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:

E - Diagnosis of Vitamin B12 Deficiency - Active B12 (Holotranscobalamin, HoloTC)

EA - Active B12 (Holotranscobalamin, HoloTC) - Early Research
EB - Active B12 (Holotranscobalamin, HoloTC) - Axis-Shield/Abbott Laboratories Publications
EC - Active B12 (Holotranscobalamin, HoloTC) - Commercially Sponsored Reports
ED - Active B12 (Holotranscobalamin, HoloTC) - Independent Reports
EE - Active B12 (Holotranscobalamin, HoloTC) - Meeting Posters and Abstracts
EF - Active B12 (Holotranscobalamin, HoloTC) - Lab Announcements
EG - Active B12 (Holotranscobalamin, HoloTC) - Patents, Approvals, Legal
EH - Active B12 (Holotranscobalamin, HoloTC) - Clinical Trials

You can go to a section by selecting the link.

Active B12 (Holotranscobalamin, HoloTC) - Early Research

Number	Article Link
EA01	Transcobalamins I and II as natural transport proteins of vitamin B12, C A Hall, J Clin Invest. 1975 November; 56(5): 1125–1131.
EA02	The distribution of endogenous cobalamin among cobalamin-binding proteins in the blood in normal and abnormal states, R Carmel, American Journal of Clinical Nutrition, Vol 41, 713-719
EA03	The 1986 Herman award lecture. Nutrition science as a continually unfolding story: the folate and vitamin B-12 paradigm, Victor Herbert, MD, JD, Am. J. Clinical Nutrition, Vol. 46, Issue 3, 387-402, September 1, 1987
EA04	Depletion of serum holotranscobalamin II. An early sign of negative vitamin B12 balance, Herzlich B and Herbert V, Lab Invest. 1988 Mar;58(3):332-7. abstract only
EA05	B12 Binding proteins, Graham Neale, Gut, 1990, 31, 59-63
EA06	Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS, Herbert V et al, Am J Hematol. 1990 Jun;34(2):132-9 free abstract only - requires subscription for full article
EA07	Correlations between holo-transcobalamin II, holo-haptocorrin, and total B12 in serum samples from healthy subjects and patients, S N Wickramasinghe and S Fida, J Clin Pathol. 1993 June; 46(6): 537–539.
EA08	Staging vitamin B-12 (cobalamin) status in vegetarians, V Herbert, American Journal of Clinical Nutrition, Vol 59, 1213S-1222S

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Active B12 (Holotranscobalamin, HoloTC) - Axis-Shield/Abbott Laboratories Publications

Number	Article Link
EB01	Axsym Active-B12 (Holotranscobalamin) Package Insert, Abbott Laboratories
EB02	Axis-Shield HoloTC RIA Package Insert
EB03	Active-B12 (holotranscobalamin), Axis Shield
EB04	AxSym Active-B12 (holotranscobalamin), Axis-Shield & Abbott Laboratories
EB05	Why HoloTC?, Abbott Diagnostics
EB06	Holo Transcobalamin; A Predictor of Vitamin B12 Status, Terry Pry, Abbott Laboratories Australia-New Zealand
EB07	Active-B12 (Holotranscobalamin) Publication Abstracts 2007
EB08	Active B12 Introduction - What Is Active-B12, Axis-Shield
EB09	Active B12 Introduction - What Is The Function of Active-B12, Axis-Shield
EB10	Active B12 Introduction - Why Use Active-B12, Axis-Shield
EB11	Active B12 Introduction - Measuring Active-B12, Axis-Shield
EB12	Active B12 Introduction - Clinical Utility Of Active-B12, Axis-Shield
EB13	Active B12 Introduction - Case Studies, Axis-Shield
EB14	Active B12 Introduction - FAQs, Axis-Shield
EB15	B12 Deficiency - General, Axis-Shield
EB16	B12 Deficiency - Diagnosis - Haematological Signs And Symptoms, Axis-Shield
EB17	B12 Deficiency - Diagnosis - Laboratory Tests, Axis-Shield
EB18	B12 Deficiency - At Risk Groups, Axis-Shield
EB19	B12 Deficiency - Guidelines, Axis-Shield
EB20	B12 Deficiency - Treatment, Axis-Shield
EB21	Active-B12 (holotranscobalamin):The Next Level of B12 Testing
EB22	Axis-Shield plc 2007 Interim Results Presentation
EB23	Axis-Shield Interim Report 2007
EB24	New studies support utility of Axis-Shield Active-B12 test, Axis-Shield, Dundee, Scotland, 8 June 2007

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Active B12 (Holotranscobalamin, HoloTC) - Commercially Sponsored Reports

Number	Article Link
EC01	Holotranscobalamin — a sensitive marker of cobalamin malabsorption, Lindgren A. et al, European Journal of Clinical Investigation, Volume 29, Number 4, April 1999 , pp. 321-329(9) free abstract only - requires subscription for full article
EC02	Direct Assay for Cobalamin Bound to Transcobalamin (Holo-Transcobalamin) in Serum, Marius Ulleland et al, Clinical Chemistry. 2002;48:526-532
EC03	Holo-Transcobalamin Is an Early Marker of Changes in Cobalamin Homeostasis. A Randomized Placebo-controlled Study, Nexo et al, Clinical Chemistry. 2002;48:1768-1771
EC04	Holotranscobalamin as a Predictor of Vitamin B12 Status, Anne-Mette Hvas and Ebba Nexo, Clinical Chemistry and Laboratory Medicine. Volume 41, Issue 11, Pages 1489–1492, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2003.228, November 2003 free abstract only - requires subscription for full article
EC05	Holotranscobalamin as an Indicator of Dietary Vitamin B12 Deficiency, Lloyd-Wright et al, Clinical Chemistry. 2003;49:2076-2078
EC06	Low vitamin B-12 status in confirmed Alzheimer's disease as revealed by serum holotranscobalamin, Refsum et al, J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):959-61
EC07	RIA for Serum Holo-Transcobalamin: Method Evaluation in the Clinical Laboratory and Reference Interval, Saila Loikas et al, Clinical Chemistry. 2003;49:455-462
EC08	Holo-Transcobalamin Concentration and Transcobalamin Saturation Reflect Recent Vitamin B12 Absorption Better than Does Serum Vitamin B12, Mustafa Vakur Bor et al, Clinical Chemistry. 2004;50:1043-1049
EC09	Nonradioactive Vitamin B12 Absorption Test Evaluated in Controls and in Patients with Inherited Malabsorption of Vitamin B12, Mustafa Vakur Bor et al, Clinical Chemistry. 2005;51:2151-2155
EC10	Circadian variation of holo-transcobalamin (holo-TC) and related markers,Anne-Mette Hvas et al, Clinical Chemical Laboratory Medicine. Volume 43, Issue 7, Pages 760–764, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.130, 01 07 2005 free abstract only - requires subscription for full article
EC11	Holotranscobalamin – a first choice assay for diagnosing early vitamin B12 deficiency?, A.-M. HVAS & E. NEXO, Journal of Internal Medicine 2005; 257: 289–298
EC12	Plasma holotranscobalamin compared with plasma cobalamins for assessment of vitamin B12 absorption; optimisation of a non-radioactive vitamin B12 absorption test (CobaSorb), Anne-Mette Hvas et al, Clinica Chimica Acta Volume 376, Issues 1-2, 1 February 2007, Pages 150-154 free abstract only - requires subscription for full article
EC13	Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency, Joshua W. Miller et al, Clinical Chemistry. 2006;52:278-285
EC14	Holotranscobalamin and total transcobalamin in human plasma: determination, determinants, and reference values in healthy adults, Refsum H et al, Clinical Chemistry. 2006;52:129-137
EC15	Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged, Loikas, Saila et al, Clinical Chemistry & Laboratory Medicine. 45(2):197-201, February 2007 free abstract only - requires subscription for full article
EC16	Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid, Rima Obeid and Wolfgang Herrmann, Clinical Chemical Laboratory Medicine. Volume 45, Issue 12, Pages 1746–1750, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.361, December 2007 free abstract only - requires subscription for full article
EC17	Holotranscobalamin remains unchanged during pregnancy. Longitudinal changes of cobalamins and their binding proteins during pregnancy and postpartum, Anne L. Morkbak et al, Haematologica, Vol 92, Issue 12, 1711-1712 doi:10.3324/haematol.11636
EC18	Detection of Vitamin B12 Deficiency in Older People by Measuring Vitamin B12 or the Active Fraction of Vitamin B12, Holotranscobalamin, Robert Clarke et al, Clinical Chemistry. 2007;53:963-970
EC19	Holo-transcobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status, von Castel-Roberts et al, American Journal of Clinical Nutrition, Vol. 85, No. 4, 1057-1061, April 2007
EC20	Active B12 The Next Level of B12 Testing, Ralph Green, Specialty Labs Web Conference, December 13, 2007
EC21	Vitamin B12 Deficiency in the aged: Laboratory Diagnosis, Prevalence and Clinical Profile, Loikas S, Doctoral dissertation. 2007. Annales Universitatis Turkuensis.
EC22	Active B12: A Rapid, Automated Assay for Holotranscobalamin on the Abbott AxSYM Analyzer, Jeff Brady et al, Clinical Chemistry. 2008;54:567-573
EC23	Low vitamin B-12 status in confirmed Alzheimer’s disease as revealed by serum holotranscobalamin, H Refsum, A D Smith, J. Neurol. Neurosurg. Psychiatry 2003;74;959-961
EC24

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Active B12 (Holotranscobalamin, HoloTC) - Independent Reports

Number	Article Link
ED01	Measuring and Interpreting Holo-Transcobalamin (Holo-Transcobalamin II) , Ralph Carmel, Clinical Chemistry. 2002;48:407-409
ED02	Cobalamin Status (Holo-Transcobalamin, Methylmalonic Acid) and Folate as Determinants of Homocysteine Concentration, Rima Obeid et al, Clinical Chemistry 48, No. 11, 2002
ED03	Cobalamin-binding proteins in normal and cobalamin-deficient older subjects, Dieneke Z.B et al, Ann Clin Biochem 2003;40:65-69 free abstract only - requires subscription for full article
ED04	Functional Vitamin B12 Deficiency and Determination of Holotranscobalamin in Populations at Risk, Wolfgang Herrmann et al, Clinical Chemistry and Laboratory Medicine, Vol. 41, Issue 11, 1478-1488
ED05	Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms, Nilsson, Karin et al, Clinical Chemistry & Laboratory Medicine. 42(6):637-643, 2004. free abstract only - requires subscription for full article
ED06	The Usefulness of Holotranscobalamin in Predicting Vitamin B12 Status in Different Clinical Settings, Wolfgang Herrmann, Current Drug Metabolism, 2005, 6, 47-53
ED07	Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II, Xinke Chen et al, American Journal of Clinical Nutrition, Vol. 81, No. 1, 110-114, January 2005
ED08	The Importance of Holotranscobalamin Measurement, Velibor Čabarkapa et al, JMB 26: 227–230, 2007
ED09	Cobalamin (Vitamin B12) and Holotranscobalamin Changes in Plasma and Liver Tissue in Alcoholics with Liver Disease, Herman Baker et al, Journal of the American College of Nutrition, Vol. 17, No. 3, 235-238 (1998)
ED10	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
ED11	The transcobalamin receptor, redux, Donald W. Jacobsen, and Alla V. Glushchenko, Blood 2009 113: 3-4.
ED12	The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin, Edward V. Quadros, Yasumi Nakayama, and Jeffrey M. Sequeira, Blood 2009 113: 186-192.

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Active B12 (Holotranscobalamin, HoloTC) - Meeting Posters and Abstracts

Number	Article Link
EE01	Active B12 (holotranscobalamin) in different serum B12 ranges, D. M. Bobilewicz et al, AACC, July15-19 2007
EE02	HoloTC Measurement and Clinical Utility, Nexo et al, Euromedlab, 3-7th June 2007
EE03	Role of cobalamin in human metabolism and modern tools diagnosing its status, Herrmann W, et al, 6th World Congress on Hyperhomocysteinemia, June 5-9th 2007
EE04	Can holotranscobalamin replace total serum cobalamin in laboratory diagnosis of cobalamin deficiency? Obeid R, et al, 6th World Congress on Hyperhomocysteinemia, June 5-9th 2007
EE05	Clinical utility of holoTC compared to three currently used assays to determine vitamin B12 status, Scott J.M.1, et al, 6th World Congress on Hyperhomocysteinemia, June 5-9th 2007
EE06	Holotranscobalamin remains unchanged during pregnancy, Morkbak A.L.1, et al, 6th World Congress on Hyperhomocysteinemia, June 5-9th 2007
EE07	Holotranscobalamin and homocysteine as markers of cobalamin status in infants, Augoustides-Savvapoulou P., et al, 6th World Congress on Hyperhomocysteinemia, June 5-9th 2007
EE08	Vitamin B12 status in patients with renal failure, F. Bamonti, et al, AACC, July15-19 2007
EE09	Vitamin B12 and holotranscobalamin: Current status and clinical significance, Ebba Nexø, homocycteine day 2006
EE10	Holotranscobalamin - a predictor of vitamin B12 status, Anne-Mette Hvas and Ebba Nexo, Department of Clinical Biochemistry, AKH, Arhuus University Hospital, Denmark
EE11	Holotranscobalamin - A Novel Marker of Vitamin B12 Deficiency Clinical Utility, Australasian Association of Clinical Biochemistry Annual Meeting, Hobart, NZ October 2006
EE12	Direct Assay for the Quantitative of Holo-Transcobalamin in Serum and Plasma, AACC Annual Meeting Chigago, USA, July 2006
EE13	Holo-Transcobalamin: more or less than total vitamin B12?, A multicenter study, Lindemans et al, Euromedlab, 3-7th June 2007
EE14	The Role of Holotranscobalamin in the Evaluation of Vitamin B12 Status, Van Der Sluijs Veer et al, Euromedlab, 3-7th June 2007
EE15	Comparison of 3 automated assays for total vitamin B12 with measurement of Holotranscobalamin as a marker for vitamin B12 deficiency, Vanpoucke et al, Euromedlab, 3-7th June 2007
EE16	HOLOTRANSCOBALAMIN (HOLO-TC) FOR DIAGNOSING EARLY VITAMIN B12 DEFICIENCY, G.B. Lobreglio et al, Haematologica 2008: 93(s1):403 Abs.1012
EE17	HoloTranscobalamin versus total B12: An Evidence-based Perspective, Dr Zhong Lu, Melbourne Pathology, Australia

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Active B12 (Holotranscobalamin, HoloTC) - Lab Announcements

Number	Article Link
EF01	Holo TC (Holotranscobalamin) und Methylmalonsäure: Neue Marker für das metabolisch verfügbare, aktive Vitamin B12, Medizinisches Versorgungszentrum Dortmund - Dr. Eberhard & Partner, Laborinformation Nr. 81 / September 2006
EF02	Bepaling actief vitamine B12 (holoTC) Prof.dr. I.Vermes, klinisch chemicus, LABORATORIUMMEDEDELINGEN, Jaargang 5 – nummer 2 – juni 2008, Medisch Spectrum Twente
EF03	Nieuwsbrief nr. 68 d.d. 26 juni 2008 van het Erasmus Med. Centrum
EF04	Holotranscobalamin or "Active B12", SYNOPSIS 2039 20 article 4,
EF05	Investigation of low vitamin B12, Sullivan Nicolaides Pathology
EF06	Holo TC (Holotranscobalamin) und Methylmalonsäure:Neue Marker für das metabolisch verfügbare, aktive Vitamin B12, LabmedLetter Laborinformation Nr. 81 / September 2006
EF07	Neuer diagnostischer Pfad zur Diagnose eines Vitamin B12-Mangels, Institut für Medizinische Diagnostik Oderland
EF08	holo transcobalamine, Streekziekenhuis Koningin Beatrix
EF09	Holotranscobalamin, UZL Analysen-Auskunftssystem
EF10	Holotranscobalamin als sensitiver Marker zur Diagnose eines Vitamin B12-Mangels, Katharina Spanaus, UniversitäreZse ntrumf ür Labormediziunn d Pathologie, News, Ausgabe Nr. 18, Mai 2008

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Active B12 (Holotranscobalamin, HoloTC) - Patents, Approvals, Legal

Number	Article Link
EG01	United States Patent 7,279,283, Cobalamin assay
EG02	EUREKA PROJECT E!2263- HOLOTC
EG03	Demonstration of the clinical utility of holotc as an early marker of vitamin b12 deficiency, CORDIS RTD-PROJECTS
EG04	Serum Holo-transcobalamin as a Marker of Vitamin B12 (i.e., Cobalamin) Status, Medical Policy, Blue Cross of Idaho
EG05	Laboratory Section - Serum Holo-Transcobalamin as a Marker of Vitamin B12 (i.e., Cobalamin) Status, Medical Policy, Blue Regence
EG06	Serum Holo-Transcobalamin, medical coverage guideline, Blue Cross and Blue Shield of Florida
EG07	Measurement of serum holotranscobalamin as a marker of vitamin B12 status not covered, Highmark Blue Shield Policy Review & News, April 2007

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Active B12 (Holotranscobalamin, HoloTC) - Clinical Trials

Number	Article Link
EH01	Evaluation of Holotranscobalamin as an Indicator of Vitamin B12 Absorption, University of Florida, NCT00235573

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