How Does The Body Absorb Vitamin B12?

Vitamin B12 is naturally bound to protein in food, and these bonds must first be broken by gastric acid and enzymes in the stomach before they can be absorbed and used by the body. After ingestion B12 binds to a glycoprotein called haptocorrin (HC), which is secreted in saliva and gastric fluids.
This B12 complex travels to the small intestine, where digestive enzymes degrade HC and allow vitamin B12 to bind with intrinsic factor to form a complex known as IF-B12. In the ileum (final section of the small intestine), the IF-B12 complex binds to a specific receptor on the epithelial cells, which then transports it across the intestinal lining. 

Once absorbed, B12 is released from intrinsic factor and enters the bloodstream, where it binds to transcobalamin, the active transport protein that delivers the vitamin to tissues.¹

The body’s cells take up the B12-TC complex through a receptor called CD320. Once inside cells, B12 is converted to its active forms methylcobalamin (in the cytosol) and adenosylcobalamin (in the mitochondria). 

Research suggests that the IF-dependent pathway allows normal absorption of up to about 2 μg, including in people with pernicious anemia.² Absorption decreases with increasing doses.³

Sublingual B12 is not absorbed via the digestive tract but dissolved under the tongue, allowing passive diffusion of free cobalamin across the vascularized mucosa into the bloodstream.⁴

Intramuscular (IM) B12 bypasses both the digestive and mucosal routes as it is injected directly into muscle tissue. It can then pass into systemic circulation.

The absorption of B12 involves multiple steps and depends on the proper function of the digestive system. There are many points at which this process can fail, which can result in impaired absorption. 

B12 levels are most often measured with a serum B12 blood test at a lab or hospital. This test is usually recommended when a doctor suspects a malabsorption issue. You can also test your B12 levels at home with a B12 test kit, which involves a finger-prick blood sample. Note that the results of these home test kits should be confirmed with standard lab testing for an accurate diagnosis.
It should be noted that a serum test only measures the total B12 in the blood fluid, while RBC B12 measures B12 within the red blood cells, which is a more accurate measurement of tissue stores.

Serum B12 is often used as an initial test but it can show that levels are normal even when a person is deficient. RBC B12 provides a more accurate indicator of the body's actual cellular stores.

If low vitamin B12 levels and/or high homocysteine levels are detected, your health provider may then recommend testing for methylmalonic acid (MMA) and/or homocysteine levels. MMA is a metabolic byproduct that accumulates in the body when vitamin B12 deficiency is present. The level of MMA in your blood is a more sensitive indicator of B12 deficiency. Similarly, elevated homocysteine levels can mean that your B12 is low, as B12 is required for recycling homocysteine.⁵

Impairments to B12 absorption are most often acquired, which means they develop as a result of diet, age, genetics or other health conditions.

• Pernicious anemia
  Pernicious anemia is an autoimmune condition in which the body’s immune system attacks stomach cells that produce intrinsic factor, the protein required for B12 absorption.
  
• Diet
  Vegans and vegetarians are at the highest risk of B12 deficiency as the nutrient is only present in animal products. Restrictive diets that lack B12 sources are also a major contributor to deficiency.
  
• Digestive disorders
  Conditions affecting the gastrointestinal system - such as inflammatory bowel disease (IBD), Crohn's disease, celiac disease, and autoimmune gastritis - can cause inflammation in the intestinal walls, damaging cells and impairing B12 absorption.
  
• Gastrointestinal surgery
  Surgeries in which parts of the stomach or intestines are removed (e.g, gastrectomy or bariatric surgery) can significantly impair B12 absorption.
  
• Poor pancreatic function
  Pancreatic enzymes are required to break down haptocorrin and release B12 so that it can bind with intrinsic factor. Insufficient enzyme production can impair this process.⁶
  
• Medications
  Several medications can reduce stomach acid or alter digestive function, affecting the uptake of B12. Common medications linked to impaired B12 absorption include metformin, proton pump inhibitors (PPIs), anticonvulsants, and nitrous oxide.
  
• Age
  Digestive efficiency (including stomach acid production) decreases with age. Health conditions and medication use are also more common in the elderly.
  
• Genetic conditions
  Mutations in genes encoding proteins involved in B12 absorption, transport, and intracellular processing can result in impaired absorption. These include congenital pernicious anaemia, Imerslund-Gräsbeck Syndrome (caused by mutations in genes encoding cubulin and amnionless), inherited transcobalamin receptor (Haptocorrin) mutations, and intracellular cobalamin defects (CblA-CblG defects).⁷
  An MTRR mutation may also lead to B12 deficiency as it impairs the activity of methionine synthase, the enzyme that uses B12 to convert homocysteine to methionine. This means the body can’t use B12 properly, leading to B12 deficiency even if blood tests show levels as normal.⁸

To improve your B12 absorption, you first need to know what is causing your deficiency. 

Those with malabsorption disorders such as pernicious anemia or impaired digestive function will require a form of B12 that bypasses the digestive system.

• Intramuscular B12 injections are most often prescribed for treating severe B12 deficiency. This involves injecting cyanocobalamin (the synthetic form of B12) into the muscle so that it enters the bloodstream directly. In most cases, intramuscular injections (IM) are given at 1 mg/day for 1 week, followed by 1 mg/week for 1 month and then 1 mg every 1-2 months.
• Oral B12 supplements (usually cyanocobalamin) may also be prescribed at a dosage of 1000 mcg/day.  High doses are required for oral B12 because it must be broken down in the digestive tract, which involves both intrinsic factor and passive diffusion. Passive diffusion accounts for 1.2% of overall absorption, with little effect on bioavailability in patients with pernicious anemia or who have had intestinal surgery.⁹
• Cyanocobalamin nasal spray provides 500 mcg B12 per spray. This is also an effective option for restoring B12 levels as it bypasses the digestive system. However, cyanocobalamin is a synthetic form of B12 that occurs only in trace amounts in the body.

Research suggests that natural, active B12 is generally more effective for restoring B12 levels than the synthetic form, cyanocobalamin.
Active forms of B12 include methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). Hydroxocobalamin is the precursor of methylcobalamin and adenosylcobalamin.
All of these natural forms have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in the human body and in animal foods.
Several studies show that supplementing with any of the natural forms of B12 may be more efficient than cyanocobalamin.¹⁰ This is because cyanocobalamin must be processed and converted to its active form in the body before it can be used, whereas the natural forms are already available for use.¹¹ For people with certain genetic or metabolic conditions, the active forms may be preferable. Studies have also noted that individuals with particular SNPs affecting B12 absorption may improve their B12 levels more efficiently by taking one or more active forms of the nutrient; i.e., methylcobalamin, adenosylcobalamin, and hydroxycobalamin.¹²

Chronic alcohol intake can damage the lining of the gastrointestinal system, significantly affecting the absorption of micronutrients, including B12.¹³
People with alcohol addiction are at higher risk of B12 deficiency due to low intake, impaired absorption, and impaired release of vitamin B12 from food proteins.¹⁴

Research into coffee consumption and its effect on B12 absorption is limited. One observational study reported lower blood levels of some B vitamins in coffee drinkers, but this does not prove that coffee reduces B12 absorption. This effect is likely due to the diuretic effects of coffee increasing urinary excretion.¹⁵

B12 supplements that bypass the digestive tract are generally the most efficiently absorbed. These include intramuscular injections, nasal spray, and sublingual supplements. 

Sublingual B12 supplements are in the form of drops, tablets, or lozenges, and are absorbed via the mucous membranes under the tongue.
A 2024 meta-analysis found that sublingual methylcobalamin is as effective as intramuscular and sublingual cyanocobalamin for improving B12 levels.¹⁶ Studies suggest that sublingual B12 is often preferred by patients, especially those who dislike injections, and/or require long-term supplementation. Sublingual B12 is easier to administer, more comfortable and convenient, and generally obtained at a lower cost than intramuscular B12.¹⁷ The best form of B12 depends on your personal preference.