Vitamin B12 is a water-soluble vitamin. Cobalamin is the term used to refer to compounds having vitamin B12 activity.
Vitamin B12 requires a protein in the gastrointestinal tract that aids in absorption (intrinsic factor).
Hydrochloric acid also is necessary to split vitamin B12 from its peptide bonds. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, which in turn results in a reduced release of free vitamin B12 from food protein to be absorbed. This condition is associated with advanced age.
Absorption of protein-bound vitamin B12 decreases with age or deficiency of iron or folic acid, and increases during pregnancy.
Individuals with pernicious anemia (complete absence of intrinsic factor) develop vitamin B12 deficiency rapidly, in approximately 1-3 years, compared with those whose vitamin B12 deficiency stems from other causes.
The mean age at diagnosis of pernicious anemia is 60 years old. The prevalence rates for women are higher than for men.
The body stores 2000 to 5000 mcg, primarily in the liver and kidneys, and excesses are excreted by way of kidney or in bile.
Infants with vitamin B12 deficiency demonstrate a failure to thrive,
methylmalonic acidemia, marked developmental regression and poor brain
growth.
Vitamin B12 is connected to a conenzyme form and is essential for normal metabolism in all cells especially those of the gastrointestinal tract, bone marrow, and nervous system. The vitamin also functions in:
Transfer of methyl groups in the synthesis of nucleic acids, purines, and pyrimidine intermediates.
Red blood cell formation and control of pernicious anemia.
Protein, fat, and carbohydrate metabolism.
Converting homocysteine to methionine.
Neurotransmitter synthesis.
Vitamin B12 alters neurotransmitter synthesis through S-adenosylmethionine.
Vitamins B12, B6 and
folic acid work together to provide methyl groups in biological pathways and
reduce homocysteine.
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 results from 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.
Neurologic changes can occur in the absence of any hematologic abnormalities.
Many older persons have suboptimal vitamin B12 concentrations that go undetected.
Depending on the duration of symptoms, neurologic complications of vitamin B12 deficiency may or may not be reversible following treatment, while hematologic complications are completely reversed by treatment with vitamin B12.
No toxic effects have been reported for vitamin B12 at high concentrations. The No Observed Adverse Effect Level (NOAEL) is 3000
mcg. No toxic effects have been reported for vitamin B12 at high concentrations.
The No Observed Adverse Effect Level (NOAEL) is 3000 mcg. 2
Vitamin B12 is found only in foods of animal origin or in fermented foods where the bacteria produce the vitamin. Organ meats are the best source 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). However, a 1 mg daily oral dose
can substitute adequately for parenteral therapy in patients with the absence of
intrinsic factor.
Stomach acid is needed for vitamin B12 in food to be absorbed. H2 blockers and protein pump inhibitors (PPI) reduce stomach acid and therefore interfere with absorption of vitamin B12 naturally present in food. On the other hand, vitamin B12 found in supplements is available for the body to absorb without hydrochloric acid. Therefore, persons taking H2 blockers or PPIs may need to supplement vitamin B12 to prevent deficiency.
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, it is recommended to supplement in order to prevent deficiency.
Smoking tobacco can result in the reduction of vitamin B12 storage in tissues. Supplements
could benefit those who choose to use tobacco.
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.
Metformin may cause diminished oral 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.
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.
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.
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 many vitamins. Therefore, many nutrient deficiencies, including vitamin B12, can result from use of these medications. Concentrations of vitamin B12 remain in the normal range with these medications, and it is not necessary to supplement. 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.
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.
Cardiovascular Disease: Researchers at the Samsung Medical Center in Seoul, Korea, examined the relationship between plasma homocysteine concentration and stroke. The results demonstrated that the risk of cerebral infarction is 70% greater among persons with elevated blood homocysteine concentrations. This suggests that moderately elevated homocysteine concentrations may be an independent risk factor for stroke. Therefore, supplementation with folic acid and other B vitamins to lower homocysteine concentrations may provide an inexpensive means of reducing the risk of this serious, life-threatening event.6
Alzheimer Disease: Researchers at Oxford University in England examined the association between serum homocysteine concentration and the development and progression of Alzheimer disease (AD). Average homocysteine concentrations were significantly higher among case subjects than among controls, and serum concentrations of folic acid and vitamin B12 were significantly lower. The odds of having clinically diagnosed AD were twice as great and the odds of having confirmed AD were four-and-a-half times greater among persons with the highest compared with the lowest concentrations of serum homocysteine, after adjusting for sex, age, smoking, and social status. Low serum concentrations of folic acid were associated with a doubling of the odds of clinically diagnosed AD and a tripling of the odds of confirming AD, and low concentrations of vitamin B12 increased the odds of confirmed AD by more than fourfold. These findings demonstrate that elevated serum homocysteine and low concentrations of folic acid and vitamin B12 are associated with AD. A case-control study of 164 patients, including 76 patients with histologically confirmed AD, showed that serum homocysteine concentrations were higher and serum folate and vitamin B12 concentrations were lower in these patients than in matched 108 control subjects.7
Cognition and Mood: Epidemiological evidence from a number of studies demonstrated that healthy elderly subjects who had low blood concentration or intake of folate, vitamin B12, vitamin C, and riboflavin scored poorly on tests of memory and nonverbal abstract thinking. One study found significant improvement in neuropsychiatric function among cobalamin-deficient patients after vitamin B12 supplementation.8 Martin et al reported cognitive recovery after vitamin B12 supplementation in patients with B12 deficiency. 9
Breast cancer: A case-control study was conducted to investigate the incidence of breast cancer and prediagnostic serum concentrations of folate, B12 and B6. As a result, median B12 concentrations were lower among breast cancer patients than controls. Postmenopausal women with the lowest fifth of serum B12 concentrations had a significantly increased risk of breast cancer as compared to the higher four-fifths. However, no association was found between folate, B6, homocysteine and breast cancer in this study. 10
HIV: A number of studies showed that certain cobalamins inhibited productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. Additionally, investigators observed that a low serum concentration of vitamin B12 in an HIV-1-infected individual is an early and independent marker that predicts for HIV-1 disease progression and AIDS development. A study demonstrated that this antiviral activity of B12 might be mediated by an inhibition of HIV-1 integrase, an enzyme required for productive infection. 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.1112
Neural-Tube Defects (NTD): Both genetic and environmental factors are implicated in the pathogenesis of NTD; these include maternal folate deficiency, maternal cobalamin deficiency, and hyperhomocysteinemia. Findings suggest vitamin B12 status to be an independent risk factor for NTD. 13
Psychosis: Case reports and studies over many years have attributed psychotic symptoms to cobalamin deficiency. Several cases demonstrated a resolution of symptoms after administration of cobalamin. Further study is needed to refine the detection and clinical management of cobalamin deficiency in the psychiatric population. 14
Hearing Loss: Researchers at the University of Georgia studied 55 healthy women, aged 60 to 71 years. 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. When auditory function was divided into three categories: excellent, good, and impaired. A dose-response association between age-related hearing loss relation was observed for red cell folate and serum concentrations of vitamin B12 and folic acid. These findings and vitamin B12 and folic acid nutritional status suggest that inadequate dietary intake if these nutrients may increase risk of hearing loss. 15
Osteoarthritis: 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. A two month study of 26 people was conducted and showed that daily use of a combination of 6400 mcg of folic acid, 20 mcg of vitamin B12 and
acetaminophen as needed, has equal efficacy in treatment of osteoarthritis as
NSAID treatment. Therefore, use of folic acid and cobalamin supplementation may
be a good alternative to NSAID therapy for treatment of arthritis.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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