Vitamin B12 Deficiency: Risk Factors, Symptoms and the Standard Tests

Specialty Testing Guide › TruHealth Micronutrient Testing

The main risk factors for vitamin B12 deficiency are older age, long-term use of metformin or acid-reducing medicines, a vegan or mostly plant-based diet, pernicious anemia, and past stomach or bowel surgery. Most of these share one thread: they interfere with how B12 is released from food or absorbed in the gut.

Deficiency develops slowly, often over years, because the liver stores a large reserve. That is why symptoms can be easy to miss and why people with risk factors benefit from a simple blood test rather than waiting for problems to appear.

How your body absorbs B12

B12 in meat, fish, eggs and dairy is bound to protein. Stomach acid frees it, and then a protein made in the stomach, called intrinsic factor, carries it to the end of the small intestine where it is absorbed. A problem at any of these steps can lower your B12 level even if you eat plenty of it.

This chain explains most of the risk factors below. Less acid, less intrinsic factor or a damaged end of the small intestine all mean less B12 gets in. For more on how the gut shapes nutrient levels, see our guide to gut absorption and nutrient levels.

The main risk factors

• Age. Stomach acid production often falls with age, so older adults absorb less B12 from food. Supplement-form B12 does not need stomach acid to be released, which is why adults over 50 are advised to get some B12 from fortified foods or supplements.¹
• Metformin. This common diabetes medicine can lower B12 over time. In a large US diabetes prevention study, each year of metformin use was linked to a higher chance of B12 deficiency.²
• Acid-reducing medicines. In a large Northern California study, people with two or more years' supply of proton pump inhibitors or H2 blockers were more likely to be diagnosed with B12 deficiency.³
• Vegan or strict vegetarian diets. B12 comes almost only from animal foods, so people who avoid them need fortified foods or a supplement.
• Pernicious anemia. An autoimmune condition in which the body attacks the cells that make intrinsic factor. It often runs in families and is more common with other autoimmune conditions such as thyroid disease.
• Gut surgery or disease. Weight-loss surgery, removal of part of the stomach or the end of the small intestine, Crohn's disease and celiac disease all raise risk.
• Nitrous oxide. Repeated recreational use of nitrous oxide, sold as "whippets", disables B12 and can cause serious nerve damage, often while the serum B12 level still looks normal.⁴

Symptoms to watch for

Low B12 can cause megaloblastic anemia, a type of anemia with large red blood cells, and a range of nerve and mental symptoms. Common signs include:

• Tiredness, weakness or shortness of breath
• Numbness, tingling or burning in the hands and feet
• Trouble with balance or walking
• Memory problems, confusion or low mood
• A sore, smooth or red tongue

Nerve symptoms can show up without anemia, and long-standing nerve damage may not fully reverse. If you have tingling that is spreading or trouble walking, see a clinician promptly. For how these signs overlap with other nutrients, read our guide to the signs of nutrient deficiency.

Standard tests for B12

Routine screening of average-risk adults is not recommended, but testing is reasonable when you have one or more risk factors. The usual first tests are a complete blood count and a serum B12 level. When B12 comes back low-normal in someone at risk, a methylmalonic acid test helps confirm whether a deficiency is real.¹

These tests are widely available, and your primary care clinician or any Philadelphia-area lab can handle them. One caution: high-dose folic acid can correct the anemia of B12 deficiency while the nerve damage continues, so a low B12 should be found and treated directly.

Specialty panels offer another angle. TruHealth from TruDiagnostic estimates nutrient-related markers from DNA methylation patterns rather than measuring B12 in your blood.⁵ A low estimate from a test like this is a reason to check serum B12 and methylmalonic acid, not a diagnosis on its own.

What happens if you are low

Treatment depends on the cause and severity. High-dose oral B12 corrects anemia and nerve symptoms as well as injections for many people, while injections work faster and are usually chosen for severe deficiency or severe nerve symptoms.¹ People with pernicious anemia or past gut surgery typically need treatment for life. Your clinician will also look for the cause, since a low level is a clue, not the full answer.

Your next step

If you are wondering how a methylation-based nutrient estimate compares with a serum B12 level, read how this test compares with blood micronutrient tests. The micronutrient testing hub brings together every guide on testing and results.

Frequently asked questions

Related reading

• Iron deficiency and iron overload
• Do you need a multivitamin?
• Supplement safety after testing

This article is for general education and is not medical advice. Decisions about testing and treatment should be made with your clinician. If you have severe symptoms, call 911. For a suspected poisoning, call Poison Control at 1-800-222-1222.