Vitamin B12, also called cobalamin, is a water-soluble vitamin that is involved in the metabolism of every cell of the body and plays a key role in the normal functioning of the brain and nervous system and the formation of blood.1

As well as being the largest and most structurally complicated vitamin in the human system, B12 contains the biochemically rare element cobalt. Vitamin B12 was discovered as a result of its relationship to pernicious anemia, an autoimmune disease that destroys parietal cells in the stomach that secrete intrinsic factor. Intrinsic factor is crucial for the absorption of B12, so a lack of this glycoprotein leads to a B12 deficiency.


Traditionally, vitamin B12 deficiencies in the United States have been found in the elderly, due largely to gastric mucosal atrophy and poor absorption. However, one large study reported that more than 16% of otherwise healthy adults aged 26 to 49 years were also deficient in the vitamin.1

Vitamin B12 is found in fortified cereals and foods that come from animals (e.g., meat, eggs, and dairy products). Humans are independently capable of constructing vitamin B12 from foods. Unlike most nutrients, absorption of B12 begins in the mouth, where small amounts can be taken in through the mucous membrane before binding with proteins and being released by the action of digestive enzymes in stomach.1


In addition to natural changes in absorption, widespread use of acid-inhibiting medications increases the probability of B12 deficiencies, since the acid is required for absorption. One medication linked to B12 deficiencies is the popular antidiabetes agent metformin. This drug is thought to inhibit gastric absorption of B12, resulting in an estimated 30% of metformin-treated patients having B12 deficiency. One study of type 2 diabetics found that more than 26% of those on metformin had significantly low levels of vitamin B12.2

Vitamin B12 deficiency in the United States is also commonly linked to gastric bypass surgery. From 1998 to 2002, the rate of this procedure went from 7.0 per 100,000 to more than 38 per 100,000.1 Since this operation causes food to literally bypass much of the gastric mucosa, natural absorption of B12 is physiologically limited.

With B12 involved in every metabolic pathway in the human body, multiple symptoms can be traced to deficiency. Clinical presentations include anemia, cognition deficits, depression, cardiovascular disease, and such neurologic changes as peripheral neuropathy and muscle weakness.3

Vitamin B12 deficiency in the elderly has been linked to reduced cognitive function. Investigators in Finland followed more than 270 elderly subjects for seven years to study the relationship between the development of Alzheimer dementia and vitamin B12 levels. At the end of the study, B12 deficiencies were noted to have a statistically significant positive correlation with the development of dementia, independent of other risk factors.4

A common cause of mortality in the elderly is falling. Post-stroke patients are at a very high risk for falls and hip fractures. In a study of more than 600 such patients, researchers randomized the participants to either supplemental B12 or placebo and followed them for two years. At the end of the study, the treatment group had suffered six hip fractures whereas the placebo group had 27 fractures.5

Finally, the role vitamin B12 plays in cardiovascular disease is being studied. Metabolically, elevated homocysteine levels are associated with endothelial dysfunction, thrombin formation, and increased risk of cardiovascular disease. Researchers have linked B12 deficiencies to elevated homocysteine levels, with the significant result of lowering those levels when B12 is supplemented.3

The American Heart Association conducted a large study of more than 43,000 men, following them for 14 years. At the end of the observational phase, the participants had reported 725 strokes. Periodic dietary monitoring and subsequent laboratory assays found a significantly decreased risk of ischemic stroke in patients whose B12 levels were normal.6

How supplied, dose, and cost

For years, intramuscular (IM) injection was considered the only effective route of B12 supplementation. Since that belief has been disproven, supplementation has become much more accessible. Oral and sublingual dosing is now widely recognized as equally therapeutic as IM injection. Daily oral supplementation of 1,000 μg is usually recommended and is very well tolerated and inexpensive.

Safety, drug interactions

No doubt due largely to its water-solubility, very little documentation of any vitamin B12 toxicity can be found, even when taken in very large doses. Medications that inhibit gastric absorption, reduce stomach acid, or bind acids and bile salts have been shown to reduce systemic vitamin B12.3


Vitamin B12 is a key metabolic component that is often overlooked. Given the ever-increasing use of such medications as metformin and stomach-acid reducing agents, it is quite likely that health-care practitioners will frequently miss this subtle but significant problem. With almost no known negative consequence to supplementation, screening for and treating this basic nutritional deficit ought to be a daily part of your practice. Recommending OTC forms of vitamin B12 to patients meets the standard of care.


1. Baer J, St. Peter M. Vitamin B12 assessment and intervention in younger adult women. J Nurse Pract. 2011;7:117-122.

2. Hermann L, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: A cross-sectional cohort study. Br J Diab Vasc Dis. 2004;4:401-406.

3. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Physician. 2008;54:536-541.

4. Hooshmand B, Solomon A, Kåreholt I, et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study. Neurology. 2010;75:1408-1414.

5. Sato Y, Honda Y, Iwamoto J, et al. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA. 2005 2;293:1082-1088.

6. He K, Merchant A, Rimm EB, et al. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke. 2004;35:169-174. 

All electronic documents accessed April 15, 2011.