7 Signs & Symptoms of Cobalamin (Vitamin B12) Deficiency & Treatment – Research Studies

What is Vitamin B12?

Vitamin B12 or cobalamin is classified as a water-soluble vitamin, which originates from animal products. These may include eggs, red meat, and dairy. In the human body, parietal cells of the stomach release the intrinsic factor, which is a glycoprotein integral to the intestinal absorption of vitamin B12. After its absorption in the human body, vitamin B12 functions as an enzyme cofactor, contributing to the production of myelin, deoxyribonucleic acid (DNA), and fatty acids. Owing to its important role in the normal functioning of the human body, vitamin B12 deficiency may lead to neurological and hematological abnormalities. [1]  

Why Vitamin B12 is Important?

Vitamin B12 is among the many essential micronutrients that facilitate the metabolism of the body. This micronutrient is essential for the production of cellular energy and DNA. Various forms of vitamin B12 are involved in different processes. For instance, cyanocobalamin is present in food and supplements. Similarly, other forms of vitamin B12 are required as enzyme cofactors. [2]

Methionine synthase is an enzyme that catalyzes the production of purines and pyrimidines. This process is dependent on folate and methyl-cobalamin as enzyme cofactors, which mediates the formation of tetrahydrofolate and methionine from homocysteine and methyl-tetrahydrofolate. Moreover, vitamin B12 in the form of 5-deoxy adenosyl cobalamin, mediates the formation of succinyl CoA catalyzed by methymalonyl CoA mutase. [2]

After its absorption into the blood, serum vitamin B12 is carried by transcobalamin II, which is an active transport protein. The deficiency of this protein may cause decreased levels of vitamin B12 in the serum. [2] 

7 Signs & Symptoms of Cobalamin (Vitamin B12) Deficiency

1. Megaloblastic Anemia 

Individuals suffering from vitamin B12 deficiency and subsequent megaloblastic anemia may present with weakness, lightheadedness, palpitation, and shortness of breath. The breakdown of large red blood cell (RBC) precursors can also give rise to jaundice. The physical examination findings of megaloblastic anemia patients include tachycardia, enlarged spleen or splenomegaly, and pallor. The development of anemia is based on the fact that the deficiency of vitamin B12 leads to defective production of DNA, resulting in a lack of full maturation of the nucleus whereas the cytoplasm reaches complete maturation, giving rise to large RBC precursors. [3]

2. Diarrhea 

Individuals suffering from vitamin B12 deficiency may also experience malabsorption and episodes of loose bowel movements, which is associated with pernicious anemia. In this condition, the parietal cells of the stomach are destroyed by the body’s immune system. Diarrhea is also associated with helminthic infections, which may cause a deficiency of vitamin B12 in the body due to impaired absorption in the gut. [4]

3. Paresthesia and Tingling 

Paresthesia is one of the main neurological symptoms of vitamin B12 deficiency. This is associated with the lack of adequate production of myelin and the resultant demyelination of the nervous system. The manifestations of neurological impairment also include ataxia and numbness. [5]

4. Greater Infections 

Since vitamin B12 contributes to the production of DNA in the immune cell precursors, the deficiency of vitamin B12 in the body leads to an increased risk of the development and severity of infections. Cobalamin deficiency influences the maturation of T lymphocytes, the function of phagocytes, and viral replication. Studies have also demonstrated that vitamin B12 deficiency in human immunodeficiency virus (HIV) patients tends to cause a longer duration of infection. Therefore, individuals with vitamin B12 deficiency suffer from longer and more severe infections compared to individuals with normal levels of vitamin B12. [6]

5. Impaired Memory and Cognition 

The deficiency of vitamin B12 has several neuropsychiatric manifestations. One of the most common manifestations is behavioral disturbances. A severe deficiency of vitamin B12 can cause memory loss. Vitamin B12 deficiency may also cause a greater burden of cognitive decline. [7]

6. Visual Disturbances 

Individuals suffering from vitamin B12 deficiency can develop optic neuropathy and resultant impaired visual acuity. In the early stages of vitamin B12 deficiency, the optic nerve appears normal, however, which later culminates in the development of optic neuropathy. The most common presentation of vitamin B12 deficiency-related optic neuropathy includes painless, progressive, and bilateral loss of vision and abnormal color vision. Visual disturbances also include optic neuritis. [8]

7. Muscle Weakness 

Demyelination of peripheral nerves in vitamin B12 deficiency in elderly individuals can give rise to pain, muscle weakness, and numbness in the limbs, caused by significant damage to the nerve fibers. These abnormalities result in sarcopenia, impaired balance, and ataxia. Sarcopenia is a result of age-related loss of mass of skeletal muscle, associated with physical dysfunction and loss of muscle strength. This contributes to increased mortality and disability. The underlying reason is based on defective differentiation and proliferation of stem cells that are important for the regeneration of skeletal muscle. This is further combined with slowing nerve impulses down the demyelinated nerves, which reduces muscle mass. Greater levels of homocysteine in vitamin B12 deficiency also cause damage to the skeletal muscle fibers. [9]

Vitamin B12 Deficiency Treatment 

The evaluation of vitamin B12 deficiency includes lab tests comprising peripheral blood smear, complete blood count (CBC), and levels of serum vitamin B12 and folate. After confirmation of vitamin B12 deficiency, the physician must address the cause of the deficiency. The treatment of vitamin B12 deficiency is based on the duration of treatment and the cause of the deficiency. Vitamin B12 is administered through the intramuscular route in individuals diagnosed with vitamin B12 deficiency. [1] 

Take advantage of free consultation with one of our Health Coach through the chat icon on the website to determine of vitamin B12 deficiency along with the identification of appropriate dosages. ASTR program recommends taking all types of B vitamins together because they depend on each other for absorption. Too much of one vitamin may cause a deficiency of another, which is why it is recommended that all vitamin Bs are taken together in a single capsule.


  1. Ankar A, Kumar A. Vitamin B12 Deficiency. [Updated 2022 Oct 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441923/
  2. O’Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients2(3), 299–316. https://doi.org/10.3390/nu2030299 
  3. Hariz A, Bhattacharya PT. Megaloblastic Anemia. [Updated 2022 Dec 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537254/ 
  4. Layden, A. J., Täse, K., & Finkelstein, J. L. (2018). Neglected tropical diseases and vitamin B12: a review of the current evidence. Transactions of the Royal Society of Tropical Medicine and Hygiene112(10), 423–435. https://doi.org/10.1093/trstmh/try078 
  5. Ekabe, C. J., Kehbila, J., Abanda, M. H., Kadia, B. M., Sama, C. B., & Monekosso, G. L. (2017). Vitamin B12 deficiency neuropathy; a rare diagnosis in young adults: a case report. BMC research notes10(1), 72. https://doi.org/10.1186/s13104-017-2393-3 
  6. Batista, K. S., Cintra, V. M., Lucena, P. A. F., Manhães-de-Castro, R., Toscano, A. E., Costa, L. P., Queiroz, M. E. B. S., de Andrade, S. M., Guzman-Quevedo, O., & Aquino, J. S. (2022). The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection. Nutrition reviews80(3), 561–578. https://doi.org/10.1093/nutrit/nuab092 
  7. Issac, T. G., Soundarya, S., Christopher, R., & Chandra, S. R. (2015). Vitamin B12 deficiency: an important reversible co-morbidity in neuropsychiatric manifestations. Indian journal of psychological medicine37(1), 26–29. https://doi.org/10.4103/0253-7176.150809 
  8. Ata, F., Bint I Bilal, A., Javed, S., Shabir Chaudhry, H., Sharma, R., Fatima Malik, R., Choudry, H., & Bhaskaran Kartha, A. (2020). Optic neuropathy as a presenting feature of vitamin B-12 deficiency: A systematic review of literature and a case report. Annals of medicine and surgery (2012)60, 316–322. https://doi.org/10.1016/j.amsu.2020.11.010 
  9. Chae, S. A., Kim, H. S., Lee, J. H., Yun, D. H., Chon, J., Yoo, M. C., Yun, Y., Yoo, S. D., Kim, D. H., Lee, S. A., Chung, S. J., Soh, Y., & Won, C. W. (2021). Impact of Vitamin B12 Insufficiency on Sarcopenia in Community-Dwelling Older Korean Adults. International journal of environmental research and public health18(23), 12433. https://doi.org/10.3390/ijerph182312433