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

2007 ◽  
Vol 45 (2) ◽  
Author(s):  
Saila Loikas ◽  
Pertti Koskinen ◽  
Kerttu Irjala ◽  
Minna Löppönen ◽  
Raimo Isoaho ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Total Vitamin ◽  
B12 Deficiency ◽  
Total Homocysteine

AbstractClin Chem Lab Med 2007;45:197–201.

scholarly journals Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency

2020 ◽  
Vol 9 (8) ◽  
pp. 2335 ◽  
Author(s):  
Sopak Supakul ◽  
Floris Chabrun ◽  
Steve Genebrier ◽  
Maximilien N’Guyen ◽  
Guillaume Valarche ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Plasma Homocysteine ◽  
Plasma Vitamin ◽  
Creatinine Ratio ◽  
Normal Range ◽  
B12 Deficiency ◽  
High Degree

Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62–0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0–98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

Chemotherapy-induced suppression of serum holotranscobalamin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20639-e20639
Author(s):  
G. Tisman ◽  
S. J. Kutik ◽  
Y. A. Khan
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Statistical Significance ◽  
Active Form ◽  
Vitamin B12 Deficiency ◽  
Total Serum ◽  
Significant Drop ◽  
Before And After ◽  
B12 Deficiency ◽  
Total Homocysteine

e20639 Purpose: Chemotherapy-induced damage to the stomach and small intestine may inhibit the absorption of vitamin B12. To assess the risk of chemotherapy causing acute vitamin B12 deficiency, we primarily measured the active form of vitamin B12, holotranscobalamin, but also total serum B12, methylmalonic acid, and total homocysteine. Experimental Design: We studied 21 patients that were actively on chemotherapy and recorded values for holotranscobalamin, total serum B12, methylmalonic acid, total homocysteine, and cystatin-c. Measurements were taken both before and after four doses of chemotherapy. T-tests were employed to determine statistical significance. Results: There was a statistically significant drop in holotranscobalamin after chemotherapy in eighteen out of twenty-one patients (p = 2.64x10–3). Three patients were vitamin B12 deficient as defined by total B12 < 300 pg/ml. Neither methylmalonic acid (p = 3.95x10–1), nor total homocysteine (p = 4.34x10–1), showed any significant changes. Conclusions: Chemotherapy caused an acute deficiency of the only metabolically active form of vitamin B12, holotranscobalamin, despite B12 supplementation. We suggest monitoring patients for changes in holotranscobalamin to ensure that prolonged deficiency does not occur. The clinical implications of acute lowering of holotranscobalamin remain unknown. No significant financial relationships to disclose.

scholarly journals Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency

2006 ◽  
Vol 52 (2) ◽  
pp. 278-285 ◽  
Author(s):  
Joshua W Miller ◽  
Marjorie G Garrod ◽  
Alan L Rockwood ◽  
Mark M Kushnir ◽  
Lindsay H Allen ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Reference Intervals ◽  
Plasma Vitamin ◽  
Roc Curve Analysis ◽  
Total Vitamin ◽  
B12 Deficiency ◽  
Elderly Cohort

Abstract Background: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status. Methods: We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age ≥60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 deficiency. Results: Low total vitamin B12 (&lt;148 pmol/L) and low holoTC (&lt;35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (&gt;350 nmol/L) and homocysteine (&gt;13 μmol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%–6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B12 (P ≤0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentrations of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B12 and/or holoTC within the reference intervals (P &lt;0.001). Conclusions: HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.

scholarly journals Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

2011 ◽  
Vol 57 (10) ◽  
pp. 1436-1443 ◽  
Author(s):  
Dorte L Lildballe ◽  
Sergey Fedosov ◽  
Paul Sherliker ◽  
Harold Hin ◽  
Robert Clarke ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Population Based ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
B12 Deficiency ◽  
Total Homocysteine ◽  
Nested Case Control

BACKGROUND Low vitamin B12 concentrations have been associated with higher risks of cognitive impairment, but whether these associations are causal is uncertain. The associations of cognitive impairment with combinations of vitamin B12, holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B12 transport proteins transcobalamin and haptocorrin, have not been previously studied. METHODS We performed a population-based cross-sectional study of 839 people 75 years old or older. We examined the association of cognitive function as measured by mini–mental state examination scores, with markers of vitamin B12 status. Spearman correlations as well as multivariate-adjusted odds ratios and 95% CIs for cognitive impairment were calculated for extreme thirds of serum concentrations of vitamin B12, holotranscobalamin, methylmalonic acid, total homocysteine, combination of these markers in a wellness score, heaptocorrin, and transcobalamin for all data and with B12 analogs in a nested case-control study. RESULTS Cognitive impairment was significantly associated with low vitamin B12 [odds ratio 2.3 (95% CI 1.2–4.5)]; low holotranscobalamin [4.1 (2.0–8.7)], high methylmalonic acid [3.5 (1.8–7.1)], high homocysteine [4.8 (2.3–10.0)] and low wellness score [5.1 (2.61–10.46)]. After correction for relevant covariates, cognitive impairment remained significantly associated with high homocysteine [4.85 (2.24–10.53)] and with a low wellness score [5.60 (2.61–12.01)] but not with transcobalamin, haptocorrin, or analogs on haptocorrin. CONCLUSIONS Cognitive impairment was associated with the combined effects of the 4 biomarkers of vitamin B12 deficiency when included in a wellness score but was not associated with binding proteins or analogs on haptocorrin.

The relationship between the cobalt nutrition of ewes and the vitamin B12 status of ewes and their lambs

1987 ◽  
Vol 38 (6) ◽  
pp. 1071 ◽  
Author(s):  
MF Quirk ◽  
BW Norton
Keyword(s):  
Vitamin B12 ◽  
Milk Production ◽  
Acid Concentration ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Lactation Performance ◽  
Lower Productivity ◽  
Cotton South ◽  
B12 Deficiency ◽  
The Relationship

An experiment was undertaken at Mt Cotton, south-east Queensland, to investigate the relationship between the cobalt nutrition of ewes and the occurrence of vitamin B12 deficiency in ewes and their lambs. Ewes received either no supplementary cobalt (C), 0.03 mg cobalt day-1 (LC), 0.06 mg cobalt day-1 (HC) or a cobalt bullet and grinder (CB). LC and HC ewes received their supplement as a weekly drench. Supplementation commenced prior to joining, and ewes subsequently grazed pangola grass pastures containing between 0.05 and 0.11 mg kg-1 cobalt.Cobalt supplementation of ewes increased their liveweight, reproductive and lactation performance. The milk production of ewes was influenced by the level of supplementation, with C, LC, HC and CB ewes producing 31.1, 41.5, 47.7 and 50.31. of milk respectively during the first 4 weeks of lactation. The lower productivity of C ewes was associated with concentrations of vitamin B12 in serum of less than 200 pg ml-1 and with the presence of detectable concentrations of methylmalonic acid (>80 8moles l-1) and formiminoglutamic acid (>30 8moles l-1) in their urine.The growth of lambs was influenced by the cobalt nutrition of their dams; the mean liveweight gain from birth to weaning (14 weeks of age) for lambs from C, LC, HC and CB ewes was 95, 158, 194 and 231 g day-1. Vitamin B12 deficiency was evident in lambs reared by C ewes from 4 weeks of age, but lambs from LC and HC ewes did not become deficient until 8 and 12 weeks of age respectively. Lambs from CB ewes remained free of signs of deficiency prior to weaning. Urinary formiminoglutamic acid concentration was a more reliable indicator of vitamin B12 status in young lambs than urinary methylmalonic acid concentration. The concentrations of vitamin B12 in the serum of lambs were low in all groups (< 150 pg ml-1) and were generally unaffected by the cobalt nutrition of their dams.A dietary cobalt intake of about 0.15 mg day-1 appeared to be necessary for optimal milk production from ewes. However, this level of dietary cobalt was inadequate for provision of sufficient quantities of maternal vitamin B12 to meet the requirements of lambs in the later stages of lactation.

scholarly journals Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient

2018 ◽  
Vol 55 (6) ◽  
pp. 685-692 ◽  
Author(s):  
Saskia LM van Loon ◽  
Anna M Wilbik ◽  
Uzay Kaymak ◽  
Edwin R van den Heuvel ◽  
Volkher Scharnhorst ◽  
...  
Keyword(s):  
Data Mining ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
The Elderly ◽  
Vitamin B ◽  
Data Mining Approach ◽  
Number Of Patients ◽  
B12 Deficiency ◽  
The Relationship

Background Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient’s vitamin B12, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90–300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.

scholarly journals Polymorphisms in the Transcobalamin Gene: Association with Plasma Homocysteine in Healthy Individuals and Vascular Disease Patients

2002 ◽  
Vol 48 (9) ◽  
pp. 1383-1389 ◽  
Author(s):  
Karin JA Lievers ◽  
Lydia A Afman ◽  
Leo AJ Kluijtmans ◽  
Godfried HJ Boers ◽  
Petra Verhoef ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vascular Disease ◽  
Vitamin B12 Deficiency ◽  
Potential Effect ◽  
Sequence Variants ◽  
Cvd Risk ◽  
Plasma Thcy ◽  
B12 Deficiency ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Abstract Background: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD). Intracellular vitamin B12 deficiency may lead to increased plasma total homocysteine (tHcy) concentrations and because transcobalamin (TC) is the plasma transporter that delivers vitamin B12 to cells, genetic variation in the TC gene may affect intracellular vitamin B12 availability and, consequently, tHcy concentrations. Methods: We examined five sequence variants, i.e., I23V, G94S, P259R, S348F, and R399Q, in the TC gene as possible determinants of tHcy and, concordantly, as possible risk factors for CVD in 190 vascular disease patients and 601 controls. We also studied potential effect-modification of vitamin B12 by genotype. Results: In individuals with high vitamin B12, 259PP individuals had lower tHcy concentrations than 259PR and 259RR individuals. Homozygous 23VV individuals had lower fasting tHcy concentrations than their 23IV and 23II peers. None of the genotypes defined by the three other sequence variants showed an association with tHcy concentrations, nor was any TC genotype associated with an increased CVD risk. Conclusions: In individuals in the highest quartile of the vitamin B12 distribution (&gt;299 pmol/L), tHcy concentrations are lower in 259PP homozygotes than in 259PR and 259RR individuals. Therefore, 259PP individuals, who represent &gt;25% of the general population, may be more susceptible to reduction of plasma tHcy concentrations by increasing the vitamin B12 status.

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