Three binding proteins are involved in the transport of vitamin B12 around the body - Intrinsic Factor (IF), transcobalamin (TC) and haptocorrin (HC). These binding proteins ensure the efficient uptake of the very small amounts of vitamin B12 available from the diet. When TC and HC bind vitamin B12 the resulting complexes are known as holotranscobalamin (HoloTC) and holohaptocorrin (HoloHC) to distinguish them from the proteins carrying no vitamin.
The major fraction in the circulation, HoloHC, represents 70-90% of vitamin B12 in the blood but is biologically inert. HoloTC represents only 10-30% of vitamin B12 circulating in the blood but is the only form of vitamin B12 that can be taken up by cells in the body. The TC protein alone transports vitamin B12 from its site of absorption in the ileum to tissues and cells. The vitamin is then internalised as the HoloTC (vitamin B12 bound to transcobalamin) complex via a specific receptor-mediated uptake. This process delivers vitamin B12 into the cells of the body and provides the vitamin as a co-enzyme for essential cellular functions such as DNA synthesis.
As HoloTC has a shorter circulating half-life compared to HoloHC the earliest change that occurs on entering negative vitamin B12 balance is very likely to be a decrease in serum HoloTC concentration.
The measurement of Total Serum B12 suffers from some limitations; in particular, most of the measured cobalamin is bound to biologically inert HC. Several studies have been published which conclude that HoloTC would be a better indicator of vitamin B12 status than Total Serum B12. As expected, HoloTC levels are low in patients with biochemical signs of vitamin B12 deficiency.
Low values have been reported in vegetarians, vegans, and in populations with a low intake of vitamin B12. Notably, low levels of HoloTC but not Total B12 in serum were reported in patients with Alzheimer’s disease compared to levels in a healthy control group. HoloTC levels reflect vitamin B12 status, independent of recent absorption of the vitamin.