementation of 1000 meg/daily for 3 consecutive days as an outpatient, then 1000 meg/weekly for 1 month and monthly thereafter. Mr. S's mental status improved gradually. By the fifth injection, his MMSE score was 27/30, and previously noted NCA deficits had remitted. His vibratory sensation in the lower extremities was also improving. Lethargy and cognitive slowing had disappeared, and he was now taking the initiative in conversation.


     The careful and complete NCA in this patient proved to be a valuable tool in disclosing and monitoring the subtle neurological and cognitive features of a potentially treatable cause of dementia. These reported NCA deficits have proved to be a consistent pattern in identifying four previous, similar cases of reversible (350-400 pg/mL) vitamin B12 dementias in our clinic.
     As with other reports, this case supports the notion that mental manifestation of B12 deficiency can precede hematologic abnormalities. A IV-stage model of the development of B12 deficiency has suggested that myelin or other neurological damage can occur in the first two stages when B12 levels can still be within the "normal" range. Others have suggested transcobalamin II saturation (a major binding protein of serum B12) may be a more sensitive test to detect the B12 imbalance. To date, however, no one has suggested reevaluating the lower normal U.S. serum B12 limits.
Moreover, there is intercontinental disagreement as to the normal range of serum vitamin B12 levels. The current lower normal parameter limit of 200 pg/mL used in the United States is based on the hematological criteria, and should not be accepted automatically when encountering a psychiatric/dementia-like disorder. In fact, the lower limits of vitamin B12 in Japan and some European countries are 500-550 pg/mL, which are based on neurological criteria.
     Most psychiatric and dementia workups in older people include measurement of serum B12 levels regardless of hematological abnormalities. We propose that a lower normal borderline B12 level should prompt further investigation, such as transcobalamin II levels, or an empirical trial of IM vitamin B12 supplementation because of its cost efficacy. NCA should be sought because it provides valuable clues to the localization and differential diagnosis among organic, functional, and metabolic mental disorders. A reassessment of United States normal serum vitamin B12 levels based on neurological criteria with age and gender norms may be warranted.

      Mark Goodman, PhD
      X. Helen Chen, MD
    Dina Darwish, MD

The Union Memorial Hospital
Baltimore, MD

Goodman, M., Chen, X., & Darwish, D. (October 1996). Reversible vitamin B12 dementia despite normal B12 levels: Are U.S. lower normal B12 limits too low Journal of the American Geriatric Society, 44 (10), 1274-1275.