An audit of holotranscobalamin (“Active” B12) and methylmalonic acid assays for the assessment of vitamin B12 status: Application in a mixed patient population

Four biomarkers are commonly employed to diagnose B12 deficiency: vitamin B12 (B12), holotranscobalamin (HoloTC), methylmalonic acid (MMA), and homocysteine (Hcy). 4cB12, a combined index of the B12 status, has been suggested to improve the recognition of B12 deficiency. We aimed to evaluate the four different markers for detecting B12 deficiency, as determined by 4cB12. Within a large, mixed patient population, 11,833 samples had concurrent measurements of B12, HoloTC, MMA, and Hcy. 4cB12 was calculated according to the methods described by Fedosov. Diagnostic cutoffs as well as diagnostic accuracy for the detection of B12 deficiency were assessed with receiver operating characteristic (ROC) analysis. The median age was 56 years, and women accounted for 58.8% of the samples. Overall, the area under the curve (AUC) for the detection of subclinical B12 deficiency was highest for HoloTC (0.92), followed by MMA (0.91), B12 (0.9) and Hcy (0.78). The difference between HoloTC and B12 was driven by a significantly higher AUC for HoloTC (0.93) than for B12 (0.89), MMA (0.91), and Hcy in women 50 years and older (0.79; p<0.05 for all). In the detection of subclinical B12 deficiency, there were no significant differences in the AUCs of HoloTC, B12, and MMA among men and women <50 years. In conclusion, in women<50 years and in men, HoloTC, MMA, or Hcy do not appear superior to B12 for the detection of B12 deficiency. For women 50 years and older, HoloTC seems to be the preferred first-line marker for the detection of subclinical B12 deficiency.

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

Australian Journal of Agricultural Research ◽

10.1071/ar9871071 ◽

1987 ◽

Vol 38 (6) ◽

pp. 1071 ◽

Cited By ~ 19

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.

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

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563218778300 ◽

2018 ◽

Vol 55 (6) ◽

pp. 685-692 ◽

Cited By ~ 1

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.

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Methylmalonic acid and vitamin B12 in patients with heart failure

Hellenic Journal of Cardiology ◽

10.1016/j.hjc.2019.10.010 ◽

2020 ◽

Vol 61 (5) ◽

pp. 330-337 ◽

Cited By ~ 2

Author(s):

Kali Polytarchou ◽

Yannis Dimitroglou ◽

Dimitrios Varvarousis ◽

Nikolaos Christodoulis ◽

Christina Psachoulia ◽

...

Keyword(s):

Heart Failure ◽

Vitamin B12 ◽

Methylmalonic Acid ◽

Patients With Heart Failure

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Comparative Bioavailability of Synthetic B12 and Dietary Vitamin B12 Present in Cow and Buffalo Milk: A Prospective Study in Lactovegetarian Indians

Nutrients ◽

10.3390/nu11020304 ◽

2019 ◽

Vol 11 (2) ◽

pp. 304 ◽

Cited By ~ 2

Author(s):

Namita Mahalle ◽

Vijayshri Bhide ◽

Eva Greibe ◽

Christian Heegaard ◽

Ebba Nexo ◽

...

Keyword(s):

Prospective Study ◽

Vitamin B12 ◽

Methylmalonic Acid ◽

Buffalo Milk ◽

Dietary Vitamin ◽

Comparative Bioavailability ◽

Total Homocysteine ◽

A Prospective Study ◽

Oral Doses ◽

Over Time

We assessed improvements in the vitamin B12 status of Indian lactovegetarians receiving four weeks supplementation with natural B12 in milk versus cyano-B12 in capsules. Three groups (n = 22, 23, 22) received daily oral doses of cyano-B12 (2 × 0.76 µg) or milk (2 × 200 mL) from a cow or buffalo (amounting to B12 ≈ 2 × 0.76 µg). Their blood was examined at baseline and each following week. The baselines (median (min/max)) indicated a low B12 status: plasma B12 (116(51/314)) pmol/L, holotranscobalamin (holoTC) (30(7/119)) pmol/L, total homocysteine (Hcy) (24(10/118)) µmol/L, methylmalonic acid (MMA) (0.58(0.15/2.2)) µmol/L and combined B12 index (cB12) (−1.32 − (−3.12/+0.29)). Shifts from the baselines (B12, holoTC, cB12) and ratios to the baselines (Hcy, MMA) were analyzed over time. The cyano-B12 treatment gave more total B12 in plasma at week one (+29 pmol/L, p = 0.004) but showed no further increase. Other biomarkers changed more comparably between the three groups (p ≥ 0.05): holoTC showed a transient spike that leveled off, Hcy finally decreased to 0.8 × baseline, while MMA showed marginal changes. The combined indexes improved comparably (p = 0.6) in all groups (+0.2(−0.3/+0.9), p ≤ 0.002). In conclusion, the tested formulations similarly improved B12 status, but did not normalize it.

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