Vitamin B12

Vitamin B12/Drug Interactions:

  • AlcoholAlcohol: According to secondary sources, excessive alcohol intake lasting longer than two weeks may decrease vitamin B12 absorption from the gastrointestinal tract.
  • Alzheimer's agentsAlzheimer's agents: A systematic review of observational human research concluded that serum vitamin B12 levels were lower in Alzheimer's disease patients (123). The effects of vitamin B12 supplementation on the prevention and/or progression of Alzheimer's disease remain unclear.
  • Angiotensin-converting enzyme inhibitors (ACEIs)Angiotensin-converting enzyme inhibitors (ACEIs): In human clinical research, therapy with ACE inhibitors was associated with a decline in serum vitamin B12 levels (64).
  • AntibioticsAntibiotics: According to anecdotal reports, long term antibiotic use may deplete vitamin B12 levels.
  • AnticonvulsantsAnticonvulsants: 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 (66; 67).
  • AntihypertensivesAntihypertensives: Hypertension following intravenous administration of hydroxocobalamin has been reported in human clinical research (52; 59). In clinical research, therapy with ACE inhibitors was associated with a decline in serum vitamin B12 levels (64).
  • Antigout agentsAntigout agents: According to case report data, correction of megaloblastic anemia with vitamin B12 may precipitate gout in susceptible individuals (63).
  • AntineoplasticsAntineoplastics: In epidemiological research, elevated levels of vitamin B12 and folate were associated with increased prostate cancer risk (22). Human research suggests that elevated serum vitamin B12 levels associated with tumor markers may indicate poor survival in hepatocellular carcinoma patients (23). Another study found a correlation between vitamin B12 and folic acid supplementation and increased incidence of lung cancers (24).
  • AspirinAspirin: In human research, there was a higher prevalence of vitamin B12 deficiency in patients using acetylsalicylic acid (aspirin) compared to nonusers (65).
  • Bile acid sequestrantsBile acid sequestrants: In vitro, colestipol (Colestid?) and cholestyramine (Questran?) resins have been shown to be highly bound to vitamin B12-intrinsic factor complex (68). Secondary sources suggest that bile acid resins may reduce vitamin B12 absorption.
  • Cardiovascular agentsCardiovascular agents: In clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (58). Hypertension following intravenous administration of hydroxocobalamin has been reported in clinical studies (52; 59).
  • ChloramphenicolChloramphenicol: In vitro, chloramphenicol has been found to inhibit the biosynthesis of vitamin B12 (87).
  • ColchicineColchicine: According to animal research, colchicine may induce the malabsorption of several nutrients, including vitamin B12 (69).
  • Gastrointestinal agentsGastrointestinal agents: Nausea and dysphagia have been reported in clinical research (59). According to secondary sources, diarrhea has also been reported. One study suggested that elevated serum vitamin B12 levels associated with tumor markers may indicate poor survival in hepatocellular carcinoma patients (23).
  • HematologicsHematologics: According to case report data, treatment of vitamin B12 deficiency may lead to polycythemia vera (61), which is characterized by an increase in blood volume and the number of red blood cells. According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (62).
  • H2 blockersH2 blockers: According to human research, prolonged reduction in the secretion of gastric acid and pepsin caused by long-term use of H2 blockers may reduce absorption of vitamin B12 (70; 71).
  • MetforminMetformin: In patients with type 2 diabetes, metformin use has been shown to reduce serum folic acid and vitamin B12 levels (72; 73; 74; 64).
  • NeomycinNeomycin: According to a review, absorption of vitamin B12 may be reduced by neomycin (75).
  • Neurologic agentsNeurologic agents: Supplementation of vitamin B12 has been shown to resolve a variety of neurological symptoms in infants, caused by severe vitamin B12 deficiency (124). According to a review, elevated serum homocysteine and low folate and vitamin B12 levels may be associated with poor cognitive function, cognitive decline, and dementia (2). According to reviews, supplementation of B vitamins, including vitamin B12, may have a role in preventing dementia by way of lowering homocysteine levels (125; 28). In a meta-analysis, higher blood levels of homocysteine were found to be associated with increased depression in later life (126). 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 (127).
  • NicotineNicotine: According to secondary sources, nicotine may reduce serum vitamin B12 levels. The need for vitamin B12 supplementation has not been adequately studied (83; 84).
  • Nitrous oxideNitrous oxide: A case of symptomatic vitamin B12 deficiency after nitrous oxide administration in a patient with subclinical B12 deficiency was reported (76). A case of nitrous oxide-induced vitamin B12 deficiency myelopathy was reported (128). It was hypothesized that the cause was due to deficient methylation or how vitamin B12 regulates cytokines and growth factors.
  • Oral contraceptivesOral contraceptives: Available data regarding the effects of oral contraceptives on vitamin B12 serum levels are conflicting. Some research has found reduced serum levels in birth control pill users, but others have found no effect despite the use of birth control pills for up to six months (77; 78; 79; 129).
  • Osteoporosis agentsOsteoporosis agents: In human research, supplementation with vitamin B12 and folate decreased fracture incidence by 75% (130).
  • Para-aminosalicylic acidPara-aminosalicylic acid: In preliminary research, para-aminosalicylic acid has been shown to inhibit vitamin B12 absorption (80; 81).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): According to human research, prolonged reduction in the secretion of gastric acid and pepsin caused by long-term use of PPIs may reduce absorption of vitamin B12 (70; 71). In people receiving long-term PPI therapy, oral vitamin B12 supplementation at RDA doses may not help prevent deficiency (131). Treatment with cyanocobalamin nasal spray may help improve vitamin B12 status (104).
  • StimulantsStimulants: According to secondary sources, vitamin B12 may interact with stimulants. 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 (132).
  • ZidovudineZidovudine: Reduced serum vitamin B12 levels may occur when zidovudine (AZT, Combivir?, Retrovir?) therapy is started. However, available data suggest that vitamin B12 supplements are not helpful for people taking zidovudine (85).

    • Vitamin B12/Herb/Supplement Interactions:

  • Alzheimer's agentsAlzheimer's agents: A systematic review of observational human research concluded that serum vitamin B12 levels were lower in Alzheimer's disease patients (123). The effects of vitamin B12 supplementation on the prevention or progression of Alzheimer's disease remain unclear.
  • AntibioticsAntibiotics: According to anecdotal reports, long-term antibiotic use may deplete vitamin B12 levels.
  • AnticonvulsantsAnticonvulsants: 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 (66; 67).
  • Antigout agentsAntigout agents: According to case report data, correction of megaloblastic anemia with vitamin B12 may precipitate gout in susceptible individuals (63).
  • AntilipemicsAntilipemics: In vitro, colestipol (Colestid?) and cholestyramine (Questran?) resins have been shown to be highly bound to vitamin B12-intrinsic factor complex (68). Secondary sources suggest that bile acid resins may reduce vitamin B12 absorption.
  • AntineoplasticsAntineoplastics: In epidemiological research, elevated levels of vitamin B12 and folate were associated with increased prostate cancer risk (22). Human research suggested that elevated serum vitamin B12 levels associated with tumor markers may indicate poor survival in hepatocellular carcinoma patients (23). Another study found a correlation between vitamin B12 and folic acid supplementation and an increased incidence of lung cancers (24).
  • Antiulcer and gastric acid-reducing agentsAntiulcer and gastric acid-reducing agents: According to human research, prolonged reduction in the secretion of gastric acid and pepsin caused by long-term use of H2 blockers may reduce absorption of vitamin B12 (70; 71). According to human research, prolonged reduction in the secretion of gastric acid and pepsin caused by long-term use of PPIs may reduce absorption of vitamin B12 (70; 71). In people receiving long-term PPI therapy, oral vitamin B12 supplementation at RDA doses may not help prevent deficiency (131). Treatment with cyanocobalamin nasal spray may help improve vitamin B12 status (104).
  • Cardiovascular agentsCardiovascular agents: In clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (58). Hypertension following intravenous administration of hydroxocobalamin has been reported in clinical studies (52; 59).
  • ContraceptivesContraceptives: Available 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 have found no effect despite the use of birth control pills for up to six months (77; 78; 79).
  • Folic acidFolic acid: Folic acid supplementation may mask vitamin B12 deficiency and delay its diagnosis (133; 134). In vitamin B12 deficiency, folic acid can produce hematologic improvement in anemia, while allowing potentially irreversible neurological damage to progress (135). Vitamin B12 status should be determined before folic acid is given as a monotherapy. Addition of 1mg of cobalamin to folic acid supplements may lessen the masking of vitamin B12 deficiency by folic acid (136).
  • Gastrointestinal agentsGastrointestinal agents: Nausea and dysphagia have been reported in clinical research (59). According to secondary sources, diarrhea has also been reported. One study suggested that elevated serum vitamin B12 levels associated with tumor markers may indicate poor survival in hepatocellular carcinoma patients (23).
  • HematologicsHematologics: According to case report data, treatment of vitamin B12 deficiency may lead to polycythemia vera (61), which is characterized by an increase in blood volume and the number of red blood cells. According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (62).
  • HypotensivesHypotensives: Hypertension following intravenous administration of hydroxocobalamin has been reported in clinical human research (52; 59). In clinical research, therapy with ACE inhibitors was associated with a decline in serum vitamin B12 levels (64).
  • Neurologic agentsNeurologic agents: Supplementation of vitamin B12 has been shown to resolve a variety of neurological symptoms in infants caused by severe vitamin B12 deficiency (124). According to a review, elevated serum homocysteine and low folate and vitamin B12 levels may be associated with poor cognitive function, cognitive decline, and dementia (2). According to reviews, supplementation of B vitamins, including vitamin B12, may have a role in preventing dementia by way of lowering homocysteine levels (125; 28). In a meta-analysis, higher blood levels of homocysteine were found to be associated with increased depression in later life (126). 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 (127).
  • Omega-3 fatty acidsOmega-3 fatty acids: According to a review, B vitamins, including vitamin B12, and omega-3 fatty acids may have the potential for synergistic protective effects with respect to cardiovascular disease (137).
  • Osteoporosis agentsOsteoporosis agents: In human research, supplementation with vitamin B12 and folate decreased fracture incidence by 75% (130).
  • PotassiumPotassium: Potassium supplements may reduce absorption of vitamin B12 in some people. This effect has been reported with potassium chloride (81; 82). According to case report data, correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia in susceptible individuals (62).
  • SalicylatesSalicylates: In preliminary research, para-aminosalicylic acid has been shown to inhibit vitamin B12 absorption (80; 81).
  • StimulantsStimulants: According to secondary sources, vitamin B12 may interact with stimulants. 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 (132).
  • TobaccoTobacco: According to secondary sources, nicotine may reduce serum vitamin B12 levels. The need for vitamin B12 supplementation has not been adequately studied (83; 84).
  • Vitamin CVitamin C: In laboratory research, vitamin C has been shown to cause the degradation of vitamin B12 in multivitamin supplements (86). In human research, patients receiving megadoses of ascorbic acid had low serum vitamin B12 levels (138); however, other human research suggests that it is highly unlikely that ascorbic acid will deplete all stores of cobalamins and that this may only pose a threat in patients with errors in cobalamin metabolism (139). In vitro, ascorbic acid and vitamin B12 in food lacked an effect on each other (140).

    • Vitamin B12/Food Interactions:

  • Folic acidFolic acid: Folic acid supplementation may mask vitamin B12 deficiency and delay its diagnosis (133; 134). In vitamin B12 deficiency, folic acid can produce hematologic improvement in anemia, while allowing potentially irreversible neurological damage to progress (135). Vitamin B12 status should be determined before folic acid is given as a monotherapy. Addition of 1mg of cobalamin to folic acid supplements may lessen the masking of vitamin B12 deficiency by folic acid (136).
  • Omega-3 fatty acidsOmega-3 fatty acids: According to a review, B vitamins, including vitamin B12, and omega-3 fatty acids may have the potential for synergistic protective effects with respect to cardiovascular disease (137).
  • PotassiumPotassium: Potassium supplements may reduce absorption of vitamin B12 in some people. This effect has been reported with potassium chloride (81; 82). According to case report data, correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia in susceptible individuals (62).
  • Vitamin CVitamin C: In laboratory research, vitamin C has been shown to cause the degradation of vitamin B12 in multivitamin supplements (86). In human research, patients receiving megadoses of ascorbic acid had low serum vitamin B12 levels (138); however, other human research suggests that it is highly unlikely that ascorbic acid will deplete all stores of cobalamins and that this may only pose a threat in patients with errors in cobalamin metabolism (139). In vitro, ascorbic acid and vitamin B12 in food lacked an effect on each other (140).

    • Vitamin B12/Lab Interactions:

  • Blood pressureBlood pressure: Hypertension following intravenous administration of hydroxocobalamin has been reported in clinical human research (52; 59).
  • Complete blood count (CBC)Complete blood count (CBC): According to case report data, treatment of vitamin B12 deficiency may lead to polycythemia vera (61), which is characterized by an increase in blood volume and the number of red blood cells.
  • Serum homocysteineSerum homocysteine: In a systematic review, a combination of vitamin B12, vitamin B6, and folic acid were reported to lower fasting plasma total homocysteine by 20-50% (141; 142; 143; 144; 145; 146; 147). In human research, the addition of B vitamins led to a 25% decrease in homocysteine levels from baseline (p<0.001) in normal subjects and a 37% decrease in homocysteine levels from baseline in patients with hyperhomocysteinemia (?15mcM/L, p<0.001) (148).
  • Serum potassiumSerum potassium: According to case report data, correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia in susceptible individuals (62).
  • Uric acidUric acid: According to case report data, correction of megaloblastic anemia with vitamin B12 has been shown to precipitate gout in susceptible individuals (63).