Vitamin B12 is an essential nutrient that plays many crucial roles in the body. It helps make DNA, nerve cells, and red blood cells. It also supports brain function and the nervous system. Vitamin B12 is found naturally in animal foods like meat, fish, eggs, and dairy. It can also be taken as a supplement.
B12 deficiency is usually caused by conditions that affect absorption in the digestive tract. However, certain diseases can also lead to lower B12 levels. When the body lacks sufficient B12, it can lead to anemia and neurological problems like numbness, trouble walking, and memory loss.
What is Vitamin B12?
Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays essential roles throughout the body. It is involved in DNA and red blood cell production, brain and nerve function, and metabolism.1
There are a few different forms of B12 in supplements and fortified foods: cyanocobalamin, methylcobalamin, hydroxocobalamin, and adenosylcobalamin.2
The daily recommended intake of B12 is:3
– Infants: 0.4 mcg
– Children: 0.9–1.8 mcg
– Adults: 2.4 mcg
– Pregnant women: 2.6 mcg
– Breastfeeding women: 2.8 mcg
Vitamin B12 is naturally found in animal foods like meat, fish, eggs, and dairy products. It can also be taken as a supplement or consumed in fortified foods like cereal and plant-based milk.1
Roles of Vitamin B12 in the Body
Vitamin B12 has several critical functions in the body:4
– DNA synthesis – It helps make the DNA that holds your genes. This DNA is necessary for cell division and growth.
– Red blood cell formation – B12 is needed to produce hemoglobin and red blood cells. Hemoglobin carries oxygen throughout the body.
– Neurological function – It helps maintain healthy nerve cells and is needed for neurotransmitters that send signals between the brain and body.
– Metabolic processes – B12 is a cofactor for enzymes involved in energy metabolism throughout the body.
– Cardiovascular health – It may help regulate homocysteine levels, a compound associated with heart disease risk.
Without adequate B12, the body cannot complete these vital processes properly.
Causes of B12 Deficiency
The leading causes of B12 deficiency include:5,6
– Pernicious anemia – This autoimmune disease damages the stomach cells needed for B12 absorption.
– Other malabsorption issues – Conditions affecting the stomach, intestines, or pancreas can reduce B12 absorption from food. These include celiac disease and Crohn’s disease.
– Medications – Some medicines like proton pump inhibitors and metformin can impair B12 absorption.
– Surgeries – Procedures like gastric bypass surgery, bowel resection, or stomach removal can decrease B12 absorption.
– Inadequate intake – Vegans, vegetarians, older adults, and others with limited diets may not get enough B12 from their food.
– Pregnancy and breastfeeding – Higher B12 needs during pregnancy and breastfeeding can deplete stores.
In developing nations, inadequate intake is the most common cause of deficiency. In wealthier countries, reduced absorption is the primary cause.7
Certain medical conditions like digestive disorders, autoimmune diseases, and chronic illnesses can make you more prone to B12 deficiency by impairing absorption or increasing needs for the vitamin.
Diseases Linked to B12 Deficiency
Several diseases are associated with increased rates of B12 deficiency or can contribute to lower B12 levels.
Pernicious Anemia
Pernicious anemia is an autoimmune condition and the leading cause of B12 deficiency worldwide.8
In pernicious anemia, the immune system mistakenly attacks the stomach cells that produce intrinsic factor. Intrinsic factor is a protein needed for B12 absorption in the intestines.
Without intrinsic factor, the body cannot adequately absorb dietary B12 from food. Even consuming high amounts of B12 will not resolve the deficiency unless the underlying issue with intrinsic factor is treated.
Pernicious anemia affects around 0.1% of the general population but is more common in those over 60 years old.9 It is also twice as common in women than men.10
In addition to B12 deficiency, symptoms of pernicious anemia include:11
– Fatigue
– Shortness of breath
– Heart palpitations
– Numbness/tingling in hands and feet
– Difficulty walking
– Cognitive changes like confusion and memory loss
– Glossitis (red, swollen tongue)
Pernicious anemia is diagnosed through blood tests checking B12 levels, anemia markers, and autoantibodies involved in the disease. It is treated with B12 injections or high oral doses along with managing any neurological symptoms.
Atrophic Gastritis
Atrophic gastritis is a chronic inflammatory condition affecting the stomach lining. It results in thinning of the stomach wall and impaired production of stomach acids and intrinsic factor.12
In some cases, it is an autoimmune condition similar to pernicious anemia. Atrophic gastritis can also be caused by:
– Chronic H. pylori bacteria infection
– Long term proton pump inhibitor use
– Chronic alcohol consumption
– Smoking
– Some nutrient deficiencies like iron and B12 deficiency13
Atrophic gastritis affects around 10–30% of adults worldwide.14 It becomes more common with age.
The impaired absorption of vitamin B12 due to low intrinsic factor can lead to pernicious anemia in some individuals with atrophic gastritis.
Gastrectomy/Gastric Bypass Surgery
Surgical removal of part or all of the stomach (gastrectomy) significantly alters the digestion and absorption of food and nutrients like vitamin B12.
Partial gastrectomy is sometimes performed to treat stomach cancer, ulcers, or perforations. This involves removal of 30–50% of the stomach.
Total gastrectomy removes the entire stomach and is done for advanced stomach cancer. It is always followed by reconstruction of the digestive tract.15
Gastric bypass surgery for weight loss also bypasses part of the stomach and small intestine, decreasing absorption.
All types of gastrectomy procedures reduce gastric acid and intrinsic factor secretion, resulting in impaired vitamin B12 absorption and increased risk of pernicious anemia.16
Those who have undergone gastrectomy require B12 injections or high dose supplements, especially if they develop anemia or neurological symptoms.
Celiac Disease
Celiac disease is an autoimmune disorder triggered by gluten intake. In celiac disease, gluten exposure causes damage to the small intestine, resulting in impaired nutrient absorption.17
About 5–10% of people with celiac disease have a related B12 deficiency. Impaired absorption in the intestine contributes to the lower B12 levels.18
Strict adherence to a gluten-free diet and B12 supplementation when needed can help manage celiac disease and prevent deficiency.
Inflammatory Bowel Diseases
Inflammatory bowel diseases like Crohn’s disease and ulcerative colitis cause chronic inflammation and damage in the digestive tract.19
This can impair absorption of vitamin B12 from food in the small intestine. Deficiency rates in Crohn’s disease patients range from 5–38%. Up to 20% of those with ulcerative colitis have reduced B12.20
Managing the underlying digestive condition can help prevent nutrient deficiencies. B12 injections may also be used to normalize B12 status.
Pancreatic Insufficiency
Conditions affecting the pancreas like chronic pancreatitis, cystic fibrosis, and pancreatic cancer can reduce production of digestive enzymes.21
Pancreatic insufficiency decreases the breakdown and absorption of vitamin B12 found naturally in foods. B12 supplementation is needed to prevent deficiency in those with pancreatic conditions.
Medications
Some medications can impact nutrient metabolism and absorption in the body. Long-term use of certain medicines is associated with an increased risk of B12 deficiency.
– **Metformin** – This diabetes drug reduces B12 absorption, especially at high doses. Up to 30% of those taking metformin long term may develop a deficiency.22
– **Proton pump inhibitors** – PPIs like omeprazole (Prilosec) reduce stomach acid. Low stomach acid impairs the separation of B12 from food proteins, decreasing absorption of the vitamin.23
– **Histamine H2 receptor antagonists** – These medicines like ranitidine (Zantac) and famotidine (Pepcid) can also lower stomach acid and B12 absorption, especially with prolonged use.24
Anyone taking these medications long term should have their B12 status monitored and supplement if needed to prevent deficiency.
Thyroid Disease
Thyroid hormones regulate metabolism throughout the body. Both hypothyroidism and hyperthyroidism have been linked to reduced vitamin B12 levels.25
In hypothyroidism, a sluggish metabolism and impaired absorption can contribute to deficiency.
Those with hyperthyroidism appear to have increased B12 turnover and utilization, depleting body stores. Treating the thyroid condition may help normalize B12 levels.
Diabetes
About 22% of people with diabetes have low blood levels of vitamin B12.26
The exact mechanisms are unclear but may involve impaired absorption due to high blood sugar levels or nerve damage in the digestive tract from diabetic neuropathy.27
Metformin use, a common diabetes medication that reduces B12 absorption, likely contributes to the increased deficiency rates.
Alcohol Abuse
Chronic excessive alcohol intake is associated with lower vitamin B12 levels.
Up to 80–90% of alcoholics have a B12 deficiency, often accompanied by folate deficiency.28
Multiple aspects of alcoholism can result in deficiency:29
– Poor diet and malnutrition in alcohol abusers
– Impaired absorption and storage of B12
– Alcohol toxicity damaging the bone marrow’s ability to use B12
– Liver disease from alcohol further decreasing B12 availability
B12 injections and supplementation may help resolve deficiency in those recovering from alcoholism.
Pregnancy and Breastfeeding
B12 needs increase during pregnancy and breastfeeding due to demands from the growing fetus and for breastmilk production.
Pregnant women require 2.6 mcg per day, up from 2.4 mcg.3 Breastfeeding women need an estimated 2.8 mcg daily.
Mild B12 deficiency is common during pregnancy, estimated around 25–29% in observational studies.30
Inadequate intake, along with depleted maternal stores and increased fetal demand, can contribute to lower B12 levels. This deficiency may persist into the breastfeeding period if stores are not replenished.31
Prenatal vitamins containing B12 and consuming B12-rich foods can help prevent insufficiency during pregnancy and lactation.
Symptoms of B12 Deficiency
Mild to moderate vitamin B12 deficiency may have no obvious symptoms for years. As deficiency worsens, it can cause:32
– Fatigue
– Weakness
– Constipation or diarrhea
– Loss of appetite
– Weight loss
– Neurological disorders like numbness, tingling, and problems walking or thinking
– Psychological issues like depression, memory loss, and dementia
– Vision loss or eye twitching
– Pale skin
– Smooth, sore tongue
Severe and prolonged deficiency can lead to permanent nerve damage and dementia.4
Deficiency also causes megaloblastic anemia, which presents as symptoms of fatigue, dizziness, shortness of breath, and palpitations.33
High-risk groups for B12 deficiency who should be screened include:34
– Older adults
– Vegans or vegetarians
– Those with digestive disorders
– Patients who have undergone GI surgery like gastric bypass
– People taking medications that reduce B12 absorption
Early detection and treatment of B12 deficiency is important to avoid neurological damage and other complications.
Diagnosis of B12 Deficiency
Doctors may order blood tests to diagnose vitamin B12 deficiency, including:8
– **Serum B12** – Levels less than 200 pg/mL indicate deficiency. Borderline deficiency is 200–300 pg/mL.
– **Methylmalonic acid** – This compound is elevated when B12 status is low.
– **Homocysteine** – High levels indicate B12 deficiency.
– **Complete blood count** – Checks for anemia and large red blood cells characteristic of megaloblastic anemia.
– **Intrinsic factor antibodies** – Presence indicates pernicious anemia.
Examining blood cells under a microscope can reveal the enlarged, oddly shaped red blood cells seen in B12 deficiency anemia.
Bone marrow biopsy may sometimes be done to check for anemia caused by B12 deficiency.
Treatment for B12 Deficiency
Treatment of B12 deficiency involves B12 replacement, usually by injection or high oral doses.8
**Injections** – For those with absorption issues like pernicious anemia, monthly B12 injections are frequently used to resolve deficiency. Doses of 1,000 mcg per injection are typical.
**Oral doses** – Large oral doses of up to 2,000 mcg per day of B12 supplements may be used if deficiency is less severe and absorption is not significantly impaired.
**Improving absorption** – If deficiency is due to a condition like celiac disease, treating the underlying problem can help improve absorption and restore normal B12 status.
Treatment also aims to manage any neurological symptoms until B12 levels normalize. Complete recovery may take up to a year. Lifelong, continued supplementation and monitoring of B12 levels are often necessary after treatment.
Preventing B12 Deficiency
Preventing vitamin B12 deficiency centers around:35
– Consuming B12-rich foods like meat, eggs, dairy, fish, and fortified grains. If following a vegan diet, take a B12 supplement or eat B12-fortified foods.
– If you have conditions that reduce B12 absorption like celiac disease or atrophic gastritis, get levels tested regularly. Supplement as needed.
– Speak with your doctor about screening for B12 deficiency if you take long-term medications like proton pump inhibitors or metformin.
– Pregnant and breastfeeding women should take a prenatal vitamin with B12 and eat B12-rich foods.
– Older adults should have B12 levels checked, especially if they have neurological symptoms like frequent falls or memory lapses.
Addressing any B12 deficiency early, before severe symptoms occur, can prevent permanent neurological damage and disability. Monitoring levels yearly or every few years can detect a deficiency before it becomes advanced.
Conclusion
Vitamin B12 deficiency has a variety of causes, from inadequate intake to conditions affecting absorption like pernicious anemia. Several chronic diseases are associated with higher rates of deficiency as well.
Low B12 can lead to anemia, neurological issues, and even irreversible nerve damage if left untreated. Getting levels checked regularly and treating any deficiency is important, especially for those at increased risk. Consuming B12-rich foods or taking supplements can prevent development of a deficiency.
With proper screening and prompt treatment when needed, complications related to B12 deficiency can be avoided. Healthcare providers play an essential role in identifying at-risk patients, ordering appropriate diagnostic tests, and recommending effective management based on the underlying cause to restore normal B12 status.