An assessment of serum vitamin B12 and folate in patients with Crohn's disease.

Crohn's disease is a chronic inflammatory condition that can involve any area in the gastrointestinal tract often involving the distal ileum where vitamin B12 is specifically absorbed. The aim of this study was to ascertain serum vitamin B12 and folate levels in order to investigate the correlation among these vitamin levels and disease activation, localization, duration and age at the onset of the disease. Study population included 103 patients with Crohn's disease and a healthy control group of 114 individuals. C-reactive protein, vitamin B12, folate levels were studied along with hemogram analyses. The results were evaluated in statistical comparisons. While serum vitamin B12 levels and serum folate levels were 161.9 ±â€…63.2(73-496) pg/mL and 4.9 ±â€…1.4(1.2-9.4) ng/mL in the Crohn's patient group respectively, they were 321.7 ±â€…126.3(85-680) pg/mL and 7.6 ±â€…3.8(3-25.1) ng/mL in the control group respectively. Vitamin B12 and folate levels were distinctly lower in patients with Chron's disease than those of the control group (P < .001). The intragroup analysis of the patient group revealed that low vitamin B12 levels were significantly lower in the moderate group classified according to the Crohn's Disease Activity Index (P < .001), along with those in the L1 group with terminal/distal ileal involvement (P < .001). Vitamin B12 and folate deficiencies are quite prevalent in patients with Crohn's disease while this condition can lead to various complications and they prove to be important risk factors associated especially with thrombosis and its complications. Patients must be regularly followed-up for vitamin B12 and folate levels to supplement them where needed.

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.

Characteristics of patients with vitamin B12-responsive neuropathy: a case series with systematic repeated electrophysiological assessment.

BACKGROUND: Vitamin B12 (B12) has a fundamental role in both central and peripheral nervous system function at all ages. Neurologic manifestations may be the earliest and often the only manifestation of B12 deficiency. Mostly because of the poor sensitivity of methods of determination for B12 levels, peripheral neuropathy remains a classical but underdiagnosed complication of B12 deficiency. So the clinical and electrophysiological characteristics of B12-responsive neuropathy are not well known. METHODS: A retrospective study of patients with B12-responsive neuropathy was conducted at our hospital on a 3-year period. The criteria for inclusion were: (a) neuropathy confirmed by the electrophysiological study (nerve conduction study); and (b) improvement of at least 1 point of the total Overall Neuropathy Limitations Scale score after vitamin B12 treatment. RESULTS: Nine patients were identified. Serum B12 level was low in only four. Four patients had sensorimotor (predominantly sensory) axonal polyneuropathy while five had only sensory neuronopathy. Six improved in less than 1 month after B12 supplementation. CONCLUSION: B12-responsive neuropathy is a more heterogeneous group of neuropathy than previously described. B12 deficiency is a cause of peripheral neuropathy and should systematically be ruled out in the clinical setting of idiopathic neuropathy or sensory neuronopathy because of potential reversibility. ABBREVIATIONS: B12: vitamin B12; CMAP: compound muscle action potentials; DRG: dorsal root ganglia; ENMG: electroneuromyography; MCCT: motor central conduction time; MEP: motor evoked potentials; MMA: methylmalonic acid; MMCoAM: L-methylmalonyl-CoenzymeA mutase; ONLS: overall neuropathy limitations scale; SCV: sensory conduction velocities; SNAP: sensory nerve action potentials; SNN: sensory neuronopathy; SSS: SNAP sum score.

An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.

The vitamin B12 status of infants depends on maternal B12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B12 injections. Marked catch-up of developmental milestones was noted after treatment with B12. Investigations of parents showed normal B12 in the father and combined B12 and iron deficiency in the mother. Maternal B12 deficiency, most likely masked by iron deficiency, led to severe B12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B12 status during pregnancy.

Vitamin B12 screening in metformin-treated diabetics in primary care: were elderly patients less likely to be tested?

Low serum B12 level is a common occurrence in patients with type 2 diabetes (T2DM) treated with metformin. There is lack of evidence concerning blood testing of vitamin B12 and current clinical guidelines make no recommendations on the detection or prevention of vitamin B-12 deficiency during metformin treatment. Our objective was to examine the current practice and clinical determinants of vitamin B12 testing in metformin treated T2DM patients. Data were collected from health maintenance organization patients, and consisted of T2DM patients who were newly prescribed metformin from 2008 to 2013. Patients were randomly divided into two subgroups: referred for a vitamin B12 blood test, and did not receive a referral. The demographic data and medical characteristics were analyzed. 5131 patients began taking metformin during the study period. Of these 2332 (44.5 %) had vitamin B12 tested. Significant differences were found between the groups in regard to glycosylated hemoglobin, low density lipoprotein, systolic blood pressure, dyslipidemia, chronic renal failure, and disease duration. A significant positive association (p < .05) was found between vitamin B12 testing and insulin treatment, retinopathy, neuropathy and hypertension. Vitamin B12 in elderly (>75 years) patients was significantly lower (p < .01). Insulin treatment, hypertension, and chronic diabetic complications in metformin treated T2DM patients are associated with higher rates of vitamin B12 testing. T2DM patients 75 years and above were less likely to be tested for B12 deficiency.

Assessment of brain cognitive functions in patients with vitamin B12 deficiency using resting state functional MRI: A longitudinal study.

INTRODUCTION: The resting state functional MRI (rsfMRI) approach is useful to explore the brain's functional organization in health and disease conditions. In this study, using rsfMRI the alteration in brain due to vitamin B12 deficiency and reversibility of these alterations following therapy was studied. METHODS: Thirteen patients with clinical and biochemical evidence of vitamin B12 deficiency were recruited in this study. Fifteen age and sex matched healthy controls were also included. Patients and controls were clinically evaluated using neuropsychological test (NPT). The analysis was carried out using regional homogeneity (ReHo) and low frequency oscillations (LFO) of BOLD signals in resting state. Six patients were also evaluated with rsfMRI and NPT after 6 weeks replacement therapy. RESULTS: ReHo values in patients with vitamin B12 deficiency were significantly lower than controls in the entire cerebrum and the brain networks associated with cognition control, i.e., default mode, cingulo-opercular and fronto-parietal network. There was no significant difference using LFO and it did not show significant correlations with NPT scores. ReHo showed significant correlation with NPT scores. All the 6 patients showed increase in ReHo after replacement therapy. CONCLUSION: We conclude that brain networks associated with cognition control are altered in patients with vitamin B12 deficiency, which partially recover following six weeks of replacement therapy. This is the first study to evaluate the rsfMRI in the light of clinical neuropsychological evaluation in patients. rsfMRI may be used as functional biomarker to assess therapeutic response in vitamin B12 deficiency patients.

Informing disinvestment with limited evidence: cobalamin deficiency in the fatigued.

OBJECTIVES: Health technology reassessment and disinvestment can be difficult due to uncertainties regarding available evidence. Pathology testing to investigate cobalamin (vitamin B12) deficiency is a strong case in point. We conducted a 3-month economic evaluation of five strategies for diagnosing and treating cobalamin deficiency in adult patients hypothetically presenting with new unexplained fatigue in the primary care setting. The first consultation per patient was considered. Screening tests other than serum cobalamin were not included. METHODS: A cost-effectiveness analysis was undertaken using a decision tree to represent the diagnostic / treatment pathways, with relevant cost and utility scores assigned to different stages in the evaluation process. Input parameter values were estimated from published evidence, supplemented by expert opinion, with sensitivity analysis undertaken to represent parameter uncertainty. RESULTS: Ordering serum vitamin B12 to assess cobalamin deficiency among patients with unexplained fatigue was not cost-effective in any patient population, irrespective of pretest prevalence of this deficiency. For patients with a pretest prevalence above 1 percent, treating all with oral vitamin B12 supplements without testing was most cost-effective, whereas watchful waiting with symptoms monitoring was most cost-effective for patients with lower pretest prevalence probabilities. CONCLUSIONS: Substantial evidence gaps exist for parameter estimation: questionable cobalamin deficiency levels in the fatigued; debatable treatment methods; unknown natural history of the condition. Despite this, we reveal a robust path for disinvestment decision making in the face of a paradox between the evidence required to inform disinvestment compared with its paucity in informing initial funding decisions.

Diffusion tensor tractography and neuropsychological assessment in patients with vitamin B12 deficiency.

INTRODUCTION: Structural imaging of the brain does not demonstrate any changes in a vast majority of patients with vitamin B12 deficiency, even in advanced stages. In this study, we aimed to assess and correlate the functional integrity of the brain fiber tracts using diffusion tensor tractography with neuropsychological examination in patients with vitamin B12 deficiency. METHODS: The study was conducted at two tertiary care centers. Thirty-two patients with vitamin B12 deficiency were enrolled and subjected to diffusion tensor tractography, as an extension of diffusion tensor imaging, and neuropsychological assessment. Tests of significance were done to detect changes, pre- and post-vitamin B12 supplementation in the diffusivity parameters (fractional anisotropy and mean diffusivity) and the neuropsychological test scores. RESULTS: Statistically significant changes were observed in the diffusivity parameters and the neuropsychological test scores between the controls and the patients with vitamin B12deficiency in the pre- and post-treatment phases. CONCLUSIONS: This is the first study to evaluate the diffusion tensor tractography (DTT) parameters in the light of clinical neuropsychological assessment in patients with vitamin B12 deficiency. Utilization of DTT parameters may antedate structural changes and may quantify the neurocognitive deficits.

Assessment of peripapillary retinal nerve fiber layer thickness in children with vitamin B12 deficiency.

PURPOSE: Vitamin B(12) deficiency is a worldwide problem. It affects all ages, including children. It is one of the most common nutritional disorders and can cause harmful effects on the nervous system. In this study, we compared the peripapillary retinal nerve fiber layer thickness (RNFLT) in a healthy control group with children with vitamin B(12) deficiency. In our study, we aimed to evaluate the effect of vitamin B(12) deficiency on the RNFLT in children with the optical coherence tomography (OCT) method. METHODS: Sixty-six children with a diagnosis of vitamin B(12) deficiency (patient group) and 66 age- and sex-matched healthy children (control group) were enrolled in this prospectively designed study. Blood counts, vitamin B(12) levels, folate levels, and full biochemical parameters were obtained for all the subjects in each group. Peripapillary RNFLT measurements were performed with Cirrus HD spectral domain OCT. RESULTS: The thickness of the superior retinal nerve fiber layer (RNFL) in the vitamin B(12) deficiency group was significantly lower than that of the control group (p = 0.037). Although the average thickness of the RNFL was lower in the patient group, there was no statistically significant differences (p = 0.216). In the vitamin B(12) deficiency group, the average RNFL thickness and the superior RNFL thickness were significantly correlated with vitamin B(12) levels ((r1) = 0.353, (p1) < 0.004 and (r2) = 0.416, (p2) = 0.001, respectively). CONCLUSION: Our study showed that a deficiency in vitamin B(12), elsewhere it is important for the development of the central nervous system, is associated with a reduction in the thickness of the superior RNFL.

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.

The oldest old: red blood cell and plasma folate in African American and white octogenarians and centenarians in Georgia.

OBJECTIVE: To determine the overall folate status of a population-based multi-ethnic sample of octogenarians and centenarians and the specific dietary, demographic and physiological factors associated with observed abnormalities. DESIGN: Population-based multiethnic sample of adults aged 80 to 89 and 98 and above. SETTING: Northern Georgia, USA. PARTICIPANTS: Men and women aged 80 to 89 (octogenarians, n = 77) and 98 and older (centenarians, n = 199). ANALYSES: Wilcoxon rank sum tests, and Chi square and logistic regression analyses were used to examine associations of low and high folate status with hematological indicators and other variables of interest. RESULTS: The prevalence of low red blood cell (RBC) folate was low overall, but tended to be higher in centenarians than in octogenarians (6.5% vs. 1.3%, p = 0.058; defined as RBC folate < 317 nmol/L). The risk of having lower RBC folate (< 25th vs. > 25th percentile for RBC folate for 60yr+ in NHANES 1999-2000) was greater in association with vitamin B12 deficiency (OR = 5.36; 95%CI: 2.87-10.01), African American race (OR = 4.29; 95%CI: 2.08-8.83), and residence in a skilled nursing facility (OR = 3.25; 95%CI: 1.56-6.78) but was not influenced by age, gender, B-vitamin supplement use, high/low food score or presence of atrophic gastritis. Combined high plasma folate and low vitamin B12 status was present in some individuals (n=11), but was not associated with increased prevalence of anemia or cognitive impairment in this study. CONCLUSIONS: Low RBC folate status (< 317 nmol/L) was rare in this post folic acid fortification sample of octogenarians and centenarians. RBC folate status (< 25th percentile) was strongly associated with 1) vitamin B12 deficiency, which has strong implications for vitamin treatment, and 2) with being African American, suggesting racial disparities exist even in the oldest old.

Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression.

BACKGROUND: The role of folate, vitamin B(12) and homocysteine levels in depression is not clear. AIMS: To investigate cross-sectional and prospective associations between folate, B(12) and homocysteine levels and late-life depression. METHOD: A total of 732 Korean people aged 65 years or over were evaluated at baseline. Of the 631 persons who were not depressed, 521 (83%) were followed over a period of 2-3 years and incident depression was ascertained with the Geriatric Mental State schedule. Serum folate, serum vitamin B(12) and plasma homocysteine levels were assayed at both baseline and follow-up. RESULTS: Lower levels of folate and vitamin B(12) and higher homocysteine levels at baseline were associated with a higher risk of incident depression at follow-up. Incident depression was associated with a decline in vitamin B(12) and an increase in homocysteine levels over the follow-up period. CONCLUSIONS: Lower folate, lower vitamin B(12) and raised homocysteine levels may be risk factors for late-life depression.

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.

Treatment of vitamin b(12)-deficiency anemia: oral versus parenteral therapy.

OBJECTIVE: To evaluate the use of oral cyanocobalamin therapy in the treatment of cobalamin (vitamin B(12))-deficient anemia. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1966-May 2000) and through secondary sources. DATA SYNTHESIS: Cobalamin-deficient anemia is among the most common diagnoses in older populations. Cobalamin-deficient anemia may be diagnosed as pernicious anemia, resulting from the lack of intrinsic factor required for cobalamin absorption or as protein malabsorption from the inability to displace cobalamin from protein food sources. Several studies provide evidence that daily oral cyanocobalamin as opposed to monthly parenteral formulations may adequately treat both types of cobalamin-deficient anemias. CONCLUSIONS: Daily oral cyanocobalamin at doses of 1000-2000 microg can be used for treatment in most cobalamin-deficient patients who can tolerate oral supplementation. There are inadequate data at the present time to support the use of oral cyanocobalamin replacement in patients with severe neurologic involvement.

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.

[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.

Anemia secondary to combined deficiencies of iron and cobalamin.

The focus of attention on combined-deficiency anemia is often on concurrent deficiencies of cobalamin (vitamin B12) and folate, emphasizing the correction of megaloblastic changes with folate alone and risking neurologic sequelae of uncorrected simultaneous cobalamin deficiency. Simultaneous deficiencies of cobalamin and iron, however, may be a more common cause of combined-deficiency anemia. Variability in red blood cell morphologic characteristics in this setting reflects the relative degree of deficiency of each of these substrates. A patient with combined cobalamin and iron deficiency anemia with microcytic, hypochromic indices and the absence of hypersegmented neutrophils was treated. This case and the literature reviewed emphasize the need to consider combined-deficiency states in all cases of anemia.