Vitamin B12 is a water-soluble vitamin. Vitamin B12 includes the free vitamin (cyanocobalamin) and two coenzymes, methylcobalamin and 5-deoxyadenosylcobalamin.
Vitamin B12 is released from dietary proteins by pepsin and HCl in the stomach. It is then bound by R-protein and then the complex travels to the small intestine; in the duodenum, R-protein is hydrolyzed and free vitamin B12 is released. Free vitamin B12 is then bound by a second protein called the intrinsic factor which is required for absorption of the vitamin in the ileum.
At low levels of intake (0.1 mcg), approximately 80% of consumed vitamin B12 is absorbed by humans with healthy digestive systems. At higher intakes, absorption of vitamin B12 rapidly drops to approximately 3%.
Unlike other water-soluble vitamins, vitamin B12 is stored in the human body. The body stores between 5 and 12 mg of vitamin B12, primarily in the liver and kidneys, and excesses are excreted by way of kidney or in bile.
Vitamin B12 is essential for two types of enzymatic reactions in humans, methyl group transfer and transfer of a hydrogen atom from one carbon to an adjacent carbon atom.
Vitamin B12 participates in three essential enzymatic reactions in the human body, one requires methylcobalamin and two require 5-deoxyadenosylcobalamin. Methionine synthetase requires methylcobalamin for conversion of homocysteine to methionine. Methylmalonyl CoA mutase (converts L-methylmalonyl CoA to succinyl CoA) and leucine aminomutase (isomerizes L-leucine and beta-leucine).
Males 9 to 13 years 14+ years 19+ years Females 9 to 13 years 14 to 18 years 19+ years
1.8 2.4 2.4
1.8 2.4 2.4
ND ND ND
ND ND ND
Pregnancy <= 18 years 19 to 50 years
2.6 2.6
ND ND
Lactation <= 18 years 19 to 50 years
2.8 2.8
ND ND
* Values for infants are Adequate Intake (AI), others are RDA. ND=Not determinable due to lack of data of adverse
effects in this age group and concern with regard to lack of ability to handle
excess amounts.
Vitamin B12 deficiencies manifest primarily as anemia and neurologic changes, although a deficiency of this vitamin inhibits DNA synthesis, which affects growth and repair of all cells.
Pernicious anemia is a form of megaloblastic anemia caused by either inadequate vitamin B12 intake or reduced gastric secretion of intrinsic factor, which inhibits absorption.
The hematologic effects of vitamin B12 deficiency are indistinguishable from those of folate deficiency. These include pallor of skin, tiredness, syncope, headache, shortness of breath, and palpitations. Hematologic complications are completely reversed by treatment with vitamin B12.
Neurologic changes due to vitamin B12 deficiency can occur in the absence of any hematologic abnormalities. Depending on the duration of symptoms, neurologic complications of vitamin B12 deficiency may or may not be reversible following treatment.
Vitamin B12 is found only in foods of animal origin or in fermented foods where bacteria produce the vitamin. Organ meats are the best sources of vitamin B12 (liver, kidney, heart, and pancreas), followed by clams, oysters, extra-lean beef, seafood, eggs, milk and yogurt, chicken, cheese, and miso (a fermented soybean product). For people who lack intrinsic factor, it has been found that a 1 mg daily oral dose can substitute adequately for parenteral therapy.
Atrophic gastritis with decreased pepsin production is prevalent in the elderly. Consequently, absorption of food-bound vitamin B12 is lower in older than in younger, healthier people.
Alcohol reduces the absorption of dietary cobalamin. In addition, it can interfere with storage of vitamin B12 in the body. Daily vitamin B12 supplements could prevent deficiency for people who consume excessive alcohol.
Since the primary sources of vitamin B12 in the diet are animal products, vegetarians have a high risk of developing B12 deficiency. Therefore, supplements are recommended for vegetarians to prevent deficiency.
Smoking tobacco can reduce storage of vitamin B12 in tissues. Supplements could benefit those who choose to use tobacco.
Metformin may cause diminished absorption of vitamin B12. Reduced serum levels of vitamin B12 occur in a significant percentage of patients taking metformin chronically.
Absorption of vitamin B12 from the GI tract may be decreased by aminoglycoside antibiotics, such as gentamicin, tobramycin, and amikacin. The concurrent administration of chloramphenicol, an antibiotic agent, and vitamin B12 may decrease the hematopoietic response to vitamin B12 in vitamin B12-deficient patients. Serum vitamin B12 concentrations of these patients should be monitored, and other antibiotics should be considered.
Absorption of vitamin B12 may be decreased by anticonvulsants such as phenytoin, phenobarbital, and primidone.
Colchicine, an antiinflammatory medication for the treatment of gout, has been reported to reduce absorption of vitamin B12 if taken more than two weeks. Both colchicine and vitamin B12 deficiency are reported to cause neuropathies, but it remains unclear whether neuropathies caused by colchicine could be due to vitamin B12 depletion. Neomycin-induced malabsorption of vitamin B12 may be increased by concurrent administration of colchicine. Vitamin B12 supplementation may be beneficial during long-term colchicine therapy.
Predinisone, an anti-inflammatory agent, has been shown to increase the absorption of vitamin B12 and secretion of intrinsic factor in the stomach in a few patients with pernicious anemia, but not in patients with partial or total gastrectomy. The clinical importance of these findings is unknown. It is advisable to consult with a physician or pharmacist about vitamin use before beginning therapy.
Chemotherapeutic drugs such as methotrexate, antiparasitic agents such as pyrimethamine, and other anti-infective medications invalidate blood assays for vitamin B12, giving false-positive test results for intrinsic factor antibodies that are present in blood in 50% of the patients with pernicious anemia.
Bile acid sequestrants such as cholestyramine and colestipol decrease the enterohepatic reabsorption of vitamin B12. Concentrations of vitamin B12 usually remain in the normal range with these medications. However, multivitamin-mineral supplements may be advisable.
Chronic use of salicylates has been shown to reduce blood concentrations of vitamin B12. Antituberculosis drugs such as isoniazids (INH) are structurally similar to salicylates and may decrease absorption of vitamin B12. People should consider using daily multivitamin/mineral supplements during therapy.
Proton pump inhibitors (PPIs) such as lansoprazole, used to treat ulcers, may interfere with the absorption of vitamin B12 from food, but not from supplemental vitamin B12, due to PPI-induced low stomach acidity. It is advisable to take vitamin B12 supplementation to prevent this problem. There is some evidence that cranberry juice may increase the vitamin's absorption possibly because the juice is somewhat acidic.
Cimetidine, an H2 blocker used to treat ulcers, given 4 times daily (1,000 mg total) reduces absorption of dietary vitamin B12, but not supplemental vitamin B12, in some peptic patients. It is advisable to take vitamin B12 supplementation to decrease malabsorption.
Zidovudine, an antiviral agent used to treat HIV infection, may deplete concentrations of vitamin B12. It is advisable to take vitamin B12 supplementation.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
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.
The Vitamin Intervention for Stroke Prevention Trial (VISP) evaluated the efficacy of vitamins B6, B12, and folic acid for reducing risk of stroke, myocardial infarction, and death for patients with ischemic stroke. Participants (3,680 adults) were randomly assigned to receive daily supplements of vitamin B6 (25 mg), vitamin B12 (0.4 mg), and folic acid (2.5 mg) or vitamin B6 (0.200 mg), vitamin B12 (0.006 mg), and folic acid (0.020 mg) daily for two years. Supplements were found to lower homocysteine levels but no changes in risk for stroke, myocardial infarction, or death were found. A subgroup of participants (2,155 patients with an average age of 66 years) was more likely to benefit from vitamin therapy. For this subgroup, risk for the combined endpoint of stroke, coronary disease, or death was reduced by 21% (unadjusted P=0.049). The subgroup was selected by excluding those likely to have B12 malabsorption, receiving parenteral B12 and other supplements, and those with renal failure. It was concluded that in the era of food folate fortification, response to vitamin therapy to lower homocysteine was largely dependent on initial vitamin B12 status. The authors concluded that certain subgroups may require higher doses of vitamin B12 or other therapies.17,18
Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products
This study evaluated the role of B12 as an important determinant of homocysteine levels in the era of folic acid fortification. The researchers measured total carotid plaque area by ultrasound and determined homocysteine and serum B12 levels in 421 people with vascular disease. Seventeen percent of participants were found to have vitamin B12 deficiency. The mean area of carotid plaque was found to be significantly larger among the group of patients whose B12 levels were below the median (1.36 (standard deviation [SD] 1.27) cm2 vs. 1.09 (SD 1.0) cm2; p = 0.016). These results indicate that vitamin B12 deficiency was evident in people with vascular disease and that this deficiency was correlated with carotid plaque size for these participants. Further studies are required to investigate this correlation.19
Homocysteine lowering and cardiovascular events after acute myocardial infarction
The Norwegian Vitamin Trial (NORVIT) evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients with a history of acute myocardial infarction (MI). A total of 3,749 men and women were randomly assigned to receive folic acid (0.8 mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg), folic acid and vitamin B12, vitamin B6 alone, or placebo. Patients were seen at a 2 month follow-up visit and at a final visit after 2 to 3.5 years. Despite a substantial reduction in plasma total homocysteine, intervention with B vitamins did not lower the risk of recurrent cardiovascular disease or death after an acute MI. In the group receiving folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased rate of events (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05). Researchers concluded that B vitamin intervention not be recommended after acute MI.11
Homocysteine lowering with folic acid and B vitamins in vascular disease
The Heart Outcomes Prevention Evaluation (HOPE) 2 trial evaluated whether therapy with homocysteine-lowering B vitamins reduced the risk for major vascular events in a high risk population. A total of 5,522 patients aged 55 years or older with vascular disease or diabetes participated in the trial. Participants randomly assigned to consume a daily supplement with a B vitamin combination (2.5 mg folic acid, 50 mg vitamin B6, 1 mg vitamin B12) or a placebo for an average of 5 years. The results showed that daily administration of the B vitamin combination significantly lowered homocysteine but had no beneficial effects on major vascular events in a high risk population with vascular disease.12
Homocysteine and Vitamin B12 Status Relate to Bone Turnover Markers, Broadband Ultrasound Attenuation, and Fractures in Healthy Elderly People
The relationship of homocysteine and vitamin B12 with bone turnover markers, broadband ultrasound attenuation (BUA,) and fractures incidence was studied in 1267 individuals of the Longitudinal Aging Study Amsterdam. Results suggest high homocysteine and low B12 levels were significantly associated with low BUA, high markers of bone turnover, and increased risk of fracture.20
Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study
To investigate the relationship between serum vitamin B12 and bone loss in women, a subset of participants in the original Study of Osteoporotic Fractures were included in a new study. Of the original 9,704 white women aged at least 65 years, non-estrogen using women who had serum samples taken at baseline and continued for both follow up points were included, a total of 83 women. Two years after baseline, BMD of the hip was measured, with repeat measurements of both calcaneal and hip BMD after 5.9 and 3.5 years of follow-up respectively. Vitamin B12 assays were performed from serum samples. Women in the lowest quintile of vitamin B12 levels experienced an annual change of -1.6% (95% confidence interval, -2.4% to -0.8%) in total hip BMD. Women in higher quintiles experienced an annual change of with -0.2% (-0.5% to 0.2%). Researchers concluded that low serum vitamin B12 levels were associated with increased rates of hip, but not calcaneal, bone loss in older women.23
Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans
This study explored the association between homocysteine, B-vitamin status and bone health. Researchers collected data from 1,553 men and women aged 55 years and older who underwent DEXA scans of the hip as participants in phase 2 of the third U.S. National Health and Nutrition Examination Survey. Serum vitamin B12 concentration was related to bone mineral density (BMD) in a dose-response fashion up to a concentration of 200 pmol/L. Participants with homocysteine concentrations higher than 20 micromol/L had significantly lower BMD than those with homocysteine concentrations lower than 20 micromol/L. The OR (95% CI) for osteoporosis/osteopenia was 2.0 (1.0 to 3.9) for a serum vitamin B12 concentration below the 25th percentile. After adjusting for various other risk factors, it was found that bone mineral density (BMD) decreased and osteoporosis increased significantly with increasing serum MMA. These findings suggest elevated homocysteine and low vitamin B12 status are associated with BMD in older Americans.8
Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease
This case-control study examined the link between Alzheimer’s progression and blood levels of total homocysteine, folate, and vitamin B12. Included were 164 patients with a clinical diagnosis of dementia of Alzheimer type, including 76 patients with histologically confirmed Alzheimer’s disease, and 108 control subjects. Elevated serum homocysteine levels and low folic acid and vitamin B12 concentrations were found in participants with dementia of Alzheimer type and in confirmed Alzheimer’s disease compared to controls. The odds ratio was 4.5 (95% confidence interval, 2.2-9.2) for confirmed AD associated with a tHcy level in the top third compared with the bottom third of the control distribution, after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. Radiological evidence of disease progression in people with dementia of Alzheimer type during three years of follow-up was greater among those with higher baseline tHcy levels. The results of the study demonstrate that elevated serum homocysteine and low concentrations of folic acid and vitamin B12 are associated with Alzheimer’s disease.7
Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study
The effects of cobalamin repletion in twenty-two elderly subjects with low serum cobalamin and evidence of cognitive dysfunction was examined. Participants received 1000 mg of intramuscular vitamin B12 daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of 6 months. Results revealed that eleven of the eighteen that completed the study, showed cognitive improvement after 6 months. There was a dramatic link between duration of cognitive symptoms and response to therapy. These results demonstrate that vitamin B12 may improve cognitive function in some elderly people and that there may be a window of opportunity before declines no longer respond to vitamin B12 repletion.9
Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression.
A cross-sectional prospective study investigated the relationship between folic acid, vitamin B12, homocysteine, and depression in a group of older Korean adults. At baseline, 732 participants over the age of 65 years were enrolled in the study; 631 were not depressed at baseline while 101 were found to be depressed using the Geriatric Mental State schedule. Participants were followed for two to three years. Low folate and low vitamin B12 levels and elevated homocysteine at baseline were associated with an increased risk for depression at follow-up. Depression at baseline was associated with a decline in vitamin B12 and an increase in homocysteine at follow-up. These results suggest that vitamin B12, folate, and homocysteine are important factors to consider with age-related depression.6
A prospective study on folate, B12, and pyridoxal 5’-phosphate (B6) and breast cancer
A nested case-control study evaluated the incidence of breast cancer and prediagnostic serum concentrations of folate, B12 and B6 in 2 cohorts. Average B12 levels were lower among 195 breast cancer cases than 195 matched controls with statistically significant differences in a subgroup of postmenopausal women. The findings further suggest a threshold effect for B12 with an increased risk of breast cancer among postmenopausal women in the lowest 1/5 verses the higher 4/5 of the control.10
Low serum vitamin B-12 concentrations are associated with faster human immunodeficiency virus type 1 (HIV-1) disease progression
Micronutrient levels were assessed in 310 HIV+ men with a follow-up period of 9 years. Investigators observed that a low serum concentration of vitamin B12 in HIV-1-infected individual is an early and independent marker that predicts for HIV-1 disease progression and AIDS development. Since cobalamin can be administered in very high doses to humans with little or no toxicity, this agent might be useful as therapeutic agents to slow the disease progression.11
Cobalamin inhibition of HIV-1 integrase and integration of HIV-1 DNA into cellular DNA
Previous studies by Weinberg and colleagues showed that certain cobalamins inhibited productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. The same researchers demonstrated in this study that antiviral activity of B12 might be mediated by an inhibition of HIV-1 integrase, an enzyme required for viral replication. The researchers suggest cobalamins and cobinamides represent novel inhibitors of HIV-1 integrase and may be useful as anti-viral treatments.12
Neural-tube defects (NTD) are associated with low concentrations of cobalamin (vitamin B12) in amniotic fluid
Both genetic and environmental factors are implicated in the pathogenesis of NTD; these include maternal folate deficiency, maternal cobalamin deficiency, and hyperhomocysteinemia. These findings suggest vitamin B12 status to be an independent risk factor for NTD.13
Case reports and studies have linked psychotic symptoms to cobalamin deficiency and depressive disorders to folate deficiency. Several cases demonstrated a resolution of psychotic symptoms after administration of cobalamin. Clinicians should be aware of the possibility of folate and cobalamin deficiencies in psychiatric populations. More research is needed, however, to improve detection and clinical management of these vitamin deficiencies in psychiatric populations.14
Age-related hearing loss, vitamin B-12, and folate in elderly women
Researchers at the University of Georgia assessed 55 healthy women, aged 60 to 71 years, for hearing function and evaluated whether age-related hearing loss was associated with poor B12 and folate status. It was found that serum concentration of folic acid and vitamin B12 were more than 30% lower among hearing-impaired women than among those with normal hearing. These findings suggest inadequate dietary intake of vitamin B12 and folic acid may increase risk of hearing loss.15
Osteoarthritis is a debilitating disease affecting over 50 million of people in the U.S. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary treatment to control pain and increase mobility, but often have intolerable side effects.
The effect of folate and cobalamin on osteoarthritic hands
A two month double-blinded, crossover study evaluated the effects of folate and B12 supplements in 26 people diagnosed with osteoarthritis of the hands. Results suggest that daily use of a combination of 6400 mcg of folic acid, 20 mcg of vitamin B12, and acetaminophen as needed, is comparable to NSAID treatment.16
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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