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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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Objectives: Anaemia is a significant problem in the elderly, and the cause of anaemia in approximately one third of the general population is unidentified. To date, only a few studies have focused on hospitalised patients., Patients and Methods: We prospectively included anaemic patients (according to OMS criteria) aged 65 years and older who were hospitalised in the internal medicine department. The typical clinical data were collected, and a standardised set of biological tests, including cupraemia was performed., Results: Of 360 total patients, 191 (53%) patients were anaemic; however, 96 patients were excluded because their data were incomplete. Of the remaining 95 patients that were included, 45 were men (47.4%) and 50 were women (52.6%); the mean patient age was 79.7 years (66-101 years). At least one cause of anaemia was diagnosed in 87 of the 95 (91.6%) patients, and anaemia was multifactorial in 44 of the 95 (46.3%) cases. The five most prominent causes of anaemia were inflammation (62.1%), iron deficiency (30.5%), folic acid deficiency (21%), chronic renal failure (17.9%) and cobalamin deficiency (11.6%). Microcytosis was present in only 27.5% of the patients who had an iron deficiency, and macrocytosis was present in only 7.4% of the patients who had a folic acid and/or cobalamin deficiency. The cause of anaemia could not be identified for 8 of the patients. The cupraemia was normal in all the patients., Conclusion: A predefined protocol for older hospitalised patients was ability to identify the aetiology of anaemia in 91.6% of the cases; strikingly, anaemia was frequently caused by more than one factor (43.5%). Diagnostic orientation based on the mean corpuscular volume does not appear to correlate with mean cellular volume profile. Finally, anaemia caused by an unknown aetiology is rare and copper deficiency was not documented in any case., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study is to validate the efficacy and safety of oral cobalamin therapy in the treatment of cobalamin deficiency related to various causes., Patient and Method: It's a retrospective study, including 31 patients with documented cobalamin deficiency related to food-cobalamin malabsorption (n=20) and pernicious anemia (n=11). These patients were treated at least for 3 months with oral cyanocobalamin, between 125 to 1000microg per day. Serum cobalamin levels and hematological parameters were compared before and after the therapy and in relation with the nature of cobalamin deficiency. Safety data were also recorded., Results: After 3 months of therapy, the serum cobalamin levels have significantly increased in all the patients, with a mean of +161.6±79.3pg/mL in the food-cobalamin malabsorption group (P<0,00005) and +136.7±67.4pg/mL in the pernicious anemia group (P<0,0001). Hematological parameters have been normalized in 90 % of the patients, independently of the cause of the cobalamin deficiency. Only 1 patient presented an urticarial reaction., Conclusion: This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

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.

The objective of this review was to evaluate oral cobalamin (vitamin B(12)) therapy in adult and elderly patients, from the perspective of a hematologist. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Data from our working group, the 'Groupe d'étude des carences en vitamine B(12)des Hôpitaux Universitaires de Strasbourg', have also been included. Several prospective studies in well-determined population (n = 4), prospective randomized studies (n = 3) and a systematic review by the Cochrane group (n = 1) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency, particularly hematological abnormalities or manifestations. These studies suggest that at least 1000 microg/day of oral cyanocobalmin are needed for pernicious anemia and a mean daily dose of 250 microg for food-cobalamin malabsorption. This present review confirms the previously reported efficacy of oral cobalamin treatment in adult and elderly patients.

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age), but is often unrecognized because of its subtle clinical manifestations; although they can be potentially serious, particularly from a neuropsychiatric and hematological perspective. In the general population, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome, which has only recently been identified, is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Besides these syndromes, mutations in genes encoding endocytic receptors involved in the ileal absorption and cellular uptake of cobalamin have been recently uncovered and explain, at least in part, the hereditary component of megaloblastic anemia. Management of cobalamin deficiency with cobalamin injections is currently well codified, but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Prospective randomized studies (n=3), a systematic review by the Cochrane group (n=1) and prospective studies in a well defined population (n=5) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature does not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment. This review confirms the previously reported efficacy of oral cobalamin treatment in elderly patients. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections.

Purpose: During last decades, several progresses have been made in the diagnosis of cobalamin (vitamin B12) deficiency. Routine used of cobalamin standardized assays have potentially modified the frequency and the type of hematologic abnormalities., Current Knowledge and Key Points: Current studies on cobalamin deficiency, including more precise definitions and the description of new etiologies of cobalamin deficiency in adults, as the food-cobalamin malabsorption syndrome, show that hematological abnormalities are generally incomplete compared to historical descriptions of megaloblastic anemia. Nevertheless, they include severe manifestations in 10% of the patients: pancytopenia, severe anemia (hemoglobin < 6 g/dl) or hemolytic anemia and pseudo thrombotic microangiopathy related to cobalamin deficiency. These studies also show the efficacy of new treatment modalities including oral cobalamin administration., Prospects and Projects: Future studies will confirm these data with the routine use of the new cobalamin assay: holotranscobalamin and validate the usefulness of oral cobalamin therapy.

With the introduction of automated assays for measuring serum cobalamin levels over the last decades, the hematological manifestations related to cobalamin deficiency have been changed from the description reported in 'old' studies or textbooks. We studied the hematological manifestations or abnormalities in 201 patients (median age: 67 +/- 6 years) with well-documented cobalamin deficiency (mean serum vitamin B12 levels 125 +/- 47 pg/ml) extracted from an observational cohort study (1995-2003). Assessment included clinical features, blood count and morphological review. Hematological abnormalities were reported in at least two-third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%), macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level was 10.3 +/- 0.4 g/dl and the mean erythrocyte cell volume 98.9 +/- 25.6 fl. Approximately 10% of the patients have life-threatening hematological manifestations with documented symptomatic pancytopenia (5%), 'pseudo' thrombotic microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl; 2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities was achieved in at least two-thirds of the patients, equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. This study, based on real data from a single institution with a large number of consecutive patients with well-documented cobalamin deficiency, confirms several 'older' findings that were previously reported before the 1990s in several studies and in textbooks.

Objectives: The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM)., Patients and Method: Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment., Results: 85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline)., Conclusions: Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

Purpose: Update of the adult cobalamin deficiencies., Current Knowledge and Key Points: More precise definitions establish the true cobalamin deficiencies and determine their real epidemiology. The current clinical data suggest the concept of food-cobalamin malabsorption as the leading etiology of cobalamin deficiency. The new features of cobalamin deficiency include neurological, gynecological and vascular manifestations. Current treatment modalities include nasal, sublingual and oral cobalamin administration., Prospects and Projects: Studies are in the way to establish the relevance of the new clinical manifestations and to validate the usefulness of oral cobalamin therapy.

Purpose: Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences., Subjects and Methods: We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency., Results: The median patient age was 76 +/- 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum homocysteine level of 22.1 +/- 9.3 micromol/L. The mean hemoglobin level was 10.9 +/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin., Conclusions: This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.

Objective: Non-dissociation of vitamin B12 from its carrying proteins is the most frequent cause of vitamin B12 deficiency in the elderly. The aim of this study was to determine the initial dose of oral cyanocobalamin that would correct the B12 vitamin deficiency within one week., Methods: This was an open, prospective, study on 30 elderly patients suffering from vitamin deficiency (B12 < 0.20 microg/L) induced by food-cobalamin malabsorption. Ten patients (group I) were treated with a daily dose of 1000 microg of oral cyanocobalamin (from D1 to D8), 10 (group II) with 1000 microg every other day (D1, D3, D5 and D7), 5 (group III) with 1000 microg every 4 days (D1 and D5) and 5 (group IV) with 1000 microg only on D1. The biological response was assessed by control measurement of vitamin B12 serum levels on the 8th day., Results: Mean vitamin B12 serum levels had significantly increased (p < 0.01) in groups I, II and III, but not in group IV. The dose-effect, assessed by the mean increase in vitamin B12 serum levels, was significantly greater (p < 0.05) in groups I (0.25 microg/L) and II (0.18 microg/L), than in groups III and IV (0.09 microg/L)., Conclusion: This prospective study shows that an oral dose of 1000 microg of cyanocobalamin every 4 days, which corresponds to 250 microg per day, was sufficient to correct B12 vitamin deficiency induced by food-cobalamin malabsorption within one week. However, initial doses of 1000 microg per day or every other day would be preferable because of the greater dose-effect with daily doses higher than 500 microg. A randomised study is warranted to validate these preliminary results.

Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

Purpose: Update on cobalamin deficiencies in adults., Current Knowledge and Key Points: More precise definitions establish real cobalamin deficiency and determine epidemiological features. Current data on cobalamin metabolism suggest the concept of non-dissociation of vitamin B12 from its carrier proteins (NDB12), a generalization of the food-cobalamin malabsorption concept. The new features of cobalamin deficiency include neurological, gynecological and vascular manifestations. Current treatment modalities include nasal and oral administration of cobalamin., Prospects and Projects: Validate the concept of NDB12 and the usefulness of oral cobalamin therapy, establish the relevance of the new clinical manifestations.

Background: It has been suggested that oral cobalamin (vitamin (B12)) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption. However, the duration of this treatment was not determined., Patients and Method: In an open-label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption, who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month., Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment., Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 x 10(6)/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05)., Conclusion: Our findings suggest that crystalline cyanocobalamin, 250-1000 microg/day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.

Purpose: Approximately 15% of people over 60 years old have a cobalamin (Cbl) deficiency in relation with a food-cobalamin malabsorption (FCM). But to date, only case reports or small series have been reported. The aim of this study was to describe the clinical characteristics of the FCM in old subjects., Methods: Sixty patients, at least 65 years old, presenting a Cbl deficiency related to FCM, were extracted from a cohort study of the Hôpitaux universitaires de Strasbourg, France (n = 169). All these patients had an established diagnosis of Cbl deficiency and met the Carmel's criteria of FCM. Their clinical data were retrospectively analysed., Results: The median age of the 60 patients was 75 years and the female/male ratio was 2.3. The principal clinical symptoms were peripheral neuropathy (35%), confusion and dementia (30%) and anemia-related manifestations such as asthenia and edemas of the legs (20%). Average hemoglobin was 10.7 +/- 2.5 g/dl and average mean erythrocyte cell volume was 95.5 +/- 13.8 fl. There was an anemia, a leucopenia, a thrombocytopenia and a pancytopenia in respectively 27%, 18%, 15% and 8% of the cases. Average serum vitamin B(12) and homocystein levels were with 138 +/- 42 pg/ml and 22.5 +/- 15.2 micro mol/l. No patient had anti-intrinsic factor antibody and the Schilling's test was normal in all patients. Main disorders associated with FCM were atrophic gastritis (59%), long-term metformin or antiacid intake (17%), chronic alcohol intake (8%) and idiopathic FCM (n = 10). Sixteen patients have been successfully treated with oral crystalline cyanocobalamin (500 +/- 280 micro g/d)., Conclusions: This study shows that: firstly, the Cbl deficiency related to FCM may be responsible of severe neurological and hematologic manifestations in approximately 20% of the elderly patients; secondly, the disorders associated with the FCM are multiple in old age, with mainly atrophic gastritis; and thirdly, in clinical practice, oral cyanoCbl treatment may be successful.

Purpose: Standard treatment of vitamin B12 deficiency involves regular intramuscular cobalamin administration. The aim of this study was to determine whether oral cobalamin treatment may be an effective therapy for treating older patients with cobalamin deficiency related to nutritional deficiency and food-cobalamin malabsorption., Patients and Methods: We prospectively studied 20 patients older than 80 years with established cobalamin deficiency related to food-cobalamin malabsorption (n=14) and nutritional deficiency (n=6) who received 1000 micro g of oral cyanocobalamin per day. Levels of serum cobalamin and blood counts were determined at baseline and after the first week of treatment., Results: After an average of 8 days of treatment, 17 out of 20 patients normalized their serum cobalamin levels; the patients had increased their serum cobalamin level (mean increase of 0.23 micro g/L; p<0.01 compared with baseline), reticulocyte count (mean increase of 27400/mm(3); p<0.05), hemoglobin levels (mean increase of 0.7 g/dL; NS), and decreased the mean erythrocyte volume (mean decrease of 0.7 fL; NS)., Conclusion: Our findings suggest that cyanocobalamin given orally during one week may be an effective treatment for cobalamin deficiency related to food-cobalamin malabsorption and nutritional deficiency and may avoid painful intra-muscular injections in older patients.

Background: The standard treatment for cobalamin (vitamin B(12)) deficiency involves regular intramuscular cobalamin injection. It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption., Subjects and Methods: We prospectively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months. Complete blood counts and serum cobalamin, homocysteine, and folate levels were determined at baseline and after 3 months of treatment. Patients were reexamined after 6 months., Results: After 3 months of treatment, all patients had increased hemoglobin levels (mean increase, 1.9 g/dL; 95% confidence interval: 0.9 to 3.9 g/dL;P <0.01 compared with baseline) and decreased erythrocyte cell volume (mean decrease, 7.8 fL; 95% confidence interval: 0.9 to 16.5 fL;P<0.001). However, 2 patients had only minor, if any, responses. Serum cobalamin levels were increased in all 8 patients in whom it was measured., Conclusion: Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption.

Introduction: In young subjects, the discovery of a cobalamine deficiency (Biermer's disease) at the time of neuropsychiatric disorders even of isolated MRI anomalies is a rare event (less than 0.01%)., Exegesis: We report two observations of cobalamine deficiency, in patients 30 and 37 years old, revealed by acroparesthesia and spontaneous hypersignal in the T2 sequence of MRI and by a peripheral sensitive neuropathy respectively., Conclusion: The neuropsychiatric demonstrations of pernicious anemia are polymorphic with, sometimes, isolated spinothalamic attacks. The MRI can contribute to the diagnosis but more often leads to an erroneous diagnosis. Our observations are of special interest because symptoms occurred apart from supplementation of folates and recovered ad integrum with an early treatment by vitamin B12.

Purpose: New hypotheses have recently been developed on vitamin B12 deficiency and the frequently observed occurrence in the elderly subject of food cobalamin malabsorption, i.e., the non-dissociation of B12 and its carrier protein (ND B12), and the possibility of rectifying this imbalance by oral crystalline B12 supplementation. The aim of this study was therefore to confirm these hypotheses in a series of patients aged over 75 years with anemia due to B12 deficiency., Methods: A retrospective study was carried out over a 5-year period on patients aged over 75 years presenting with megaloblastic anemia (hemoglobin [Hb] < 12 g/dL) and vitamin B12/cobalamin deficiency (B12 < 160 pg/mL)., Results: Twenty cases were analyzed. The average age of the patient population was 82.5 +/- 6 years, and the F/M sex ratio was 1:2. Mean Hb levels were 7.9 +/- 2.4 g/dL, mean serum B12 levels were 83 +/- 24 pg/mL, and mean homocysteinemic levels were 35 +/- 27 mumol/L. The diagnosis was as follows: food cobalamin malabsorption/ND B12 (n = 10), Biermer's disease/pernicious anemia (n = 5), malabsorption due to pancreatic insufficiency (n = 1), and low dietary B12 levels (n = 1). Disorders associated with ND B12 were: atrophic gastritis and Helicobacter pylori infection (n = 6), antacid or biguanide intake (n = 3), alcohol abuse (n = 2), or idiopathic syndrome (n = 2). In the patients who were followed up (n = 10), i.m. (n = 5) or oral (n = 5) administration of crystalline B12 resulted in the correction of hematological abnormalities., Conclusion: In the elderly subject, food cobalamin/ND B12 malabsorption appears to be the main cause of B12 deficiency, and is frequently associated with atrophic gastritis. In these cases, administration of oral crystalline B12 may be an efficient means of treating this disorder.