Health Care Professional Information

Scientific Name
Cyanocobalamin
Common Name

Cyanocobalamin, cobalamin

Clinical Summary

Vitamin B-12 refers to the group of compounds that consists of cyanocobalamin, hydroxocobalamin, and related substances and is part of the vitamin B-complex family. It is essential for normal nerve function, DNA synthesis, hematopoiesis, fatty acid metabolism, and amino acid synthesis in the mitochondria. It also plays an important role in the metabolism of homocysteine and the synthesis of S-adenosylmethionine. Vitamin B-12 is naturally synthesized by bacteria and is abundant in diets that include meat and dairy products. Following oral intake, it is absorbed in the intestine after binding to intrinsic factor that is secreted in the stomach. Deficiency can occur in patients who have malabsorption syndromes and in people who follow a strict vegetarian diet. Lack of B-12 can lead to a wide variety of hematologic, neurologic, and psychiatric disorders and may increase the risk of cardiovascular diseases (11).
Low serum B-12 level has been associated with increased bone turnover and fracture risk (1).
Repletion of vitamin B-12 may improve response in patients resistant to antidepressants (19).

When used as homocysteine-lowering therapy, vitamin B-12, folate, and vitamin B-6 may have cardiovascular benefits after coronary interventions (13). However, increased risk of in-stent restenosis with such treatment has been reported in patients after coronary stenting (8). Vitamin B-12 supplementation as part of the homocysteine-lowering therapy does not improve cognitive function (2) (5) (9) (21).

Clinical studies show increased intake of vitamin B-12 together with folate and vitamin B-6 may lower the risk of breast cancer (7) (15) (16) and cervical cancer (4), but has no effect on the risk of lung cancer (3). Findings from another study indicate that a combination of folate and vitamins B6 and B12 did not have an effect on overall risk of invasive cancer or breast cancer (17). However, recent data suggest higher cancer incidence and mortality in patients with ischemic heart disease following supplementation with vitamin B12 and folic acid (18). Further studies are needed to confirm these findings in other populations.
Supplementation with vitamin B-12 and folic acid reduces the toxicity of Pemetrexed, a chemotherapeutic agent, in patients with non-small cell lung cancer (NSCLC) (20).

Food Sources
  • Meat
  • Poultry
  • Fish
  • Shellfish
  • Dairy
  • Fortified Cereals
Purported Uses
  • B-12 deficiency
  • Pernicious anemia
  • Cardiovascular disease
  • Breast cancer
  • Fatigue
  • Cognitive function
  • Stroke
  • Restless leg syndrome
  • Lung cancer
  • Sleep disorders
Mechanism of Action

Vitamin B-12 is involved in the transfer of methyl groups and methylation reactions essential for the synthesis of phospholipids and neurotransmitters in the CNS. B-12 is also required for the synthesis of nucleic acid, notably DNA, and the metabolism of fatty acids and amino acids in the mitochondria (2). In humans, two enzymatic reactions are dependent on B-12. Vitamin B-12 functions as a coenzyme in a methyl transfer reaction that converts homocysteine to methionine. B-12 also participates in the reaction that converts L-methylmalonyl-coenzyme A (CoA) to succinyl-CoA (11). In the first enzyme reaction methylcobalamin is used to recycle the folate cofactor 5-methyltetrahydrofolate to tetrahydrofolate thereby, allowing the folate cofactor to participate in a cycle involving the biosynthesis of purines, pyrimidines. During this reaction, homocysteine is converted to methionine yielding the methyl groups required for methylation that is essential for biosynthesis (14).

Pharmacokinetics

Absorption
The acidic environment of the stomach facilitates the release of B-12 that is bound to food. The parietal cells of the stomach release intrinsic factor which binds to the vitamin in the duodenum. The vitamin B-12/Intrinsic factor complex assists the absorption of B-12 in the terminal ileum. Evidence supports the existence of a second avenue of absorption that does not rely on intrinsic factor or an intact ileum. As much as 1% of a large oral dose of B-12 is absorbed by this secondary mechanism (11). Drugs that reduce gastric intrinsic factor secretion can also reduce the absorption of B-12. Patients with pernicious anemia are not able to produce intrinsic factor and cannot absorb vitamin B-12 orally.
Distribution
Once absorbed, B-12 is bound to transcobalamin II and is distributed throughout the body with the largest amount taken up in the liver (11).
Metabolism/Excretion
Approximately 0.1% of body stores of B-12 are lost per day with equal amounts excreted through the digestive and urinary tracts (14).

Contraindications

Vitamin B-12 may increase the risk of in-stent restenosis in patients after coronary stenting (8).

Adverse Reactions
  • Reported:
    A case of rosacea fulminans has been reported in a 17-year-old girl after consumption of high doses of vitamin B-6 and vitamin B-12 for 2 weeks (6).
Herb-Drug Interactions
  • Medication that interferes with or suppresses gastric acid and intrinsic factor production can lead to a decrease in vitamin B-12 absorption (11).
  • Folic acid intake in amounts greater than the Tolerable Upper Intake Level may mask vitamin B-12 deficiency symptoms (12).
Literature Summary and Critique

Eussen SJ, de Groot LC, Joosten LW, et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr 2006;84(2):361-70.
In this-study, 195 participants with mild B-12 deficiency aged >=70 years were assigned to receive 1000mcg vitamin B-12, 1000mcg B-12 plus 400mcg folic acid, or placebo for 24 weeks. Cognitive function was assessed before and after treatment using a neuropsychological test battery including domains of attention, construction, sensomotor speed and memory. Memory function improved in the placebo group more so than in the group who only received B-12 (P = 0.0036). Neither B-12 supplementation alone, or in combination with folic acid, showed any improvement in cognitive function in test subjects after 24 weeks.

Zhang SM, Willett WC, Selhub J, et al. Plasma folate, vitamin B-6, vitamin B-12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 2003;95(5):373-80.
In this prospective nested case-control study within the Nurse's Health Study, 32,826 women had blood samples obtained in 1989 and 1990 and were followed through 1996 for the development of breast cancer. 712 breast cancer patients and 712 matched controls were identified. Higher levels of plasma folate were associated with lower breast cancer risk especially in women with moderate alcohol consumption. (>= 15g/day) and in post menopausal women. Pre-menopausal women with the highest plasma B-12 levels also have lower breast cancer risk. The authors conclude that their findings suggest a chemopreventive role in breast cancer for folate and B-6 may contribute to a reduction in risk of breast cancer.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
References
  1. Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, et al. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 2005;20(6):921-9.
  2. 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;165(10):1167-72.
  3. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men. Am J Epidemiol 2001;153(7):688-94.
  4. Hernandez BY, McDuffie K, Wilkens LR, et al. Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control 2003;14(9):859-70.
  5. Hvas AM, Juul S, Lauritzen L, et al. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord 2004;81(3):269-73.
  6. Jansen T, Romiti R, Kreuter A, et al. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15(5):484-5.
  7. Lajous M, Lazcano-Ponce E, Hernandez-Avila M, et al. Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomarkers Prev 2006;15(3):443-8.
  8. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350(26):2673-81.
  9. McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354(26):2764-72.
  10. Nakagawa K, Kudoh S, Matsui K, et al. A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours. Br J Cancer 2006;95(6):677-82.
  11. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician 2003;67(5):979-86.
  12. Rampersaud GC, Kauwell GP, Bailey LB. Folate: a key to optimizing health and reducing disease risk in the elderly. J Am Coll Nutr 2003;22(1):1-8.
  13. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 2002;288(8):973-9.
  14. Scott JM. Bioavailability of vitamin B12. Eur J Clin Nutr 1997;51 Suppl 1:S49-53.
  15. Shrubsole MJ, Jin F, Dai Q, et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 2001;61(19):7136-41.
  16. Zhang SM, Willett WC, Selhub J, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 2003;95(5):373-80.
  17. Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. 2008 Nov 5;300(17):2012-21.
  18. Ebbing M, Bonaa KH, Nygard O, et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA 2009;302(19):2119-2126.
  19. Kate N, Grover S, Agarwal M. Does B12 deficiency lead to lack of treatment response to conventional antidepressants? Psychiatry (Edgmont). 2010 Nov;7(11):42-4.
  20. Ohe Y, Ichinose Y, Nakagawa K, et al. Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer. Clin Cancer Res. 2008 Jul 1;14(13):4206-12.
  21. Kang JH, Cook N, Manson J, et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr. 2008 Dec;88(6):1602-10.

Consumer Information

How It Works

Bottom Line: Vitamin B-12, in combination with folate and vitamin B-6, may reduce breast cancer risk.

Vitamin B-12 is involved in synthesis of phospholipids, neurotransmitters, DNA, and the metabolism of fatty acids and amino acids in the cells. It is found in meat, fish, dairy products and fortified cereal. Drugs that reduce stomach acid secretion or production of intrinsic factor can reduce the absorption of B-12. High levels of folic acid intake may mask a B-12 deficiency.
Patients should discuss supplement use with their physicians.

Purported Uses
  • Pernicious Anemia
    The injectable form of B-12 is used as prescription drug to treat pernicious anemia.
  • Hyperhomocysteinemia/Cardiovascular disease
    Vitamin B-12, when combined with folate and B-6, can reduce homocysteine levels which may offer benefit for cardiovascular disorders.
  • Breast Cancer
    Some studies show a reduction in breast cancer risk with Vitamin B12 when used in combination with folate and B-6.
  • Cognitive function
    Neither B-12 supplementation alone, or in combination with folic acid, showed any improvement in cognitive function in a clinical study.
  • Fatigue
    Some studies report improvement with intramuscular injections of B-12.
  • Restless legs syndrome
    A few studies suggest possible benefit.
  • Stroke
    This use is not backed by data.
  • Sleep Disorders
    There is no scientific evidence to support this use.
  • Lung Cancer
    Findings from one study suggest that B-12 levels have no effect on the risk of lung cancer.
Research Evidence

Improving Cognitive function
A randomized placebo-controlled clinical trial found neither B-12 supplementation alone or in combination with folate showed any improvement in cognitive function.

Breast Cancer Prevention
In a prospective case-control study within the Nurse's Health Study, higher levels of plasma folate were found to associate with lower breast cancer risk especially in women with moderate alcohol consumption and in post menopausal women. Pre-menopausal women with the highest plasma B-12 levels also have lower breast cancer risk. The findings suggest a chemopreventive role in breast cancer for folate and B-6 and that food rich in folate and B-6 may contribute to a reduction in risk of breast cancer.

Side Effects
  • A case of rosacea fulminans (a skin condition) following consumption of high doses of B-6 and B-12 for 2 weeks has been reported.
  • Vitamin B-12 may increase the risk of in-stent restenosis (narrowing of blood vessel) in patients after coronary stenting.
Special Point

Medication that reduces stomach acid and intrinsic factor production may decrease the absorption of vitamin B-12.

E-mail your questions and comments to aboutherbs@mskcc.org.