• Profile

Depression could be a result of Vitamin B12 Deficiency! Discussing Symptoms & Management Approaches: Dr Aneesh Basheer

M3 India Newsdesk Sep 12, 2022

The following article provides detailed clinical management which would help the physician handle patients with vitamin B12 deficiency.

Key takeaways

  1. Vitamin B12 deficiency is more prevalent among the elderly and those hospitalised for chronic diseases.
  2. A high index of suspicion is needed as symptoms and signs may be non-specific and involve hematologic, neurologic and gastrointestinal systems.
  3. Neurological manifestations such as subacute combined degeneration may precede anaemia and sometimes occur in its absence as well.
  4. The combination of absent ankle reflexes and extensor plantar response indicates subacute combined degeneration of the spinal cord.
  5. Hyper-segmented neutrophils are highly suggestive of vitamin B12 deficiency apart from macrocytosis.
  6. Treatment involves intramuscular vitamin B12. Duration depends on the underlying cause with pernicious anaemia and chronic malabsorption states requiring lifelong supplementation.


Vitamin B12 deficiency is estimated to occur in about 2% of the population. In the elderly and those with chronic illnesses, it may be as high as 15%. In developed countries, malabsorption appears to be the commonest cause while in developing nations, dietary deficiency may be the most frequent reason for the deficiency. The specific aetiology of vitamin B12 deficiency may be classified as:


Persons who followed a strict vegan diet are prone since vitamin B12 is absent in plant sources. Breastfed infants of mothers with vitamin B12 deficiency are also at risk of developing a deficiency.

Defective absorption

  1. This may occur due to poor availability of intrinsic factor that is produced from stomachs such as pernicious anaemia (autoantibodies to intrinsic factor or parietal cells), gastrectomy, bariatric surgery or chronic atrophic gastritis.
  2. Binding with IF is essential for the final absorption of vitamin B12 from the ileum.
  3. It may also be due to impaired absorption at the level of ileum as in the case of celiac disease, bacterial overgrowth, ileal resection or fish tapeworm infection.

Uncommon causes

Such as pancreatic insufficiency inherited deficiency of transcobalamin II and use of drugs that may affect absorption such as metformin, neomycin, proton pump inhibitors and nitrous oxide.

Therefore, persons with one or more of the above potential risk factors presenting with symptoms suggestive of anaemia, pancytopenia, neuropsychiatric changes or neuropathy must be carefully evaluated for vitamin B12 deficiency. In addition, routine health checkups revealing anaemia with macrocytosis may provide clues to underlying vitamin B12 deficiency.

Clinical presentation

  1. Many persons are asymptomatic. Fatigue and exercise intolerance due to worsening anaemia may be subtle and ignored, delaying the diagnosis.
  2. Oral mucosal changes may present as burning due to stomatitis and glossitis.
  3. Mood and personality changes often indicate long-standing or severe deficiency.
  4. Paresthesia and numbness of extremities, and unsteadiness while walking indicates neuropathy and posterior column involvement. Gait disturbances may be pronounced during the night or when vision is compromised, typical of sensory ataxia.
  5. In more severe deficiency, the corticospinal tracts are also affected leading to myelopathy. Subacute combined degeneration refers to the symptom complex resulting from degenerative changes involving corticospinal tracts and posterior columns.

Physical examination

  1. It may demonstrate varying degrees of pallor and stomatitis or glossitis.
  2. The tongue may be red and beefy. Mild jaundice may be noted due to extravascular hemolysis from ineffective erythropoiesis.
  3. Knuckle hyperpigmentation that reverses with treatment has been reported as a specific sign although it may be seen only in a small proportion of patients.

Neurological examination

  1. It is necessary to identify loss of vibration and/or position sense, and Romberg’s sign.
  2. The combination of absent ankle jerk (due to peripheral neuropathy) and extensor plantar response (due to myelopathy) is very characteristic although it may be seen in Fredrich’s ataxia and neurosyphilis.
  3. Besides, one or more of the following neurologic symptoms/signs may be present including depression, dementia, optic atrophy and Lhermitte sign (shock-like sensation radiating along the spine on neck flexion).
  4. In B12 deficiency, these features might be present even in the absence of or before the development of anaemia.


The following tests are usually indicated:

Full blood count: Anaemia of varying degrees with a high MCV is usual. In severe cases, pancytopenia is observed.

Peripheral blood picture: Macro-ovalocytes identifiable as larger than normal RBC without the central pallor is observed. Besides, the demonstration of hyper-segmented neutrophils (defined as at least 5% neutrophils with 5 or more lobes or 1% neutrophils with 6 or more lobes) is a very useful diagnostic finding.

Biochemical tests: Serum vitamin B12 levels are usually reduced (< 200 pg/ml) but depend on the standardisation of the assay used. Besides, prior ingestion of vitamin B12 (which is a component of many over-the-counter multivitamin tablets) can interfere with levels. Elevated serum methylmalonic acid can be a useful test in doubtful cases when available.

Bone marrow studies: These are typically not required to make a diagnosis. However, in patients who present with pancytopenia and lack typical findings in peripheral blood smear, this is very useful. Hypercellular marrow with megaloblastic erythropoiesis is the characteristic finding.

Other studies: If dietary deficiency is obvious, no further testing is required. In other cases, further testing may be needed to identify the cause. This may require serum gastrin levels, endoscopy with gastric biopsies, assays for intrinsic factors or antibodies to intrinsic factors if pernicious anaemia is suspected. Studies using radiolabeled cobalamin for malabsorption are no longer used.


  1. While there is no doubt that the replacement of vitamin B12 is the treatment, several regimens are practised by clinicians. One of the widely accepted regimens includes daily intramuscular injections of cyanocobalamin (1000 micrograms) for a week followed by weekly doses of 1000 micrograms for four to six weeks and then once in 6-12 months lifelong in conditions like pernicious anaemia.
  2. When intramuscular injections are contraindicated due to thrombocytopenia, intravenous preparations may be used till counts improve. Alternatively, oral vitamin B12 preparations may be used in mild cases as approximately 1% of an oral dose may be absorbed passively without binding to intrinsic factors. In this case, doses of 1000-2000 micrograms daily for prolonged periods will often be needed.
  3. In B12 deficiency, treatment dramatically improves mood changes and mucosal symptoms such as glossitis. Early objective change is a reticulocyte response of 1-2 weeks followed by changes in haemoglobin. Neuropathy and other cognitive symptoms may take longer or show no improvement, particularly if they have been longstanding.


Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Aneesh Basheer is an Academician Professor of Medicine from Kerala. He is an expert reviewer of international peer-reviewed medical journals and case reports.

Only Doctors with an M3 India account can read this article. Sign up for free or login with your existing account.
4 reasons why Doctors love M3 India
  • Exclusive Write-ups & Webinars by KOLs

  • Nonloggedininfinity icon
    Daily Quiz by specialty
  • Nonloggedinlock icon
    Paid Market Research Surveys
  • Case discussions, News & Journals' summaries
Sign-up / Log In
M3 app logo
Choose easy access to M3 India from your mobile!

M3 instruc arrow
Add M3 India to your Home screen
Tap  Chrome menu  and select "Add to Home screen" to pin the M3 India App to your Home screen