Vitamin B12

What does it do? Vitamin B12 is needed for normal nerve cell activity, DNA replication, and production of the mood-affecting substance SAMe (S-adenosyl-L-methionine). Vitamin B12 acts with folic acid and vitamin B6 to control homocysteine levels. An excess of homocysteine is associated with an increased risk of heart disease, stroke, and potentially other diseases such as osteoporosis and Alzheimer’s disease.

Vitamin B12 deficiency causes fatigue. Years ago, a small, double-blind trial reported that even some people who are not deficient in this vitamin had increased energy after vitamin B12 injections, compared with the effect of placebo injections.¹ In recent years, however, the relationship between B12 injections and the energy level of people who are not vitamin B12-deficient has been rarely studied. In a preliminary trial, 2,500–5,000 mcg of vitamin B12, given by injection every two to three days, led to improvement in 50–80% of a group of people with chronic fatigue syndrome (CFS), with most improvement appearing after several weeks of vitamin B12 shots.² The ability of vitamin B12 injections to help people with CFS remains unproven, however. People with CFS interested in considering a trial of vitamin B12 injections should consult a doctor. Oral or sublingual (administered under the tongue) B12 supplements are unlikely to obtain the same results as injectable B12, because the body’s ability to absorb large amounts is relatively poor.

Vitamin B12 has been used in connection with the following conditions (refer to the individual health concern for complete information):

Rating	Health Concerns
	Anemia (if deficient) Depression (in people with vitamin B12 deficiency) High homocysteine (combination with folic acid and vitamin B6) Pernicious anemia (Vitamin B12 deficiency)
	Anemia (for thalassemia if deficient) Age-related cognitive decline (in people with vitamin B12 deficiency) Bell’s palsy Canker sores (for deficiency only) Chronic fatigue syndrome Cystic fibrosis (in people with vitamin B12 deficiency) Infertility (male) Low back pain (in combination with vitamin B1 and vitamin B6) Sickle cell anemia (for sickle cell patients with B12 deficiency) Cyanide poisoning
	Alzheimer’s disease Asthma Atherosclerosis Bipolar disorder Bursitis Crohn’s disease Dermatitis herpetiformis (in people with vitamin B12 deficiency) Diabetes Down's syndrome Heart attack Hepatitis HIV support Hives Immune function Insomnia Lung cancer (reduces risk) Osteoporosis (to lower homocysteine) Pain Phenylketonuria (in people with vitamin B12 deficiency) Preeclampsia Pre- and post-surgery health Retinopathy (associated with childhood diabetes) Schizophrenia Seborrheic dermatitis (injection) Shingles (herpes zoster)/postherpetic neuralgia (injection) Stroke Tinnitus (injection) Vitiligo
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

Who is likely to be deficient? Vegans (vegetarians who also avoid dairy and eggs) frequently become deficient, though the process often takes many years. People with malabsorption conditions, including those with tapeworm infestation and those with bacterial overgrowth in the intestines, often suffer from vitamin B12 deficiency. Malabsorption of vitamin B12 can also result from pancreatic disease, the effects of gastrointestinal surgery, or various prescription drugs.⁵

Pernicious anemia is a special form of vitamin B12 malabsorption due to impaired ability of certain cells in the stomach to make intrinsic factor—a substance needed for normal absorption of vitamin B12. By definition, all people with pernicious anemia are vitamin B12-deficient. They require either vitamin B12 injections or oral supplementation with very high levels (1000 mcg per day) of vitamin B12.

Older people with urinary incontinence⁶ and hearing loss⁷ have been reported to be at increased risk of B12 deficiency.

Infection with Helicobacter pylori, a common cause of gastritis and ulcers, has been shown to cause or contribute to adult vitamin B12 deficiency. H. pylori has this effect by damaging cells in the stomach that make intrinsic factor—a substance needed for normal absorption of vitamin B12. In one trial, H. pylori was detected in 56% of people with anemia due to vitamin B12 deficiency. Successful eradication of H. pylori led to improved blood levels of B12 in 40% of those infected.⁸ Other studies have also suggested a link between H. pylori infection and vitamin B12 deficiency.⁹ ¹⁰ Elimination of H. pylori infection does not always improve vitamin B12 status. People with H. pylori infections should have vitamin B12 status monitored.

In a preliminary report, 47% of people with tinnitus and related disorders were found to have vitamin B12 deficiencies that may be helped by supplementation.¹¹

HIV-infected patients often have low blood levels of vitamin B12.¹²

A disproportionate amount of people with psychiatric disorders are deficient in B12.¹³ Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.¹⁴

A preliminary study found that postmenopausal women who were in the lowest one-fifth of vitamin B12 consumption had an increased risk of developing breast cancer.¹⁵

Although blood levels of vitamin B12 may be higher in alcoholics, actual body stores of vitamin B12 in the tissues (e.g., the liver) of alcoholics is frequently deficient.¹⁶ ¹⁷

Low blood levels of vitamin B12 are sometimes seen in pregnant women, however, this does not always indicate a vitamin B12 deficiency.¹⁸ The help of a healthcare professional is needed to determine when a true vitamin B12 deficiency exists in pregnant women with low blood levels of the vitamin.

Hydroxocobalamin (a form of vitamin B12) has been recognized for more than 40 years as an effective antidote to cyanide poisoning. It is currently being used in France for that purpose. Because of its safety, hydroxocobalamin is considered by some researchers to be an ideal treatment for cyanide poisoning.((REF: Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 2001;37:635–41.))

Are there any side effects or interactions? Oral vitamin B12 supplements are not generally associated with any side effects.

Although quite rare, serious allergic reactions to injections of vitamin B12 (sometimes even life-threatening) have been reported.²⁸ ²⁹ Whether these reactions are to the vitamin itself, or to preservatives or other substances in the injectable vitamin B12 solution, remains somewhat unclear. Most, but not all, injectable vitamin B12 contains preservatives.

If a person is deficient in vitamin B12 and takes 1,000 mcg or more of folic acid per day, the folic acid supplementation can improve the anemia caused by vitamin B12 deficiency. The effect of folic acid on vitamin B12 deficiency-induced anemia is not a folic acid toxicity. Rather, the folic acid supplementation is acting to correct one of the problems caused by B12 deficiency. The other problems caused by a lack of vitamin B12 (mostly neurological) do not improve with folic acid supplements, and can become irreversible if vitamin B12 is not provided to someone who is vitamin B12 deficient.

Some doctors are unaware that vitamin B12 deficiencies often occur without anemia—even in people who do not take folic acid supplements. This lack of knowledge can delay diagnosis and treatment of people with vitamin B12 deficiencies. This can lead to permanent injury. When such a delayed diagnosis occurs in someone who inadvertently erased the anemia of vitamin B12 deficiency by taking folic acid supplements, the folic acid supplementation is often blamed for the missed diagnosis. This problem is rare and should not occur in people whose doctors understand that a lack of anemia does not rule out a vitamin B12 deficiency. Anyone supplementing 1,000 mcg or more per day of folic acid should be initially evaluated by a doctor before the folic acid can obscure a proper diagnosis of a possible B12 deficiency.

Are there any drug interactions? Certain medications may interact with vitamin B12. Refer to the drug interactions safety check for a list of those medications.

References:

1. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277–83.

2. Lapp CW, Cheney PR. The rationale for using high-dose cobalamin (vitamin B12). CFIDS Chronicle Physicians’ Forum, 1993;Fall:19–20.

3. Rauma AL, Torronsen R, Hanninen O, Mykkanen H. Vitamin B12 status of long term adherents of a strict uncooked vegan diet (“living food diet”) is compromised. J Nutr 1995;125:2511–5.

4. Takenaka S, Sugiyama S, Ebara S, et al. Feeding dried purple laver (nori) to vitamin B12-deficient rats significantly improves vitamin B12 status. Br J Nutr 2001;85:699–703.

5. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency. A guide for the primary care physician. Arch Intern Med 1999;159:1289–98 [review].

6. Rana S, D’Amico F, Merenstein JH. Relationship of vitamin B12 deficiency with incontinence in older people. J Am Geriatr Soc 1998;46:931 [letter].

7. Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999;69:564–71.

8. Kaptan K, Beyan C, Ural AU, et al. Helicobacter pylori—is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med 2000;160:1349–53.

9. Perez-Perez GI. Role of Helicobacter pylori infection in the development of pernicious anemia. Clin Infect Dis 1997;25:1020–2 [review].

10. Fong TL, Dooley CP, Dehesa M, et al. Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Gastroenterology 1991;100:328–32.

11. Shemesh Z, Attias J, Ornan M, et al. Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss. Am J Otolaryngol 1993;14:94–9.

12. Remacha AF, Cadafalch J. Cobalamin deficiency in patients infected with the human immunodeficiency virus. Semin Hematol 1999;36:75–87.

13. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720–8.

14. Penninx BW, Guralnik JM, Ferrucci L, et al. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry 2000;157:715–21.

15. Wu K, Helzlsouer KJ, Comstock GW, et al. A prospective study on folate, B12, and pyridoxal 5’-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:209–17.

16. Kanazawa S, Herbert V. Total corrinoid, cobalamin (vitamin B12), and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism. Lab Invest 1985;53:108–10.

17. Cravo ML, Camilo ME. Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status. Nutrition 2000;16:296–302 [review].

18. Pardo J, Peled Y, Bar J, et al. Evaluation of low serum vitamin B(12) in the non-anaemic pregnant patient. Hum Reprod 2000;15:224–6.

19. Goldberg TH. Oral vitamin B12 supplementation for elderly patients with B12 deficiency. J Am Geriatr Soc 1995;43:SA73 [abstr #P258].

20. Lederle FA. Oral cobalamin for pernicious anemia—medicine’s best kept secret? JAMA 1991;265:94–5 [commentary].

21. Kondo H. Haematological effects of oral cobalamin preparations on patients with megaloblastic anemia. Acta Haematol 1998;99:200–5.

22. Waif SO, Jansen CJ, Crabtree RE, et al. Oral vitamin B12 without intrinsic factor in the treatment of pernicious anemia. Ann Intern Med 1963;58:810–7.

23. Crosby WH. Oral cyanocobalamin without intrinsic factor for pernicious anemia. Arch Intern Med 1980;140:1582.

24. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927–36.

25. Lindenbaum J, Rosenberg IH, Wilson PWF, et al. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr 1994;60:2–11.

26. Verhaeverbeke I, Mets T, Mulkens K, Vandewoulde M. Normalization of low vitamin B12 serum levels in older people by oral treatment. J Am Geriatr Soc 1997;45:124–5 [letter].

27. Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet 1999;354:740–1. [letter]

28. Snowden JA, Chan-Lam D, Thomas SE, Ng JP. Oral or parenteral therapy for vitamin B12 deficiency. Lancet 1999;353:411 [letter].

29. Hovding G. Anaphylactic reaction after injection of vitamin B12. Br Med J 1968;3:102.