Staging vitamin B−12 (cobalamin) status in vegetarians

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Abstract
When one stops eating vitamin B−12 (cobalamins), one passes through four stages of negative cobalamin balance: serum depletion [low holotranscobalamin II, ie, low vitamin B−12 on transcobalamin II (TCII)], cell depletion (decreasing holohaptocorrin and low red cell vitamin B−12 concentrations), biochemical deficiency (slowed DNA synthesis, elevated serum homocysteine and methylmalonate concentrations), and, finally, clinical deficiency (anemia). Serum vitamin B−12 is on two proteins: the circulating vitamin B−12 delivery protein, TCII, and the circulating vitamin B−12 storage protein, haptocorrin. Because TCII is depleted of vitamin B−12 within days after absorption stops, the best screening test for early negative vitamin B−12 balance is a measurement of vitamin B−12 on TCII (holoTCII). HoloTCII falls below the bottom of its normal range long before total serum vitamin B−12 (which is mainly vitamin B−12 on haptocorrin) falls below the bottom of its normal range.