Metformin Usage Index and assessment of vitamin B12 deficiency among metformin and non-metformin users with type 2 diabetes mellitus.

AIM: The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D). METHODS: We recruited 2887 patients with T2D between January 2018 and November 2019 and categorized them into two groups (metformin and non-metformin users) matched for age, mean duration of diabetes, and BMI. We calculated the "Metformin Usage Index" (MUI) which was defined as the product of the dose of metformin (mg) used and its duration divided by 1000. Vitamin B12 levels were compared between the two groups, and its association with MUI was assessed using correlation and multistep logistic regression analyses. RESULTS: Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001]. Overall, a vitamin B12 level < 300 pg/ml was found in 52.2% of the subjects. There was a significant association between an MUI > 5 and a high risk of vitamin B12 deficiency [P < 0.01]. The highest risk was observed among patients with an MUI > 15 [odds ratio (OR) 6.74, 95% CI 4.39-10.4] followed by patients with an MUI > 10 (OR 5.12, 95% CI 3.12-8.38). CONCLUSIONS: The MUI can be employed as a risk assessment tool for evaluation of vitamin B12 deficiency in patients with T2D. Further prospective studies are required to determine the MUI thresholds in populations with good nutritional statuses and low prevalence of vitamin B12 deficiency.

Assessment of the Dose-Response Relationship Between Folate Exposure and Cognitive Impairment: Synthesizing Data from Documented Studies.

The dose-response relationship between folate levels and cognitive impairment among individuals with vitamin B12 deficiency is an essential component of a risk-benefit analysis approach to regulatory and policy recommendations regarding folic acid fortification. Epidemiological studies provide data that are potentially useful for addressing this research question, but the lack of analysis and reporting of data in a manner suitable for dose-response purposes hinders the application of the traditional evidence synthesis process. This study aimed to estimate a quantitative dose-response relationship between folate exposure and the risk of cognitive impairment among older adults with vitamin B12 deficiency using "probabilistic meta-analysis," a novel approach for synthesizing data from observational studies. Second-order multistage regression was identified as the best-fit model for the association between the probability of cognitive impairment and serum folate levels based on data generated by randomly sampling probabilistic distributions with parameters estimated based on summarized information reported in relevant publications. The findings indicate a "J-shape" effect of serum folate levels on the occurrence of cognitive impairment. In particular, an excessive level of folate exposure is predicted to be associated with a higher risk of cognitive impairment, albeit with greater uncertainty than the association between low folate exposure and cognitive impairment. This study directly contributes to the development of a practical solution to synthesize observational evidence for dose-response assessment purposes, which will help strengthen future nutritional risk assessments for the purpose of informing decisions on nutrient fortification in food.

Laboratory assessment of vitamin B12 status.

The detection and correction of vitamin B12 (B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12 It is only holotranscobalamin that is taken up by cells to meet metabolic demand. Although receiver operator characteristic curves show holotranscobalamin measurement to be a moderately more reliable marker of B12 status than serum B12, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B12 insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B12 status markers that reflect cellular utilisation rather than abundance are available. Two forms of B12 act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration >20 µmol/L may suggest B12 deficiency in folate-replete patients. In the second B12-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B12 deficiency excess methylmalonyl-CoA is hydrolysed to methylmalonic acid. A serum concentration >280 nmol/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B12 status in all patients. Sequential assay selection algorithms or the combination of multiple markers into a single diagnostic indicator are both approaches that can be used to mitigate inherent limitations of each marker when used independently.

Low serum levels of vitamin B12 in older adults with normal nutritional status by mini nutritional assessment.

Undernutrition as well as low levels of vitamin B12 and folic acid are common problems among older adults. However, recommended routine nutritional status assessment tools may result in inadequate vitamin serum levels to go unnoticed. Therefore, the aim of this study is to evaluate the inadequacy of serum levels of vitamin B12 and folic acid within Mini Nutritional Assessment (MNA) classification categories among older adults. A cross-sectional study was conducted with 97 older adults residing in care homes in Portugal. Undernutrition was identified through the MNA, and serum levels of vitamin B12 and folic acid were measured using chemiluminescence. Cognitive function, depressive symptoms and functional characteristics were also assessed using the Abbreviated Mental Test Score, the Epidemiologic Studies Depression Scale and the Barthel Index, respectively. The mean age of older adults was 82.2 (6.3) years; 3.1% were undernourished and 26.8% were at undernutrition risk. In the MNA normal nutritional status group, 11.8% presented vitamin B12 deficiency (<200 pg/ml), 32.4% had low serum levels (200-400 pg/ml) and 4.4% had folic acid deficiency (<3 ng/ml). A high proportion of older adults with low serum levels of vitamin B12 presenting normal nutritional status by MNA was identified. This finding emphasizes the need to evaluate serum vitamin B12 levels, independently of the MNA results.

Vitamin B12 concentration and its association with sociodemographic factors in Colombian children: Findings from the 2010 National Nutrition Survey.

OBJECTIVE: Rapid changes in dietary patterns, economic development, and urbanization in low- to middle-income countries are fueling complex malnutrition states that need better characterization using population-level data. The aim of this study was to describe the key findings related to vitamin B12 status to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. METHODS: We analyzed cross-sectional data from 6910 Colombian children between the ages of 5 and 12. Serum vitamin B12 concentrations were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. RESULTS: Of the children assessed, 2.8% had vitamin B12 deficiency, defined as levels <200 pg/mL, and 18.1% had marginal vitamin B12 deficiency, defined as levels between 200 and 300 pg/mL. A multivariate logistic regression analysis revealed increased risks for vitamin B12 deficiency among children ages ≥9 y and for those living in the eastern, western, and southern regions of the country. No significant associations were found for ethnic groups, socioeconomic status, or urbanity levels. Being 11 y of age (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.56-3.00; P = 0.0001), living in the west (Pacific) region of the country (OR, 3.92; 95% CI, 3.14-4.90; P = 0.0001), and being male (OR, 1.41; 95% CI, 1.20-1.65; P = 0.0001) were the factors most strongly associated with an increased risk for vitamin B12 deficiency. CONCLUSIONS: Compared with data from other Latin American countries, Colombian children have a lower prevalence of vitamin B12 deficiency; however the prevalence of marginal deficiency is substantial. Continued surveillance and implementation of interventions to improve dietary patterns among the high-risk groups identified should be considered.

Regional, Socioeconomic, and Dietary Risk Factors for Vitamin B-12 Deficiency Differ from Those for Folate Deficiency in Cameroonian Women and Children.

BACKGROUND: Representative data on folate and vitamin B-12 dietary intake and status in low-income countries are rare, despite the widespread adoption of folic acid fortification. OBJECTIVE: The purpose of this study was to evaluate folate and vitamin B-12 intake, status, and risk factors for deficiency before implementation of a national fortification program in Cameroon. METHODS: A nationally representative cross-sectional cluster survey was conducted in 3 ecologic zones of Cameroon (South, North, and the 2 largest cities, Yaoundé/Douala), and information on dietary intake was collected from 10 households in each of 30 randomly selected clusters per zone. In a subset of women and their 12- to 59-mo-old children (n = 396 pairs), plasma folate and vitamin B-12, as well as breast milk vitamin B-12, were analyzed. RESULTS: Vitamin B-12 and folate dietary intake patterns and plasma concentrations were similar for women and children. In the subsample, 18% and 29% of women and 8% and 30% of children were vitamin B-12 (≤ 221 pmol/L) and folate (< 10 nmol/L) deficient, respectively. Mean dietary folate ranged from 351 µg dietary folate equivalents/d in the North to 246 µg dietary folate equivalents/d in Yaoundé/Douala; plasma folate was negatively associated with socioeconomic status (P = 0.001). Plasma vitamin B-12 deficiency was similar in the South and North, 29% and 40%, respectively, but was only 11% in Yaoundé/Douala, and was positively associated with socioeconomic status. Mean breast milk vitamin B-12 was statistically significantly lower in the North (101 pmol/L) than in the South (296 pmol/L) or Yaoundé/Douala (349 pmol/L). CONCLUSIONS: Folate intake and status are inadequate among women and young children in Yaoundé/Douala, whereas low vitamin B-12 intake and status are more common in poor and rural areas, especially in the North. Different strategies may be needed to control deficiency of these nutrients in different regions of Cameroon.

Predicted efficacy of the Palestinian wheat flour fortification programme: complementary analysis of biochemical and dietary data.

OBJECTIVE: To utilize complementary biochemical and dietary data collected before the initiation of national flour fortification to (i) identify micronutrient insufficiencies or deficiencies and dietary inadequacies in Palestinian women and children in vulnerable communities and (ii) assess the suitability of the current wheat flour fortification formula. DESIGN: Quantitative dietary intake questionnaires were administered and fasting venous blood samples collected in randomly selected households in Gaza City and Hebron. The impact of fortification was simulated by estimating the additional micronutrient content of fortified wheat flour. SETTING: Households in Gaza City and Hebron that were not receiving food aid from social programmes. SUBJECTS: Non-pregnant women (18-49 years) and children aged 36-83 months. RESULTS: The micronutrients with highest prevalence of insufficiency were vitamin D in women (84-97 % with serum 25-hydroxyvitamin D <50 nmol/l) and vitamin B12 in women and children (43-82 % with serum B12 <221 pmol/l). Deficiencies of vitamin A, Fe and Zn were also of public health concern. Current levels of wheat flour fortificants were predicted to improve, but not eliminate, micronutrient intake inadequacies. Modification of fortificant concentrations of vitamin D, thiamin, vitamin B12, Zn and folic acid may be indicated. CONCLUSIONS: Micronutrient insufficiencies or deficiencies and intake inadequacies were prevalent based on either biochemical or dietary intake criteria. Adjustments to the current fortification formula for wheat flour are necessary to better meet the nutrient needs of Palestinian women and children.

Vitamin B12 serostatus in Colombian children and adult women: results from a nationally representative survey.

OBJECTIVE: Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence of vitamin B12 deficiency and marginal deficiency in Colombian children and women and examines the sociodemographic correlates of serum vitamin B12 concentrations in these groups. DESIGN: Cross-sectional, nationally representative survey. SETTING: Colombia. SUBJECTS: Children <18 years old (n 7243), pregnant women (n 1781), and non-pregnant women 18-49 years old (n 499). RESULTS: The overall prevalence of vitamin B12 deficiency (serum vitamin B12<148 pmol/l) and marginal deficiency (serum vitamin B12=148-221 pmol/l) was, respectively, 6.6 % (95 % CI 5.2%, 8.3%) and 22.5% (95% CI 21.1%, 23.9%). Pregnant women had the highest prevalence of deficiency (18.9 %; 95 % CI 16.6 %, 21.5 %) compared with non-pregnant adult women (18.5%; 95% CI 4.4%, 53.1%) and children (2.8 %; 95 % CI 2.3 % %, 3.3 %). In multivariable analyses among children, mean serum vitamin B12 was positively associated with female sex (12 pmol/l higher compared with males; P=0.004), secondary or higher education of the household head (12 pmol/l higher compared with primary or less; P=0.009) and food security (21 pmol/l higher compared with severe food insecurity; P=0.003). In multivariable analyses among pregnant women, mean serum vitamin B12 was positively associated with education of the household head and inversely associated with living in the National territories, Eastern or Pacific regions. CONCLUSIONS: The prevalence of vitamin B12 deficiency and marginal deficiency in Colombian women and children is substantial. The burden falls largely on adult women, those with lowest education and those living in the poorest, most rural regions of the country.

Prospective assessment of peripheral neuropathy in Duodopa-treated parkinsonian patients.

BACKGROUND: Although peripheral neuropathies (PN) have been described in patients with Parkinson's disease (PD) treated with oral dopaminergic therapies, anecdotal reports of subacute severe PN have been reported during treatment with enteral levodopa/carbidopa infusion (Duodopa). AIM OF THE STUDY: We prospectively assessed clinical and electrophysiological data of 15 consecutive patients with PD treated with Duodopa for a mean follow-up of 9 months. METHODS: Nerve conduction studies and a clinical evaluation with a standardized battery of peripheral neuropathy scales were performed at baseline and after a mean follow-up of 9 months. RESULTS: At baseline, mild signs of PN were observed in three subjects, and vitamin B12 serum levels were found to correlate with the amplitude of sural sensory action potentials. Follow-up data were available for 10/15 subjects: one patient developed a subacute sensory-motor PN and three subjects with pre-existing PN showed a moderate worsening of electrophysiological and clinical features. Subclinical electrophysiological alterations of peripheral nerves were observed in two subjects. No significant changes were observed in vitamin B12, folate, homocysteine and methylmalonic acid levels. CONCLUSIONS: In this consecutive series of patients treated with Duodopa, we observed one subacute sensory-motor PN and few length-dependent alterations of peripheral nerves, similar to those described during oral levodopa treatment.

Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX Study (ISRCTN48153354).

BACKGROUND: Older people are at increased risk of vitamin B12 deficiency and the provision of fortified foods may be an effective way to ensure good vitamin B12 status in later life. AIM: To evaluate the effectiveness of a vitamin B12 fortified food provided by a national program of complementary food for older people on plasma vitamin B12 levels. SUBJECTS AND METHODS: A random sub-sample of 351 subjects aged 65-67 y from a large cluster randomised controlled trial provided blood samples at baseline and after 24 months of intervention. The intervention arm (10 clusters 186 participants) received a vitamin B12 fortified food designed to deliver 1.4 µg/day, while the control arm did not receive complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate levels determined by radioimmunoassay were used to estimate the effect of intervention on vitamin B12 levels, adjusting for baseline levels and sex. RESULTS: Attrition at 24 months was 16.7% and 23.6% in the intervention and control arms respectively (p = 0.07). Over 24 months of intervention, mean (95% CI) serum vitamin B12 decreased from 392 (359-425) pmol/dL to 357 (300-414) pmol/dL (p < 0.07) in the intervention arm and from 395 (350-440) pmol/dL to 351 (308-395) pmol/dL in the control arm. There was no significant effect of the intervention on folate status. DISCUSSION: Our findings suggest that foods fortified with 1.4 µg/daily vitamin B12 as provided by Chile's national programme for older people are insufficient to ensure adequate vitamin B12 levels in this population. Chile has a long and successful experience with nutrition intervention programs; however, the country's changing demographic and nutritional profiles require a constant adjustment of the programs.

Indications for cobalamin level assessment in departments of internal medicine: a prospective practice survey.

BACKGROUND: Cobalamin (Cb) blood levels are frequently measured among inpatients, but the relevance of Cb determination has not been correctly assessed in this clinical setting. PURPOSE: We aimed to prospectively evaluate current indications compared to traditional guidelines for assessing Cb blood levels among inpatients from internal medicine departments. STUDY DESIGN: This study was conducted in French departments of internal medicine between 2008 and 2009. Inpatients who underwent Cb blood level determination during a 6-week study period were eligible. RESULTS: 380 consecutive adult patients were included. The three most common indications for Cb assessment were anaemia (62.6%), cognitive impairment (20.2%) and undernutrition (17.4%). Traditional indications (ie, macrocytic non-regenerative anaemia, isolated macrocytosis, dementia and proprioceptive disorders) accounted for only 33.9% of all tests. Cb deficiency was identified in 40 (10.5%) of the 380 patients tested. Overall, traditional indications were not associated with a significantly higher prevalence of patients with low Cb levels than current guidelines (14% vs 8.8%; p=0.119). Non-regenerative macrocytic anaemia was the only indication with a significantly better performance compared to all other indications (11 of 62 patients (17.7%) vs 29 of 318 patients (9.1%); OR 2.15 (1.01-4.57), p=0.047). The main aetiological causes of Cb deficiency were intake deficiency, pernicious anaemia and food-Cb malabsorption. Homocysteine or methylmalonic acid dosage testing was very rarely performed. CONCLUSIONS: Traditional indications did not perform better than other indications observed in current practice for identifying low Cb levels among inpatients from internal medicine departments. Future studies are needed to establish robust guidelines for inpatient screening.

Combined cobalamin and iron deficiency anemia: a diagnostic approach using a model based on age and homocysteine assessment.

Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B12 and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B12 (LB12) was considered when serum vitamin B12 was ≤200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy >17 µM/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B12 levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B12 (B12) ≤100 pmol/L showed vitamin B12 deficiency. Moreover, vitamin B12 deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B12 ≤200 and Hcy >17 µmol/L, [Formula: see text]. Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B12 deficiency and IDA were identified). In summary, low vitamin B12 was found in 18 % of patients with IDA. Vitamin B12 deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B12 should be evaluated in IDA patients over 60 years. This diagnostic model needs to be validated in a different population.

Vitamin B12 and cognitive function: an evidence-based analysis.

BACKGROUND: More than 2.9 million serum vitamin B12 tests were performed in 2010 in Ontario at a cost of $40 million. Vitamin B12 deficiency has been associated with a few neurocognitive disorders. OBJECTIVE: To determine the clinical utility of B12 testing in patients with suspected dementia or cognitive decline. METHODS: Three questions were addressed: Is there an association between vitamin B12 deficiency and the onset of dementia or cognitive decline? Does treatment with vitamin B12 supplementation improve cognitive function in patients with dementia or cognitive decline and vitamin B12 deficiency? What is the effectiveness of oral versus parenteral vitamin B12 supplementation in those with confirmed vitamin B12 deficiency? A literature search was performed using MEDLINE, Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination database, from January 2002 until August 2012. RESULTS: Eighteen studies (7 systematic reviews and 11 observational studies) were identified to address the question of the association between B12 and the onset of dementia. Four systematic reviews were identified to address the question of the treatment of B12 on cognitive function. Finally, 3 randomized controlled trials were identified that compared oral B12 to intramuscular B12. CONCLUSIONS: Based on very low quality evidence, there does appear to be an association between elevated plasma homocysteine levels (a by-product of B vitamins) and the onset of dementia. Based on moderate quality evidence, but with less than optimal duration of follow-up, treatment with B12 supplementation does not appreciably change cognitive function. Based on low to moderate quality of evidence, treatment with vitamin B12 and folate in patients with mild cognitive impairment seems to slow the rate of brain atrophy. Based on moderate quality evidence, oral vitamin B12 is as effective as parenteral vitamin B12 in patients with confirmed B12 deficiency. PLAIN LANGUAGE SUMMARY: Low levels of vitamin B12 have been associated with neurocognitive disorders. This evidence-based analysis assessed the usefulness of serum vitamin B12 testing as it relates to brain function. This review found very low quality evidence that suggests a connection between high plasma homocysteine levels (a by-product of B vitamin metabolism in the body) and the onset of dementia. Moderate quality of evidence indicates treatment with vitamin B12 does not improve brain function. Moderate quality of evidence also indicates treatment using oral vitamin B12 supplements is as effective as injections of vitamin B12.

The importance of methylmalonic acid dosage on the assessment of patients with neurological manifestations following bariatric surgery.

Vitamin B12 or cyanocobalamin is an important substance that is included in several metabolic pathways. Its deficiency is a common event after bariatric surgery, decreasing the vitamin B12 absorption after almost all of the stomach and duodenum are eliminated from the digestion process. Neurological manifestations of cyanocobalamin deficiency are not uncommon. We report a case of a young woman who developed ataxia, weakness and peripheral neuropathy after bariatric surgery, but with normal value of vitamin B12 dosage. For the diagnosis, it was necessary to dose methylmalonic acid. We discuss the importance of methylmalonic acid dosage after bariatric surgery in patients who present suspect of cyanocobalamin deficiency with normal values of this vitamin and the role of proton pump inhibitor use and vitamin supplementation in patients with early neurological presentation.

Total homocysteine and cognition in a tri-ethnic cohort: the Northern Manhattan Study.

OBJECTIVE: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. METHOD: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. RESULTS: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI -3.6, -0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE -2.2 points; 95% CI -3.5, -0.9). CONCLUSIONS: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors.

Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence.

The concentration of total homocysteine (tHcy) in serum and plasma is elevated in both folate and cobalamin deficiencies, whereas methylmalonic acid (MMA) in serum, plasma, or urine is a specific marker of cobalamin function. The combined measurement of both metabolites is useful for the diagnosis and follow-up of these deficiency states. In addition, tHcy is elevated under various pathologic states (eg, renal failure), and hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, cognitive dysfunction, and adverse pregnancy outcomes. The diagnostic utility of tHcy and MMA concentrations as markers of folate and cobalamin deficiencies in healthy and diseased children has been documented. This article briefly summarizes the biochemical background of tHcy and MMA and the associations of tHcy and MMA with various disease states and focuses on novel data obtained in infants, children, and adolescents, with emphasis on cobalamin status in infants. The utility of tHcy and MMA as indicators of cobalamin and folate deficiencies in adults can be extended to infants and older children. Furthermore, as in adults, tHcy is related to unhealthy lifestyle factors and is a risk factor for vascular disease. High MMA concentrations in newborns, occasionally denoted as benign methylmalonic aciduria, may reflect impaired cobalamin function.

Biological and environmental determinants of plasma homocysteine.

This article gives an overview over common physiological, lifestyle, and pathological conditions that may modulate the homocysteine status. The interplay of several environmental factors, including age, gender, nutrition, smoking, and coffee consumption and physical activity with commonly used drugs and prevalent diseases are described. In most cases, an abnormal homocysteine status is not caused by a single factor alone but often is the result of combined effects. We address these frequently found "clusters" of homocysteine-modulating factors. Finally, we give an overview of likely causes of hyperhomocysteinemia found in an authentic material. This material is based on 2462 routine measurements of plasma total homocysteine carried out at the Haukeland University Hospital. The data represent the total number of combined homocysteine and methylmalonic acid determinations, requested by general practitioners in Norway during February 1998.

Cobalamin deficiency in general practice. Assessment of the diagnostic utility and cost-benefit analysis of methylmalonic acid determination in relation to current diagnostic strategies.

Diagnosing cobalamin deficiency is often difficult. We investigated the diagnostic strategies that 224 general practitioners used to assess cobalamin status and the criteria on which they based their decisions to supplement patients. From all serum cobalamin analyses carried out at a single laboratory during 1993, individuals with serum cobalamin concentrations <300 pmol/L were identified, and one patient per general practitioner was included. When serum methylmalonic acid (s-MMA) values >0.376 micromol/L were used as the "reference standard" for cobalamin deficiency, the serum cobalamin assay had a diagnostic sensitivity of 0.40 and a specificity of 0.98. With the same reference standard, the diagnostic accuracy of the physicians' decision to supplement patients had the same specificity but a higher sensitivity (0.51). Cost-benefit analysis indicated that measurement of s-MMA can be recommended in patients with serum cobalamin >60-90 pmol/L and <200-220 pmol/L, depending on its diagnostic accuracy.

[Megaloblastic anemia: rapid and economical study]. / Anemia megaloblástica: su estudio en forma rápida y económica.

The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.