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minerals

Vitamin B12 () Snapshot Monograph

Vitamin B12 name(s): (Cyanocobalamin) Vitamin B12 Most Frequent Reported Uses: Cyanocobalamin • regulation • Neurological health, including (Cobamamide) diabetic neuropathy, cognitive Hydroxycobalamin (European) function, vascular , stroke prevention • , including pernicious and megaloblastic • Sulfite sensitivity

Cyanocobalamin Introduction: Vitamin B12 was isolated from extract in 1948 and reported to control pernicious . Cobalamin is the generic name of vitamin B12 because it contains the heavy metal , which gives this water-soluble vitamin its red color. Vitamin B12 is an essential growth factor and plays a role in the of cells, especially those of the , , and nervous tissue.

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

© Copyright 2013, Integrative Health Resources, LLC | www.metaboliccode.com A in gastric secretions called 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. The body actually reabsorbs vitamin B12 in the intestines and returns much of it to the liver, allowing for very little to be excreted from the body. However, when there are problems in the intestines, such as the microflora being imbalanced resulting in gastrointestinal inflammation, then vitamin B12 deficiencies can occur. A poor , high in refined and , and many can also deplete vitamin B12 from the body.

Functions: • Methyl Donor: Primary functions of vitamin B12 is 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 . Eleveated levels of homocysteine are associated with an increased risk of serveral chronic diseases, including resistance/type 2 Diabetes, cardiovascular diseases, digestive conditions, bone health and neurological conditions including decreasing cognitive function. • Neurological Health: Required for the synthesis of , the insulation around nerves. It plays a major role in the functioning and maintenance of the . • Hydrogen Carrier: Functions as a hydrogen carrier in hydrogen transfer reactions. • Red Blood Cells: Necessary for the maturation of red blood cells. • Metabolism: Involved in various aspects of protein, fat, and metabolism.

Dosage:

Cyanocobalamin (oral)

DRI* 3.0mcg daily

ODA** 10 – 1,000 mcg daily

* The Dietary Reference Intakes (DRI) are the most recent set of dietary recommendations established by the and Nutrition Board of the Institute of Medicine, 1997-2001. They replace previous RDAs, and may be the basis for eventually updating the RDIs.

**The Optimum Daily Allowance (ODA) represents a reference level beyond the RDI, and is often many times higher than the RDI to prevent diseases such as aging or cancer. These numbers are based on clinical use.

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Methylcobalamin: 1,500 – 6,000 mcg/day in divided doses Aenosylcobalamin: 3,000 mcg/day

Symptoms of Deficiency: • Vitamin B12 deficiencies manifest primarily as anemia and neurological changes. inhibits DNA synthesis, which affects the growth and repair of all cells. The symptoms of vitamin B12 deficiency include: , , tongue and mouth irregularities, (abnormally enlarged red blood cells), , confusion and loss (especially in the elderly), poor blood clotting and easy bruising, 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. • Meatless diets are deficient in vitamin B12. Strict vegetarians are urged to use a vitamin B12 supplement. • Those with an increased need for vitamin B12 include: o Memory related issue o Substance Abusers o Chronic Illness o Recent Surgery o Burns o Malignancies of or Bowel o Vegetarians • The following drugs can cause a depletion of vitamin B12, which may increase an individual’s need for vitamin B12: o Oral contraceptives o Antibiotics o Antivirals including didanosine, lamivudine, stavudine, zalcitabine, and zidovudine o Biguanides, o acid sequestrants including cholestyramine and colestipol o Clofibrate and fenofibrate o o H-2 receptor antagonists including , , , and o Phenytoin o Proton pump inhibitors including and

© Copyright 2013, Integrative Health Resources, LLC | www.metaboliccode.com o Timed-release chloride medications

Side Effects and Warnings: • There are no known toxicities associated with vitamin B12. • There are some reports in the literature of increased circulating levels of vitamin B12 and folic acid leading to a weak, but positive association the an increased incidence of prostate cancer (Collin et al, 2010; Collin, 2013). The 2008 European Prospective Investigation into Cancer and Nutrition study reported that there were no significant associations observed from circulating concentrations of or vitamin B12 and the risk of prostate cancer (Johansson et al, 2008).

Food 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 . Organ meats are the best source of vitamin B12, followed by clams, oysters, , eggs, , , and cheese.

© Copyright 2013, Integrative Health Resources, LLC | www.metaboliccode.com Vitamin B12 Patient Snapshot

Uses: • Vitamin B12 is essential for functions in the metabolism of cells, especially those of the GI tract, bone marrow, and nervous tissue. • Vitamin B12, along with and folic acid, help decrease a compound in the body called homocysteine. Homocysteine is associated with an increased risk of many chronic diseases, including memory impairment, blood regulation, heart and blood vessel disease.

Dosage: DRI* 3.0mcg daily

ODA** 10 – 100mcg daily

* The Dietary Reference Intakes (DRI) are the most recent set of dietary recommendations established by the Food and Nutrition Board of the Institute of Medicine, 1997-2001. They replace previous RDAs, and may be the basis for eventually updating the RDIs.

**The Optimum Daily Allowance (ODA) represents a reference level beyond the RDI, and is often many times higher than the RDI to prevent diseases such as aging or cancer. These numbers are based on clinical use.

Special Concerns: • If you are taking prescription or non-prescription medications, have a pre-existing medical condition, or are pregnant and/or breastfeeding, talk with your healthcare provider before taking any . • If you are at risk for prostate cancer or prostate diseases, make sure to talk with your doctor before taking vitamin and supplements. • Do not take if there is an allergy to any component of this dietary supplement. • Those with an increased need for vitamin B12 include: o Vegetarians o Substance Abusers o Chronic Illness o Recent Surgery o Burns o Cancer of Pancreas or Bowel • The following medications may deplete vitamin B12 from the body. When taking these medications, it is best to supplement your diet with vitamin B12: o Oral contraceptives o Antibiotics o Antivirals including didanosine, lamivudine, stavudine, zalcitabine, and zidovudine o Biguanides, metformin o Bile acid sequestrants including cholestyramine and colestipol o Clofibrate and fenofibrate o Colchicine o H-2 receptor antagonists including cimetidine, famotidine, nizatidine, and ranitidine o Phenytoin o Proton pump inhibitors including lansoprazole and omeprazole o Timed-release potassium chloride medications

DISCLAIMER: Statements made are for educational purposes and have not been evaluated by the US Food and Drug Administration. They are not intended to diagnose, treat, cure, or prevent any disease. If you have a medical condition or disease, please talk to your doctor prior to using the recommendations given.

© Copyright 2013, Integrative Health Resources, LLC | www.metaboliccode.com References: Andres E, Kurtz JE, Perrin AE, et al. Oral cobalamin therapy for the treatment of patients with food- cobalamin . Am J Med 2001;111:126-9.

Benito-Leon J, Porta-Etessam J. Shaky-leg syndrome and vitamin B12 deficiency. N Engl J Med 2000;342:981.

Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care. CMAJ. 2000;163:21-9.

Collin SM, Metcalfe C, Refsum H, et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport , and risk of prostate cancer: a case-control study, systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1632-42.

Erol I, Alehan F, G;uuml;m;uuml;s A. West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia. Dev Med Child Neurol 2007;49(10):774-6.

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.

Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.

Haggarty P, McCallum H, McBain H, Effect of and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet 2006 May 6;367(9521):1513-9.

Johansson M, Appleby PN, Allen NE, et al. Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition study. Epidemiol Biomarkers Prev. 2008;17(2):279-85.

Kumar N. Neurologic presentations of nutritional deficiencies. Neurol Clin. 2010;28(1):107-70. Review.

Lehman JS, Bruce AJ, Rogers RS. Atrophic from vitamin B12 deficiency: a case misdiagnosed as burning mouth disorder. J Periodontol 2006 Dec;77(12):2090-2.

McCaddon A. vitamin B12 in and ageing; clinical and genetic aspects. Biochimie. 2013;95(5):1066-76.

Seal EC, Metz J, Flicker L, et al. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc 2002;50:146-51.

Selhub J, Morris MS, Jacques PF, Rosenberg IH. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. 2009;89(2):702S-6S. Erratum in: Am J Clin Nutr. 2009;89(6):1951.

Stabler SP. deficiency. N Engl J Med. 2013;368(21):2041-2.

Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials.Acta Neurol Taiwan 2005 Jun;14(2):48-54.

Suzuki DM, Alagiakrishnan K, Masaki KH, et al. Patient acceptance of intranasal cobalamin gel for vitamin B12 replacement therapy. Hawaii Med J. 2006;65(11):311-4.

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Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565-75.

Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 2005 Jul 20;(3):CD004655.

Van Wijngaarden JP, Doets EL, Szczecinska A, et al. Vitamin B12, folate, homocysteine and bone health in adults and elderly people: a systematic review with meta-analysis. J Nutr Metab. 2013;2013:486186.

Yajnik CS, Lubree HG, Thuse NV, et al. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India. Asia Pac J Clin Nutr 2007;16(1):103-9.

DISCLAIMER: Statements made are for educational purposes and have not been evaluated by the US Food and Drug Administration. They are not intended to diagnose, treat, cure, or prevent any disease. If you have a medical condition or disease, please talk to your doctor prior to using the recommendations given.

© Copyright 2013, Integrative Health Resources, LLC | www.metaboliccode.com