Vitamin B12

Vitamin B12 and the Immune System

Published studies demonstrate that low vitamin B12 levels are linked to a decrease in the immune system.  Vitamin B12 plays an important role in white blood cell production, acting as an immunomodulator. A study found that patients deficient in vitamin B12 had a decrease in the absolute number of CD8+ cells and suppressed NK cell activity (both are white blood cells). When patients were treated with B12 (the methylated form), augmentation of CD8+ cells was observed. The authors of the study concluded that vitamin B12 may acts as immunomodulator for cellular immunity, hence it is beneficial to our immune system.

What are B vitamins and what is vitamin B12?

Vitamin B is a water soluble vitamin. There are 8 types of vitamin B and each type has a different role. B vitamins may help with blood cell production, cognitive development, and increased energy.

Vitamin B12 helps keep the body’s nerve and blood cells healthy, and supports DNA production. It is a coenzyme involved in the metabolism of cells and plays a role in DNA synthesis and regulation, as well as fatty acid and amino acid metabolism.

Vitamin B12 may help prevent a type of anemia known as megaloblastic anemia. People with megaloblastic anemia may feel tired and weak. In pregnancy vitamin B12 promotes blood formation and may prevent birth defects. Vitamin B12 may lower homocysteine levels, which is thought to help prevent dementia and heart disease.

How does the body absorb vitamin B12?

There are two steps that are required for the body to absorb vitamin B12 from food. The first step involves hydrochloric acid, found in the stomach, which separates vitamin B12 from protein.  The second step involves intrinsic factor, a protein made in the stomach, combining with vitamin B12. Once intrinsic factor combines with vitamin B12 the body can then absorb it.  Some people have pernicious anemia, a condition in which they cannot make intrinsic factor. As a result, they have trouble absorbing vitamin B12 from all foods and dietary supplements. With this condition to bypass the gut, vitamin B12 injections are preferred.

What are symptoms or signs of low vitamin B12 levels?

Symptoms include premature graying hair, tingling and numbness in hands and feet, pernicious anemia, fatigue, constipation, weight loss. Deficiency tends to be rare, even in vegetarians, while children and babies are more at risk.

What are good dietary sources of vitamin B12?

Good sources include fish, dairy, meat, tempeh and miso.

What is the best form of vitamin B12?

The best form of Vitamin B12 is sublingual tablets (dissolved under the tongue), oral liquid, or B12 injections.

Vitamin B12 shots are preferred over tablets in the following situations: 

1.    You have low B12 levels (<200 ng/mL) and are experiencing symptoms (mental slowness, weakness and tingling in your extremities)

2.    You have a GI disorder that might affect the absorption of Vitamin B12 (such as celiac disease, IBD, SIBO, bariatric surgery, etc.)

3.    You are taking a medication that limits your absorption such as a proton pump inhibitors (PPI’s) or metformin therapy

4.    You have the autoimmune disorder called pernicious anemia, which attacks vitamin B12 absorption by not making enough intrinsic factor. As mentioned before intrinsic factor is needed for vitamin B12 absorption

Which populations are at a greater risk for deficiencies?

People higher risk for deficiencies include the following:

1.    Vegetarians and vegans (do not eat meat)

2.    People aged 60 or over (more prone to chronic gastritis caused by H. Pylori)

3.    People who regular use proton pump inhibitor’s (PPI’s) to help prevent stomach acid and  people on diabetes drugs like metformin

4.    People with Crohn’s disease, ulcerative colitis celiac or IBS

5.    Women with a history of infertility and miscarriage

Are there any medications that may put someone at risk for vitamin B12 deficiencies?

There are certain medications that may increase the risk of vitamin B12 deficiency. These medications include stomach acid reducing medications, such as H2 blockers (examples include Zantac, Pepcid) and proton pump inhibitors (examples include Prilosec and Nexium). In addition, the following medications may reduce vitamin B12 absorption: colchicine commonly used for gout, metformin commonly used for diabetes, and AZT commonly used for AIDS. In addition, birth control may cause vitamin B12 deficiency (including also a deficiency in vitamin B2, magnesium, selenium and zinc).

What are the different types of vitamin B12? Which one is the best form to supplement with?

Vitamin B12 is cobalamin as it is the only vitamin that contains small amounts of cobalt. Cobalamin cannot be obtained from plants (as plants do not need vitamin B12) or sunlight and is produced in the gut of animals.

The different forms of cobalamin include: methylcobalamin, adenosylcobalamin, hydroxocobalamin and cyanocobalamin.

Methylcobalamin is the natural form that exists in the body and is readily absorbed.  This is an active form of vitamin B12 and works with several enzymes to synthesize amino acids, produce red blood cells, repair DNA and assist with other important physiologic processes. There are claims that this form of vitamin B12 helps maintain normal circadian rhythms to assist with sleep and supports the body with methylation processes. It also assists with recycling homocysteine, which is linked to cardiovascular disease.

Adenosylcobalamin is another natural and active form of vitamin B12. It is required for cell energy and metabolism. The body is able to interconvert between adenosylcobalamin and methylcobalamin.

Hydroxycobalamin is a synthetic type of vitamin B12. This form is either engineered in the laboratory from bacteria or it is produced by bacteria in the digestive tract from food. It is a precursor to the active forms of vitamin B12. This means the body converts this form to the active forms: adenosylcobalamin and methylcobalamin. It is a precursor to the active forms of vitamin B12.

Cyanocobalamin is a man-made form that contains a cyanide molecule. Cyanide provides this form of vitamin B12 stability. Although cyanide is commonly associated with poison the amount is inconsequential to cause harm. The FDA has approved its use and it has been demonstrated not to cause toxicity. The body easily converts cyanocobalamin to the active forms.  The body does this by the liver detoxing the cyanide molecule and modifying the vitamin to methylcobalamin by attaching a methyl group.


1.    Tamura J, Kubota K, Murakami H, Sawamura M, Matsushima T, Tamura T, et al. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol. 1999;116(1):28–32.

2.    Mikkelsen K., Apostolopoulos V. (2019) Vitamin B12, Folic Acid, and the Immune System. In: Mahmoudi M., Rezaei N. (eds) Nutrition and Immunity. Springer, Cham