Vitamin B12 has several critical roles in human nutrition. On its own, vitamin B12 is required for the creation of cellular energy from dietary fats and proteins. It is also associated with the production of hemoglobin; as such, vitamin B12 deficiency can lead to hemoglobin-deficient anemia. The other functions of vitamin B12 are mostly performed in conjunction with folic acid. Together, these nutrients are used in the synthesis of methionine and S-adenosylmethionine (SAMe). SAMe donates methyl groups for the synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It also donates a methyl group for the recycling of homocysteine back to methionine.¹ Thus, a shortage of vitamin B12, leading to a shortage of SAMe, can result in a toxic build-up of homocysteine.

Less well understood is the role of vitamin B12 in the health of myelin and the nervous system. While we know that deficiency will result in myelin degradation and a well-recognized neuropathy, the mechanism behind this has not been fully elucidated. One possible etiology is based on deficiency of SAMe. SAMe is important for the production and maintenance of myelin, especially for the creation of structural phospholipids. SAMe is also used in the production of the neurotransmitters dopamine, norepinephrine, and serotonin, which may help explain why symptoms of depression and cognitive impairment are sometimes reported with low vitamin B12.

Recommended Intake

The recommended dietary allowance (RDA) of vitamin B12 is very low, ranging from 0.9 to 1.2mcg for children aged 1 to 8 years, 1.8mcg for those aged 9 to 13 years, and 2.4mcg for individuals aged 14 years or older, with slightly higher requirements for pregnant (2.6mcg) and lactating (2.8mcg) individuals.² There is no tolerable upper limit for vitamin B12. Toxicity has never been demonstrated even at doses 10,000 times higher than the RDA.

Vitamin B12 is naturally found in animal products, and it is often added to fortified cereals and nutritional yeasts. Good sources of vitamin B12 include beef liver, clams, fortified nutritional yeast, salmon, tuna, ground beef, and milk. The bioavailability of vitamin B12 depends on the source, with bioavailability being about three-times higher in dairy products than meat, poultry, or fish and about 50-percent higher in dietary supplements than food sources.²

Storage and Risk of Deficiency 

Unlike most water-soluble vitamins, the body stores a significant amount of vitamin B12.Most storage is in the liver, but the heart, spleen, kidneys, and brain also store vitamin B12. Since the total average body storage is 2 to 10mg, and the daily usage is about 2.5mcg, it can take a long time for a vitamin B12 deficiency to present, even in a complete absence of intake. 

In the general population, vitamin B12 deficiency is estimated to occur in 3 to 30 percent of adults. The incidence of deficiency increases markedly with age, and studies suggest that at the age of 65 years, 15 percent of the population is deficient. Causes of deficiency include pernicious anemia (which affects up to 2% of adults and accounts for >70% of reported deficiencies), atrophic gastritis, infection with Helicobacter pylori, veganism, alcoholism, fad dieting, poor nutrient intake (especially in the elderly), diseases of the terminal ileum, human immunodeficiency virus (HIV) infection, multiple sclerosis, the use of certain prescription medications (e.g., proton pump inhibitors [PPIs]), and bariatric surgery.

Because of the multiple roles of the stomach in vitamin B12 digestion and absorption, gastrointestinal surgery is a significant risk for deficiency. Loss of hydrochloric acid, gastric churning, pepsin, and intrinsic factor (IF) are all causes of vitamin B12 malnutrition. Both partial and total gastrectomy are considered to be serious risks for B12 deficiency—this includes gastric bypass, duodenal switch (DS), and gastric sleeves. However, gastric banding has also been shown to produce a conditional increase in vitamin B12 requirements.

Signs and Symptoms of Deficiency

Early signs of vitamin B12 deficiency include fatigue, weakness, shortness of breath, and loss of appetite. The classic triad of symptoms is the combined presentation of weakness, paresthesia, and sore tongue. Paresthesia is usually the symptom patients identify. Classic complaints include numbness, coldness, cramping, and shooting pains. While “glove and stocking” distribution neuropathy is associated with this deficiency, most cases begin in the feet, and rarely are all limbs affected at once. Individuals might report symptoms of neuropathy in one area only, such as a single foot. Associated complaints may include clumsiness and gait abnormality. Megaloblastic anemia, low counts of white and red blood cells and/or platelets, palpitations, weight loss, and infertility are other symptoms of vitamin B12 deficiency.²

Depression and mild dementia are also reported as common symptoms of vitamin B12 deficiency.³ Although these can actually be presenting symptoms, they may be difficult to distinguish, as there are no features that would identify vitamin B12 deficiency as the cause.

Other complaints are typically manifestations of more advanced disease or are more rare. These may include (in no particular order) confusion, altered mental status, burning of the lip and mouth, ataxia, spasticity, contractures, paraplegia, muscular wasting, optic atrophy, delusions, disorientation, orthostatic hypotension, and psychosis.

Prevention and Treatment

Vitamin B12 deficiency is typically treated with intramuscular injections, to avoid barriers to absorption.² Daily requirements of vitamin B12 are small, but the absorption when IF and gastric acid are low is greatly impaired. Studies indicate that large oral doses (greater than 500mcg) are well tolerated and well absorbed even in patients with pernicious anemia. A 2003 review article in American Family Physician¹¹ recommends daily dosing of 1,000mcg. 

A diagnosis of vitamin B12 deficiency should be taken seriously and treated aggressively. If using oral or sublingual dosing, 2,000mcg per day for 2 to 4 weeks is recommended. If injecting B12, 1,000mcg daily for 1 to 2 weeks is usually adequate. These regimens should transition into the maintenance doses, and individuals should be followed closely by a physician for clinical resolution. 

While individuals with a deficiency should be encouraged to include vitamin B12-rich foods in their diets, it is unlikely that patients with malabsorptive procedures will absorb much from dietary sources.

Interactions

B12 supplements can interfere with the absorption of some antibiotics (notably tetracycline). This is easily remedied by taking them two or more hours apart. Medications that lower gastric acid, including antacids, PPIs, and H2-blockers, can reduce vitamin B12 absorption. Some medications for diabetes and epilepsy can impair vitamin B12 status over time due to altered metabolism. Large doses of folate can correct the anemia of vitamin B12 deficiency, thus potentially masking it. If patients also have low iron stores, it should be noted that treatment of vitamin B12 deficiency may produce a further lowering of iron levels due to increased erythropoiesis. Thus, if trying to correct a combined deficiency, a temporary increase in iron supplementation may be required. 

This article was adapted with permission from: Jacques J. Vitamin B12 (cobalamin). Micronutrition For The Weight Loss Surgery Patient. Edgmont, PA: Matrix Medical Communications; 2005:47–55.

Additional Sources

1. Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine: Pharmacokinetics and pharmacodynamics. Am J Med. 1987;83(5A):35–42.
2. National Institutes of Health Office of Dietary Supplements. Vitamin B12: fact sheet for professionals. Updated 22 Dec 2022. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. Accessed 20 Nov 2023.
3. Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005;19(1):59–65.