Vitamin B12 in Health and Disease

Vitamin B12, also known as cobalamin, is an important nutrient involved in metabolism. As a water-soluble vitamin, it is naturally present in certain foods, added to others, and available in the form of dietary supplements and prescription medications. Vitamin B12 plays an important role in various physiological processes, such as red blood cell formation, cell metabolism, nerve function, and DNA production. A lack of vitamin B12 often leads to problems such as anemia and heart and blood vessel disease.

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Absorption of Vitamin B12

To be absorbed by the body, vitamin B12, which is bound to protein in food, needs to be released. The process begins in the mouth, where food mixes with saliva. The liberated vitamin B12 then attaches to haptocorrin, a protein found in saliva. In the stomach, hydrochloric acid and gastric protease further release vitamin B12 from its food source, allowing it to bind with haptocorrin. In the duodenum, digestive enzymes separate vitamin B12 from haptocorrin, and the freed vitamin B12 combines with intrinsic factor, a protein secreted by the stomach's parietal cells that facilitates transport and delivery. This complex is then absorbed in the distal ileum through receptor-mediated endocytosis. However, if vitamin B12 is added to fortified foods or dietary supplements, it is already in a free form and does not require the initial separation step from protein.

Figure 1. Absorption, enterohepatic circulation and intracellular metabolism of vitamin B12.
(Source: Green, R. et al., 2017)

Measurement of Vitamin B12

The measurement of vitamin B12 levels is an important tool in assessing an individual's vitamin B12 status. There are several methods commonly used to measure vitamin B12 levels in clinical practice.

• Serum Vitamin B12 Measurement: This is the most commonly used method for assessing vitamin B12 status. It involves measuring the total amount of vitamin B12 present in the serum or plasma. The measurement is typically performed using immunoassays or microbiological assays. The cutoff values for normal vitamin B12 levels may vary slightly between laboratories, but most laboratories define subnormal levels as below 200 or 250 pg/mL (148 or 185 pmol/L).
• Holotranscobalamin (HoloTC) Measurement: HoloTC is the biologically active form of vitamin B12 that is bound to transcobalamin, a carrier protein. The measurement of holoTC provides an assessment of the functional, available vitamin B12 levels in the body. HoloTC measurement is considered to be a more specific indicator of vitamin B12 deficiency compared to total serum vitamin B12 levels.
• Methylmalonic Acid (MMA) Measurement: MMA is a metabolite that accumulates in the body when there is a deficiency of vitamin B12. Elevated levels of MMA in the blood or urine indicate impaired vitamin B12 status. MMA measurement is highly sensitive and specific for vitamin B12 deficiency. A cutoff value of 0.271 micromol/L is often used to indicate vitamin B12 deficiency.
• Homocysteine Measurement: Homocysteine is an amino acid whose metabolism is influenced by vitamin B12. In vitamin B12 deficiency, homocysteine levels tend to rise. Measuring total plasma homocysteine levels can provide an indirect assessment of vitamin B12 status. However, it is important to consider that elevated homocysteine levels can also be influenced by other factors such as folate deficiency and kidney function.

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