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Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition of low blood levels of vitamin B12. In mild deficiency, a person may feel tired and have a reduced number of red blood cells (anemia). In moderate deficiency, there may be inflammation of the tongue and the beginning of neurological problems including abnormal sensations such as pins and needles, while severe deficiency may include reduced heart function and greater neurological problems. Neurological problems may include changes in reflexes, poor muscle function, memory problems, decreased taste, and in extreme cases psychosis. Sometimes temporary infertility may also occur. In young children, symptoms include poor growth, poor development, and difficulties with movement. Without early treatment, some of the changes may be permanent.
Vitamin B12 (Cobalamin) is a water-soluble vitamin that is derived from animal products such as red meat, dairy, and eggs. Intrinsic factor is a glycoprotein that is produced by parietal cells in the stomach and necessary for the absorption of B12 in the terminal ileum. Once absorbed, B12 is used as a cofactor for enzymes that are involved in the synthesis of DNA, fatty acids, and myelin. As a result, a B12 deficiency can lead to hematologic and neurologic symptoms. B12 is stored in excess in the liver; however, in cases in which B12 cannot be absorbed for a prolonged period (e.g., dietary insufficiency, malabsorption, lack of intrinsic factor), hepatic stores are depleted, and deficiency occurs.[rx][rx][rx]
Causes of Vitamin B12 Deficiency
Vitamin B12 deficiency has 3 primary etiologies:
Autoimmune – Pernicious anemia is an autoimmune condition in which antibodies to intrinsic factor are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factor, resulting in an inability of B12 to be absorbed by the terminal ileum.
Malabsorption – Parietal cells in the stomach produce intrinsic factor; therefore, any patient with a history of gastric bypass surgery may be at risk for developing a B12 deficiency because their new alimentary pathway bypasses the site of intrinsic factor production. In patients with normal intrinsic factor production, any damage to the terminal ileum, such as surgical resection due to Crohn disease, will impair the absorption of B12 and lead to a deficiency. Other damage to the small intestine, such as inflammation from Celiac disease or infection with the tapeworm Diphyllobothrium latum, may also result in a B12 deficiency.
Dietary Insufficiency – Vitamin B12 is stored in excess in the liver; however, patients who have followed a strict vegan diet for approximately three years may develop a B12 deficiency from a lack of dietary intake.
- Inadequate dietary intake of vitamin B12 – Vitamin B12 occurs in animal products (eggs, meat, milk) and in some edible algae. B12 isolated from bacterial cultures is also added to many fortified foods, and available as a dietary supplement. Vegans, and to a lesser degree vegetarian, may also be at risk for B12 deficiency due to inadequate dietary intake of B12, if they do not supplement. Children are at a higher risk for B12 deficiency due to inadequate dietary intake, as they have fewer vitamin stores and a relatively larger vitamin need per calorie of food intake.
- Selective impaired absorption of vitamin B12 due to intrinsic factor deficiency – This may be caused by the loss of gastric parietal cells in chronic atrophic gastritis (in which case, the resulting megaloblastic anemia takes the name of “pernicious anemia”), or may result from wide surgical resection of stomach (for any reason), or from rare hereditary causes of impaired synthesis of intrinsic factor. B12 deficiency is more common in the elderly because gastric intrinsic factor, necessary for absorption of the vitamin, is deficient, due to atrophic gastritis.
- Impaired absorption of vitamin B12 – in the setting of more generalized malabsorption or maldigestion syndrome. This includes any form due to structural damage or wide surgical resection of the terminal ileum (the principal site of vitamin B12 absorption).
- Forms of achlorhydria – (including that artificially induced by drugs such as proton pump inhibitors and histamine 2 receptor antagonists) can cause B12 malabsorption from foods, since acid is needed to split B12 from food proteins and salivary binding proteins. This process is thought to be the most common cause of low B12 in the elderly, who often have some degree of achlorhydria without being formally low in intrinsic factor. This process does not affect the absorption of small amounts of B12 in supplements such as multivitamins since it is not bound to proteins, as is the B12 in foods.
- Surgical removal of the small bowel – (for example in Crohn’s disease) such that the patient presents with short bowel syndrome and is unable to absorb vitamin B12. This can be treated with regular injections of vitamin B12.
- Long-term use of ranitidine hydrochloride may contribute to a deficiency of vitamin B12.
- Untreated celiac disease may also cause impaired absorption of this vitamin, probably due to damage to the small bowel mucosa. In some people, vitamin B12 deficiency may persist despite treatment with a gluten-free diet and require supplementation.
- Some bariatric surgical procedures, especially those that involve removal of part of the stomach, such as Roux-en-Y gastric bypass surgery. (Procedures such as the adjustable gastric band type do not appear to affect B12metabolism significantly).
- Bacterial overgrowth within portions of the small intestine, such as may occur in blind loop syndrome, (a condition due to a loop forming in the intestine) may result in increased consumption of intestinal vitamin B12 by these bacteria.
- The diabetes medication metformin may interfere with B12 dietary absorption.
- A genetic disorder, transcobalamin II deficiency can be a cause.
- Alcoholism – if a “diet” of excessive alcohol intake is substituted for a diet adequate in sources of B12.
- Nitrous oxide exposure, and recreational use.
- Infection with the Diphyllobothrium latum tapeworm
- Chronic exposure to toxigenic molds and mycotoxins found in water damaged buildings.
- Increased needs by the body due to AIDS, or hemolysis the breakdown of red blood cells.
Can Calcium Supplements Protect Against PPI-Induced Vitamin B12 Deficiency?
Vitamin B12 is a member of the water-soluble B-vitamin family and therefore is an essential nutrient that must be acquired from the diet [rx]. Vitamin B12 belongs to a class of naturally occurring colbalt-containing compounds known as cobalamins, which contain a planar corrin ring that binds a single colbalt atom. Colbalt is the functional part of vitamin B12, which serves as an enzyme cofactor for two vitamin B12-dependent, enzyme-catalyzed reactions in mammals.
Patients taking acid reducers long term are at greater risk for hypochlorhydria-induced vitamin B12 malabsorption.
Both proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) can block the activity of intrinsic factor. However, the risk is widely inconsistent across studies due to variable samples and confounding designs.
Atrophic gastritis, Crohn’s disease, celiac disease, total or partial gastrectomy, gastric surgery, pancreatectomy, pancreatitis, and ileal resection can also cause vitamin B12 malabsorption. Calcium supplementation may reverse the effect of hypoparathyroidism and metformin-induced vitamin B12 malabsorption.
The Journal of Nutrition Health and Aging recently published a study that shows calcium supplements temper gastric acid inhibitor-induced vitamin B12 malabsorption. This retrospective cross-sectional study collected data from the Quebecois Geriatric Assessment Unit inpatients discharged from January 2008 through March 2012.
Enrolled patients received scheduled H2RA or PPI therapy upon admission. The researchers excluded patients with missing records and hospital stays shorter than 5 days. The prevalence of vitamin B12 deficiency in this cohort (41.3%) was similar to that seen in other studies enrolling patients in rehabilitation units.
Previous studies have shown that calcium chelators decrease intestinal vitamin B12 absorption. No research has shown that PPIs or H2RAs have chelating actions, but PPIs limit absorption of calcium carbonate, the most commonly used calcium supplement.
Quite by accident, the researchers found that patients taking PPIs (but not H2RAS) without concomitant calcium supplements were more likely to have vitamin B12 deficiency than those taking PPIs plus calcium. This indicated that calcium modifies the effect of PPIs significantly.
In the study, calcium supplements protected patients from the effect of gastric acid reducers. Inconsistent prevalence of calcium supplement co-administration between studies can explain the variable risk of vitamin B12 absorption.
The researchers concluded that calcium supplements reduce the vitamin B12 malabsorption effect of gastric acid reducers. They believe future studies should consider calcium supplement co-administration to be a confounder in the risk of vitamin B12 malabsorption.
up date May2017
(HealthDay News) — People who take certain acid-reflux medications might have an increased risk of vitamin B-12 deficiency, according to new research.
Taking proton pump inhibitors (PPIs) to ease the symptoms of excess stomach acid for more than two years was linked to a 65 percent increase in the risk of vitamin B-12 deficiency. Commonly used PPI brands include Prilosec, Nexium and Prevacid.
Researchers also found that using acid-suppressing drugs called histamine-2 receptor antagonists — also known as H2 blockers — for two years was associated with a 25 percent increase in the risk of B-12 deficiency. Common brands include Tagamet, Pepcid and Zantac.
“This study raises the question of whether or not people who are on long-term acid suppression need to be tested for vitamin B-12 deficiency,” said study author Dr. Douglas Corley, a research scientist and gastroenterologist at Kaiser Permanente’s division of research in Oakland, Calif.
Corley said, however, that these findings should be confirmed by another study. “It’s hard to make a general clinical recommendation based on one study, even if it is a large study,” he said.
Vitamin B-12 is an important nutrient that helps keep blood and nerve cells healthy, according to the U.S. Office of Dietary Supplements (ODS). It can be found naturally in meat, fish, poultry, eggs, milk and other dairy products. According to the ODS, between 1.5 percent and 15 percent of Americans are deficient in B-12.
Although most people get enough B-12 from their diet, some have trouble absorbing the vitamin efficiently. A deficiency of B-12 can cause tiredness, weakness, constipation and a loss of appetite. A more serious deficiency can cause balance problems, memory difficulties and nerve problems, such as numbness and tingling in the hands or feet.
Stomach acid is helpful in the absorption of B-12, Corley said, so it makes sense that taking medications that reduce the amount of stomach acid would decrease vitamin B-12 absorption.
More than 150 million prescriptions were written for PPIs in 2012, according to background information included in the study. Both types of medications also are available in lower doses over the counter.
Corley and his colleagues reviewed data on nearly 26,000 people who had been diagnosed with a vitamin B-12 deficiency and compared them to almost 185,000 people who didn’t have a deficiency.
While 12 percent of people with a vitamin B-12 deficiency had taken PPIs for more than two years, 7.2 percent of those without a deficiency had taken the medications long-term.
Of those with a deficiency, 4.2 percent took an H2 blocker for two years or longer, while 3.2 percent of those without a deficiency took the drugs for two years or more.
The risk of developing a vitamin B-12 deficiency was 65 percent higher for the long-term PPI users and 25 percent higher for those taking H2 blockers, according to the study.
People who took higher doses were more likely to develop a vitamin B-12 deficiency. People who took an average of 1.5 PPI pills per day had almost double the risk of developing a deficiency compared to those who averaged 0.75 pills per day, the study found.
Women had a greater risk of deficiency than men, and people younger than 30 taking these medications had a greater risk of developing a deficiency than older people, according to the study.
The risk of vitamin B-12 deficiency decreases when you stop taking the medications, but doesn’t disappear completely, Corley said.
The study’s findings were published in the Dec. 11 issue of the Journal of the American Medical Association. Although the study found an association between taking acid-reflux drugs long-term and having a higher risk of a B-12 deficiency, it didn’t establish a cause-and-effect relationship.
If you’re taking acid-suppressing medications, Corley said, “our study doesn’t recommend stopping those medications, but you should take them at the lowest effective dose.” And people shouldn’t start taking vitamin B-12 supplements on their own, but should discuss it with their doctor, he said.
One expert had concerns about how frequently acid-suppressing drugs are used.
“This study found an adverse effect associated with taking these drugs,” said Victoria Richards, an associate professor of medical sciences at the Frank H. Netter M.D. School of Medicine at Quinnipiac University, in Hamden, Conn. “It’s also concerning that these drugs are used at such a high rate. Why do so many people have the need to suppress acid so much?”
The bottom line, Richards said, is that if you are having any symptoms of vitamin B-12 deficiency and you’ve been taking these medications, talk to your doctor about whether you should be tested for a deficiency. Tell your doctor if you’ve been taking over-the-counter acid-suppressing medications, so your doctor can properly evaluate your risk.
Interactions with: Vitamin B12 (Cobalamin)
If you are currently being treated with any of the following medications, you should not use vitamin B12 supplements without first talking to your health care provider.
Medications that reduce levels of B12 in the body include:
- Anticonvulsants — include phenytoin (Dilantin), phenobarbital, primidone (Mysoline)
- Chemotherapy medications — particularly methotrexate
- Colchicine — used to treat gout
- Bile acid sequestrants — used to lower cholesterol; include colestipol (Colestid), cholestyramine (Questran), and colsevelam (Welchol)
- H2 blockers — used to reduce stomach acid; include cimetidine (Tagamet), famotidine (Pepcid AC), ranitidine (Zantac)
- Metformin (Glucophage) — medication taken for diabetes
- Proton pump inhibitors — used to reduce stomach acid; include esomeprazole (Nexium), lansprazole (Prevacid), omeprazole (Prilosec), rabeprazole (Aciphex)
Antibiotics, Tetracycline:Vitamin B12 should not be taken at the same time as tetracycline because it interferes with the absorption and effectiveness of this medication. Vitamin B12 should be taken at different times of the day from tetracycline. (All vitamin B complex supplements act in this way and should be taken at different times from tetracycline.)
In addition, long-term use of antibiotics can deplete vitamin B levels in the body, particularly B2, B9, B12, and vitamin H (biotin), which is considered part of the B complex vitamins.