Vitamin B12: Roles, Sources, Absorption, Deficiency, and Supplements

Vitamin B12, also known as cobalamin, is a vital water-soluble vitamin that plays various essential roles in the human body. It is naturally present in certain foods, added to others, and can also be obtained through dietary supplements or prescription medications. The term “cobalamins” collectively refers to compounds that exhibit vitamin B12 activity due to their cobalt content. The metabolically active forms of vitamin B12 are methylcobalamin and 5-deoxyadenosylcobalamin, while hydroxycobalamin and cyanocobalamin become biologically active after conversion to the former two forms. Vitamin B12 deficiency will be explored in detail in this article.

Chemical structure of Vitamin B12
Chemical structure of Vitamin B12

Importance of Vitamin B12

Vitamin B12 plays a crucial role in various physiological processes, making it essential for overall health.

  • It is necessary for the development, myelination, and proper functioning of the central nervous system.
  • Vitamin B12 is involved in the formation of healthy red blood cells and prevents anemia.
  • It acts as a cofactor for enzymes methionine synthase and L-methylmalonyl-CoA mutase.
  • Methionine synthase converts homocysteine to methionine, an essential amino acid for the production of S-adenosylmethionine, a universal methyl donor for DNA, RNA, proteins, and lipids.
  • L-methylmalonyl-CoA mutase participates in the metabolism of propionate, aiding in energy production.
  • Vitamin B12 supports cognitive functioning and critical thinking skills.
  • It contributes to DNA synthesis, promoting cellular replication and growth.
  • Vitamin B12 may help prevent congenital abnormalities and protect against macular degeneration.
  • Adequate intake of vitamin B12 is crucial for overall health and vitality. 

Absorption of Vitamin B12

The absorption journey begins in the mouth, where vitamin B12 is released from protein-bound forms during food mixing and saliva interaction. This liberated vitamin B12 then binds with haptocorrin, a cobalamin-binding protein found in saliva.

As digestion progresses, the stomach’s hydrochloric acid and gastric protease work together to further release vitamin B12 from its food matrix, enabling it to bind with haptocorrin. In the duodenum, specific digestive enzymes separate vitamin B12 from haptocorrin, leading to its combination with intrinsic factor.

Intrinsic factor, a binding protein secreted by the stomach’s parietal cells, acts as a crucial transporter and delivery agent. The resulting complex of vitamin B12 and intrinsic factor is then absorbed in the distal ileum through a process called receptor-mediated endocytosis.

However, when vitamin B12 is present in fortified foods or dietary supplements, it is already in its free form and does not require the separation step. This facilitates its direct absorption without the need for complex binding and digestion processes.

Sources of Vitamin B12

Obtaining sufficient vitamin B12 through a balanced diet is achievable for most individuals. However, certain groups may benefit from supplementation. Older adults, vegetarians, vegans, and individuals with conditions that affect their ability to absorb vitamin B12 from food sources may find oral supplements beneficial.

Pregnant and breastfeeding women who follow vegetarian or vegan diets are specifically advised to take vitamin B12 supplements. While the 2020-2025 Dietary Guidelines for Americans emphasize meeting nutritional needs primarily through food sources, fortified foods and dietary supplements can be useful in ensuring adequate nutrient intake, especially during specific life stages like pregnancy.

Certain medications, such as metformin, proton pump inhibitors, and H2 receptor agonists, may interfere with the absorption of vitamin B12 from foods.

To build a healthy dietary pattern that includes sufficient vitamin B12, it is advisable to consume a variety of foods from different food groups. This includes incorporating vegetables, fruits, whole grains (including fortified cereals), dairy products, and protein sources like lean meats, poultry, eggs, seafood, beans, peas, lentils, nuts, seeds, and soy products into your meals. Fish and red meat are particularly excellent sources of vitamin B12, while poultry and eggs also contain this nutrient.

It is essential to limit the intake of added sugars, saturated fats, sodium, and alcoholic beverages. Additionally, monitoring calorie intake to align it with energy requirements is crucial for maintaining a healthy dietary pattern.

By following these guidelines and consuming a diverse range of nutrient-rich foods, it is possible to meet the recommended intake of vitamin B12 and maintain overall health.

What is Vitamin B12 Deficiency?

Vitamin B12 deficiency is a condition that occurs when the body does not have enough vitamin B12, which can result from inadequate intake or impaired absorption. This essential nutrient plays a critical role in the production of red blood cells, DNA synthesis, and the proper functioning of the nervous system. 

Several factors contribute to the development of vitamin B12 deficiency, including difficulties in absorbing the vitamin from food, a deficiency of intrinsic factor (often linked to pernicious anemia), gastrointestinal surgeries, prolonged use of specific medications like metformin or proton pump inhibitors, and dietary insufficiencies.

Symptoms of Vitamin B12 Deficiency:

  1. Megaloblastic anemia: Abnormally nucleated red blood cells, low white and red blood cell counts, and platelet deficiency.
  2. Glossitis: Inflammation of the tongue.
  3. Fatigue: Extreme tiredness and lack of energy.
  4. Palpitations: Irregular or rapid heartbeat.
  5. Pale skin: Skin appears paler than usual.
  6. Dementia: Cognitive impairment and memory loss.
  7. Weight loss: Unexplained and unintended weight loss.
  8. Infertility: Difficulty conceiving or maintaining a pregnancy.
  9. Neurological changes: Numbness and tingling in the hands and feet.
  10. Depression and psychological problems: Ranging from mild depression and anxiety to confusion and dementia.
  11. Vision problems: Issues with vision and visual perception.
  12. Muscle weakness: Reduced strength and muscle function.
  13. Mouth ulcers: Painful sores in the mouth.
  14. Problems with memory, understanding, and judgement.

It’s important to note that some symptoms can occur even without anemia. Vitamin B12 deficiency has also been associated with depression.

Symptoms of Vitamin B12 deficiency
Symptoms of Vitamin B12 deficiency

Causes of Vitamin B12 Deficiency

  1. Inadequate dietary intake: Not consuming enough vitamin B12-rich foods or foods fortified with vitamin B12 can lead to deficiency.
  2. Gastritis: Inflammation of the stomach lining, which can impair vitamin B12 absorption due to a lack of hydrochloric acid.
  3. Pernicious anemia: A rare condition where the body is unable to produce intrinsic factor, a protein necessary for vitamin B12 absorption.
  4. Digestive diseases: Conditions like Crohn’s disease and celiac disease can hinder the proper absorption of vitamin B12 in the digestive system.
  5. Gastrointestinal surgery: Procedures such as gastric bypass surgery can impact the absorption of vitamin B12.
  6. Alcohol use disorder: Excessive alcohol consumption can damage the digestive system, leading to vitamin B12 deficiency.
  7. Transcobalamin II deficiency: A rare genetic disorder that disrupts the transport of vitamin B12 within the body.

Vitamin B12 deficiency can develop gradually, as the body stores a substantial amount of vitamin B12 in the liver, providing reserves for several years. However, low or marginal vitamin B12 status without apparent symptoms is common, particularly among individuals with limited intake of vitamin B12-rich foods. The prevalence of deficiency varies depending on the cutoff levels and biomarkers used for assessment. Studies have reported rates of low vitamin B12 levels ranging from 3% (cutoff less than 200 pg/mL) to 26% (cutoff less than 350 pg/mL) among adults.

Vitamin B12 Deficiency Treatment

1.    Vitamin B12 injections: 

The primary treatment for vitamin B12 deficiency involves administering vitamin B12 through injections. This method bypasses any absorption barriers and ensures direct delivery of the nutrient into the bloodstream.

2.    High-dose oral supplements: 

In certain cases, high oral doses of vitamin B12 (ranging from 1,000 to 2,000 mcg) can be effective in normalizing serum vitamin B12 levels. Research, such as a Cochrane review, has shown that very high oral doses can be comparable to intramuscular administration in their ability to raise vitamin B12 levels.

3.    Maintenance supplementation: 

After the initial treatment, individuals with vitamin B12 deficiency may need to continue with regular maintenance supplementation. This involves taking lower doses of vitamin B12 orally or through other forms, such as sublingual tablets or nasal sprays, to sustain adequate levels of the nutrient.

4.    Dietary adjustments: 

Alongside supplementation, adopting a diet rich in vitamin B12 sources is important for long-term management of deficiency. Foods like meat, fish, eggs, and dairy products are natural sources of vitamin B12. Vegetarians and vegans may need to rely on fortified foods or consider vitamin B12 supplements to meet their needs.

5.    Monitoring and follow-up: 

Regular monitoring of vitamin B12 levels through blood tests is necessary to assess the effectiveness of treatment and ensure optimal levels are maintained. Healthcare professionals will determine the frequency of follow-up based on individual needs.

Risk Factors for Vitamin B12 Deficiency

  1. Advanced age: Individuals over the age of 75 are at a higher risk of developing vitamin B12 deficiency. Age-related changes in the body can impair the absorption of vitamin B12.
  2. Gastrointestinal disorders: Digestive system disorders like celiac disease and Crohn’s disease can interfere with the proper absorption of vitamin B12. The compromised digestive function makes it difficult for the body to utilize vitamin B12 from food sources.
  3. Pernicious anemia: People with pernicious anemia, an autoimmune condition, have a higher risk of vitamin B12 deficiency. This condition prevents the production of intrinsic factor, a protein necessary for vitamin B12 absorption.
  4. Weight loss surgery: Individuals who have undergone gastrointestinal surgeries, such as gastric bypass, may have reduced absorption capacity for vitamin B12, leading to an increased risk of deficiency.
  5. Excessive alcohol consumption: Chronic alcoholism can damage the digestive system and hinder the absorption of vitamin B12, contributing to deficiency.
  6. Medication use: Certain medications can lower vitamin B12 levels in the body. These include metformin (used to manage diabetes), proton pump inhibitors (PPIs used to treat GERD and peptic ulcers), histamine H2 blockers (reduce stomach acid), and oral birth control pills (oral contraceptives).
  7. Vegan or vegetarian diet: Individuals who follow strict vegan or vegetarian diets are more susceptible to vitamin B12 deficiency as the vitamin is primarily found in animal-derived foods. Without adequate supplementation or consumption of fortified foods, these diets may not provide sufficient vitamin B12.
  8. Autoimmune and immune system disorders: Conditions like Sjögren’s syndrome and type 1 diabetes increase the risk of vitamin B12 deficiency. Individuals with these disorders may have impaired absorption or increased metabolic demands for vitamin B12.

Recommended Intake of Vitamin B12

  • Recommended Dietary Allowance (RDA): The RDA for vitamin B12 varies based on age, gender, and life stage. For men and women aged 14 years and older, the RDA is 2.4 micrograms (mcg) per day. During pregnancy, the RDA increases to 2.6 mcg daily, and during lactation, it further increases to 2.8 mcg daily.
  • Tolerable Upper Intake Level (UL): There is no established UL for vitamin B12 due to the lack of known toxicity. However, high doses of vitamin B12 supplements, specifically 25 mcg per day or higher, may potentially increase the risk of bone fractures. It is generally recommended to adhere to the recommended daily intake unless advised otherwise by a healthcare professional.
  •  Adequacy of Intake: The majority of people in the United States consume sufficient amounts of vitamin B12. Data from the National Health and Nutrition Examination Survey (NHANES) show that only a small percentage of men and women have intakes below the Estimated Average Requirement (EAR) for vitamin B12.
  • Average Intake: Average daily intakes of vitamin B12 from food sources are 5.94 mcg for men aged 20 and older and 3.78 mcg for women. For children aged 2-19, mean daily intakes range from 3.76 mcg to 4.55 mcg.

Vitamin B12 Supplement

For individuals who have difficulties absorbing vitamin B12 from food sources, supplementation may be necessary. Certain populations, including older adults, people with pernicious anemia, and those with intestinal disorders, may experience challenges in absorbing vitamin B12 from their diet.

Vitamin B12 supplements can be taken orally or in the form of a nasal spray. However, it’s important to note that oral supplements may not be effective in many cases of deficiency. In such instances, doctors may recommend vitamin B12 injections.

Vitamin B12 supplements can be purchased from health food stores and online. However, it’s crucial to exercise caution as these supplements are not FDA regulated. It is recommended to obtain them from reliable sources.

Vitamin B12 is available in various forms in dietary supplements, with cyanocobalamin being the most common form. Other forms include adenosylcobalamin, methylcobalamin, and hydroxycobalamin.

The absorption rates of vitamin B12 in supplements do not vary based on the form of the vitamin. At doses below 1-2 mcg, absorption rates are approximately 50%, provided they do not exceed the cobalamin-binding capacity of intrinsic factor. However, absorption rates significantly decrease at doses above 1-2 mcg, for example, only about 2% at doses of 500 mcg and 1.3% at doses of 1,000 mcg.

Treating Vitamin B12 or Folate Deficiency Anemia

The treatment for vitamin B12 and folate deficiency anemia is typically straightforward and involves the use of injections or tablets to replenish the missing vitamins.

Initially, vitamin B12 supplements are often administered through injections. Depending on the underlying cause of your B12 deficiency, you may then be prescribed B12 tablets to be taken between meals or regular injections.

The duration of treatment varies, as it may last until your vitamin B12 levels have improved or it may be required for the rest of your life.

To restore folate levels, folic acid tablets are used and typically need to be taken for a period of 4 months.

In certain cases, improving your diet can also help in treating the condition and prevent its recurrence.

Vitamin B12, specifically in the forms of cyanocobalamin and hydroxycobalamin, can be administered parenterally as a prescription medication, usually through intramuscular injection. This method is commonly used to treat vitamin B12 deficiency caused by conditions like pernicious anemia and malabsorption issues.

Alternatively, vitamin B12 is available as a prescription nasal gel spray, which has been shown to effectively increase vitamin B12 levels in adults and children. Research indicates that the bioavailability of intranasal administration is similar to that of an oral dose.


Certain medications and supplements can potentially interact with vitamin B12. It’s important to be aware of these interactions: 

  • Aminosalicylic acid (Paser): This medication used to treat digestive problems may hinder the absorption of vitamin B12 in your body. 
  • Colchicine (Colcrys, Mitigare, Gloperba): Taking this anti-inflammatory drug for gout attacks might reduce your body’s ability to absorb vitamin B12.
  • Metformin (Glumetza, Fortamet, others): This diabetes drug may decrease your body’s ability to absorb vitamin B12. • 
  • Proton pump inhibitors: Stomach acid-reducing drugs like omeprazole (Prilosec) and lansoprazole (Prevacid) can potentially reduce the absorption of vitamin B12. 
  • Vitamin C (ascorbic acid) supplements: Taking vitamin B12 with vitamin C may decrease the availability of vitamin B12 in your body. To avoid this interaction, it is recommended to take vitamin C supplements at least two hours after taking a vitamin B12 supplement.

Prevention of Vitamin B12 deficiency

Vitamin B12 deficiency can be prevented by adopting the following strategies: 

  • Maintain a balanced diet that includes an adequate intake of meat, poultry, seafood, dairy products, and eggs, as these are rich sources of vitamin B12. 
  • For individuals who follow a vegetarian or vegan diet or have medical conditions that affect nutrient absorption, it is important to supplement their diet with vitamin B12. This can be achieved through the use of multivitamins or other supplements specifically containing vitamin B12, as well as consuming foods fortified with vitamin B12. 

If you opt for vitamin B12 supplements, it is advisable to inform your doctor to ensure the correct dosage and to check for any potential interactions with other medications you may be taking.


  1. Office of Dietary Supplements – Vitamin B12:
  2. National Institutes of Health (NIH) Office of Dietary National Institute of Diabetes and Digestive and Kidney Diseases – Vitamin B12 Deficiency Anemia:
  3. Mayo Clinic – Vitamin B12 deficiency anemia:
  4. National Health Service (NHS) – Vitamin B12 or folate deficiency anaemia:
  5. Merck Manual – Vitamin Deficiency, Dependency, and Toxicity:,-dependency,-and-toxicity/vitamin-b12-deficiency
  6. American Society of Hematology – Vitamin B12 Deficiency:
  7. Medscape – Vitamin B12 Deficiency Anemia:
  8. World Health Organization (WHO) – Folate and folic acid deficiency:
  9. American Family Physician – Diagnosis and Treatment of Vitamin B12 Deficiency:
  10. National Center for Biotechnology Information (NCBI) – Folate and Vitamin B12-Related Mechanisms Involved in Cognitive and Emotional Functioning:

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Binod G C

I'm Binod G C (MSc), a PhD candidate in cell and molecular biology who works as a biology educator and enjoys scientific blogging. My proclivity for blogging is intended to make notes and study materials more accessible to students.

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