REFERENCES AND LINKS

THE VITAMIN B12 AND FOLATE PATHOLOGY INVESTIGATION

THE INVESTIGATION OF ERRORS IN PATHOLOGY TESTS

FOR VITAMIN B12 AND FOLATE DEFICIENCY

BY MEANS OF MEDICAL EXPERIMENTS

INTRODUCTION	THE SERUM VITAMIN B12 INVESTIGATION	THE METHYLMALONIC ACID INVESTIGATION
THE HOMOCYSTEINE INVESTIGATION	THE HOLOTRANSCOBALAMIN INVESTIGATION	THE FOLATE INVESTIGATION
REFERENCES AND LINKS	B12 AND FOLATE INFORMATION	RESPONSES TO INVESTIGATION

VITAMIN B12 REFERENCES

FOLATE REFERENCES

VITAMIN B12 LINKS

FOLATE LINKS

B12 Deficiency References

Part A - Errors in Pathology

Part B - Causes

Part C - Consequences

Part D - Diagnosis - General

Part E - Diagnosis - HoloTC

Part F - Treatment

Part G - Miscellaneous

Index

This page contains the following sections:

B - Causes of Vitamin B12 Deficiency

BA - Causes of Vitamin B12 Deficiency - Inadequate Intake
BB - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Achlorhydria
BC - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Pernicious Anaemia
BD - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Hypothyroid
BE - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Gastrointestinal Surgery
BF - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Antacids
BG - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Metformin
BH - Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Other
BJ - Causes of Vitamin B12 Deficiency - Defective Transport
BK - Causes of Vitamin B12 Deficiency - Metabolic Enzyme Deficiency
BL - Causes of Vitamin B12 Deficiency - Increased Requirement - Pregnancy
BM - Causes of Vitamin B12 Deficiency - Increased Requirement - Hyperthyroid
BN - Causes of Vitamin B12 Deficiency - Increased Excretion - Liver Disease
BP - Causes of Vitamin B12 Deficiency - Destruction by Toxins - Nitrous Oxide
BQ - Causes of Vitamin B12 Deficiency - Destruction by Toxins - Mercury
BR - Causes of Vitamin B12 Deficiency - Destruction by Toxins - Other

You can go to a section by selecting the link.

Causes of Vitamin B12 Deficiency - Inadequate Intake

Number	Article Link
BA01	Vitamin B12 and Vegan Diets, Stephen Walsh, Vegan Society, UK
BA02	Vitamin B12: Are You Getting It?, Jack Norris, Vegan Outreach
BA03	Vitamin B12 Information Sheet, Vegetarian Society
BA04	Vitamin B12, Vitamin and mineral requirements in human nutrition, WHO
BA05	Dietary Guidelines for Australian Adults, NHMRC 2003
BA06	Dietary Supplement Fact Sheet: Vitamin B12, Office of Dietary Supplements • NIH Clinical Center • National Institutes of Health
BA07	Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes, NHMRC
BA08	Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring Study, Katherine L Tucker et al, American Journal of Clinical Nutrition, Vol. 71, No. 2, 514-522, February 2000
BA09	Vegan Diets Are Lethal, Victor Herbert, Letter to the Editor, New York Times, submitted May 2, 1999.
BA10	Vegetarian eating, Better Health Channel, Victoria
BA11	Vegetarian Eating, AIS Sports Nutrition
BA12	B-Vitamin Status and Concentrations of Homocysteine in Austrian Omnivores, Vegetarians and Vegans, D. Majchrzak et al, Ann Nutr Metab 2006;50:485–491 free abstract only - requires subscription for full article
BA13	Vegetarianism and vitamin B-12 (cobalamin) deficiency, Aok C Antony, American Journal of Clinical Nutrition, Vol. 78, No. 1, 3-6, July 2003
BA14	Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians, Wolfgang Herrmann et al, American Journal of Clinical Nutrition, Vol. 78, No. 1, 131-136, July 2003
BA15	Total Homocysteine, Vitamin B12, and Total Antioxidant Status in Vegetarians, Herrmann et al, Clinical Chemistry. 2001;47:1094-1101
BA16	Vitamin B12 Importance, Dr. Gabriel Cousens, Living and Raw Foods
BA17	Recommended dietary intakes (RDI) of vitamin B-12 in humans, Victor Herbert, American Journal of Clinical Nutrition, Vol 45, 671-678
BA18	In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations, Jacob Selhub et al, PNAS \| December 11, 2007 \| vol. 104 \| no. 50 \| 19995-20000
BA19	Health effects of vegetarian and vegan diets, Timothy J. Key et al, Proceedings of the Nutrition Society (2006), 65, 35–41
BA20	The vegetarian lifestyle and DNA methylation, Jurgen Geisel et al, Clin Chem Lab Med 2005;43(10):1164–1169
BA21	Are we ready for mandatory fortification with vitamin B-12?, Helga Refsum and A David Smith, American Journal of Clinical Nutrition, Vol. 88, No. 2, 253-254, August 2008
BA22	B12: An essential part of a healthy plant-based diet, Stephen Walsh, Food for all our futures, 35th World Vegetarian Congress, Heriot Watt University, Edinburgh, Scotland, July 8-14, 2002
BA23	B12 and the Vegan Diet - All You Need To Know About Vitamin B12 in Vegetarian and Vegan Diets, Justine Butler, Vegetarian & Vegan Foundation
BA24	Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial, Renate M Winkels et al, American Journal of Clinical Nutrition, Vol. 88, No. 2, 348-355, August 2008 free abstract only - requires subscription for full article
BA25	Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets, 1: J Am Diet Assoc. 2003 Jun;103(6):748-65.
BA26	vitamin B12 - what every vego needs to know, Vegetarian Action
BA27	Vitamin B12 Deficiency—the Meat-eaters’ Last Stand, McDougall Newsletter, Vol. 6, No. 11
BA28	Vitamin B12, A Stewart TRUSWELL, Nutrition & Dietetics 2007; 64 (Suppl. 4): S120–S125

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Achlorhydria

Number	Article Link
BB01	Cobalamin, the stomach, and aging, R Carmel, American Journal of Clinical Nutrition, Vol 66, 750-759
BB02	Atrophic gastritis as a cause of hyperhomocysteinaemia, L. Santarelli et al, Alimentary Pharmacology & Therapeutics, Volume 19 Issue 1 Page 107-111, January 2004
BB03	Vitamin B12 deficiency as a cause of hyperhomocysteinaemia, K. Kaptan & C. Beyan, Alimentary Pharmacology & Therapeutics, Volume 19 Issue 6 Page 703-703, March 2004
BB04	Vitamin B12 deficiency in Israel, S. Malnick & S. Goland, Alimentary Pharmacology & Therapeutics, Volume 19 Issue 6 Page 703-704, March 2004

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Pernicious Anaemia

Number	Article Link
BC01	Pernicious Anemia, Ban-Hock Toh et al, N Engl J Med NEJM. 1997;337:1441-1448. free abstract only - requires subscription for full article
BC02	Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race, R Carmel, Clin Exp Immunol. 1992 July; 89(1): 74–77.

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Hypothyroid

Number	Article Link
BD01
BD02

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Gastrointestinal Surgery

Number	Article Link
BE01	Elevated Methylmalonic Acid and Total Homocysteine Levels Show High Prevalence of Vitamin B12 Deficiency after Gastric Surgery, Anne E. Sumner et al, Annals of Internal Medicine, 1 March 1996, Volume 124 Issue 5, Pages 469-476
BE02

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Antacids

Number	Article Link
BF01	Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy, A. BELLOU et al, Journal of Internal Medicine, Volume 240 Issue 3 Page 161-164, September 1996
BF02	Effect of Long-Term Gastric Acid Suppressive Therapy on Serum Vitamin B12 Levels in Patients with Zollinger-Ellison Syndrome, Basel Termanini, American Journal of Medicine, Volume 104, Issue 5, Pages 422-430 (May 1998) free abstract only - requires subscription for full article
BF03	Is the long-term use of proton pump inhibitors safe?, Wail Malaty et al, THE JOURNAL OF FAMILY PRACTICE, September 2004 (Vol. 53, No. 9)
BF04	Long-term use of proton pump inhibitors and vitamin B12 status in elderly individuals, W. P. J. den Elzen et al, Alimentary Pharmacology & Therapeutics, Volume 27 Issue 6, Pages 491 - 497 free abstract only - requires subscription for full article
BF05	Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors, L. LAINE et al, Aliment Pharmacol Ther 2000; 14: 651-668.
BF06	Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor, Ruscin JM et al, Ann Pharmacother. 2002 May;36(5):812-6.free abstract only - requires subscription for full article

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Metformin

Number	Article Link
BG01	Drug Interactions of Medications Commonly Used in Diabetes, Curtis Triplitt, Diabetes Spectrum 19:202-211, 2006
BG02	Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin, WA Bauman et al, Diabetes Care, Vol 23, Issue 9 1227-1231
BG03	Metformin-related vitamin B12 deficiency, Kin Wah Liu et al, Age and Ageing 2006 35(2):200-201
BG04	Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin, Rose Zhao-Wei Ting et al, Arch Intern Med. 2006;166:1975-1979.
BG05	Vitamin B12 Status of Patients Treated With Metformin: A Cross-Sectional Cohort Study, Leif Sparre Hermann; Bo Nilsson; Staffan Wettre, Br J Diabetes Vasc Dis. 2004; 4 (6): 401-406

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Causes of Vitamin B12 Deficiency - Gastrointestinal Malabsorption - Other

Number	Article Link
BH01	Review article: is there a link between micronutrient malnutrition and Helicobacter pylori infection?, J. Salgueiro et al, Alimentary Pharmacology & Therapeutics, Volume 20 Issue 10 Page 1029-1034, November 2004
BH02	Genetic Variants Associated with Vitamin B12, Press Release, Harvard School of Public Health
BH03	Mild Transcobalamin I (Haptocorrin) Deficiency and Low Serum Cobalamin Concentrations, Ralph Carmel, Clinical Chemistry 49:8, 1367–1374 (2003)

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Causes of Vitamin B12 Deficiency - Defective Transport

Number	Article Link
BJ01	Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood, R Carmel, B Tatsis and L Baril , Blood, Volume 49, Issue 6, pp. 987-1000, 06/01/1977
BJ02	Transcobalamin 776CG polymorphism negatively affects vitamin B-12 metabolism, Kristina M von Castel-Dunwoody et al, American Journal of Clinical Nutrition, Vol. 81, No. 6, 1436-1441, June 2005

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Causes of Vitamin B12 Deficiency - Metabolic Enzyme Deficiency

Number	Article Link
BK01	Causes of and diagnostic approach to methylmalonic acidurias, J Inherit Metab Dis 2008 Jun; 31(3):350-60. free abstract only - requires subscription for full article
BK02	Disorders of Intracellular Cobalamin Metabolism, David Adams and Charles P Venditti, GeneReviews, February 25 2008
BK03	Gene Identification for the cblD Defect of Vitamin B12 Metabolism, David Coelho et al, N Engl J Med. 2008 Apr 3;358(14):1454-64 free abstract only - requires subscription for full article
BK04	Genetic determinants of the homocysteine level, GERE SUNDER-PLASSMANN and MANUELA FODINGER, Kidney International, Vol. 63, Supplement 84 (2003), pp. S141–S144
BK05	Genetics Home Reference Handbook, U.S. National Library of Medicine
BK06	Organic Acid Disorders, (MMA) Methylmalonic Acidemia, Center for Congenital and Inherited Disorders, Department of Public Health
BK07	Methylmalonic Acidemia, Charles P Venditti, GeneReviews
BK08	Methylmalonic Aciduria (Cbl A, Cbl B) - Sequencing MMAA and MMAB Genes, Emory Genetics Laboratory
BK09	Methylmalonic Aciduria (MMA) - Methylmalonyl CoA Mutase (MUT) Sequencing, Emory Genetics Laboratory
BK10	MUT, MMAA and MMAB Gene Analysis in Methylmalonic Acidemia, Information Sheet on Methylmalonic acidemia, GeneDx, Inc.
BK11	Screening Newborns for Inborn Errors of Metabolism by Tandem Mass Spectrometry, Bridget Wilcken et al, N Engl J Med 2003;348:2304-12.
BK12	The cblD Defect Causes Either Isolated or Combined Deficiency of Methylcobalamin and Adenosylcobalamin Synthesis, Terttu Suormala et al, J. Biol. Chem., Vol. 279, Issue 41, 42742-42749, October 8, 2004
BK13	Combined methylmalonic aciduria and homocystinuria (cblC): Phenotype–genotype correlations and ethnic-specific observations, Chantal F. Morel,Molecular Genetics and Metabolism Volume 88, Issue 4, August 2006, Pages 315-321 free abstract only - requires subscription for full article
BK14	Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type, Jordan P Lerner-Ellis et al, Nature Genetics 38, 93 - 100 (2006) free abstract only - requires subscription for full article
BK15	Late-onset cobalamin-C disorder: A challenging diagnosis, Tawfeg I. Ben-Omran et al, Am J Med Genet Part A 143A:979-984. free abstract only - requires subscription for full article
BK16	Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance, Anne Chun-Hui Tsai et al, Am J Med Genet Part A 143A:2430-2434 free abstract only - requires subscription for full article
BK17	SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness, Rosalba Carrozzo et al, Brain. 2007 Mar;130(Pt 3):862-74. Epub 2007 Feb 14.
BK18	The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum, C Thauvin-Robinet et al, Journal of Neurology, Neurosurgery, and Psychiatry 2008;79:725-728 free abstract only - requires subscription for full article
BK19	VITAMIN B12 METABOLIC DEFECT WITH METHYLMALONICACIDEMIA AND HOMOCYSTINURIA, Northwest Regional Newborn Screening Program, Oregon
BK20	Disorders of Propionate and Methylmalonate Metabolismis, Wayne A. Fenton, Roy A. Gravel, David S. Rosenblatt, OMMBID Part 9 Chapter 94
BK21	Inherited Disorders of Folate and Cobalamin Transport and Metabolism, David S. Rosenblatt / Wayne A. Fenton, OMMBID Part 17 Chapter 155
BK22	Neuropsychiatric Disturbances in Presumed Late-Onset Cobalamin C Disease, Emmanuel Roze et al, Arch Neurol. 2003;60:1457-1462.
BK23	Genetics of homocysteine metabolism and associated disorders, Brustolin S, Giugliani R, Félix TM, Braz J Med Biol Res. 2010 Jan;43(1):1-7. Epub 2009 Dec 4.

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Causes of Vitamin B12 Deficiency - Increased Requirement - Pregnancy

Number	Article Link
BL01
BL02

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Causes of Vitamin B12 Deficiency - Increased Requirement - Hyperthyroid

Number	Article Link
BM01
BM02

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Causes of Vitamin B12 Deficiency - Increased Excretion - Liver Disease

Number	Article Link
BN01
BN02

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Causes of Vitamin B12 Deficiency - Destruction by Toxins - Nitrous Oxide

Number	Article Link
BP01	Nitrous Oxide Anesthesia–Associated Myelopathy, Rose-Marie Marié, Arch Neurol. 2000;57:380-382.
BP02	MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia – two cases, S. Ilniczky et al, European Journal of Neurology, Volume 9 Issue 1 Page 101-104, January 2002
BP03	Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: Case report and literature review, Mike A. Singer et al, Muscle & Nerve Volume 37 Issue 1, Pages 125 - 129
BP04	Severe combined degeneration of the spinal cord after nitrous oxide anaesthesia in a vegetarian, M Rösener and J Dichgans, J Neurol Neurosurg Psychiatry. 1996 March; 60(3): 354.
BP05	Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide, W. Krajewski et al, British Journal of Anaesthesia 2007 99(6):812-818

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Causes of Vitamin B12 Deficiency - Destruction by Toxins - Mercury

Number	Article Link
BQ01	Vitamin B12 and mercury, Christina Bolander-Gouaille, A report of DUMEX-ALPHARMA, International Pharmaceuticals Division
BQ02	Vitamin B12 - metals disturb transport!, Monica Kauppi, Heavy Metal Bulletin 2(3):8-10 December 1995

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Causes of Vitamin B12 Deficiency - Destruction by Toxins - Other

Number	Article Link
BR01	Vitamin B12, Am J Clin Nutr Herbert 34 (5): 971.
BR02

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