Cobalamin Treatment Research Articles

Reversible Gait Disturbance Due to Vitamin B12 Deficiency

Vitamin B12 deficiency causes a variety of symptoms in the hematologic, gastrointestinal tract, and neurologic deficit. We report a rare case of progressive gait disturbance, bradykinesia and dysarthria which was that vitamin B12 deficiency was diagnosed as the cause, and symptoms improved after intramuscular cobalamin treatment. Vitamin B12, homocysteine, and methylmalonic acid tests are recommended for patients with progressive gait disturbance, even in the absence of obvious anemia symptoms.

An Exceptional Case of Cobalamin Deficiency that Presented with Extremely High Indirect Bilirubin Levels

Cobalamin deficiency anemia is a type of anemia that present with weakness, fatigue, icteric sclera and neuropathy. Main causes of cobalamin deficiency are low intake or decreased absorption (gastric and intestinal causes). In present case, we report a 65-year-old male who presented to the emergency department with signs and symptoms of cobalamin deficiency including bilateral peripheral neuropathy, icteric skin and sclera, and abdominal pain in right upper quadrant. He had low cobalamin and extremely high bilirubin levels (8mg/dL) in serum. After the diagnosis of cobalamin deficiency established, 1mg daily cobalamin treatment initiated for five days which would follow weekly and monthly intramuscular injections consequently. Hemolysis and other causes of elevated indirect bilirubin levels were excluded in differential diagnosis. Clinical and laboratory improvements were achieved after the treatment. In conclusion, physicians should kept in mind cobalamin deficiency even in subjects with unusual high levels of indirect bilirubin.

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5–75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.

Effects of cobalamin on meiotic resumption and developmental competence of growing porcine oocytes

This study was performed to explore the effects of cobalamin treatment during in vitro maturation (IVM) of porcine oocytes. Specifically, the effects of cobalamin exposure on nuclear and cytoplasmic maturation of oocytes, diameter, glutathione (GSH) and reactive oxygen species (ROS) levels of matured oocytes, as well as development and gene expression of porcine parthenogenetic and cloned embryos were assessed. Cumulus–oocyte complexes were exposed to 200 pM cobalamin for 22 h or incubated for 22 h without cobalamin (controls). The mean diameter of cobalamin-treated oocytes was greater than that of control oocytes (160.0 vs. 154.5 μm; p < 0.05). GSH level increased but ROS level decreased in the cobalamin-treated oocyte group. Parthenogenetic embryos derived from cobalamin-treated oocytes showed improved oocyte maturation (91.3% vs. 83.8%), cleavage (88.9% vs. 82.1%), and blastocyst formation (38.7% vs. 31.9%) rates compared with control embryos (p < 0.05). Similarly, cloned embryos derived from cobalamin-treated oocytes showed higher oocyte maturation (89.2% vs. 82.2%), cleavage (87.5% vs. 80.3%), and blastocyst formation (30.0% vs. 23.8%) rates than control embryos (p < 0.05). Furthermore, in parthenogenetic and cloned embryos, total cell number, inner cell mass (ICM), trophectoderm (TE) expression, and ICM: TE ratio were higher in the cobalamin-treated group compared to that in the control group (p < 0.05). Cloned embryos in the cobalamin-treated group showed higher mRNA expression levels of POU5F1, DPPA2, and NDP52IL than control group embryos. Together, these results demonstrate that cobalamin treatment during IVM improves the developmental competence of porcine oocytes by neutralizing the free radicals produced in the IVM medium.

Methylcobalamin Affects Thiol Metabolism and Bioenergetic Status Across a Broad Range of Concentrations

ObjectiveTo assess metabolic responses of SH‐SY5Y human neuronal cells to a broad range of cobalamin concentrations.BackgroundCobalamin (Vitamin B12) consists of a heme‐like corrin ring with a cobalt atom that coordinates both a lower axial dimethylbenzimidazole ligand and a variable upper ligand. The upper axial ligand determines the biological activity of the molecule, and upon uptake into cells, the pre‐existing upper axial ligand is enzymatically cleaved and replaced by either a methyl group or deoxyadenosine group. Methylcobalamin (MeCbl) serves as a cofactor for methionine synthase, facilitating conversion of homocysteine to methionine. Plasma cobalamin concentrations are typically in the picomolar range. However, much higher concentrations have been employed pharmacologically to reverse post‐operative shock or treat cyanide poisoning. The role of cobalamin in these settings extends beyond its role as a cofactor and likely reflects the ability of corrin rings to interact with endogenous gasotransmitters, such as nitric oxide and hydrogen sulfide. In these high‐dose clinical applications, the underlying mechanisms leading to clinical benefits are incompletely understood, but may involve modulation of cellular metabolism.MethodsSH‐SY5Y cells were plated at 2.5 × 10^5 cells/well in 6‐well plates containing DMEM, 10% FBS, and penicillin‐streptomycin‐fungizone. After 48h of growth, media was replaced for a further 24h. Cells were maintained in media containing increasing concentrations (10 pM to 1 mM) of MeCbl for either the final hour or the final 24 hours of experiments. Lysates were processed for targeted metabolomic profiling of the methionine cycle and associated pathways via LC/MS. Bioenergetic parameters (oxygen consumption rate and glycolysis‐related extracellular acidification) were evaluated with a Seahorse XFp apparatus following MeCbl dose‐escalation experiments.ResultsWe observed significant changes in several methionine cycle and transsulfuration pathway metabolites as a function of MeCbl concentration. S‐adenosylmethionine (SAM) was decreased at 1h starting with 1 nM MeCbl. At 24h SAM was decreased at 10 uM MeCbl and higher. The SAM to S‐adenosylhomocysteine (SAH) ratio (SAM/SAH) decreased in a similar fashion by approximately 25%. Methionine and SAH did not change. 1 uM MeCbl and higher decreased cystathionine at 24h in a dose‐dependent manner, with 1 mM decreasing cystathionine by 45%. Lanthionine was decreased at both 1h and 24h starting at low nanomolar MeCbl concentrations. Cysteine was affected by the highest MeCbl concentrations. MeCbl increased oxygen consumption rate (OCR) at 1 mM. In the micromolar range MeCbl increased ECAR, but 1 mM dramatically decreased ECAR.ConclusionMeCbl exerts significant changes across a wide range of concentrations, likely reflecting its non‐cofactor role. While further investigation is needed, effects may involve the ability of corrin rings to modulate gasotransmitters. Understanding these mechanisms may reveal the origin of clinical benefits observed with high‐dose cobalamin treatment.Support or Funding InformationThis research was supported with a fellowship from the American Foundation for Pharmaceutical Education (AFPE).

Vitamin B12-deficiency anemia in infants: clinical presentation, current diagnostic and treatment

Vitamin B12 (cobalamin) deficiency in infants exclusively breastfed is usually the result of its deficiency in the mothers (vegetarians or in the presence of unrecognized pernicious anemia or malabsorption syndrome). Cobalamin is crucial for the normal development of the nervous system, the production of erythrocytes and the synthesis of DNA. The classic manifestation of its deficiency is megaloblastic anemia and, in advanced cases, pancytopenia. However, infants often present neurological symptoms (fatigue, failure to thrive, regress of developmental skills, lethargy, motor disorders), as a consequence of inadequate myelination of the brain. Cobalamin treatment is effective in the most children, however, the neurological deficit varying degrees may persist. The long-term prognosis depends on overall duration of vitamin B12 deficiency and severity of symptoms. The article presents our own interesting clinical observations. Parents gave their permission for using personal data for clinical research and publications.

State of the art review: oral and nasal vitamin B12 therapy in the elderly.

The objective of this narrative review was to provide an update on oral and nasal vitamin B12 (cobalamin) therapy in elderly patients. Relevant articles were identified by 'PubMed' and 'Scholar Google' search from January 2010 to July 2018 and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the 'Cochrane Library' and the 'ISI Web of Knowledge'. Data retrieved from international meetings were also used, as was information retrieved from commercial sites on the web and data from 'CARE B12' research group. For oral vitamin B12 therapy, four prospective randomized controlled trials, eight prospective studies, one systematic and four reviews fulfilled our inclusion criteria. The studies included mainly or exclusively elderly patients (≥65-year-olds). In all of the studies, the mean age of the patients was at least 70 years except for two. The present review documents that oral vitamin B12 replacement at 1000 μg daily proved adequate to cure vitamin B12 deficiency, with a good safety profile. The efficacy was particularly marked when considering the noticeable improvement in serum vitamin B12 levels and haematological parameters, such as haemoglobin level, mean erythrocyte cell volume and reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. For nasal vitamin B12, only a few preliminary studies were available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 injections in elderly patients. Oral vitamin B12 treatment avoids the discomfort, inconvenience and cost of monthly injections.

Different Presentations of Patients with Transcobalamin II Deficiency: A Single-Center Experience from Turkey

Objective:Transcobalamin II deficiency is a rare autosomal recessive disease characterized by decreased cobalamin availability, which in turn causes accumulation of homocysteine and methylmalonic acid. The presenting clinical features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia, neurologic abnormalities, and also recurrent infections due to immune abnormalities in early infancy.Materials and Methods:Here, we report the clinical and laboratory features of six children with transcobalamin II deficiency who were all molecularly confirmed.Results:The patients were admitted between 1 and 7 months of age with anemia or pancytopenia. Unexpectedly, one patient had a serum vitamin B12 level lower than the normal range and another one had nonsignificantly elevated serum homocysteine levels. Four patients had lymphopenia, four had neutropenia and three also had hypogammaglobulinemia. Suggesting the consideration of transcobalamin II deficiency in the differential diagnosis of immune deficiency. Hemophagocytic lymphohistiocytosis was also detected in one patient. Furthermore, two patients had vacuolization in the myeloid lineage in bone marrow aspiration, which may be an additional finding of transcobalamin II deficiency. The hematological abnormalities in all patients resolved after parenteral cobalamin treatment. In follow-up, two patients showed neurological impairments such as impaired speech and walking. Among our six patients who were all molecularly confirmed, two had the mutation that was reported in transcobalamin II-deficient patients of Turkish ancestry. Also, a novel TCN2 gene mutation was detected in one of the remaining patients.Conclusion:Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction. Early recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis.

Impact of Cyanocobalamin and Methylcobalamin on Inflammatory Bowel Disease and the Intestinal Microbiota Composition.

Patients with inflammatory bowel disease (IBD) are usually advised to supplement various types of vitamin B12, because vitamin B12 is generally absorbed in the colon. Thus, in the current study, the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on IBD symptoms will be investigated. Then, whether and how the application of various cobalamins would modify the taxonomic and functional composition of the gut microbiome in mice will be examined carefully. Dextran-sulfate-sodium-induced IBD mice were treated with MECBL or CNCBL; disease activity index (DAI) scores and intestinal inflammatory conditions of mice were evaluated. Fecal samples were collected; microbiota composition was determined with a 16s rRNA analysis; functional profiles were predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt); and short-chain fatty acids were measured. The consequence of higher relative abundances of Enterobacteriaceae and isomeric short-chain fatty acids by cobalamin treatment revealed that a high concentration of CNCBL but not MECBL supplementation obviously aggravated IBD. A microbial ecosystem rich in Escherichia/ Shigella and low in Lactobacillus, Blautia, and Clostridium XVIII was observed in IBD mice after a high concentration of CNCBL supplementation. In cobalamin-dependent enzymes, CNCBL was more efficient in the adenosylcobalamin system than MECBL and vice versa in the MECBL system. The distinct effects of various cobalamins were associated with the distribution and efficiency of vitamin-B12-dependent riboswitches. CNCBL had a strong inhibitory effect on all riboswitches, especially on btuB and pocR riboswitches from Enterobacteriaceae. CNCBL aggravated IBD via enhancing the proportion of Enterobacteriaceae organisms through riboswitch and enzyme systems. The present study provides a critical reference for offering a suitable amount and type of cobalamin during a symbiotic condition.

State of art of oral vitamin B12 (cobalamin) treatment in Biermer's disease (pernicious anemia)

State of art of oral vitamin B12 (cobalamin) treatment in Biermer's disease (pernicious anemia)

Effects of Cobalamin (Vitamin B12) on Gentamicin Induced Nephrotoxicity in Rat.

Background The main side effect of gentamicin is nephrotoxicity. The effect of cobalamin (Cob) was investigated on gentamicin nephrotoxicity in rats. Methods Renal injury induced by i.p. injection of gentamicin (100 mg/kg) for 8 consecutive days. Cobalamin (6 mg/kg/day, i.p) treatment was done for 8 consecutive days as co-treatment and post-treatment protocol. Results Cobalamin significantly increased creatinine clearance levels and renal blood flow which were reduced by gentamicin. Also, cobalamin significantly improved serum electrolytes (sodium and potassium) levels which were disturbed by gentamicin. Cobalamin significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid per oxidation and ameliorated renal tissue damage mediated by gentamicin. Conclusion The results of the current study indicated that cobalamin effectively protected the kidney tissue against gentamicin induced acute nephrotoxicity in rats. The antioxidant and anti-inflammatory activities can be supposed the main factors responsible for the nephroprotective effect of cobalamin.

Review of oral vitamin B12 (cobalamin) therapy

&lt;p&gt;Vitamin B12 (cobalamin) deficiency is particularly common in adults and elderlies (&amp;gt;15%). Management of cobalamin deficiency with cobalamin injections is currently well codified, but new routes of vitamin B12 administration (oral and nasal) are being studied, especially oral vitamin B12 therapy for food-cobalamin malabsorption. Three prospective randomized studies, a systematic review by the &lt;em&gt;Cochrane&lt;/em&gt; group and five prospective cohort studies were found and provide evidence that oral vitamin B12 treatment may adequately treat cobalamin deficiency. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume, reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. Oral cobalamin treatment &lt;ins cite="mailto:Nosaltres" datetime="2007-02-07T00:39"&gt;avoid&lt;/ins&gt;s&lt;ins cite="mailto:Nosaltres" datetime="2007-02-07T00:39"&gt; the discomfort, inconvenience and cost of monthly injections&lt;/ins&gt;.&lt;/p&gt;

Novel Mouse Models of Methylmalonic Aciduria Recapitulate Phenotypic Traits with a Genetic Dosage Effect

Methylmalonic aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the newborn period with failure to thrive and metabolic crisis leading to coma or even death. Survivors remain at risk of metabolic decompensations and severe long term complications, notably renal failure and neurological impairment. We generated clinically relevant mouse models of MMAuria using a constitutive Mut knock-in (KI) allele based on the p.Met700Lys patient mutation, used homozygously (KI/KI) or combined with a knockout allele (KO/KI), to study biochemical and clinical MMAuria disease aspects. Transgenic Mut(ki/ki) and Mut(ko/ki) mice survive post-weaning, show failure to thrive, and show increased methylmalonic acid, propionylcarnitine, odd chain fatty acids, and sphingoid bases, a new potential biomarker of MMAuria. Consistent with genetic dosage, Mut(ko/ki) mice have lower Mut activity, are smaller, and show higher metabolite levels than Mut(ki/ki) mice. Further, Mut(ko/ki) mice exhibit manifestations of kidney and brain damage, including increased plasma urea, impaired diuresis, elevated biomarkers, and changes in brain weight. On a high protein diet, mutant mice display disease exacerbation, including elevated blood ammonia, and catastrophic weight loss, which, in Mut(ki/ki) mice, is rescued by hydroxocobalamin treatment. This study expands knowledge of MMAuria, introduces the discovery of new biomarkers, and constitutes the first in vivo proof of principle of cobalamin treatment in mut-type MMAuria.

Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000g, results from a randomized intervention trial.

BackgroundExclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months.MethodsLevels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months.At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month.ResultsExcept for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01).Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03).ConclusionsThe findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency.Clinical trial registrationClinicalTrials.gov, number NCT01201005

Effects of Long-Term Cobalamin Treatment on the Expression of the Epidermal Growth Factor System in Mouse Kidney

Background: The epidermal growth factor (EGF) system plays an important role in the development and function of the kidneys. Studies have suggested this system to protect against acute renal injury and to prevent the progression of chronic kidney disease. We have demonstrated that cobalamin (Cbl) modulates the expression of the EGF system in mouse spinal cord. Here, we explore the effects of Cbl treatment on the mouse kidney expression of members of the EGF system comparing these with the expression in the submaxillary gland and liver. Methods: Following four weeks of administrating different doses of Cbl, we analysed kidney, submaxillary gland, and liver mRNA levels of the four EGF system receptors and the activating ligands EGF and heparin-binding EGF-like growth factor using quantitative reverse transcription-PCR. In addition, we analysed mRNA expression of the renal tubular injury markers, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Results: In controls, kidney expression of EGF system receptors and ligands was similar to or more than twice the levels in the submaxillary gland. A relatively high expression of the EGF receptor was observed in liver tissue, but only low or no expression of other EGF related molecules. Treatment with Cbl decreased expression of the EGF system in the kidneys in a dose-dependent manner, while no or little change was observed in other organs. No alterations were observed in the markers of kidney tubular injury after Cbl administration. Conclusions: Our results show modulation of the renal EGF system expression in mice following long term Cbl administration. This may have implications for prevention of progressive kidney disease. In addition, differences in the expression of the EGF receptors and ligands in liver, submaxillary gland and kidney were demonstrated.

A Novel mtDNA Large-Scale Mutation Clinically Exclusively Presenting With Refractory Anemia

We report a rare case of juvenile cobalamin deficiency who presented at the age of 17 years. He was underweight and had skin changes, normocytic anemia, and autonomic dysfunction, which led to adynamic ileus and acute postrenal failure. The expected macrocytosis was masked by an underlying alpha-thalassemia trait. The patient had an excellent response to parenteral cobalamin treatment.

Juvenile Cobalamin Deficiency in a 17-Year-Old Child With Autonomic Dysfunction and Skin Changes

We report a rare case of juvenile cobalamin deficiency who presented at the age of 17 years. He was underweight and had skin changes, normocytic anemia, and autonomic dysfunction, which led to adynamic ileus and acute postrenal failure. The expected macrocytosis was masked by an underlying alpha-thalassemia trait. The patient had an excellent response to parenteral cobalamin treatment.

Cobalamin F Disease Detected by Newborn Screening and Follow-up on a 14-Year-Old Patient

The cobalamin F (cblF) defect is caused by disturbed lysosomal release of cobalamin (vitamin B(12)) into the cytoplasm caused by mutations in the LMBRD1 gene. We present the clinical and biochemical characterization of a patient with newly diagnosed cblF disease and a follow-up on a 14-year-old patient. The new patient presented with elevation of propionyl carnitine found on a newborn screen. The patient was small for gestational age, exhibited dysmorphic features and mild developmental delay, and had trigonocephaly and ventricular septal defect. There was biochemical normalization and clinical improvement within 3 weeks of parenteral cobalamin treatment. The other patient presented at 4 weeks of life with failure to thrive and feeding difficulties. She was treated only with monthly cyanocobalamin shots. The patient has never experienced metabolic decompensation. She had short stature and was an average student with no behavioral concerns. Her metabolic derangements normalized after switching to weekly hydroxycobalamin. The available data on 14 patients with confirmed cblF disease suggest variability in age of onset, presenting symptoms, response to treatment, and long-term complications. Common clinical findings include small for gestational age, feeding difficulties, growth failure, and developmental delays. Some patients have congenital heart defects, dysmorphic features, and other congenital anomalies.

Efficacy of oral cobalamin (vitamin B12) therapy

Importance of the field: Cobalamin (vitamin B12) deficiency is particularly common in the elderly (> 15%). Management of cobalamin deficiency with cobalamin injections is well codified at present, but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.Areas covered in this review: The objective of this review is to evaluate the efficacy of oral cobalamin treatment in elderly patients. To reach this objective, PubMed data were systematically searched for English and French articles published from January 1990 to July 2008. Data from our research group on cobalamin deficiency (Groupe d’Etude des CAREnce vitamine B12 – CARE B12) were also analyzed.What the reader will gain: Three prospective randomized studies, a systematic review by the Cochrane group and five prospective cohort studies were found and provide evidence that oral cobalamin treatment may adequately treat cobalamin deficiency. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume and reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections.Take home message: Our experience and the present analysis support the use of oral cobalamin therapy in clinical practice.

Functional vitamin B12 deficiency in alcoholics: An intriguing finding in a retrospective study of megaloblastic anemic patients

Background Measurement of serum cobalamin levels is the standard investigation for assessing Vitamin B12 deficiency. However some patients with clinical evidence of cobalamin deficiency may have serum levels within the normal range. Since falsely increased values of cobalamin can be caused by alcoholic liver disease, we evaluated the impact of this disease on the diagnosis of cobalamin and folic acid deficiency. Methods We reviewed data of 101 adult patients with megaloblastic anemia assessed by measuring in parallel serum cobalamin, serum folate and red blood cell folate levels. Further tests were performed in order to find the cause of megaloblastosis. All patients were treated with cobalamin and/or folic acid therapy. Results Vitamin B12, folate and both deficiency were found in 86, 5 and 6 cases respectively. Normal cobalamin serum levels, normal serum and erythrocyte folate levels were found only in 3 patients, all alcohol-dependent, while in another alcoholic borderline vitamin B12 serum levels were found. All the four patients responded to cobalamin treatment. Conclusion Some alcohol-dependent patients with megaloblastic anemia may respond to vitamin B12 treatment despite normal cobalamin serum levels; therefore in alcoholics caution is urged in the interpretation of these vitamin assays, because of possible functional vitamin B12 deficiency.