Holotranscobalamin (HoloTC, Active-B12) and Herbert’s model for the development of vitamin B12 deficiency: a review and alternative hypothesis

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Table 1 Herbert’s hypothesis—differences between 1986 and 1994 models

Analyte	Model	Deficiency stage
Analyte	Model		1	2	3	4
	1986	Normal	Negative B₁₂ balance	B₁₂ depletion	B₁₂-deficient erythropoiesis	B₁₂-deficiency anaemia
	1994	Normal	Early negative B₁₂ balance	B₁₂ depletion	Damaged metabolism: B₁₂-deficient erythropoiesis	Clinical damage: B₁₂-deficiency anemia
HoloTC (pmol/L)	1986	>22	<15	<15	<9	<9
HoloTC (pmol/L)	1994	>37	<30	<30	<30	<30
TC saturation (%)	1986	>5	<5	<2	<1	<1
TC saturation (%)	1994	>5	<4	<4	<4	<4
HoloHC (pmol/L)	1986	>111	>111	<111	<74	<74
HoloHC (pmol/L)	1994	>133	>133	<111	<74	<74
MMA high	1986	No	No	No	?	Yes
MMA high	1994	No	No	No	?	Yes
tHcy high	1986	–	–	–	–	–
tHcy high	1994	No	No	No	Yes	Yes

Data in this table was derived from Herbert (1987, 1994)
HoloTC concentration converted from pg/mL to pmol/L, using formula from Herbert (1987): HoloTC (pmol/L) = HoloTC (pg/mL) × 0.74
Two stages preceding “Normal”, added by Herbert in the 1994 model, omitted from this table