Detection of Vitamin B12 Deficiency in Older People by Measuring Vitamin B12 or the Active Fraction of Vitamin B12, Holotranscobalamin

Clarke, Robert; Sherliker, Paul; Hin, Harold; Nexø, Ebba; Hvas, Anne Mette; Schneede, Joern; Birks, Jacqueline; Ueland, Per Magne; Emmens, Kathleen; Scott, John M.; Molloy, Anne M.; Evans, John Grimley

doi:10.1373/clinchem.2006.080382

Cited by 113 publications

(122 citation statements)

References 18 publications

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“…The 40 pmol/L cut-off value we selected was also reported by other authors (18)(19)(20). We also verified the predictive ability of HoloTC at this threshold for selected tB 12 cut-off points.…”

Section: Discussionsupporting

confidence: 81%

“…However, a recent study by Clarke et al (18) showed that using cut-off thresholds of equal sensitivity and specificity (45 and 200 pmol/L for HoloTC and tB 12 , respectively), HoloTC had slightly better diagnostic accuracy compared with vitamin B 12 in detecting actual vitamin B 12 deficiency in subjects with normal renal function, although neither test can be recommended to screen asymptomatic individuals. This is in contrast somewhat to an earlier study by our group demonstrating the importance of HoloTC assay in monitoring cobalamin status in asymptomatic subjects at risk of developing sub-clinical vitamin B 12 deficiency due to some physio-pathological condition (e.g., elderly, obese subjects) and/or life-style risk factor (e.g., smokers, vegans) (25).…”

Section: Discussionmentioning

confidence: 99%

“…Current assays measure serum tB 12 concentration, a small percentage (10%-30%) of which, HoloTC, is metabolically active (18). Recently, studies focused on HoloTC to evaluate the potential reliability and diagnostic usefulness of an active B 12 assay for predicting vitamin B 12 status in different clinical settings (1, 2, 8, 10).…”

Section: Discussionmentioning

confidence: 99%

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Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory

Bamonti

Moscato

Novembrino

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: A reliable early marker is required for diagnosis of cobalamin deficiency. We calculated an appropriate holotranscobalamin (HoloTC) cut-off point for identifying cobalamin deficiency using an immunoenzymatic assay. Methods: Determination of the cut-off threshold and correlation between HoloTC and the other diagnostic parameters routinely used for vitamin B 12 deficiency wtotal vitamin B 12 (tB 12 ), folate, homocysteinex were measured in 250 routine blood specimens from 107 men (mean age 59.0"18.8 years) and 143 women (mean age 54.2"23.1 years). The inclusion criterion was serum tB 12 concentration F221 pmol/L. Results: Analytical performance results agreed with those reported by others. A weak correlation (Rs0.42) was found between HoloTC and tB 12 . A 40 pmol/L cut-off threshold was chosen for HoloTC and the associated sensitivity and

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory

Bamonti

Moscato

Novembrino

et al. 2009

Clinical Chemistry and Laboratory Medicine

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“…Both case studies and epidemiological studies have reported that excessive intakes of folic acid among older adults with vitamin B 12 deficiency are associated with a more rapid progression of neuropathy or cognitive impairment (20,21,(32)(33)(34) . About 10-25 % of older adults have biochemical evidence of low vitamin B 12 status, defined by a low serum concentration (<45 pmol/l) of holotranscobalamin, which is a more sensitive test of vitamin B 12 deficiency than conventional vitamin B 12 testing (27) . There have been reports that patients with pernicious anaemia who are treated with folic acid have an accelerated decline in neurological function (32)(33)(34) .…”

Section: Possible Hazards Of Folic Acidmentioning

confidence: 99%

B-vitamins and prevention of dementia

Clarke

2008

Proc. Nutr. Soc.

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Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B 12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case-control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B 12 , raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B 12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individualpatient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.Folate: Vitamin B 12 : Homocysteine: Dementia

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“…Thus algorithms for laboratory diagnosis of a B 12 -deficient status recommend the initial measurement of B 12 and HoloTC. Clarke et al state that HoloTC has better diagnostic accuracy than B 12 (77 % v. 73 %) and that the diagnostic utility is superior in the overall population as well as in patients with renal impairment (8) .…”

mentioning

confidence: 99%

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

Koenig

Stanga

Zerlauth

et al. 2012

Public Health Nutr.

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Objective: Data about vitamin B 12 (B 12 ) deficiency in the general population are scarce. The present study was performed to determine the prevalence of B 12 deficiency in the general population of the Principality of Liechtenstein, as well as to identify sub-populations potentially at high risk. Design: Retrospective study. Setting: Ambulatory setting, population of the Principality of Liechtenstein. Subjects: Seven thousand four hundred and twenty-four patients seeking medical attention whose serum samples were referred for routine work-up in an ambulatory setting were consecutively enrolled. Serum total B 12 was determined in all patients in this cohort. In addition, for a subgroup of 1328 patients, serum holotranscobalamin was also measured. Prevalence of B 12 deficiency was calculated. Further, multivariate logistical regression models were applied to identify covariates independently associated with B 12 deficiency and depletion. Results: Nearly 8 % of the general population was suffering from either B 12 depletion or deficiency. The ratio between B 12 depletion and deficiency was 2:1 for all age ranges. Pathological changes were detected predominantly in older people. Female gender was a significant predictor of B 12 depletion. In the cohort, nearly 40 % exhibited either depletion or deficiency of B 12 . Conclusions: B 12 depletion and deficiency are common in Liechtenstein, a Central European country. The measurement of biochemical markers represents a costefficient and valid assessment of the B 12 state. When a deficiency of B 12 is diagnosed at an early stage, many cases can be treated or prevented, with beneficial effects on individual outcomes and subsequent potential reductions in health-care costs.

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Detection of Vitamin B12 Deficiency in Older People by Measuring Vitamin B12 or the Active Fraction of Vitamin B12, Holotranscobalamin

Cited by 113 publications

References 18 publications

Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory

Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory

B-vitamins and prevention of dementia

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

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Detection of Vitamin B12 Deficiency in Older People by Measuring Vitamin B12 or the Active Fraction of Vitamin B12, Holotranscobalamin

Cited by 113 publications

References 18 publications

Determination of serum holotranscobalamin concentrations with the AxSYM active B12 assay: cut-off point evaluation in the clinical laboratory

Determination of serum holotranscobalamin concentrations with the AxSYM active B12 assay: cut-off point evaluation in the clinical laboratory

B-vitamins and prevention of dementia

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

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Product

Resources

About

Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory

Determination of serum holotranscobalamin concentrations with the AxSYM active B₁₂ assay: cut-off point evaluation in the clinical laboratory