Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B₁₂ (cobalamin) absorption in patients with AIDS

Abstract

In AIDS, as previously found in pernicious anemia (PA), the earliest serum marker of subnormal vitamin B12 (cobalamin) absorption, and therefore of negative B12 balance, is low serum holotranscobalamin II (holo-TC II; B12-TC II) despite normal total serum B12 level, normal serum homocysteine, and normal classic (oral free radio-B12) Schilling test. This may be accompanied by subtle and insidious damage to hematopoietic, immunologic, neuropsychiatric, nutritional and alimentary systems, confirmed by correction on therapeutic trial with B12 therapy. Our studies suggest such selective B12 deficiency occurs in about half of the HIV-1 infected, in part due to frequent depression of B12 absorption by HIV-1 attack on the gastric mucosa and/or opportunistic infection attack on the small bowel, and in part due to a telescoping of the continuum of the stages of negative B12 balance in relation to damage to B12 delivery by the infective and/or systemic disease process. In AIDS, when total serum B12 is normal despite tissue depletion of B12, if the classic Schilling test does not reveal subnormal food B12 absorption, the food Schilling test does. We hypothesize that DNA-synthesizing cells of the hematopoietic, immunologic, neurologic and other systems which have surface receptors solely for holo-TC II, and which have low B12 stores, rapidly become dysfunctional due to B12 deficiency when holo-TC II is low, while cells (such as liver cells) which also have surface receptors for holohaptocorrin (B12-haptocorrin) remain B12-replete. We believe this to be another example of the concept of selective nutrient deficiency in one cell line but not another.

A longitudinal study of serum cobalamins and its binding proteins in lactating women

“…the holoTC). This is in excellent agreement with recent data, suggesting that holoTC rather than cobalamins is a sensitive marker of vitamin B 12 status (Herbert et al, 1990;Nexo et al, 2002;Herrmann et al, 2003;Hvas and Nexo, 2003).…”

Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12)

“…It is considered an earlier biomarker for changes in cobalamin status than serum cobalamin concentration (Herzlich and Herbert, 1988;Herbert et al, 1990;Nexø et al, 2002;Green, 2011).…”

Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.

“…Serum holoTCII represents the bioavailable form of vitamin B 12 and has a half-life of 6 min and, as such, is responsive to dietary pertubation (11,15,16). In the normal adult, ϳ80% of total serum vitamin B 12 is on haptocorrin (formerly called transcobalamin [TC] I and TC III), a circulating vitamin B 12 storage protein with a half-life of 2 weeks and with cell surface receptors only on reticuloendothelial storage cells (15,16). We further demonstrated that this malabsorption of vitamin B 12 is reversible by oral calcium supplementation.…”