Presentation #179, 3rd International Conference on Homocysteine Metabolism (Chair: Prof. G. Andria, University Federico II, Naples), Hilton Sorrento Palace Hotel & Conference Center, Sorrento,Italy, 1-5 July 2001, as part of Session #6, "Homocysteine and psychogeriatric diseases" (26 presentations [#170-195]) [#179 is on p. 130 of the published Abstracts Book]). This superb conference of leading homocysteine researchers from all over the world presented, in 8 Sessions, their latest research results on: 1. Homocysteine and adverse outcomes of pregnancy; 2. Animal studies; 3. Genes and enzymes in homocysteine and folate metabolism; 4. Mechanisms of homocysteine action; 5. Diagnostic aspects; 6. Homocysteine and psychogeriatric diseases; 7. Homocysteine and cardiovascular diseases; 8. Homocysteine and other diseases (renal diseases, diabetes, etc.)
#179. LOSS OF RECENT MEMORY (WHERE IN THE PARKING LOT IS MY CAR? ETC.) IN PERSONS AGE >50 IS OFTEN UNRECOGNIZED SUBTLE VITAMIN B12DEFICIENCY, ±HYPERHOMOCYSTEINEMIA, PRODUCING INADEQUATE SYNTHESIS OF NEW BRAIN CELLS, BUT NO ANEMIA. Herbert, V. Mount Sinai-NYU Health System & Bronx VA Med Ctr.
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 ěnormalî
serum methylmalonate and total B12, have subtle B12 deficiency, with
low serum holotranscobalamin (holo-TC) (B12-TC) (~60% of that 50%
have hyperhomocysteinemia [Flynn, Green, Miller, Herbert, et al; Herbert, FASEB
J 2000; 14, March]) often with subtle neural damage (loss of recent memory,
then 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 ěnormal 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, low within a
week of cessation of B12 absorption, so B12 not adequately
delivered to holo TC receptors on DNA-synthesizing neurons, glial and Schwann
cells. Because only ~20% of circulating B12 is on delivery protein TC
[‡-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).
V.H. CV# 831A.
