Vitamin B12 (also known as cobalamin) is a substance necessary for maintaining basic human functions, such as the growth and development of red blood cells and the nervous system. Vitamin B12 deficiency (vitamin B12 deficiency) means that the amount of vitamin B12 consumed by the body is lower than the amount required for the body to function normally, which in turn leads to a series of diseases. The main symptoms are as follows: muscle weakness, numbness or tingling in the hands and feet, difficulty walking, nausea, decreased appetite, weight loss, excitability, lack of energy or easy fatigue (fatigue), diarrhea, mouth or tongue pain, and increased heart rate.

Adults need about 2.4 micrograms (μg) of vitamin B12 per day, and those who are pregnant or breastfeeding need more. The amount of vitamin B12 required by infants and children varies with age. It can be treated with vitamin B12 medications through daily diet, oral or injection. Potential serious complications due to lack of diagnosis include spinal cord degeneration and pancytopenia.

Diagnostic markers for Vitamin B12 deficiency

Vitamin B12 deficiency also results in decreased levels of holotranscobalamin (Holo-TC) and increased levels of methylmalonic acid (MMA). Methylmalonic acid is considered the gold standard for diagnosing vitamin B12 deficiency because it is a specific marker that is elevated when vitamin B12 is insufficient, even when serum B12 levels appear normal. Elevated MMA levels reflect impaired vitamin B12 metabolism, making it an important tool for early detection and intervention. Previous studies have shown that Holo-TC is the active form of vitamin B12 that is available to cells and is a more specific tool for diagnosing early vitamin B12 deficiency compared to total B12.

Most patients were aged 20-70 years, with 57% being female and 43% being male; Holo-TC had a sensitivity of 98.9%, a specificity of 50.00%, a PPV of 98.90%, and an NPV of 50%. Vitamin B12 has a sensitivity of 63%, a specificity of 50%, a PPV of 98.33%, and an NPV of 2.85%. The diagnostic accuracy of Holo-TC and vitamin B12 is 97.8% and 63%, respectively. Between the two, Holo-TC has a higher diagnostic accuracy than vitamin B12 and can be used as the primary test for patients suspected of vitamin B12 deficiency.

Vitamin B12 and Disease

Anemia

Megaloblastic anemia is characterized by abnormally large red blood cells, which is caused by a lack of vitamin B12 or folic acid, both of which are essential for DNA synthesis. Insufficient vitamin B12 can cause severe neurological damage, so early detection of vitamin B12 deficiency is crucial to prevent irreversible damage.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex chronic disease characterized by extreme fatigue. However, many symptoms of CFS/ME are similar to those of vitamin B12 deficiency. Most CFS patients have been shown to have functional vitamin B12 deficiency and functional vitamin B2 deficiency, as opposed to nutritional vitamin B12 deficiency. This functional B12 deficiency occurs despite the finding of elevated serum B12, thus presenting as paradoxical vitamin B12 deficiency. Therefore, CFS due to functional B2 deficiency presents as paradoxical B12 deficiency. Maintenance of vitamin B12 functional activity depends primarily on the adequacy of functional B2, and therefore, to resolve CFS, functional B2 deficiency must be resolved before vitamin B12 can be used for effective treatment.

Treatments

Vitamin B12 deficiency can be treated with vitamin B12. It is usually treated with cyanocobalamin, which is a man-made form of vitamin B12. Treatment options for vitamin B12 include:

Oral vitamin B12 medications.

Vitamin B12 intramuscular injection (an injection into a muscle).

Vitamin B12 nasal gel.

Vitamin B12 nasal spray.

References:

[1] NOAREEN TUFAIL. Comparing Holotranscobalamin and Total Vitamin B12 in Diagnosing Vitamin B12 Deficiency in Megaloblastic Anemia Patients.[J]. Cureus, 2024, 16 10: e71278. DOI:10.7759/cureus.71278.

[2] HAIYAN WANG. Oral vitamin B₁₂ versus intramuscular vitamin B₁₂ for vitamin B₁₂ deficiency.[J]. ACS Biomaterials Science & Engineering, 2018: CD004655. DOI:10.1002/14651858.CD004655.pub3.

[3] Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome[J]. International journal of psychiatry, 2022. DOI:10.33140/ijp.07.3.01.

[4] PETRUHINA K. Vitamin B12 deficiency anemia: diagnosis and treatment[J]. Clinical Medicine and Pharmacology, 2024, 53. DOI:10.12737/2409-3750-2024-9-4-14-20.