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Vitamin B12

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Also listed as: Cobalamin, Cyanocobalamin
Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Adenosylcobalamin, AdoB12, B complex, B complex vitamin, B-12, bedumil, cobalamin, cobalamins, cobamin, cyanocobalamin, cyanocobalamine, cyanocobalaminum, cycobemin, hydroxocobalamin, hydroxocobalaminum, hydroxocobemine, idrossocobalamina, methylcobalamin, vitadurin, vitamin B-12, vitamina B12 (Spanish), vitamine B12 (French).

Background
  • Vitamin B12 is an essential water-soluble vitamin that is commonly found in a variety of foods, such as fish, shellfish, meat, eggs, and dairy products. Vitamin B12 is frequently used in combination with other B vitamins in a vitamin B complex formulation. Vitamin B12 plays an important role in supplying essential methyl groups for protein and DNA synthesis. Vitamin B12 is bound to the protein in food. Hydrochloric acid in the stomach releases B12 from protein during digestion. Once released, B12 combines with a substance called intrinsic factor (IF) before it is absorbed into the bloodstream.
  • The human body stores several years' worth of vitamin B12 in the liver, so nutritional deficiency of this vitamin is extremely rare. However, deficiency can result from being unable to use vitamin B12. Inability to absorb vitamin B12 from the intestinal tract can be caused by pernicious anemia. Vitamin B12 deficiency is common in the elderly. HIV-infected persons and vegetarians who are not taking in proper amounts of B12 are also prone to deficiency.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


Vitamin B12 deficiency is a cause of megaloblastic anemia, in which red blood cells are larger than normal and the ratio of nucleus size to cell cytoplasm is increased. There are other potential causes of megaloblastic anemia, including folate deficiency or various inborn metabolic disorders. Pernicious anemia is a type of megaloblastic anemia caused by vitamin B12 deficiency, and it should be treated with vitamin B12. Patients with anemia should be evaluated by a physician in order to diagnose and address the underlying cause.

A


Studies have shown that a deficiency of vitamin B12 can lead to abnormal neurologic and psychiatric symptoms. These symptoms may include ataxia (shaky movements and unsteady gait), muscle weakness, spasticity, incontinence, hypotension (low blood pressure), vision problems, dementia, psychoses, and mood disturbances. Researchers have reported that these symptoms may occur when vitamin B12 levels are just slightly lower than normal and are considerably above the levels normally associated with anemia. People at risk for vitamin B12 deficiency include strict vegetarians, elderly people, breastfed infants, and people with increased vitamin B12 requirements associated with pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, or liver or kidney disease. Administering vitamin B12 orally, intramuscularly, or intranasally is effective for preventing and treating dietary vitamin B12 deficiency.

A


Some patients diagnosed with Alzheimer's disease have been found to have abnormally low vitamin B12 levels in their blood. The effects of vitamin B12 supplementation on the prevention or progression of Alzheimer's disease remain unclear. Well-designed clinical trials are needed before a conclusion can be made.

C


There are conflicting findings about the potential benefit or harm of taking folic acid plus vitamin B6 and vitamin B12 following angioplasty. Some evidence suggests that lowering homocysteine levels with prescription-strength folic acid and vitamins B12 and B6 for six months following coronary angioplasty reduced the risk of revascularization of target lesions and overall adverse cardiac events. Others have found this combination supplementation to increase restenosis (reoccurrence of narrowing of a blood vessel). Further research is needed before a conclusion can be made.

C


Researchers at Johns Hopkins University have reported that women with breast cancer tend to have lower vitamin B12 levels in their blood serum than do women without breast cancer. However, another study found no association between vitamin B12 levels and breast cancer risk. Supplementation with a combination of folic acid, vitamin B6, and vitamin B12 did not decrease the risk of breast cancer. Further research is needed before conclusions can be made.

C


High homocysteine levels in the blood (hyperhomocysteinemia) has been suggested as being a risk factor for cardiovascular disease, blood clotting abnormalities, atherosclerosis, myocardial infarction (heart attack), and ischemic stroke. Taking vitamin B12 supplements in combination with other B vitamins (mainly folic acid) has been shown to be effective for lowering homocysteine levels. It is not clear whether lowering homocysteine levels results in reduced cardiovascular morbidity and mortality. More evidence is needed to fully explain the association of total homocysteine levels with vascular risk and the potential use of vitamin supplementation.

C


Some evidence suggests that vitamin B12 supplementation may have a role in preventing cervical cancer. Further research is warranted in this area.

C


Taking vitamin B12 by mouth, in methylcobalamin form, does not seem to be effective for treating delayed sleep phase syndrome. Supplemental methylcobalamin with bright light therapy may be helpful for adolescents with circadian rhythm sleep disorders. More research is needed in this area.

C


Elevated serum homocysteine levels have been associated with lower neuropsychological test scores. However, there was a lack of association between low vitamin B12 blood levels and cognitive decline, Alzheimer's disease, or dementia; or between vitamin B12 concentrations and cognitive domains. There was conflicting evidence in regard to the relationship of serum folate and vitamin B12 status with cognitive impairment. More research is needed before a conclusion can be made.

C


Higher blood levels of homocysteine are associated with increased depression in later life. However, a combination of folic acid, vitamin B12, and vitamin B6 was no better than placebo with respect to symptoms of depression in older men. Well-designed clinical trials are needed to confirm any potential benefit.

C


Some evidence suggests that supplementation with vitamin B12 may be helpful to diabetic neuropathy patients, primarily through symptomatic relief. Higher-quality studies are needed in the area.

C


There is some evidence that intramuscular injections of vitamin B12 given twice per week may improve the general well-being and happiness of patients complaining of tiredness or fatigue. However, fatigue has many potential causes. Well-designed clinical trials are needed before a conclusion can be made.

C


Some evidence suggests that a combination of vitamins including vitamin B12 may help prevent fractures. Additional research is necessary.

C


Some evidence suggests that vitamin B12 in combination with fish oil may be superior to fish oil alone when used daily to reduce total serum cholesterol and triglycerides. Well-designed clinical trials of vitamin B12 supplementation alone are needed before a conclusion can be drawn.

C


Administering vitamin B12 intramuscularly seems to be effective for treating familial selective vitamin B12 malabsorption (Imerslund-Grasbeck disease). Further research is needed to confirm these results.

C


Preliminary research suggests that vitamin B12 may be effective for elbow pain, but evidence is lacking. Further research is needed.

C


Clinical reports show that shaky-leg syndrome may be caused by disturbances in the cerebellum or related structures due to vitamin B12 deficiency. Further research is needed to confirm these results.

C


Early study suggests that a daily combination including folic acid, vitamin B12, and vitamin B6 may be a simple and relatively inexpensive way to reduce sickle cell disease patients' inherently high risk of endothelial damage. Further research is needed to confirm these results.

C


A clinical study found a correlation between vitamin B12 and folic acid supplementation and increased incidence of lung cancer in patients with heart disease in Norway, where folic acid fortification of foods is reportedly lacking. More high-quality research is needed with vitamin B12 alone to better understand this relationship.

D


In people with a history of stroke, neither high-dose nor low-dose vitamin B12 combinations containing pyridoxine, vitamin B12, and folic acid seem to affect risk of recurring stroke.

D
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Aging, AIDS, allergies, amyotrophic lateral sclerosis, asthma, autism, chemotherapy side effects, chronic fatigue syndrome, diabetes, energy level enhancement, growth disorders (failure to thrive), hemorrhage, immunosuppression, improving concentration, inflammatory bowel disease, kidney disease, Leber's disease, liver disease, male infertility, malignant tumors, memory loss, mood (elevate), mouth and throat inflammation (atrophic glossitis), movement disorders (tremor), multiple sclerosis, myoclonic disorders (spinal myoclonus), neural tube defects, periodontal disease, poisoning (cyanide), prevention of pregnancy complications, protection from tobacco smoke, psychiatric disorders, seborrheic dermatitis, seizure disorders (West syndrome), tendonitis, thrombosis, thyrotoxicosis / thyroid storm (adjunct iodides), tinnitus, vitiligo.

Dosing

Adults (18 years and older)

  • Recommended dietary allowances (RDAs) are 2.4 micrograms daily for adults and adolescents aged 14 years and older, 2.6 micrograms daily for adult and adolescent pregnant females, and 2.8 micrograms daily for adult and adolescent lactating females. Because 10-30% of older people do not absorb food-bound vitamin B12 efficiently, those over 50 years of age should meet the RDA by eating foods fortified with B12 or by taking a vitamin B12 supplement. Supplementation of 25-100 micrograms daily has been used to maintain vitamin B12 levels in older people. A doctor and pharmacist should be consulted for use in other indications.
  • For vitamin B12 deficiency, 125-2,000 micrograms of cyanocobalamin has been taken by mouth daily for up to 2.5 years or longer. Five hundred micrograms of sublingual (under the tongue) vitamin B12 has been used daily for up to four weeks. The following doses have been given intravenously (through the veins): 1,000 micrograms of intramuscular cobalamin once daily for 10 days (after 10 days, the dose was changed to once per week for four weeks, followed by once per month for life); 1,000 micrograms of intramuscular cyanocobalamin given on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 of treatment. For vitamin B12 deficiency caused by long-term PPI therapy, cyanocobalamin nasal spray has been used for eight weeks. The exact dosage is unclear. One clinical trial tested patients' acceptance of intranasal vitamin B12 replacement therapy (500 micrograms per week).
  • To lower homocysteine levels, 60-400 micrograms of vitamin B12 has been taken by mouth daily, as part of a B vitamin combination used for up to four years.
  • For prevention of anemia, the following doses have been taken by mouth: 2-10 micrograms of vitamin B12 daily combined with iron and/or folic acid for up to 16 weeks; 100 micrograms of vitamin B12 every other week plus daily folic acid and/or iron for up to 12 weeks.
  • For cognitive function, the following doses have been taken by mouth: 10 micrograms or 50 micrograms of cyanocobalamin daily for one month; and one milligram of cyanocobalamin weekly for four weeks. One 1,000 microgram vitamin B12 injection has been used daily for five days, followed by one 1,000 microgram injection monthly for five months.
  • For acute cyanide poisoning, an intravenous infusion of five grams of hydroxocobalamin (up to 20 grams) has been used.
  • For depression, one milligram of cyanocobalamin, through intramuscular injections, was used weekly for four weeks.
  • For hereditary sideroblastic anemia, 100 micrograms of intramuscular vitamin B12 has been used monthly, with or without daily folic acid, for up to four months.

Children (under 18 years old)

  • Recommended dietary allowances (RDAs) have not been established for all pediatric age groups; therefore, adequate intake (AI) levels have been used instead. The RDAs and AI levels of vitamin B12 are as follows: for infants 0-6 months old, 0.4 micrograms (AI); for infants 7-12 months old, 0.5 micrograms (AI); for children 1-3 years old, 0.9 micrograms; for children 4-8 years old, 1.2 micrograms; and for children 9-13 years old, 1.8 micrograms.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Vitamin B12 supplements should be avoided in people sensitive or allergic to cobalamin, cobalt, or any other product ingredients.

Side Effects and Warnings

  • Vitamin B12 is generally considered safe when taken in amounts that are not higher than the recommended dietary allowance (RDA). There are not enough scientific data available about the safety of larger amounts of vitamin B12 during pregnancy or breastfeeding.
  • Use cautiously in patients with cardiovascular concerns. After coronary stenting, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12 followed by oral administration daily has been shown to increase rates of restenosis (reoccurrence of narrowing of a blood vessel). Due to the potential for harm, this combination of vitamins should not be recommended for patients receiving coronary stents.
  • Use cautiously in patients with elevated blood pressure, as high blood pressure following intravenous administration of hydrocobalamin has been reported.
  • Use cautiously in patients with dermatologic concerns, as pustular or papular rash, pruritus, and erythema have been reported. Vitamin B12 and pyridoxine have been associated with cases of rosacea fulminans, characterized by intense erythema with nodules, papules, and pustules. Symptoms may persist for up to four months after the supplement is stopped and may require treatment with systemic corticosteroids and topical therapy. Pink or red skin discoloration has also been reported.
  • Use cautiously in patients with genitourinary concerns, as urine discoloration has been reported.
  • Use cautiously in patients with gastrointestinal concerns, as nausea, difficulty swallowing, and diarrhea have been reported.
  • Use cautiously in patients with hematological concerns, as, according to case report data, treatment of vitamin B12 deficiency may lead to polycythemia vera, which is characterized by an increase in blood volume and the number of red blood cells.
  • Use cautiously in patients with subnormal serum levels of potassium, as the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia in susceptible individuals.
  • Use cautiously in patients with a history of gout, or elevated uric acid levels, as the correction of megaloblastic anemia with vitamin B12 may precipitate gout in susceptible individuals.
  • Use cautiously in patients taking the following agents, as they have been associated with reduced absorption or reduced serum levels of vitamin B12: ACE inhibitors, acetylsalicylic acid (aspirin), antibiotics, anticonvulsants, bile acid sequestrants, colchicine, H2 blockers, metformin, neomycin, nicotine, nitrous oxide, oral contraceptives, para-aminosalicylic acid, potassium chloride, proton pump inhibitors (PPIs), and zidovudine (AZT, Combivir®, Retrovir®). Additionally, vitamin C may cause the degradation of vitamin B12 in multivitamin supplements, and chloramphenicol may inhibit the biosynthesis of vitamin B12.
  • Avoid in patients sensitive or allergic to cobalamin, cobalt, or any other vitamin B12 product ingredients.

Pregnancy and Breastfeeding

  • Vitamin B12 is likely safe when used orally in amounts that do not exceed the recommended dietary allowance (RDA). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.

Interactions

Interactions with Drugs

  • Excessive alcohol intake lasting longer than two weeks may decrease vitamin B12 absorption from the gastrointestinal tract.
  • Therapy with ACE inhibitors has been associated with a decline in serum vitamin B12 levels.
  • Long-term antibiotic use may deplete vitamin B12 levels.
  • Anticonvulsants such as carbamazepine, oxcarbazepine, and valproic acid have been associated with reduced vitamin B12 absorption and reduced serum and cerebrospinal fluid levels in some patients.
  • Aspirin users may be more prone to vitamin B12 deficiency than nonusers.
  • Bile acid resins such as colestipol (Colestid®) and cholestyramine (Questran®) may reduce vitamin B12 absorption.
  • Chloramphenicol has been found to inhibit the biosynthesis of vitamin B12.
  • Colchicine may induce the malabsorption of several nutrients, including vitamin B12.
  • H2 blockers include cimetidine (Tagamet®), famotidine (Pepcid®), and nizatidine (Axid®). Long-term use of H2 blockers may reduce absorption of vitamin B12.
  • Metformin may reduce serum folic acid and vitamin B12 levels.
  • Neomycin may reduce the absorption of vitamin B12.
  • Nicotine may reduce serum vitamin B12 levels.
  • Nitrous oxide may cause symptomatic vitamin B12 deficiency.
  • Data regarding the effects of oral contraceptives on vitamin B12 serum levels are conflicting. Some studies have found reduced serum levels in birth control pill users, but others studies have found no such effect.
  • Para-aminosalicylic acid may inhibit vitamin B12 absorption.
  • Proton pump inhibitors (PPIs) include omeprazole (Prilosec®, Losec®), lansoprazole (Prevacid®), rabeprazole (AcipHex®), pantoprazole (Protonix®, Pantoloc®), and esomeprazole (Nexium®). Long-term use of proton pump inhibitors may reduce absorption of vitamin B12.
  • Reduced serum vitamin B12 levels may occur when zidovudine (AZT, Combivir®, Retrovir®) therapy is started. However, data suggest that vitamin B12 supplements are not helpful for people taking zidovudine.
  • Vitamin B12 may also interact with Alzheimer's agents, antigout agents, anticancer agents, aspirin, blood pressure-lowering agents, cardiovascular agents, gastrointestinal agents, hematologic agents, neurologic agents, and stimulants.

Interactions with Herbs and Dietary Supplements

  • Long-term antibiotic use may deplete vitamin B12 levels.
  • Folic acid supplementation may mask vitamin B12 deficiency and delay its diagnosis. In vitamin B12 deficiency, folic acid can produce hematologic improvement in anemia, while allowing potentially irreversible neurological damage to progress. Vitamin B12 status should be determined before folic acid is given as a monotherapy.
  • Hormonal herbs and supplements may interact with vitamin B12. Data regarding the effects of oral contraceptives on vitamin B12 serum levels are conflicting. Some studies have found reduced serum levels in birth control pill users, but other studies have found no such effect.
  • B vitamins, including vitamin B12, and omega-3 fatty acids may have the potential for synergistic protective effects with respect to cardiovascular disease.
  • Potassium supplements may reduce absorption of vitamin B12 in some people. This effect has been reported with potassium chloride. Correction of megaloblastic anemia with vitamin B12 can result in fatal hypokalemia in susceptible individuals.
  • Vitamin C has been shown to cause the degradation of vitamin B12 in multivitamin supplements.
  • Vitamin B12 may also interact with Alzheimer's agents, antigout agents, anticancer agents, antiseizure agents, antiulcer agents, aspirin, blood pressure-lowering agents, cardiovascular agents, gastrointestinal agents, hematologic agents, lipid-lowering agents, neurologic agents, nicotine-containing agents (such as tobacco), salicylates, and stimulants.

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008 May 7;299(17):2027-36.
  2. Andres E, Serraj K, Mecili M, Ciobanu E, Vogel T, Weitten T. Update of oral vitamin B12. Ann Endocrinol (Paris). 2009 Dec;70(6):455-61. Epub 2009 Aug 15.
  3. Bjørke-Monsen AL, Torsvik I, Saetran H, et al. Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation. Pediatrics 2008 Jul;122(1):83-91.
  4. Erol I, Alehan F, Gümüs A. West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia. Dev Med Child Neurol 2007 Oct;49(10):774-6.
  5. Eussen SJ, de Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med 2005 May 23;165(10):1167-72.
  6. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.
  7. Haggarty P, McCallum H, McBain H, Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet 2006 May 6;367(9521):1513-9.
  8. Lehman JS, Bruce AJ, Rogers RS. Atrophic glossitis from vitamin B12 deficiency: a case misdiagnosed as burning mouth disorder. J Periodontol 2006 Dec;77(12):2090-2.
  9. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008 Oct 8;(4):CD004514.
  10. Molloy AM, Kirke PN, Brody LC, et al. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 2008 Jun;29(2 Suppl):S101-11; discussion S112-5.
  11. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Physician 2008 Apr;54(4):536-41.
  12. Seal EC, Metz J, Flicker L, et al. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc 2002;50:146-51.
  13. Suzuki DM, Alagiakrishnan K, Masaki KH, et al. Patient acceptance of intranasal cobalamin gel for vitamin B12 replacement therapy. Hawaii Med J 2006 Nov;65(11):311-4.
  14. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-75.
  15. Yajnik CS, Lubree HG, Thuse NV, et al. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India. Asia Pac J Clin Nutr 2007;16(1):103-9.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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