Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 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 gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

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

QJM ◽

10.1093/qjmed/hcz046 ◽

2019 ◽

Vol 113 (1) ◽

pp. 5-15

Author(s):

E Andrès ◽

A -A Zulfiqar ◽

T Vogel

Keyword(s):

Elderly Patients ◽

Vitamin B12 ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

The Elderly ◽

Cochrane Library ◽

Oral Vitamin ◽

Hand Search ◽

Noticeable Improvement ◽

Google Search

Summary 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.

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Prevalence of vitamin B12 deficiency among individuals with type 2 diabetes mellitus in a South Indian rural community

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20180104 ◽

2018 ◽

Vol 7 (2) ◽

pp. 309 ◽

Cited By ~ 2

Author(s):

Shailendra D. ◽

Rizwan Kalani ◽

K. M. Venkat Narayan ◽

Dorairaj Prabhakaran ◽

Nikhil Tandon ◽

...

Keyword(s):

Vitamin B12 ◽

Rural Community ◽

Odds Ratio ◽

Complete Blood Count ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Oral Vitamin ◽

South Indian ◽

B12 Deficiency ◽

Vitamin B12 Supplementation

Background: To estimate the prevalence of vitamin B12 deficiency in a rural south Indian community and to evaluate the association between metformin use and prevalent vitamin B12 deficiency in people with T2DM stratified by oral vitamin B12 supplementation.Methods: Using a cross sectional study design, a random sample of people with T2DM (N=438) was recruited from a rural community. Vitamin B12 deficiency was defined as serum B12 ≤200pg/ml. Data on metformin dose, duration of use, oral vitamin B12 supplementation, and diet were collected. Laboratory measurements included complete blood count, tests for hepatic, renal, and thyroid function, as well as serum vitamin B12 levels and HbA1c.Results: The prevalence of vitamin B12 deficiency in people with T2DM was 11.2% (95% Confidence Interval (CI) 8.2%-14.1%). The odds of vitamin B12 deficiency in patients receiving a metformin dose of 2 grams/day were 4 times higher compared to those receiving ≤1 gram/day, after adjusting for oral B12 supplementation (odds ratio 4.2;95% CI 1.5-11.8). The odds of vitamin B12 deficiency in those taking metformin and receiving oral vitamin B12 supplementation were lower compared to those on metformin and not receiving vitamin B12 supplementation (adjusted odds ratio 0.20; 95% CI 0.06-0.70).Conclusions: Vitamin B12 deficiency affects 1 in 10 people with T2DM, is associated with higher dose metformin use, and oral vitamin B12 supplementation mitigates B12 deficiency in this group.

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Indigenous indicators of vitamin B12 deficiency

PERSPECTIVES IN MEDICAL RESEARCH - 2 ◽

10.47799/pimr.0802.10 ◽

2020 ◽

Vol 8 (2) ◽

pp. 38-46

Author(s):

Deepak Kumar P ◽

Darshana Makwana ◽

Pragathi Pragathi

Keyword(s):

Vitamin B12 ◽

Complete Blood Count ◽

Clinical Manifestations ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Screening Tests ◽

Mean Corpuscular Hemoglobin ◽

Cross Sectional ◽

Predictive Values ◽

B12 Deficiency

Introduction: Clinical manifestations of vitamin B12 deficiency are mostly non-specific. An entity called subclinical deficiency has become popular where the need has arisen to perform costly investigations which indicate functional deficiency of vitamin B12 even when vitamin B12 levels are normal. These factors pose a challenge in planning management of patients. Aims and objectives : The study was conducted as an attempt to identify affordable and credible laboratory indicators of vitamin B12 deficiency which can be used as screening tests before choosing patients for further evaluation or treatment. Material and Methods : This was a time bound cross-sectional study where 100 adult patients who had undergone the following investigations were randomly chosen: Complete Blood Count with red cell indices, serum bilirubin and serum vitamin B12 levels. The sensitivity, specificity and predictive values (positive-PPV and negative-NPV) of the variables that could hypothetically identify vitamin B12 deficiency, both individually or in combinations were calculated and compared. Results and conclusion : Hemoglobin, MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Hemoglobin), platelets and bilirubin were not equally distributed between vitamin B12 deficient and normal groups(p values for these variables were 0.029, 0.000, 0.000, 0.003 and 0.029 respectively).When these variables were tested individually and in combination, the combination of [MCV=95 fl or MCH=30 pg or Platelets =1.4 lakh/µl or Bilirubin =1 mg/dl] had sensitivity of 68.2%, specificity of 85.7%, PPV of 78.9% and NPV of 77.4%. This proposed combination used as a screening test has potential for wide application considering its simplicity and cost advantage.

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Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood

Blood ◽

10.1182/blood.v49.6.987.bloodjournal496987 ◽

1977 ◽

Vol 49 (6) ◽

pp. 987-1000 ◽

Cited By ~ 2

Author(s):

R Carmel ◽

B Tatsis ◽

L Baril

Keyword(s):

Vitamin B12 ◽

Binding Capacity ◽

Megaloblastic Anemia ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

High Serum ◽

The Status ◽

B12 Deficiency ◽

Long Acting

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

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EFEK FORTIFIKASI VITAMIN B12 TERHADAP KADAR VITAMIN B12 SERUM DAN HOMOSISTEIN SERUM PADA VEGETARIAN

Jurnal Ilmu Kesehatan Bhakti Husada: Health Sciences Journal ◽

10.34305/jikbh.v11i1.150 ◽

2020 ◽

Vol 11 (1) ◽

pp. 114-120

Author(s):

Susianto Susianto

Keyword(s):

Vitamin B12 ◽

Homocysteine Level ◽

Megaloblastic Anemia ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Natural Sources ◽

Serum Homocysteine ◽

Microparticle Enzyme Immunoassay ◽

B12 Deficiency ◽

Community Trial

Introduction: Vegetarians consume plant-based foods with or without eggs and milk. Vegetarians are at risk of vitamin B12 deficiency, as natural sources of vitamin B12 are limited to animal-based foods. Vitamin B12 deficiency can lead to megaloblastic anemia, nerve damage and increase homocysteine level. Higher homocysteine level can increase the risk of coronary heart disease and stroke. The objective of this study was to investigate the effect of vitamin B12 fortification on the level of serum vitamin B12 and homocysteine in vegetarian. Method: The research design was an experimental study, community trial. The samples were 42 vegetarians with vitamin B12 deficiency (< 156 pmol/L) selected from 118 vegetarians as members of Indonesia Vegetarian Society (IVS) Pekanbaru, treated by vitamin B12 fortified oatmeal for three months from March to June 2010. Serum vitamin B12 and homocysteine were measured by electrochemiluminescent immunoassay and microparticle enzyme immunoassay method respectively. Result: Prevalence of vitamin B12 deficiency in vegetarian was 35.6%. Statistical analysis showed a significant increase of serum vitamin B12 from 124.6 to 284.6 pmol/L (p=0.001) and significant decrease of serum homocysteine from 20.1 to 15.1 µmol/L (p=0.001). Conclusion: Consumption of vitamin B12 fortified oatmeal increases the level of serum vitamin B12 and decreases the level of serum homocysteine significantly in vegetarian with vitamin B12 deficiency.

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RELATIONSHIP OF MATERNAL VITAMIN B12 STATUS IN PREGNANCY WITH PRETERM BIRTH AND MATERNAL HEALTH RISKS

International Medical Journal ◽

10.37436/2308-5274-2020-2-7 ◽

2020 ◽

pp. 32-38

Author(s):

VICTORIA LAZAROVA SPASOVA ◽

LILIA IVANOVA KOLEVA ◽

MARIETA ANTONOVA POPOVA ◽

VALENTINA BOYANOVA PETKOVA ◽

MILEN VENTZISLAVOV DIMITROV

Keyword(s):

Preterm Birth ◽

Vitamin B12 ◽

Pregnant Women ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Inverse Association ◽

Maternal Vitamin ◽

B12 Deficiency ◽

The Impact ◽

In Pregnancy

Vitamin B12 is known to be vital for cell growth and population during pregnancy. This retrospective and prospective case−control study was aimed to disclose a health risk for pregnant women with vitamin B12 deficiency, as well as the one of the preterm birth. The main tasks set and performed in this research were as follows: to compare the obstetrics anamnesis between the women who gave birth on term and women who gave birth before term; to find the prevalence of vitamin B12 insufficiency in pregnancy; to determine its association with preterm birth and low birth weight; to examine its association with spontaneous abortions, and to investigate its relationship with obesity and hemoglobin levels in pregnant women. The conducted investigation involved 107 women who gave birth before the 37th week of gestation and 101 women who gave birth after the 37th week of gestation at the outpatient clinic of the University Hospital "Maichin Dom" in Bulgaria. Our study revealed a correlation between maternal vitamin B12 deficiency, overweight and low hemoglobin level. Our results showed no significant correlation between serum vitamin B12 level and the risk of preterm birth. However, we found an inverse association between vitamin B12 level and overweight before pregnancy and at the time of giving birth. As well there was confirmed the strong connection between meat consumption and vitamin B12 level. The paper emphasizes that the deficiency of the vitamin occurs most likely in the women with inadequate diets. Such a deficiency is actually confirmed to have serious health consequences for pregnant women and their offspring. Therefore further profound and numerous studies should be performed to properly assess the correlation between vitamin B12 and preterm birth, as well as to understand better the impact of vitamin B12 over pregnant women. Key words: vitamin B12, preterm birth, pregnancy, overweight, hemoglobin.

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REVERSIBLE NEUROPATHY OF VITAMIN-B12 DEFICIENCY WITH NORMAL HÆMOGLOBIN AND SERUM-VITAMIN-B12

The Lancet ◽

10.1016/s0140-6736(77)92989-0 ◽

1977 ◽

Vol 309 (8015) ◽

pp. 803 ◽

Cited By ~ 7

Author(s):

H. Melsom ◽

S. Kornstad ◽

U. Abildgaard

Keyword(s):

Vitamin B12 ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

B12 Deficiency

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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review

Nutrients ◽

10.3390/nu11112557 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2557 ◽

Cited By ~ 8

Author(s):

Martín-Masot ◽

Nestares ◽

Diaz-Castro ◽

López-Aliaga ◽

Alférez ◽

...

Keyword(s):

Celiac Disease ◽

Iron Deficiency ◽

Vitamin B12 ◽

Clinical Manifestations ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Intestinal Biopsy ◽

B12 Deficiency ◽

Endomysial Antibodies ◽

Inflammatory Bowel

Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.

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