High frequency of vitamin B12 deficiency in a Brazilian population

AbstractObjectiveThere are few studies regarding vitamin B12 deficiency in developing countries. In Brazil, a late diagnosis of vitamin B12 deficiency progressing to severe neurological damage is common. Thus, the aim of the present study was to verify the frequency of vitamin B12 deficiency in two Brazilian populations (elderly and adult participants) and to compare different methods of vitamin B12 deficiency detection.DesignFive hundred participants were recruited from health centres from south-east Brazil and were separated into two groups: 60 years old or more and 30–59 years old. Vitamin B12 and folate concentrations were measured using electrochemiluminescence immunoassay (ECI) and RIA. Methylmalonic acid (MMA) was measured by LC coupled to tandem MS. Full blood counts were acquired using standard methods.ResultsAll participants had normal blood count results and mean cell volume less than 99 fl; none of them presented folate deficiency according to the results, which were all greater than 3 ng/ml. Cobalamin levels less than 200 pmol/l were identified by one of the two or by both methods in 7·2 % of the participants aged 60 years or more and 6·4 % of the participants aged 30–59 years. MMA levels were higher in older subjects (P = 0·007) compared with younger subjects. A greater correlation of MMA v. RIA was observed than of MMA v. ECI (P = 0·0017 v. P = 0·014). MMA quantification estimated that cobalamin deficiency was present in more than 11 % of the subjects for both studied groups.ConclusionsThe study shows that vitamin B12 deficiency is frequent in Brazilian adults and suggests that RIA is more sensitive than ECl for measuring cobalamin levels.

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Cobalamin (vitamin B12) deficiency detection by urinary methylmalonic acid quantitation

Blood ◽

10.1182/blood.v59.6.1128.1128 ◽

1982 ◽

Vol 59 (6) ◽

pp. 1128-1131 ◽

Cited By ~ 39

Author(s):

EJ Norman ◽

OJ Martelo ◽

MD Denton

Keyword(s):

Methylmalonic Acid ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Cobalamin Deficiency ◽

Clinical Test ◽

Test Results ◽

Neurologic Disorders ◽

Schilling Test ◽

B12 Deficiency ◽

And Function

Abstract A study was made to assess the value of cobalamin deficiency detection through quantitation of urinary methylmalonic acid (MMA). Urinary MMA was measured in 1118 patients suffering from megaloblastic anemia, other anemias, elevated red cell mean corpuscular volume, or unexplained neurologic disorders. Patients without proven cobalamin deficiency had urinary MMA levels less than 20 micrograms/ml. All patients (n = 27) confirmed to have cobalamin deficiency showed MMA levels greater than 20 micrograms/ml. Data are presented showing the Schilling test results, the comparison of serum cobalamin to urinary MMA levels, and other basic hematologic data. MMA levels are a good indication of cobalamin distribution and function since they are directly related to a cobalamin-dependent metabolic pathway. With rapid, reliable quantitation by mass spectrometry, urinary MMA can now be a useful clinical test.

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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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Cobalamin (vitamin B12) deficiency detection by urinary methylmalonic acid quantitation

Blood ◽

10.1182/blood.v59.6.1128.bloodjournal5961128 ◽

1982 ◽

Vol 59 (6) ◽

pp. 1128-1131

Author(s):

EJ Norman ◽

OJ Martelo ◽

MD Denton

Keyword(s):

Methylmalonic Acid ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Cobalamin Deficiency ◽

Clinical Test ◽

Test Results ◽

Neurologic Disorders ◽

Schilling Test ◽

B12 Deficiency ◽

And Function

A study was made to assess the value of cobalamin deficiency detection through quantitation of urinary methylmalonic acid (MMA). Urinary MMA was measured in 1118 patients suffering from megaloblastic anemia, other anemias, elevated red cell mean corpuscular volume, or unexplained neurologic disorders. Patients without proven cobalamin deficiency had urinary MMA levels less than 20 micrograms/ml. All patients (n = 27) confirmed to have cobalamin deficiency showed MMA levels greater than 20 micrograms/ml. Data are presented showing the Schilling test results, the comparison of serum cobalamin to urinary MMA levels, and other basic hematologic data. MMA levels are a good indication of cobalamin distribution and function since they are directly related to a cobalamin-dependent metabolic pathway. With rapid, reliable quantitation by mass spectrometry, urinary MMA can now be a useful clinical test.

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Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.

Clinical Chemistry ◽

10.1093/clinchem/35.12.2277 ◽

1989 ◽

Vol 35 (12) ◽

pp. 2277-2280 ◽

Cited By ~ 36

Author(s):

K Rasmussen ◽

L Moelby ◽

M K Jensen

Keyword(s):

Methylmalonic Acid ◽

Vitamin B12 Deficiency ◽

Cobalamin Deficiency ◽

Serum Samples ◽

Linear Relationships ◽

Diagnostic Usefulness ◽

B12 Deficiency ◽

Excretion Rates ◽

Hematological Evaluation ◽

First Time

Abstract Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005).

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Vitamin B12 Deficiency and Dementia

International Psychogeriatrics ◽

10.1017/s1041610295001876 ◽

1995 ◽

Vol 7 (1) ◽

pp. 85-88 ◽

Cited By ~ 27

Author(s):

Ulisses Gabriel de Vasconcelos Cunha ◽

Fábio Lopes Rocha ◽

Josecy Maria de Souza Peixoto ◽

Maria Flávia de Morão Motta ◽

Maira Tonidandel Barbosa

Keyword(s):

Vitamin B12 Deficiency ◽

Cobalamin Deficiency ◽

Vitamin B ◽

Progressive Decline ◽

Recent Onset ◽

Beneficial Effects ◽

History Of ◽

B12 Deficiency ◽

State Examination

We set out to investigate the possible beneficial effects on cognitive function of demented patients with cobalamin deficiency after cobalamin replacement. A total of 181 consecutive, demented (DSM-III or DSM-III-R criteria and score below 24 on the Mini-Mental State Examination [MMSE] outpatients (mean age 77.5 years) were prospectively evaluated and had their vitamin B12 level measured by radioimmunoassay. The frequency of vitamin B12 deficiency (less than 200 pg/mL) was 25% (46 patients). Treatment outcome was obtained in 19 patients (19 of 46). Despite cobalamin replacement, 16 of 19 patients persisted in showing progressive decline during follow-up visits (3 to 24 months). The nonresponse to vitamin B12 replacement in most cases seems to reflect the presence of associated irreversible dementia or a follow-up of shorter duration in a few patients. All of the patients who showed some improvement (MMSE returned to normal values) had mild dementia with a history of less than 2 years. Thus, screening for B12 deficiency should be considered in patients with recent onset of mild mental status changes.

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Vitamin B12 deficiency and the excretion of ether-soluble acids in the rat

British Journal Of Nutrition ◽

10.1079/bjn19670032 ◽

1967 ◽

Vol 21 (2) ◽

pp. 309-314 ◽

Cited By ~ 5

Author(s):

B. K. Armstrong

Keyword(s):

Urinary Excretion ◽

Vitamin B12 ◽

Methylmalonic Acid ◽

Vitamin B12 Deficiency ◽

Vitamin B ◽

B12 Deficiency ◽

Males And Females

1. Urinary excretion of total ether-soluble acids and of methylmalonic acid was studied in rats on vitamin B12-deficient diets with and without a vitamin B12 supplement.2. It was shown that urinary excretion of total ether-soluble acids and methylmalonic acid was increased in vitamin B12-deficient rats and that this increase was somewhat variable between individual animals, males and females, and rats from different litters.3. The increased excretion of these acids could readily be reversed by supplementing the diet with vitamin B12.

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Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.

Clinical Chemistry ◽

10.1093/clinchem/35.12.2271 ◽

1989 ◽

Vol 35 (12) ◽

pp. 2271-2276 ◽

Cited By ~ 25

Author(s):

K Rasmussen

Keyword(s):

Urinary Excretion ◽

Methylmalonic Acid ◽

Vitamin B12 Deficiency ◽

Normal Subjects ◽

Cobalamin Deficiency ◽

Absolute Amount ◽

Ambulatory Patients ◽

B12 Deficiency ◽

First Time

Abstract Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients.

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Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents

Pediatric Research ◽

10.1038/s41390-021-01372-2 ◽

2021 ◽

Author(s):

M. Rebecca Heiner-Fokkema ◽

Ineke J. Riphagen ◽

Nicole S. Wiersema ◽

Jelmer J. van Zanden ◽

Jenny E. Kootstra-Ros ◽

...

Keyword(s):

Young Children ◽

Vitamin B12 ◽

Reference Values ◽

Methylmalonic Acid ◽

Early Recognition ◽

Vitamin B12 Deficiency ◽

Reference Intervals ◽

Cobalamin Deficiency ◽

Plasma Vitamin ◽

B12 Deficiency

Abstract Background Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals. Methods Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. Results Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. Conclusions Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. Impact We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.

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Important reminder: nitrous oxide (N2O) as a cause of functional vitamin B12 deficiency

BMJ Case Reports ◽

10.1136/bcr-2020-241414 ◽

2021 ◽

Vol 14 (7) ◽

pp. e241414

Author(s):

Abdullahi Elsheikh Mahgoub ◽

Smit Sunil Deliwala ◽

Ghassan Bachuwa

Keyword(s):

Nitrous Oxide ◽

Vitamin B12 Deficiency ◽

Serum Markers ◽

Cobalamin Deficiency ◽

Vitamin B ◽

Sensory Level ◽

Significant Other ◽

Lower Extremity Weakness ◽

Fluid Analysis ◽

B12 Deficiency

A 32-year-old woman who misused multiple substances, including nitrous oxide (N2O), sought medical advice after she subacutely developed bilateral lower extremity weakness without a sensory level but with ataxia—her significant other developed similar symptoms with vitamin B12 deficiency due to N2O intake. Laboratory results revealed macrocytic anaemia despite normal B12 and folate levels, with serum markers pointing towards functional cobalamin deficiency. Spinal MRIs and cerebrospinal fluid analysis were unremarkable. Our patient was treated with vitamin B12 supplementation with an encouraging response.

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Assessment of vitamin B12 deficiency and B12 screening trends for patients on metformin: a retrospective cohort case review

BMJ Nutrition, Prevention & Health ◽

10.1136/bmjnph-2020-000193 ◽

2021 ◽

pp. bmjnph-2020-000193

Author(s):

Darby Martin ◽

Jeet Thaker ◽

Maria Shreve ◽

Lois Lamerato ◽

Kartazyna Budzynska

Keyword(s):

Retrospective Cohort ◽

Protective Factor ◽

Vitamin B12 Deficiency ◽

Older Age ◽

Secondary Outcome ◽

Vitamin B ◽

Case Review ◽

Large Hospital ◽

Hospital System ◽

B12 Deficiency

ObjectivesOur study investigated the use of vitamin B12 testing in a large cohort of patients on metformin and assesses appropriateness and benefits of screening recommendations for vitamin B12 deficiency.DesignThis retrospective cohort study included insured adult patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin to establish compliance. The comparison group was not exposed to metformin. Primary outcome was incidence of B12 deficiency diagnosed in patients on metformin. Secondary outcome was occurrence of B12 testing in the patient population on metformin. Records dated through 31 December 2018 were analysed.SettingLarge hospital system consisting of inpatient and outpatient data base.ParticipantsA diverse, adult, insured population of patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin.ResultsOf 13 489 patients on metformin, 6051 (44.9%) were tested for vitamin B12 deficiency, of which 202 (3.3%) tested positive (vs 2.2% of comparisons). Average time to test was 990 days. Average time to test positive for deficiency was 1926 days. Factors associated with testing were linked to sex (female, 47.8%), older age (62.79% in patients over 80 years old), race (48.98% white) and causes of malabsorption (7.11%). Multivariable logistic regression showed older age as the only factor associated with vitamin B12 deficiency, whereas African-American ethnicity approached significance as a protective factor.ConclusionsBased on our study’s findings of vitamin B12 deficiency in patients on metformin who are greater than 65 years old and have been using it for over 5 years, we recommend that physicians consider screening in these populations.

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