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Drugs & supplements: vitamin b12 (print version)

Drugs & Supplements: Vitamin B12 (Print Version) Vitamin B12
URL of this page: Background
Vitamin B12 is an essential water soluble vitamin that is commonly found in a variety of foods such as fish, shellfish,meats, and dairy products. Vitamin B12 is frequently used in combination with other B vitamins in a vitamin Bcomplex formulation. It helps maintain healthy nerve cells and red blood cells, and is also needed to make DNA, thegenetic material in all cells. Vitamin B12 is bound to the protein in food. Hydrochloric acid in the stomach releasesB12 from protein during digestion. Once released, B12 combines with a substance called intrinsic factor (IF) before itis absorbed into the bloodstream.
The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremelyrare. Elderly are the most at risk. However, deficiency can result from being unable to use vitamin B12. Inability toabsorb vitamin B12 from the intestinal tract can be caused by a disease known as pernicious anemia. Additionally,strict vegetarians or vegans who are not taking in proper amounts of B12 are also prone to a deficiency state.
A day's supply of vitamin B12 can be obtained by eating 1 chicken breast plus 1 hard-boiled egg plus 1 cup plainlow-fat yogurt, or 1 cup milk plus 1 cup raisin bran.
B-12, B Complex, B Complex Vitamin, bedumil, cobalamin, cobalamins, cobamin, cyanocobalamin,cyanocobalaminum, cycobemin, hydroxocobalamin, hydroxocobalaminum, hydroxocobemine, idrossocobalamina,methylcobalamin, vitadurin, vitamin B-12.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of theseconditions are potentially serious, and should be evaluated by a qualified healthcare provider. Uses based on scientific evidence
Megaloblastic anemia - due to vitamin B12 deficiency
Vitamin B12 deficiency is a cause of megaloblastic anemia. In this type ofanemia, red blood cells are larger than normal, and the ratio of nucleus sizeto cell cytoplasm is increased. There are other potential causes of megaloblastic anemia, including folate deficiency or various inbornmetabolic disorders. If the cause is B12 deficiency, then treatment with B12is the standard approach. Patients with anemia should be evaluated by aphysician in order to diagnose and address the underlying cause.
Vitamin B12 deficiency Drugs & Supplements: Vitamin B12 (Print Version) Studies have shown that a deficiency of vitamin B12 can lead to abnormalneurologic and psychiatric symptoms. These symptoms may include: ataxia(shaky movements and unsteady gait), muscle weakness, spasticity,incontinence, hypotension, vision problems, dementia, psychoses, andmood disturbances. Researchers report that these symptoms may occurwhen vitamin B12 levels are just slightly lower than normal and are considerably above the levels normally associated with anemia. People atrisk for vitamin B12 deficiency include strict vegetarians, elderly people,and people with increased vitamin B12 requirements associated withpregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, liveror kidney disease.Administering vitamin B12 orally, intramuscularly, orintranasally is effective for preventing and treating dietary vitamin B12deficiency.
Pernicious anemia
Pernicious anemia (blood abnormality) is a form of anemia that occurs whenthere is an absence of intrinsic factor, a substance normally present in thestomach. Vitamin B12 binds with intrinsic factor before it is absorbed and used by the body. An absence of intrinsic factor prevents normal absorptionof B12 and may result in pernicious anemia. Pernicious anemia treatment isusually lifelong supplemental vitamin B12 given intramuscularly,intranasally, or by mouth.
Alzheimer's disease
Some patients diagnosed with Alzheimer's disease have been found to haveabnormally low vitamin B12 levels in their blood. However, vitamin B12 deficiency itself often causes disorientation and confusion and thus mimicssome of the prominent symptoms of Alzheimer's disease. Well-designedclinical trials are needed before a recommendation can be made.
Some evidence suggests that folic acid plus vitamin B12 and pyridoxinedaily can decrease the rate of restenosis in patients treated with balloonangioplasty. But this combination does not seem to be as effective for reducing restenosis in patients after coronary stenting. Due to the lack ofevidence of benefit and potential for harm, this combination of vitaminsshould not be recommended for patients receiving coronary stents.
Breast cancer
Researchers at Johns Hopkins University report that women with breastcancer tend to have lower vitamin B12 levels in their blood serum than dowomen without breast cancer. In a subsequent review of these findings, itwas hypothesized that vitamin B12 deficiency may lead to breast cancerbecause it could result in less folate being available to ensure proper DNA replication and repair. Higher dietary folate intake is associated with areduced risk of breast cancer. The risk may be further reduced in womenwho also consume high amounts of dietary vitamin B12 in combination withdietary pyridoxine (vitamin B6) and methionine. However, there is noevidence that dietary vitamin B12 alone reduces the risk of breast cancer.
Cardiovascular disease/hyperhomocysteinemia
Hyperhomocysteinemia (high homocysteine levels in the blood) is a risk Drugs & Supplements: Vitamin B12 (Print Version) factor for coronary, cerebral, and peripheral atherosclerosis, recurrentthromboembolism, deep vein thrombosis, myocardial infarction, andischemic stroke. Elevated homocysteine levels may be a marker instead of acause of vascular disease. However, it is not clear if lowering homocysteinelevels results in reduced cardiovascular morbidity and mortality. Folic acid, pyridoxine (vitamin B6), and vitamin B12 supplementation can reduce totalhomocysteine levels, however, this reduction does not seem to help withsecondary prevention of death or cardiovascular events such as stroke ormyocardial infarction in people with prior stroke. More evidence is neededto fully explain the association of total homocysteine levels with vascularrisk and the potential use of vitamin supplementation.
There is some evidence that intramuscular injections of vitamin B12 giventwice per week might improve the general well-being and happiness of patients complaining of tiredness or fatigue. However, fatigue has manypotential causes. Well-designed clinical trials are needed before arecommendation can be made.
High cholesterol
Some evidence suggests that vitamin B12 in combination with fish oil mightbe superior to fish oil alone when used daily to reduce total serum cholesterol and triglycerides. Well-designed clinical trials of vitamin B12supplementation alone are needed before a conclusion can be drawn.
Imerslund-Grasbeck disease
Administering vitamin B12 intramuscularly seems to be effective for treating C
familial selective vitamin B12 malabsorption (Imerslund-Grasbeck disease).
Further research is needed to confirm these results.
Shaky-leg syndrome
Preliminary clinical reports show that cyanocobalamin may help relieve tremor associated with shaky-leg syndrome. Further research is needed toconfirm these results.
Sickle cell disease
One study suggests that a practical daily combination may include folicacid, vitamin B12, and vitamin B6. This combination may be a simple and relatively inexpensive way to reduce these patients' inherently high risk ofendothelial damage. Further research is needed to confirm these results.
Circadian rhythm sleep disorders
Taking vitamin B12 orally, in methylcobalamin form, does not seem to beeffective for treating delayed sleep phase syndrome. Supplemental methylcobalamin, with or without bright light therapy, does not seem tohelp people with primary circadian rhythm sleep disorders.
Lung cancer
Preliminary evidence suggests that there is no relationship between vitamin Drugs & Supplements: Vitamin B12 (Print Version) In people with a history of stroke, neither high dose vitamin B12combinations containing pyridoxine, vitamin B12, and folic acid nor low dose combinations containing pyridoxine, vitamin B12, and folic acid seemto affect risk of recurring stroke.
Leber's disease
Vitamin B12 is contraindicated in early Leber's disease, which is hereditary optic nerve atrophy. Vitamin B12 can cause severe and swift optic atrophy.
*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 against this use; F: Strong scientific evidence against this use.
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. 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.

Aging, AIDS, allergies, amyotrophic lateral sclerosis, asthma, boosting energy, chronic fatigue syndrome, depression,depressive disorder (major), diabetes, diabetic peripheral neuropathy, hemorrhage, immunosuppression, improvingconcentration, improving mood, inflammatory bowel disease, kidney disease, liver disease, male infertility, memoryloss, multiple sclerosis, malignancy, osteoporosis, periodontal disease, protection from tobacco smoke, psychiatricdisorders, seborrheic dermatitis, tendonitis, thyrotoxicosis, tinnitus, tremor, vitiligo.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplementshave not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, withvariable ingredients, even within the same brand. The below doses may not apply to all products. You should read productlabels, and discuss doses with a qualified healthcare provider before starting therapy. Adults (18 years and older):
Recommended dietary allowances (RDAs) are 2.4 micrograms per day for adults and adolescents aged 14 years and
older, 2.6 micrograms per day for adult and adolescent pregnant females, 2.8 micrograms per day 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 per day has been used to maintain vitamin B12 levels in older
people. A doctor and pharmacist should be consulted for use in other indications. Vitamin B12 has been taken by
mouth and given by intramuscular (IM) injection by healthcare professionals.
Children (younger than 18 years):
Recommended dietary allowances (RDAs) have not been established for all pediatric age groups; therefore Adequate
Intake (AI) levels have been used instead. The RDA and AI of vitamin B12 are: infants 0-6 months, 0.4 micrograms
(AI); infants 7-12 months, 0.5 micrograms (AI); children 1-3 years, 0.9 micrograms; children 4-8 years, 1.2
micrograms; children 9-13 years, 1.8 micrograms.
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 Drugs & Supplements: Vitamin B12 (Print Version) are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a newtherapy. 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
Side Effects, Contraindications and Warnings
Caution should be used in patients undergoing angioplasty since an intravenous loading dose of folic acid, vitamin
B6 and vitamin B12 followed by oral administration taken daily after coronary stenting might actually increase
restenosis rates. Due to the potential for harm this combination of vitamins should not be recommended for patients
receiving coronary stents.
Itching, rash, transitory exanthema, and urticaria have been reported. Vitamin B12 and pyridoxine has beenassociated 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 withsystemic corticosteroids and topical therapy.
Peripheral vascular thrombosis has been reported. Treatment of vitamin B12 deficiency can unmask polycythemiavera, which is characterized by an increase in blood volume and the number of red blood cells. The correction ofmegaloblastic anemia with vitamin B12 can result in fatal hypokalemia and gout in susceptible individuals, and it canobscure folate deficiency in megaloblastic anemia. Caution is warranted.
Vitamin B12 is contraindicated in early Leber's disease, which is hereditary optic nerve atrophy. Vitamin B12 cancause severe and swift optic atrophy.
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 duringpregnancy.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods.
The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. Youshould always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, youshould speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
Excessive alcohol intake lasting longer than two weeks can decrease vitamin B12 absorption from the gastrointestinal
Aminosalicylic acid can reduce oral vitamin B12 absorption, possibly by as much as 55%, as part of a generalmalabsorption syndrome. Megaloblastic changes, and occasional cases of symptomatic anemia have occurred.
Vitamin B12 levels should be monitored in people taking aminosalicylic acid for more than one month.
An increased bacterial load can bind significant amounts of vitamin B12 in the gut, preventing its absorption. Inpeople with bacterial overgrowth of the small bowel, antibiotics such as metronidazole (Flagyl®) can actually improvevitamin B12 status. The effects of most antibiotics on gastrointestinal bacteria are unlikely to have clinicallysignificant effects on vitamin B12 levels.
The data regarding the effects of oral contraceptives on vitamin B12 serum levels are conflicting. Some studies havefound reduced serum levels in oral contraceptive users, but others have found no effect despite use of oral Drugs & Supplements: Vitamin B12 (Print Version) contraceptives for up to six months. When oral contraceptive use is stopped, normalization of vitamin B12 levelsusually occurs. Lower vitamin B12 serum levels seen with oral contraceptives probably are not clinically significant.
Limited case reports suggest that chloramphenicol can delay or interrupt the reticulocyte response to supplementalvitamin B12 in some patients. Blood counts should be monitored closely if this combination cannot be avoided.
Cobalt irradiation of the small bowel can decrease gastrointestinal (GI) absorption of vitamin B12.
Colchicine can disrupt normal intestinal mucosal function, leading to malabsorption of several nutrients, includingvitamin B12. Lower doses do not seem to have a significant effect on vitamin B12 absorption after 3 years ofcolchicine therapy. The significance of this interaction is unclear. Vitamin B12 levels should be monitored in peopletaking large doses of colchicine for prolonged periods.
Colestipol (Colestid®) and Cholestyramine (Questran®) resins can decrease gastrointestinal (GI) absorption of vitaminB12. It is unlikely that this interaction will deplete body stores of vitamin B12 unless there are other factorscontributing to deficiency. In a group of children treated with cholestyramine for up to 2.5 years there was not anychange in serum vitamin B12 levels. Routine supplements are not necessary.
H2-blockers include cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), and ranitidine (Zantac®).
Reduced secretion of gastric acid and pepsin produced by H2-blockers can reduce absorption of protein-bound(dietary) vitamin B12, but not of supplemental vitamin B12. Gastric acid is needed to release vitamin B12 fromprotein for absorption. Clinically significant vitamin B12 deficiency and megaloblastic anemia are unlikely, unlessH2-blocker therapy is prolonged (two years or more), or the person's diet is poor. It is also more likely if the personis rendered achlorhydric (with complete absence of gastric acid secretion), which occurs more frequently with protonpump inhibitors than H2-blockers. Vitamin B12 levels should be monitored in people taking high doses of H2blockers for prolonged periods.
Metformin may reduce serum folic acid and vitamin B12 levels. These changes can lead to hyperhomocysteinemia,adding to the risk of cardiovascular disease in people with diabetes. There are also rare reports of megaloblasticanemia in people who have taken metformin for five years or more. Reduced serum levels of vitamin B12 occur in upto 30% of people taking metformin chronically. However, clinically significant deficiency is not likely to develop ifdietary intake of vitamin B12 is adequate. Deficiency can be corrected with vitamin B12 supplements even ifmetformin is continued. The metformin-induced malabsorption of vitamin B12 is reversible by oral calciumsupplementation. A multivitamin preparation may also be valuable for some patients. Patients should be monitoredfor signs and symptoms of vitamin B12 and folic acid deficiency. People taking metformin chronically should beadvised to include adequate amounts of vitamin B12 in their diet, and have their serum vitamin B12 andhomocysteine levels checked annually.
Absorption of vitamin B12 can be reduced by neomycin, but prolonged use of large doses is needed to inducepernicious anemia. Supplements are not usually needed with normal doses.
Nicotine can reduce serum vitamin B12 levels. The need for vitamin B12 supplementation has not been adequatelystudied.
Nitrous oxide inactivates the cobalamin form of vitamin B12 by oxidation. Symptoms of vitamin B12 deficiency,including sensory neuropathy, myelopathy, and encephalopathy, can occur within days or weeks of exposure tonitrous oxide anesthesia in people with subclinical vitamin B12 deficiency. Symptoms are treated with high doses ofvitamin B12, but recovery can be slow and incomplete. People with normal vitamin B12 levels have sufficient vitaminB12 stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrousoxide abuse). Vitamin B12 levels should be checked in people with risk factors for vitamin B12 deficiency prior tousing nitrous oxide anesthesia.
Phenytoin (Dilantin®), phenobarbital, primidone (Mysoline®) anticonvulsants have been associated with reducedvitamin B12 absorption, and reduced serum and cerebrospinal fluid levels in some patients. This may contribute tothe megaloblastic anemia, primarily caused by folate deficiency, associated with these drugs. It has also beensuggested that reduced vitamin B12 levels may contribute to the neuropsychiatric side effects of these drugs. Drugs & Supplements: Vitamin B12 (Print Version) Patients should be encouraged to maintain adequate dietary vitamin B12 intake. Folate and vitamin B12 status shouldbe checked if symptoms of anemia develop.
Proton pump inhibitors (PPIs) include omeprazole (Prilosec®, Losec®), lansoprazole (Prevacid®), rabeprazole(Aciphex®), pantoprazole (Protonix®, Pantoloc®), and esomeprazole (Nexium®). The reduced secretion of gastricacid and pepsin produced by PPIs can reduce absorption of protein-bound (dietary) vitamin B12, but notsupplemental vitamin B12. Gastric acid is needed to release vitamin B12 from protein for absorption. Reducedvitamin B12 levels may be more common with PPIs than with H2-blockers, because they are more likely to produceachlorhydria (complete absence of gastric acid secretion). However, clinically significant vitamin B12 deficiency isunlikely, unless PPI therapy is prolonged (two years or more) or dietary vitamin intake is low. Vitamin B12 levelsshould be monitored in people taking high doses of PPIs for prolonged periods.
Reduced serum vitamin B12 levels may occur when zidovudine (AZT, Combivir®, Retrovir®) therapy is started. Thisadds to other factors that cause low vitamin B12 levels in people with HIV, and might contribute to the hematologicaltoxicity associated with zidovudine. However, data suggests vitamin B12 supplements are not helpful for peopletaking zidovudine.
Interactions with Herbs and Dietary Supplements
Folic acid, particularly in large doses, can mask vitamin B12 deficiency. In vitamin B12 deficiency, folic acid can
produce hematologic improvement in megaloblastic anemia, while allowing potentially irreversible neurological
damage to progress. Vitamin B12 status should be determined before folic acid is given as monotherapy.
Potassium supplements can reduce absorption of vitamin B12 in some people. This effect has been reported withpotassium chloride and, to a lesser extent, with potassium citrate. Potassium might contribute to vitamin B12deficiency in some people with other risk factors, but routine supplements are not necessary.
Preliminary evidence suggests that vitamin C supplements can destroy dietary vitamin B12. However, othercomponents of food, such as iron and nitrates, might counteract this effect. Clinical significance is unknown, and itcan likely be avoided if vitamin C supplements are taken at least two hours after meals.
This information is based on a systematic review of scientific literature and consensus statements edited and peer-reviewed by contributors to the Natural Standard Research Collaboration ( Ethan Basch,MD (Memorial Sloan-Kettering Cancer Center); Catherine Ulbricht, PharmD (Massachusetts College of Pharmacy);Christine Ulbricht, PharmD (University of Massachusetts); Wendy Weissner, BA (Natural Standard ResearchCollaboration).
Selected references
1. Andres E, Kurtz JE, Perrin AE, et al. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Am J Med 2. Benito-Leon J, Porta-Etessam J. Shaky-leg syndrome and vitamin B12 deficiency. N Engl J Med 2000;342:981.
3. Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care. CMAJ 2000;163:21-9.
4. Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med 1997;127:1089-92.
5. Choi, Sang-Woon. Vitamin B12 deficiency: a new risk factor for breast cancer? Nutrition Reviews, Vol. 57, August 1999, pp. 250-60.
6. 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. 5-23-2005;165(10):1167-1172.
7. 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.
8. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 9. Haggarty P, McCallum H, McBain H, Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet. 2006 10. Okawa M, Takahashi K, Egashira K, et al. Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study.
Psychiatry Clin Neurosci 1997;51:275-9.
11. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome Drugs & Supplements: Vitamin B12 (Print Version) after percutaneous coronary intervention. The Swiss Heart Study: A randomized controlled trial. JAMA 2002;288:973-9.
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. Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials.Acta Neurol Taiwan.
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. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004655.
This evidence-based monograph was prepared by the Natural Standard Research Collaboration. The information provided should not beused during any medical emergency or for the diagnosis or treatment of any medical condition. Talk to your health care provider beforetaking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment orregimen. Copyright 2007 Natural Standard ( All Rights Reserved.


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