Development Of Vitamin B12 Deficiency Research Articles

Effect of metformin therapy on the development of vitamin B12 deficiency in patients with type 2 diabetes mellitus

Introduction. For the past decades, metformin has been the drug of choice for the treatment of patients with type 2 diabetes mellitus (T2DM). However, its long-term use leads to a number of side effects, such as the development of vitamin B12 deficiency (VB12).Aim. Assess the safety of metformin use in real clinical practice in the treatment of patients with type 2 diabetes based on the analysis of the incidence of VB12 deficiency.Materials and methods. Sixty patients with T2DM aged 27 to 65 years were examined in a city polyclinic. The average anamnestic duration of T2DM was 68 [4; 291] months. All patients were on selected hypoglycemic therapy: 19 patients (31.7%) received metformin monotherapy, and 41 patients (68.3%) received metformin as part of combination therapy. The average duration of metformin therapy was 62 [3; 291] months. All patients underwent analysis of the VB12 content in the blood serum depending on the duration of metformin intake. Results. The average VB12 level in the examined patients was 345 [99; 770] pg/ml. Normal VB12 levels were observed in 51 (85%) patients (386 [221; 770] pg/ml), VB12 deficiency (<200 pg/ml) was detected in 9 (15%) patients (146 [99; 195] pg/ml), the differences between VB12 levels were significant (p < 0.05). At the same time, in 37 (61.7%) patients with normal VB12 levels, its values were assessed as borderline (in the range of 200–450 pg/ml), and amounted to 335 [221; 470] pg/ml. VB12 deficiency developed more often in patients taking metformin for more than 1 year (16.7%), borderline VB12 levels were more often found in patients taking metformin for less than a year (58.3%) and more than 5 years (71%). However, the dependence of VB12 levels on the duration of metformin intake was not significant (p > 0.05).Conclusion. Metformin use results in the development of VB12 deficiency in every sixth patient with T2DM, primarily after one year of treatment.

Vitamin B12 deficiency and neuropsychiatric symptoms in Lebanon: A cross-sectional study of vegans, vegetarians, and omnivores.

Vitamin B12 deficiency is responsible for a variety of complications, particularly neurological/neuropsychiatric complications, including depression, irritability, paresthesia and insomnia. Since vitamin B12 is found in animal-derived products, vegans/vegetarians are at a greater risk for developing vitamin B12 deficiency. This study aims to investigate the occurrence of vitamin B12 deficiency among a sample of adult Lebanese population, with a particular emphasis on assessing the severity of its neurological/neuropsychiatric signs and symptoms, especially among vegans/vegetarians. A cross-sectional study was conducted among a sample of 483 Lebanese adults. Data was collected through a standardized questionnaire that included socio-demographic characteristics, the Patient Health Questionnaire-9 (PHQ-9), Generalized anxiety disorders-7 (GAD-7), and the Insomnia Severity Index (ISI) scales. Among the participants, 11.4% were in the vegan/vegetarian group, and about 43.1% had vitamin B12 deficiency. After analyzing the PHQ-9, GAD-7 and ISI total scores, higher scores were reported in participants with vitamin B12 deficiency, compared to individuals with normal vitamin B12 serum levels (p < 0.001). Regarding the diet type, vegans/vegetarians were more susceptible to developing depression compared to omnivores (mean scores of 11.92 vs 8.02 on the PHQ-9 scale, respectively, with p < 0.001). Of the patients with vitamin B12 deficiency, 81.1% reported having paresthesia compared to 43.7% of individuals with no vitamin B12 deficiency (p < 0.001). Vitamin B12 deficiency in Lebanon is notably high and is linked to an increased risk of developing depression, generalized anxiety disorder, insomnia, and paresthesia. Vegans/vegetarians exhibit a higher susceptibility to developing depression compared to omnivores, whereas the risk of developing insomnia, generalized anxiety disorder and paresthesia was statistically insignificant when comparing vegans/vegetarians to omnivores.

Iron and Vitamin B12 Deficiency in Patients with Autoimmune Gastritis and Helicobacter pylori Gastritis: Results from a Prospective Multicenter Study.

Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85-57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32-6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients.

Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis.

The popularity of plant-based diets, characterized by a partial or complete exclusion of animal products, has increased significantly over the last 10 years. The exclusion of animal products removes the most common sources of vitamin B12, which can lead to vitamin B12 deficiency and result in irreversible damage, such as growth stunting. This aim of this systematic review and meta-analysis was to qualitatively evaluate all studies on this subject and to quantify the potential difference in vitamin B12 levels in healthy children and adolescents aged 5 to 18 years. PubMed and Embase databases were searched for relevant studies investigating vitamin B12 levels in healthy children and adolescents aged 5 to 18 years on plant-based diets. Studies were assessed qualitatively with the AXIS tool and quantitatively with Stata 16.0 software. Overall, children and adolescents on plant-based diets had a significantly lower vitamin B12 level than omnivorous children and adolescents (-97 pmol/L; 95%CI, -187 to -7; I2 = 98.5%), a difference that remained statistically significant after adjusting for methodological confounders. After subgroup analyses, this effect was not statistically significant for children and adolescents on vegetarian diets but remained significant in children and adolescents on vegan or macrobiotic diets. Moreover, total vitamin B12 intake nullified the mean difference in vitamin B12 levels. Despite high heterogeneity across studies, these results indicate that children and adolescents on plant-based diets, especially those on vegan and macrobiotic diets, may be at risk of developing vitamin B12 deficiency.

Production and characterization of cyanocobalamin-enriched tomato (Solanum lycopersicum) fruits grown using hydroponics.

Vitamin B12 is an essential vitamin that is absent in plant-derived foods such as fruits and vegetables. This can result in an increased risk of developing vitamin B12 deficiency in strict vegetarians (vegans). There are several studies that have aimed to enhance nutrients in food crops. The purpose of the present study was to fortify tomato fruits with vitamin B12 (or cyanocobalamin). Tomato plants were grown for 70 days in hydroponic culture pots and treated with 5μm of cyanocobalamin on days 1-24 after the fruiting, and then harvested for tomato fruits. The ripened tomato fruits contained 4.0 × 10-7 g of cyanocobalamin per 100 g of dry weight and showed a significant increase in glucose and lycopene levels. The present study highlights the use of a cyanocobalamin-supplementation system for the production of B12 fortified tomato fruits that can help prevent B12 deficiency in vegetarians. © 2022 Society of Chemical Industry.

Comparison of the Efficacy of Oral Methylcobalamin Tablets vs. Nasal Spray (NASO B12) in Diabetic Patients on Metformin Therapy

Context: Metformin is known to increase in the risk of developing vitamin B12 deficiency. This study aimed to compare the effectiveness of nasal spray of methylcobalamin (NASO B12) and methylcobalamin tablets for treating vitamin B12 deficiency in diabetic patients receiving metformin. Materials and Methods: In this parallel-group, comparative, open-label clinical study, patients (n = 100) were assigned to two groups: nasal spray of methylcobalamin (NASO B12) (methylcobalamin 250 µg/spray), sprayed in each nostril every alternate day for a total of seven doses (Group 1: a total of 3500 µg methylcobalamin per patient) and oral methylcobalamin tablets, a single daily dose of 1500 µg for a total of seven doses (Group 2: a total of 10,500 µg methylcobalamin per patient). The assessment of efficacy was carried out by measuring serum vitamin B12 levels at baseline, day 7, and day 14. Statistical Analysis Used: The analysis used is Student’s unpaired t-test. Results: NASO B12 treatment resulted in vitamin B12 levels of ≥400 pg/mL (recently updated normal levels as per American Academy of Family Physicians) in 86% and 92% of patients, on day 7 and day 14, respectively, whereas no patient attained ≥400 pg/mL with oral therapy. NASO B12 therapy resulted in higher mean vitamin B12 levels of 485.88 and 570.16 pg/mL when compared with 172.26 and 185.44 pg/mL with oral tablets on day 7 and day 14, respectively. Conclusion: NASO B12 provided much superior absorption of vitamin B12 when compared with oral vitamin B12 tablets and can be used as an effective alternative.

Prevalence and Risk Factors of Vitamin B12 Deficiency among Pregnant Women in Rural Bangladesh.

Vitamin B12 deficiency is associated with an increased risk of pregnancy complications and adverse birth outcomes. However, data on vitamin B12 deficiency in pregnant Bangladeshi women are limited. This study examines vitamin B12 deficiency and marginal deficiency in rural Bangladeshi women during early and late pregnancies. Some 522 women whose gestational age was <20 weeks were recruited. Serum vitamin B12 concentrations were measured at baseline and after 14 weeks of iron-folate supplementation. Logistic regression analysis examined the association of various socio-demographic, dietary, and pregnancy-related factors with vitamin B12 deficiency and marginal deficiency. Overall, 19% of the women during early pregnancy had vitamin B12 deficiency (serum vitamin B12 concentration < 203 pg/mL) and nearly 40% had marginal deficiency (serum vitamin B12 concentration 203 to <300 pg/mL). Vitamin B12 deficiency doubled to 38% during late pregnancy, while marginal deficiency slightly increased to 41.7%. The pregnant women with a gestational age of ≥27 weeks had a higher risk of developing vitamin B12 deficiency (OR = 2.61; 95% CI = 1.096–6.214) than those of a gestational age of <27 weeks. Vitamin B12 deficiency was significantly higher in pregnant women in rented accommodation (OR = 13.32; 95% CI = 1.55–114.25) than in those living in their own house. Vitamin B12 deficiency was significantly higher among women who consumed red or organ meat <3 times a week than in those who consumed it more often (OR = 2.327, 95% CI = 1.194–4.536). None of these factors were significantly associated with marginal vitamin B12 deficiency. In conclusion, vitamin B12 deficiency and marginal deficiency among pregnant rural Bangladeshi women increased as their pregnancies progressed. Increasing gestational age, living in a rented house, and the consumption of red or organ meat <3 times a week were identified as the independent risk factors of vitamin B12 deficiency in this population. Further research with more in-depth assessments of dietary vitamin B12 intakes is needed to develop an intervention program preventing vitamin B12 deficiency in this population.

Vegetarians, Pescatarians and Flexitarians with Adequate Vitamin B12 Levels Have No Increased Risk of Polyneuropathy.

In recent years, an increasing number of people adapt to a vegetarian, pescatarian or flexitarian dietary pattern that reduces the consumption of meat and fish. Although these dietary patterns have a risk for developing vitamin B12 deficiency associated polyneuropathy, it is unknown whether this risk is still increased when vitamin B12 levels are adequate. To examine whether a vegetarian, pescatarian or flexitarian dietary pattern is associated with an increased risk for idiopathic axonal polyneuropathy. We conducted a case-control study that included 256 idiopathic axonal polyneuropathy patients with adequate vitamin B12 blood levels and 630 controls. We used questionnaire data to determine the frequency of meat and fish consumption and defined dietary patterns. The vegetarian (no meat or fish consumption) and the pescatarian (fish consumption, no meat consumption) dietary patterns showed no increased risk of axonal polyneuropathy. Frequency-effect analysis and quantity-effect analysis also did not show that a reduction of meat or fish consumption (flexitarian dietary pattern), either small or large, changed the risk of axonal polyneuropathy. We did not find an increased risk for axonal polyneuropathy among people with a vegetarian, pescatarian or flexitarian diet and an adequate vitamin B12 level.

Prevalence of Vitamin B12 Deficiency In Patients With Type II Diabetes Mellitus On Metformin

Background: Diabetes Mellitus is one of the most encountered disease in our out patient department and metformin is the first drug of choice to treat Diabetes mellitus. As metformin is one of the cheapest drug, many patients use these drug for long period of time with consultation and without consultations with doctors. Patients under long term metformin use are not aware of Vitamin B12 deficiency and its associated signs and symptoms. In Nepal due to poverty, lack of education and awareness on diabetes mellitus we doctors find much difficult to explain patients on the consequences of diseases. So I decided to do this study which could be much easier to explain patients on effect of metformin of vitamin B12 levels and the consequences life style modifications and supplement of Vitamin B12 to the patients.&#x0D; Methods: This is a Cross-Sectional Study done in the patients with Type 2 diabetes were selected based on inclusion and exclusion criteria. Basic biochemical investigation were sent the lab of the National academy of medical science. Serum B12 assay were done. Vitamin B12 deficiency is defined as values &lt;150pg/ml. Association between vitamin B12 deficiency with duration of metformin therapy, duration of diabetes, with age, sex were done.&#x0D; Results: The mean vitamin B12 level is low as the duration of metformin treatment increases. The sex, age relation with development of vitamin B12 deficiency was not significant. In my study out of 210 patients 107 patients were having severe vitamin B12 deficiency level and 63 patients had a borderline Vitamin B12 deficiency level which shows that the deficiency increases as per longer use of metformin, which shows prevalence of 50.95%.&#x0D; Conclusions: Vitamin B12 deficiency occurs in type 2 diabetes mellitus patients treated with long term metformin. The duration of metformin therapy significantly affects the development of vitamin B12 deficiency. As a treating physician we always need to explain our patients about the side effect of metformin and regular follow up and investigations must be done to early diagnosis of vitamin B12 deficiency to improve the quality of life.

Review of Vitamin B12 deficiency in pregnancy: a diagnosis not to miss as veganism and vegetarianism become more prevalent.

Vegetarianism and veganism are increasingly popular. The Food Standards Agency, biennial Food and You Survey of adults aged 16years and over living in the UK, found that between 2012 and 2018 the proportion of people who reported never consuming dairy products had increased from 2% to 5%. However, veganism risks development of vitamin B12 deficiency as it is not available from plant sources. Moreover, its impact may be slow to be detected because body stores of vitamin B12 can last years. There is currently no published guidance on antenatal diagnosis and management of vitamin B12 deficiency. This paper reviews the metabolism, diagnosis and treatment of vitamin B12 in pregnancy. It concludes that national screening policymakers should consider introducing screening for B12 deficiency into the Antenatal and Newborn Screening Programmes for mothers and their infants if at risk of vitamin B12 deficiency. In the interim, national policy should be developed for prophylactic vitamin B12 supplementation in high-risk groups around the time of pregnancy.

Presence and absence of carbohydrate metabolism disorders as a factor influencing development of vitamin B12 deficiency

Objective. To study the significance of the presence and absence of carbohydrate metabolism disorders as a factor affecting the development of vitamin B12 deficiency.&#x0D; Materials and methods. The data of 206 subjects, forming two main groups were analyzed: the group of carbohydrate metabolism disorders (CMDs), which included 76 women and 71 men (n = 147); the control group, which included 33 women and 26 men (n = 59). The inclusion criteria were the following: age over 35, availability of anamnestic data on pharmacotherapy, availability of data to clarify the state of carbohydrate metabolism, availability of data on vitamin B12 and some other biochemical indices. Vitamin B12 levels 221 pmol / l were considered normal, vitamin B12 levels from 148 pmol / l to 221 pmol/l were considered borderline (or mild deficiency), and levels of 148 pmol / l or less were considered severe vitamin B12 deficiency.&#x0D; Results. The group of absent carbohydrate metabolism disorders included 59 persons and the group of carbohydrate metabolism disorders (CMDs) included T2DM patients (n = 123) and individuals with prediabetes (n = 24), i.e. the total number of the examined persons in CMD group was equal to 147. The average level of vitamin B12 in the control group (n = 59) was 401.6 and 138.06 pmol / l, and in CMD group (n = 147) it was equal to 342.1 133.10 pmol/l. The differences between the groups were statistically significant (p 0.01), that suggested the significance of CMDs as a risk factor for vitamin B12 deficiency. Vitamin B12 deficiency was combined with the presence of CMDs in 32 (21.8 %) cases. In 115 cases (78.2 %), the presence of CMDs was combined with the absence of vitamin B12 deficiency. In 8 cases (13.5 %), there were no CMDs, but there was vitamin B12 deficiency. In 51 cases (86.4 %), no CMDs and vitamin B12 deficiency was noted.&#x0D; Conclusions. Despite the presence of a statistically significant decrease in vitamin B12 levels in CMD group (342.1 133.10 pmol / l vs 401.6 and 138.06 pmol/ l; p 0.01) and a high incidence rate of vitamin B12 deficiency in CMD group (21.8 % and 13.5 %, respectively), the study results do not allow us to consider the presence of CMDs to be the risk factor for vitamin B12 deficiency.

Vitamin B12 Deficiency in type I Diabetes

Diabetes mellitus is a group of metabolic anomalies due to defect in insulin secretion/action. In type I diabetes, there is complete absence of insulin due to destruction of pancreatic beta cells, whereas type 2 diabetes usually involves insulin resistance. A complex interaction between various environmental, genetic and immunological factors leads to development of diabetes. One major problem for treating T1DM is its difficult prognosis because it leads to many complications, including autoimmune gastritis and celiac diseases. In autoimmune gastritis auto/parietal cell antibodies are formed against the intrinsic factor leading to thegastric atrophy. While in celiac disease, intestinal villi atrophy occurs. Both these conditions have a common clinical outcome which is pernicious anemia. The patients suffering from type I diabetes have approximately threefold increased risk for developing vitamin B12 deficiency as compared to the general population. The major genetic risk factor responsible for this disease is any functional change in HLA class II alleles (HLA DQ, DR and DP). These genes are present on chromosome 6 and are involved in approximately 40% cases of type I diabetes mellitus. The production of glutamic acid decarboxylase and anti-thyroid peroxidase antibodies have also been reported to be associated with this genotype. The glutamic acid decarboxylase converts glutamic acid to gamma-amino butyric acid producing hydrochloric acid from gastric parietal cells. The antibodies against this antigen can cause achlorhydria that can ultimately lead to vitamin B12 deficiency. Hematologic and neurological disorders, as well as a variety of cardiovascular diseases, are the most commonclinical manifestations of deficiency of vitamin B12.

Assessment of Vitamin B12 Deficiency and Risk Factors in Healthy Infants.

To study vitamin B12 deficiency in apparently healthy infants and their mothers and assess the risk factors. A hospital-based, cross-sectional, observational study was conducted from July 2016 through December 2017. Consecutive healthy and normally developing infants were enrolled. Red blood cell folate, plasma vitamin B12, homocysteine and methylmalonic acid levels of mothers and infants were assessed. Seventy-four healthy infants were enrolled. Male-to-female ratio was 1.5:1. Anemia in 66.2% (n = 49), low plasma B12 in 17.6% (n = 13), hyperhomocysteinemia in 48.6% (n = 36), plasma methylmalonic acid in 100% (n = 74) and 'confirmed' B12 deficiency in 38% (n = 28) infants were noted. The proportion of hyperhomocysteinemia increased to 75.7% (n = 56) infants using a lower cut-off of >10μmol/L. In mothers, low B12 in 19%, hyperhomocysteinemia in 57% and elevated plasma methylmalonic acid in 100% were noted. Median plasma B12 level was 314pg/ml (IQR 221-421), median plasma homocysteine 15.4μmol/L (IQR 11.3-21.7) and median plasma methylmalonic acid was 8.28μmol/L (IQR 4.4-13.1) in mothers. Folate deficiency was noted in 9.4% infants and 12% of mothers. Overall, 63.5% mothers were vegetarian and, 64% of the mothers of infants with confirmed vitamin B12 deficiency were pure vegetarians. Odds of developing vitamin B12 deficiency increased by more than 5 times in those whose mothers' serum vitamin B12 levels were low as compared to normal maternal vitamin B12 levels (OR 5.42; 95% CI:1.96-16.6; p 0.002). There is a high prevalence of vitamin B12 deficiency in infants and their mothers. There is urgent need to supplement our population with vitamin B12.

The frequency of vitamin B12, iron, and folic acid deficiency in the neonatal period and infancy, and the relationship with maternal levels.

Aim:The most important function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division and proliferation. Deficiency of vitamin B12 causes megaloblastic anemia, retardation of growth, and delay in neuromotor maturation. Newborns whose mothers have vitamin B12 deficiency are born with low vitamin B12 storages, and are at risk in terms of vitamin B12 deficiency symptoms during infancy. The aim of our study was to investigate the frequency of anemia and deficiency of vitamin B12, folic acid, and iron in pregnant women living in our region, in their newborn babies, and during the infancy period of these babies. Another aim of our study was to investigate the correlation between the levels of these vitamins in newborns and in their mothers.Material and Methods:In our study, 250 pregnant women at 38–42 gestational weeks, who were admitted for delivery to Gynecology and Obstetrics Clinic and their babies with a birth weight over 2500 g were included in the study.Results:We determined that 24.8% of the pregnant women had anemia, 28% had low ferritin levels, 90.4% had vitamin B 12 deficiency, and 22.4% had folic acid deficiency. Some 3.2% of the newborns had anemia, 2.8% had low ferritin levels, and 72.4% had vitamin B12 deficiency. Among the infants who presented for a follow-up visit at 6 months of age, 22.3% had anemia, 14.9% had low ferritin levels, 40.4% had vitamin B12 deficiency, and 1.06% had folic acid deficiency. In addition, we found that the levels of vitamin B12 and folic acid in newborns were related to the levels of vitamin B12 and folic acid in their mothers.Conclusion:Development of low vitamin B12 stores in newborns and the development of vitamin B12 deficiency during infancy, which may result in irreversible complications including neurologic complications, can be prevented by preventing vitamin B12 deficiency during pregnancy.

PREVALENCE AND RISK FACTORS OF VITAMIN B12 DEFICIENCY AMONG PATIENTS WITH TYPE II DIABETES ON METFORMIN: A STUDY FROM NORTHERN REGION OF UNITED ARAB EMIRATES

Objectives: This study focused on the prevalence of Vitamin B12 deficiency in UAE patients with type 2 diabetes mellitus (T2DM) who were treated with or without metformin.Methods: A cross-sectional study was conducted on 213 patients having diabetes type II were randomly selected to be part of the study in Northern Regions of the UAE, from June 2014 to February 2015. The patients aged &gt;45 years and who had taken metformin for at least 3 months were recruited with regular follow-up at the outpatient clinic. The patients were included in a survey after which they had their serum B12 levels measured. Serum B12 levels &lt;150 pg/ml are defined as the B12 deficiency.Results: About 48% of diabetic patients had confirmed the B12 insufficiency through laboratory tests. The patients on metformin had statistically lower values of B12 (p=0.002). The majority of participants n (%) took metformin had neuropathy, hypertension, dyslipidemia, numbness or paresthesia, and depression, or mood changes 140 (70%), 183 (91.5%), 134 (67%), 136 (68%), 161 (80.5%), and 120 (60%), respectively.Conclusion: Our study shows that for the patients with T2DM, long-term treatment with metformin is associated with higher chances of developing Vitamin B12 deficiency. Clinicians should, therefore, recognize this significant element and should screen diabetics who are on metformin treatment for any B12 insufficiency, which may be hidden, especially patients coming with neurologic symptoms.

Characterization of vitamin B12 compounds from marine foods

Vitamin B12 is synthesized by only certain bacteria and archaea but not by animals or plants. In marine environments, bacterial vitamin B12 is transferred and concentrated into fish and shellfish bodies by plankton in the marine food chain. Moreover, marine macrophytic red algae, Porphyra spp. specifically contain substantial amounts of vitamin B12, due to microbial interaction. Although some meats or viscera of edible fish and shellfish are excellent sources of biologically active vitamin B12, an inactive corrinoid, pseudovitamin B12, was found in some edible shellfish using liquid chromatography/electrospray ionization–tandem mass spectrometry. To prevent elderly people from developing vitamin B12 deficiency due to food protein-bound vitamin B12 malabsorption, we present a survey of marine foods containing free vitamin B12. The results of our study suggest that bonito and clam extracts (or soup stocks), which contain considerable amounts of free vitamin B12 are useful not only as seasonings and flavorings but also as excellent sources of free vitamin B12.

Prevalence of Vitamin B12 Deficiency in Patients with Type II Diabetes Mellitus on Metformin: A Study from Khyber Pakhtunkhwa.

BackgroundMetformin is the most common oral hypoglycemic used and associated with certain abnormalities. The objective was to evaluate and define the occurrence and bases of vitamin B12 deficiency amongst patients on Metformin for diabetes mellitus type II.MethodsA cross-sectional study was conducted on 209 patients having diabetes type II between January-December 2016. The patients aged > 45 years and who had taken metformin for at least three months were recruited with regular follow-up at the Endocrinology Unit of Hayatabad Medical Complex and Diabetic Center Hayatabad, Peshawar. The patients were included in a survey after which they had their serum B12 levels measured. Serum B12 levels < 150 pg/ml is defined as the B12 deficiency.ResultsAbout 29.66% of diabetic patients had confirmed the B12 insufficiency through laboratory tests. The patients on metformin had statistically lower values of B12 (P = 0.01). For the patients who smoked, vitamin B12 deficiency was significantly higher than those who did not smoke (p= <0.001). Also in patients using multivitamins, vitamin B12 deficiency was lower compared to nonusers (p=0.05).ConclusionOur study shows that for the patients with type 2 diabetes (T2DM), long-term treatment with metformin and smoking are associated with higher chances of developing vitamin B12 deficiency. Clinicians should, therefore, recognize this significant element and should screen diabetics who are on metformin treatment for any B12 insufficiency, which may be hidden, especially patients coming with neurologic symptoms. Additionally, multi vitamins taken daily may have a protective role.

Holotranscobalamin (HoloTC, Active-B12) and Herbert's model for the development of vitamin B12 deficiency: a review and alternative hypothesis.

The concentration of total vitamin B12 in serum is not a sufficiently sensitive or specific indicator for the reliable diagnosis of vitamin B12 deficiency. Victor Herbert proposed a model for the staged development of vitamin B12 deficiency, in which holotranscobalamin (HoloTC) is the first indicator of deficiency. Based on this model, a commercial immunoassay has been controversially promoted as a replacement for the total vitamin B12 test. HoloTC is cobalamin (vitamin B12) attached to the transport protein transcobalamin, in the serum, for delivery to cells for metabolism. Although there have been many published reports supporting the claims for HoloTC, the results of some studies were inconsistent with the claim of HoloTC as the most sensitive marker of vitamin B12 deficiency. This review examines the evidence for and against the use of HoloTC, and concludes that the HoloTC immunoassay cannot be used to measure vitamin B12 status any more reliably than total vitamin B12, or to predict the onset of a metabolic deficiency, because it is based on an erroneous hypothesis and a flawed model for the staged development of vitamin B12 deficiency. The author proposes an alternative model for the development of vitamin B12 deficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2252-z) contains supplementary material, which is available to authorized users.

Another Look at Metformin and Vitamin B12 Deficiency

Several studies have linked metformin to development of vitamin B12 deficiency (NEJM JW Gen Med Jul 1 2010 and BMJ 2010; 340:c2181). Now, researchers provide additional data on this potential complication. In the randomized Diabetes Prevention Program, 3200 adults at high risk for diabetes received metformin, placebo, or intensive lifestyle modification for 3 years (NEJM …

Experimental vitamin B12 deficiency in a human subject: a longitudinal investigation of the performance of the holotranscobalamin (HoloTC, Active-B12) immunoassay.

Based on Victor Herbert’s model for sequential stages in the development of vitamin B12 deficiency, the holotranscobalamin (HoloTC) immunoassay has controversially been promoted as a more specific and sensitive replacement for the total vitamin B12 test, for the diagnosis of deficiency. There have been no longitudinal studies, by means of experimental cobalamin deficiency, because ethical considerations prevent such risky studies on patients or healthy human volunteers. The objective was to provide a detailed record of the response of HoloTC, compared to total vitamin B12 and metabolites, to the development of experimental vitamin B12 deficiency in an initially replete human subject. This 54 year old male, with a vitamin B12 deficiency possibly caused by a defect in the intracellular cobalamin metabolism, ensured an initially replete condition by means of oral doses of cyanocobalamin supplements at 1000 μg/day for 12 weeks. The subject then depleted himself of vitamin B12, by withholding treatment and using a low-cobalamin diet, until significant metabolic disturbances were observed. The responses of serum total vitamin B12 and HoloTC and the two metabolites, plasma methylmalonic acid and homocysteine, were monitored by weekly blood tests. HoloTC was not significantly more sensitive than either total serum vitamin B12 or total homocysteine, and was much less sensitive than methylmalonic acid. HoloTC decreased from an initial concentration of >128 pmol/L to a minimum of 33 pmol/L on day 742, the only day on which it fell below the lower limit of the reference interval. Total vitamin B12 decreased from an initial concentration of 606 pmol/L to a minimum of 171 pmol/L on day 728. Total homocysteine increased from an initial concentration of 8.4 μmol/L to a maximum of 14.2 μmol/L on day 609. Methylmalonic acid unexpectedly contained four distinct peaks; initially at 0.17 μmol/L, it first exceeded the upper limit of the reference interval on day 386, finally reaching a maximum peak of 0.90 μmol/L on day 658. The results of this experiment are inconsistent with Herbert’s hypothesis that HoloTC is the earliest marker of vitamin B12 deficiency, and therefore do not support his model for the staged development of vitamin B12 deficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1740-5) contains supplementary material, which is available to authorized users.