Vitamin B12

Overview

Vitamin B₁₂ was isolated from liver extract in 1948 and reported to control pernicious anemia. Its structure was elucidated in 1955. Chemically, vitamin B₁₂ is a molecule with the formula of C₆₃H₉₀CoN₁₄O₁₄P. Cobalamin is the generic name of vitamin B₁₂ because it contains the heavy metal cobalt, which gives this water-soluble vitamin its red color. Vitamin B₁₂ is an essential growth factor and plays a role in the metabolism of cells, especially those of the gastrointestinal tract, bone marrow, and nervous tissue.

Several different cobalamin compounds exhibit vitamin B₁₂ activity. The most stable form is cyanocobalamin, which contains a cyanide group that is well below toxic levels. To become active in the body, cyanocobalamin must be converted to either methylcobalamin or adenosylcobalamin.

A protein in gastric secretions called intrinsic factor binds to vitamin B₁₂ and facilitates its absorption. Without intrinsic factor, only a small percentage of vitamin B₁₂ is absorbed. Once absorbed, relatively large amounts of vitamin B₁₂ can be stored in the liver.

Dosage Info

Dosage Range

Maintenance 1-25mcg daily.
Deficiency doses can be 250mcg daily, doses as high as 2,000mcg daily have been used in chronic renal insufficiency. (1)

Most Common Dosage

100mcg daily.

Dosage Forms

Tablets, capsules, liquids, liposomal sprays, effervescent tablets, sublingual lozenges, intranasal sprays, gels, and injectable (Rx only).

Adult RDI

4mcg

Adult ODA

10-100mcg

RDA

• Infants < 6 months: 0.4mcg (Adequate Intake, AI)
• Infants 7-12 months: 0.5mcg (AI)
• Children 1-3 years: 0.9mcg
• Children 4-8 years: 1.2mcg
• Children 9-13 years: 1.8mcg
• Adults >14 years: 2.4mcg
• Pregnancy: 2.6mcg
• Lactation: 2.8mcg

Interactions and Depletions

Depletions

• Oral contraceptives
• Antibiotics
• Antivirals Nucleoside Reverse Transcriptase Inhibitors
• Biguanides
• Bile acid sequestrants
• clofibrate
• colchicine
• H-2 receptor antagonists
• phenytoin
• Proton pump inhibitors
• Potassium chloride, sustained / controlled release medications

Active Forms

Cyanocobalamin and methylcobalamin

Absorption

There are two separate and distinct mechanisms for the absorption of vitamin B₁₂.

a) The physiologic mechanism involves food-bound vitamin B₁₂ being released by digestive enzyme activity. It then combines with intrinsic factor for absorption and is transported to the liver where it is stored.

b) The pharmacologic mechanism is a process of diffusion throughout the entire small intestine. However, it is estimated that only about 1 percent of any quantity of free vitamin B₁₂ is capable of being absorbed in this manner. (2)

Toxicities & Precautions

General

There are no known toxicities associated with vitamin B₁₂.

Functions in the Body

Biochemical Pathways

Primarily functions as a methyl donor, transferring methyl groups in the following:

a) Vitamin B₁₂ demethylates methyltetrahydrofolate to generate tetrahydrofolate, necessary in the synthesis of DNA. This means B₁₂ plays a role in the replication of the genetic code and is a growth factor in all cells of the body.

b) Methylcobalamin transfers a methyl group onto homocysteine, which facilitates the conversion of homocysteine to methionine.

Hydrogen Carrier

Functions as a hydrogen carrier in hydrogen transfer reactions.

Nervous System

Required for the synthesis of myelin, the insulation around nerves. It plays a major role in the functioning and maintenance of the nervous system.

Red Blood Cells

Necessary for the maturation of red blood cells.

Metabolism

Involved in various aspects of protein, fat, and carbohydrate metabolism.

Clinical Applications

Male Infertility

Treatment increases sperm count and sperm activity. (3)

Sulfite Sensitivity

1.5mg oral cyanocobalamin prevents reaction in most patients. (4)

Atherosclerosis.

Homocysteine concentrations, when elevated, are a risk factor for atherosclerotic disease. Vitamin B12 is necessary for the metabolism of homocysteine. (5) Lipid lowering medications known as “fibrates” have been shown to increase homocysteine levels. A study was conducted in which fenofibrate was given either with placebo or with vitamins including vitamin B6, vitamin B12 and folic acid. The homocysteine measurements with the vitamins were significantly lower than the measurements taken without the vitamins. The investigators suggested that the “addition of these vitamins to fenofibrate may therefore be warranted for routine use.” (6)

Depression

Without anemia is a common result of B12 deficiency in the elderly. (7)

Pernicious Anemia

Can be effectively treated using oral vitamin B₁₂. (8)

Bone Loss

Older women with low levels of vitamin B₁₂ had an increased risk of bone loss in the hip. (9)

Aids

Low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption (10) ; B12 also inhibits HIV replication in vitro. (11)

Bronchial Asthma

IM injections significantly reduce wheezing and labored breathing. (12)

Cognitive Enhancement

A literature review of recent research has noted subclinical differences in nutritional status of certain B vitamins among older adults may influence certain aspects of cognitive performance. Supplementation with folate, vitamin B12 and vitamin B6 has been effective in enhancing cognitive performance in older adults. (13)

Of note, a study evaluating 370 nondemented people 75 years old or older for three years, noted that subjects with low levels of vitamin B12 or folate had twice the risk of developing Alzheimer’s disease. A clearer association was noted when both vitamins were taken into consideration. (14)

Crohn’s Disease

B12 is low and is needed to repair damaged intestinal cells. (15)

Diabetes

Vitamin B12 may help prevent peripheral neuropathy in diabetics. (16)

Symptoms and Causes of Deficiency

Vitamin B₁₂ deficiencies manifest primarily as anemia and neurological changes. Vitamin B₁₂ deficiency inhibits DNA synthesis, which affects the growth and repair of all cells. The symptoms of vitamin B₁₂ deficiency include: fatigue, peripheral neuropathy, tongue and mouth irregularities, macrocytic anemia (abnormally enlarged red blood cells), depression, confusion and memory loss (especially in the elderly), poor blood clotting and easy bruising, dermatitis and skin sensitivity, loss of appetite, nausea and vomiting.

Pernicious anemia is normally the first symptom of vitamin B₁₂ deficiency. A B₁₂ deficiency causes a reduction in the rate of mitosis, which allows abnormally large cells to form, hence the term megaloblastic anemia. The elderly are most susceptible to vitamin B₁₂ deficiency due to atrophy of gastric parietal cells causing inadequate production of intrinsic factor. Deficiencies in the elderly manifest with neuropsychiatric symptoms such as moodiness, confusion, abnormal gait, memory loss, agitation, delusions, dizziness, dementia, and hallucinations. (17) Meatless diets are deficient in vitamin B₁₂. Strict vegetarians are urged to use a vitamin B₁₂ supplement. (18) Drugs mentioned above in the Drug-Nutrient Interaction section may inhibit B₁₂ absorption and, when taken chronically, can lead to vitamin B₁₂ depletion.

Dietary Sources

Vitamin B₁₂ is produced by microbial synthesis in the digestive tract of animals. Hence, animal protein products are the source of this nutrient. It does not occur in fruits, vegetables, grain, or legumes. Organ meats are the best source of vitamin B₁₂, followed by clams, oysters, beef, eggs, milk, chicken, and cheese.

References

1. View Abstract: Sperschneider H, Stein G, Lauterbach K, Gunther K. Diagnosis of vitamin B12 deficiency in chronic kidney insufficiency. Z Urol Nephrol. May1984;77(5):301-9.
2. Shils ME, Young VR. Modern Nutrition in Health and Disease. Philadelphia: Lea and Febiger; 1988:393.
3. View Abstract: Nagai N, et al. Treatment in Male Infertile Clinic of Kaizuka Municipal Hospital. Hinyokika Kiyo. May1988;34(5):839-46.
4. View Abstract: Anibarro B, et al. Asthma with Sulfite Intolerance in Children: A Blocking Study with Cyanocobalamin. J Allergy Clin Immunol. Jul1992;90(1):103-09.
5. View Abstract: Siri PW, et al. Vitamins B6, B12, and Folate: Association with Plasma Total Homocysteine and Risk of Coronary Atherosclerosis. J Am Coll Nutr. Oct1998;17(5):435-41.
6. View Abstract: Dierkes J, Westphal S, Kunstmann S, Banditt P, Lossner A, Luley C. Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate. Atherosclerosis. Sep2001;158(1):161-4.
7. View Abstract: Joosten E, et al. Metabolic Evidence that Deficiencies of Vitamin B12 (cobalamin), Folate, and Vitamin B6 Occur Commonly in Elderly People. Am J Clin Nutr. Oct1993;58(4):468-76.
8. View Abstract: Lederle FA. Oral Cobalamin for Pernicious Anemia: Back From the Verge of Extinction. J Am Geriatr Soc. Sep1998;46(9):1125-27.
9. View Abstract: Stone KL, et al. Low Serum Vitamin B-12 Levels Are Associated with Increased Hip Bone Loss in Older Women: A Prospective Study. J Clin Endocrinol Metab. March 2004;89(3):1217-1221.
10. View Abstract: Herzlich BC, et al. Decreased Intrinsic Factor Secretion in AIDS: Relation to Parietal Cell Acid Secretory Capacity and Vitamin B12 Malabsorption. Am J Gastroenterol. Dec1992;87(12):1781-88.
11. View Abstract: Weinberg JB, et al. Cobalamin Inhibition of HIV-1 Integrase and Integration of HIV-1 DNA into Cellular DNA. Biochem Biophys Res Commun. May1998;246(2):393-97.
12. Simon SW. Vitamin B12 Therapy in Allergy and Chronic Dermatoses. J Allergy. 1951;22:183-85.
13. View Abstract: Calvaresi E, Bryan J. B vitamins, cognition, and aging: a review. J Gerontol B Psychol Sci Soc Sci. Nov2001;56(6):P327-39.
14. View Abstract: Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B(12) and folate in relation to the development of Alzheimer’s disease. Neurology. May2001;56(9):1188-94.
15. View Abstract: Imes S, et al. Iron, Folate, Vitamin B12, Zinc, and Copper Status in Outpatients with Crohn’s Disease: Effect of Diet Counseling. J Am Diet Assoc. Jul1987;87(7):928-30.
16. Khan MA, et al. Vitamin-B12 Deficiency and Diabetic Neuropathy. Lancet. Oct1969;2(7624):768-70.
17. View Abstract: Engelborghs S, Vloeberghs E, Maertens K, et al. Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia. Int J Geriatr Psychiatry. Apr2004;19(4):365-70.
18. View Abstract: Waldmann A, Koschizke JW, Leitzmann C, Hahn A. Homocysteine and cobalamin status in German vegans. Public Health Nutr. May2004;7(3):467-72.