Loss Of Recent Memory (Where In The Parking Lot Is My Car? etc.) In Persons Age >50 Is Often Unrecognized Subtle Vitamin B₁₂ Deficiency, Producing Inadequate Synthesis Of New Brain Cells, But No Anemia.
V Herbert. Mount Sinai-NYU Health System & Bronx VA Med Ctr., NYC, NY. 
     In 1962, we reported gradual forgetfulness and irritability on a 4‡ month no-folate diet, corrected within 48 hr of 500µg oral PGA (Herbert. Trans Assoc Am Phys; 1xxv: 307-20). Consulting in London in 1999, we saw a child with a gene defect in converting OH-B₁₂ to CH₃-B₁₂, irritable and unable to store recent memory, correct within 24hr after Dr. R Bhatt injected 500µg CH₃-B₁₂. These findings are explained by new data that we make new brain cells daily to store that dayís new information (Conference: Neural Stem Cells. NY Acad Med 3/1/00). Cell division is dependent on adequate B₁₂ (and folate) in cells for new DNA synthesis. Neural cells store little B₁₂, quickly become deficient. By age 65, ~50% of Americans, despite ìnormalî serum methylmalonate and total B12, have subtle B₁₂ deficiency, with low serum holotranscobalamin II (holo-TC II) (B₁₂-TC II) (~60% of that 50% have >homocysteine [Flynn, Green, Miller, Herbert, et al; Herbert, FASEB J 2000; 14, March]) often with subtle neural damage (loss of recent memory, then loss of index toe position sense, 256 vps perception, stumbling, and eventual dementia, before anemia with serum total B₁₂ low and methylmalonate high (V Herbert [Ed.]: Vitamin B₁₂ Deficiency. Round Table Series 66, Oct 1999, Roy Soc Med Press, London). In many this is misattributed to ìnormal agingî or early Alzheimerís and untreated (V Herbert [Ed.] supra). This subtle B₁₂ deficiency may be diagnosable in the lab only by low serum holo-TC II, low within a week of cessation of B₁₂ absorption, so B₁₂ not adequately delivered to holo TCII receptors on DNA-synthesizing neurons, glial and Schwann cells. (Because only ~20% of circulating B₁₂ is on delivery protein TC II [‡-life 6 min], with ~80% on storage protein haptocorrin [‡-life 2 wk] with receptors only on RE storage cells, it can be >3 yr with no B₁₂ delivery to brain before total serum B₁₂ falls <350pg/ml). The definitive clinical test is rapid correction by 100mcg B₁₂ orally daily (vide supra).

Published in FASEB J, 2001 (March 7): 15(2, ABSTRACTS PART I), page A59. 
Presented at Saturday, March 31, 2001, Minisymposium #76 on ìBrain Aging and Nutritionî at EB2001 meeting held at the Orange County Convention Center, Orlando, Florida.                        V.H. CV#835EB2001II