Vitamin B12 Therapy

Do Your Patients Need More Vitamin B12?

Vitamin B12 (also known as cobalamin) is commonly found in animal-derived foods. While previous research suggested that the majority of the population consumes adequate levels of vitamin B12, recent studies suggest that many people do not absorb enough vitamin B12 to meet the recommended dietary intake and likely have marginal levels.1-3 Although the clinical implications of this are not completely clear, increased intake of B12-rich foods, or supplementation, may be warranted for certain individuals.

The Role of Vitamin B12 in Health

Vitamin B12 is essential for DNA synthesis, red blood cell production, neurological function, and cell metabolism.1 In addition, vitamin B12 plays an important role in the conversion of homocysteine to methionine.

Hydrochloric acid and gastric protease are required to separate vitamin B12 from protein in food, where it then combines with intrinsic factor in parietal cells for absorption. Vitamin B12 from fortified cereals and supplements is already in free form and does not require separation to bind to intrinsic factor.1

Deficiency is defined as serum vitamin B12 levels less than 170 to 250 pg/mL (or 120 to 180 picomol/L).1 Diet, autoimmune diseases (such as pernicious anemia), the aging process, medications, and gastrointestinal surgeries can interfere with the absorption of vitamin B12. According to Shipton and Thachil, 15% of adults aged 20 to 59 years old, more than 20% of those over the age of 60, and up to 35% of those over the age of 80 are likely to have marginal levels of vitamin B12.3 Because it can take as many as 10 years for clinical signs to appear, older patients should be assessed to make sure they are consuming enough sources of this vitamin and taking a supplement if indicated.

Signs of deficiency present mainly in the blood and nervous system. Symptoms of marginal B12 levels can be nonspecific and include fatigue, weakness, memory problems, such as confusion, depression, nerve damage in the hands and feet, among other neurological changes. Megaloblastic anemia is also characteristic of vitamin B12 deficiency.1

More serious manifestations can include spinal degeneration, osteoporosis, pancytopenia, macular degeneration, hearing loss, mania and psychosis, and dementia. In addition, inadequate levels of B12 can result in elevated homocysteine levels that can lead to excess inflammation and cellular stress, which is associated with early atherosclerotic disease.1

Specific populations with a high risk for vitamin B12 deficiency include1:

  • Individuals who follow a strict vegetarian or vegan diet
  • Individuals with pernicious anemia (an autoimmune disease that affects 1-2% of older adults)
  • Individuals who underwent gastrointestinal surgery
  • Individuals with intestinal diseases, such as inflammatory bowel disease

Identifying At-Risk Patients

Many health conditions and medications can impair B12 absorption, so RDs should consider the possibility of inadequate levels in patients with the following conditions6:

  • Autoimmune diseases, especially celiac, inflammatory bowel disease, or atrophic gastritis
  • Pregnant and lactating women
  • Alcoholism
  • Small intestinal bacterial overgrowth
  • Helicobacter pylori infection
  • Reduced or absent stomach acid (hypo/achlorhydria)
  • Pancreatic disease, pancreatectomy, or chronic pancreatic exocrine insufficiency
  • Ileal resection
  • Parasitic infections
  • Certain medications, including:
    • metformin
    • proton pump inhibitors (omeprazole, lansoprazole, etc)
    • histamine H2 receptor antagonists (cimetidine, famotidine, ranitidine, etc)
    • cholestyramine
    • oral birth control therapies

Implications for Practice

The best way to prevent a subclinical deficiency is to promote adequate consumption of vitamin B12-rich foods, especially in adults. The Recommended Dietary Allowance (RDA) for children aged 14 years and older and adults is 2.4 ug. Pregnant and lactating women should consume 2.6 and 2.8 ug per day, respectively.1

Good sources of vitamin B12 include salmon, trout, haddock, tuna, beef, chicken, yogurt, milk, eggs, and fortified cereals. Nori is a plant source vegans and vegetarian patients can consume to meet the RDA.7

Patients with a higher risk of vitamin B12 deficiency should consider taking supplements. The vitamin is available as in oral or sublingual forms, which can be selected based on patient’s preference as studies show no significant difference in absorption.1

Vitamin B12 is also frequently administered as an intramuscular injection. However, research shows that high oral doses of the vitamin (1000 ug per day) can raise low B12 levels as well as injections and can be more convenient and cost-effective for otherwise healthy patients.3,8

Once vitamin B12 levels are restored, a supplemental oral dose of 1000 to 2000 ug per day for those with malabsorption, or at least 6 ug per day for those with a general B12 deficiency, should help to maintain serum B12 levels.2

Contributed by Anne Danahy, MS, RDN.


  1. Vitamin B12. National Institutes of Health Office of Dietary Supplements. Updated August 22, 2018. Accessed September 25, 2018.
  2. Green R, Allen LH, Bjørke-Monsen AL, et al. Vitamin B 12 deficiency. Nat Rev Dis Primers. 2017;3:17040. doi: 10.1038/nrdp.2017.40
  3. Shipton MJ, Thachil J. Vitamin B12 deficiency–A 21st century perspective. Clin Med. 2015;15(2):145-50.
  4. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-61.
  5. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2016;42(5):316-27.
  6. Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B 12 deficiency and longterm use of acidlowering agents: a systematic review and metaanalysis. Inter Med J. 2015;45(4):409-1
  7. Watanabe, F., Yabuta, Y., Bito, T., & Teng, F. (2014). Vitamin B12-Containing Plant Food Sources for Vegetarians. Nutrients. 2014;6(5):1861–73.
  8. Castelli MC, Friedman K, Sherry J, et al. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, open-label, parallel-group study. Clin Ther. 2011;33(3):358-71.