Vitamin B12 deficiency in dialysis patients:risk factors,diagnosis,complications,and treatment:A comprehensive review

Vitamin B12 deficiency is a significant concern among patients with end-stage renal disease undergoing dialysis.However,there hasn’t been extensive research conducted on this particular patient group.The reported incidence rates vary widely,ranging from 20%to 90%,reflecting the complexity of its diagnosis.Dialysis patients often face multiple nutritional deficiencies,including a lack of essential vitamins,due to factors such as dietary restrictions,impaired absorption,and nutrient loss during dialysis.Diagnosing vitamin B12 deficiency in these patients is challenging,and addressing it is crucial to prevent complications and improve their overall quality of life.This review paper delves into the available body of evidence on vitamin B12 deficiency in dialysis patients,examining the contributing risk factors,diagnostic challenges,potential complications,and available treatment options.It provides a well-rounded perspective on the topic,making it a valuable resource for researchers,healthcare practitioners,and policymakers interested in addressing the nutritional needs of dialysis patients.

Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes

Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral hypoglycemic drug for controlling type 2 DM(T2DM)patients.Metformin is the ninth most often prescribed drug in the world,and at least 120 million diabetic people are estimated to receive the drug.In the last 20 years,there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients.Many studies have reported that vitamin B12 deficiency is related to the malabsorption of vitamin B12 among metformin-treated T2DM patients.Vitamin B12 deficiency may have a very bad complication for the T2DM patient.In this review,we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption.In addition,the review will describe the clinical outcomes of vitamin B12 deficiency in metformintreated T2DM.

Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind

To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.

Life threatening vitamin B_(12) deficiency:will timely screening make a difference?

INTRODUCTION While Vit.B12 deficiency is common,with aprevalence of about 15% in the elderly,andrecommendations for treatment available,detectionof deficiency at the pre-clinical stage by appropriatescreening does not always take place.Our report isan example of life threatening Vit.B12 deficiencydiagnosed at age 56,with the onset of Vit.B12depletion likely to have begun in the

Vitamin B12 deficiency and gastric histopathology in older patients

AIM: To compare upper gastric endoscopic and histopathologic findings in older adults in the presence and absence of B12 deficiency.METHODS: A prospective analysis of upper gastric endoscopic and gastric histopathologic findings from 30 newly identified B12-deficient patients (11 males,19 females) and 16 controls with normal B12 status (6males, 10 females) was performed. For all subjects, the indication for upper endoscopy and gastric biopsy were unrelated to B12 status. A single pathologist, blinded to B12 status, processed and interpreted the biopsy samples. Endoscopic and histopathologic findings were correlated with age, gender, hematocrit (Hct), MCV and B12 status.RESULTS: The B12-deficient group had significantly lower mean serum B12 levels compared to the controls (P＜0.00005) while their mean Hct, MCV and serum albumin levels were similar. Iron deficiency (ferritinbased) was present in 21% of B12-deficient patients and intrinsic factor antibodies were present in29% (5/17) of B12-deficient patients. The endoscopic findings revealed significantly different rates of gastritis and atrophy between the B12-deficient and control groups (P= 0.017).B12-deficient patients had significantly less superficial gastritis (62% vs 94%) and significantly more atrophic gastritis (28% vs 0%) as compared to the controls (P= 0.039). Intestinal metaplasia was similar in both groups. Helicobacter pyloriinfection rates were similar in the B12-deficient patients and controls (40% vs31%).CONCLUSION: Significantly different endoscopic findings and types of gastritis could often be observed in the presence and absence of B12 deficiency. Atrophy,based on endoscopy, and atrophic gastritis, based on histopathology, suggest the presence of B12 deficiency.Gastric histopathology is not influenced by the age,gender, Hct or MCV of the patients.

Effect of vitamin B12 deficiency anemia on peripapillary retinal nerve fiber layer

AIM:To evaluate the effect of vitamin B12 deficiency anemia(BDA)on peripapillary retinal nerve fiber layer thickness(RNFLT)using spectral domain optical coherence tomography(SD-OCT),and to determine any correlation arising thereof.METHODS:In this cross-sectional observational study,99 eyes of 50 BDA patients of age 18-65 y were compared with 100 eyes of 50 healthy control subjects.All subjects underwent comprehensive clinical,ophthalmic,and hematological evaluation,followed by peripapillary RNFLT assessment using SD-OCT.RESULTS:The mean total,inferior,nasal,and temporal RNFLT were significantly lower in BDA group as compared to control group(P<0.05).The mean total,inferior and nasal RNFLT correlated significantly(P<0.05)with serum Hb%,B12 and mean corpuscular volume(MCV)level(r=0.310,0.435,-0.386 for total;r=0.932,0.481,-0.513 for inferior;r=0.344,0.254,-0.233 for nasal;respectively),while temporal and superior RNFLT quadrant did not show any correlation with any of the hematological parameters(r=0.144,0.167,-0.096;r=0.111,0.070,-0.099;respectively).The mean total RNFLT showed progressive thinning at par with the progression of anemia,except in very severe BDA,where an inverse relationship was documented.CONCLUSION:The mean total,inferior,nasal,and temporal peripapillary RNFLT was significantly thinner in BDA patients.Peripapillary RNFLT thinning seemed to proceed at par with the progression of severity of anemia,except in very sever grade.Early assessment of peripapillary RNFLT may be crucial in BDA patients to prevent potential blinding sequelae.Peripapillary RNFLT thinning in BDA patients should be considered in the differential diagnosis of other non-glaucomatous optic neuropathies,as well.

An investigation of vitamin B12 deficiency in elderly inpatients in neurology department

Objective To investigate the status of vitamin B 12 deficiency in elderly inpatients in the department of neurology. Methods A total number of 827 patients in the department of neurology of Shanghai Punan hospital, from March 2007 to July 2008, were employed in the present study. They were 60 years or older, and the average age was 77.1±7.5 years old. All the patients were diagnosed with no severe hepatic or renal dysfunction, without any usage of vitamin B 12 during the previous 3 months before the detection. The levels of serum vitamin B 12, folate and homocysteine （Hcy） were evaluated. The patients with vitamin B 12 deficiency were screened. The resulting symptoms, positive signs of neurological examination, and the neuroelectricphysiological results were compared between patients with or without vitamin B 12 deficiency. Results Vitamin B 12 deficiency was found in 163 patients （19.71% of the total patients）, and was more prevalent in female than in male patients, also with increased incidences with aging. Patients with low levels of serum vitamin B 12 exhibited higher rate of gastrointestinal diseases, while only 9.82% of the vitamin B 12 deficient patients had megaloblastic anemia. Symptoms of vitamin B 12 deficiency included unsteadily walking in the darkness and hypopallesthesia, and some chronic diseases such as cerebral ischemia, hypertension, Parkinson＇s disease （Parkinsonism）, diabetes mellitus and coronary heart disease. Most of the vitamin B 12 deficient patients had neuroelectricphysiological abnormalities. Conclusion Vitamin B 12 deficiency is remarkably common in elderly patients in neurology department, with various and atypical clinical manifestations, and the neurological symptoms are more common than megaloblastic anemia symptoms.

Anemia after gastrectomy for early gastric cancer:Long-term follow-up observational study

AIM:To identify the incidence and etiology of anemia after gastrectomy in patients with long-term follow-up after gastrectomy for early gastric cancer.METHODS:The medical records of those patients with early gastric adenocarcinoma who underwent curative gastrectomy between January 2006 and October 2007 were reviewed.Patients with anemia in the preoperative workup,cancer recurrence,undergoing systemic chemotherapy,with other medical conditions that can cause anemia,or treated during follow up with red cell transfusions or supplements for anemia were excluded.Anemia was defined by World Health Organization criteria(Hb < 12 g/dL in women and < 13 g/dL in men).Iron deficiency was defined as serum ferritin < 20 g/dL.Vitamin B12 deficiency was defined as serum vitamin B 12 < 200 pg/mL.Iron deficiency anemia was defined as anemia with concomitant iron deficiency.Anemia from vitamin B 12 deficiency was defined as megaloblastic anemia(mean cell volume > 100 fL) with vitamin B 12 deficiency.The profile of anemia over 48 mo of follow-up was analyzed.RESULTS:One hundred sixty-one patients with gastrectomy for early gastric cancer were analyzed.The incidence of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo after surgery.The incidence of iron deficiency anemia increased during the follow up and became the major cause of anemia at 48 mo after surgery.Anemia of chronic disease and megaloblastic anemia were uncommon.The incidence of anemia in female patients was significantly higher than in male patients at 12(40.0% vs 22.0%,P = 0.033),24(45.0% vs 25.0%,P = 0.023),36(55.0% vs 28.0%,P = 0.004),and 48 mo(52.0% vs 31.0%,P = 0.022) after surgery.Patients with total gastrectomy showed significantly higher incidence of anemia than patients with subtotal gastrectomy at 48 mo after surgery(60.7% vs 31.3%,P = 0.008).The incidence of iron deficiency was significantly higher in female patients than in male patients at 6(35.4% vs 13.3%,P = 0.002),12(45.8% vs 16.8%,P < 0.001),18(52.1% vs 22.3%,P < 0.001),24(60.4% vs 20.9%,P < 0.001),36(62.5% vs 29.2%,P < 0.001),and 48 mo(66.7% vs 34.7%,P = 0.001) after surgery.CONCLUSION:Anemia was frequent after gastrectomy for early gastric cancer,with iron deficiency being the major cause.Evaluation for anemia including iron status should be performed after gastrectomy and appropriate iron replacement should be considered.

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determined. RESULTS:Of the 14 patients with severe gastricatrophy,as demonstrated by histology and serum markers,and no evidence for an ongoing H.pylori infection,eight showed H.pylori antibodies by immunoblotting.All eight had elevated PCA and 4/8 also had IF antibodies.Of the six immunoblot-negative patients with severe corpus atrophy,PCA and IF antibodies were detected in four.Among the patients with low to moderate grade atrophic gastritis(all except one with an ongoing H.pylori infection),serum markers for gastric atrophy and autoimmunity were seldom detected.However,one H.pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. CONCLUSION:Signs of H.pylori infection in autoimmune gastritis,and positive autoimmune serum markers in H.pylori gastritis suggest an etiological role for H.pylori in autoimmune gastritis.

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND： Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE： To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN： Case analysis. SETTING： Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS： A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5 - 108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS： Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187 - 1 059 ng/L and normal value of serum homocysteine was 5 - 15μ mol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES： （1） Levels of blood routine, serum vitamin B12 and homocysteine; （2） results of neuroelectrophysiological examination; （3） results of MRI examination of spinal cord; （4） prognosis. RESULTS： Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. （1） Clinical manifestations： All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs （5 cases）, unstable gait （3 cases）, limb asthenia （4 cases）, limb numbness combined with light asthenia （5 cases）, limb numbness combined with unskillful activity （3 cases）, and limb numbness combined with unstable gait （1 case）. （2） Experimental results： Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of bomocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. （3） Results of neuroelectrophysiological examination： Among all patients, 95% （20/21） patients had abnormal sensory-evoked potential, 89% （8/9） patients had abnormal motor evoked potential, 67% （10/15） patients had abnormal nerve conduction, 13% （2/15） patients had neurogenic muscle injury showed by electromyography （EMG）, 70% （7/10） patients had abnormal brain-stem auditory evoked potential, and 40% （4/10） patients had abnormal visual evoked potential. （4） Results of MRI examination of spinal cord： MRI examination demonstrated that 40% （6/15） patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B I2 therapy. CONCLUSION： Nervous system lesion caused by vitamin B 12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin BI2. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.

Biermer Disease in an Unusual Neurological Presentation without Anemia: A Case Report

Background: Biermer disease is a megaloblastic disease caused by vitamin B12 deficiency. It is a rare clinical entity especially in subsahara Africa. Case presentation: We report the case of a 45 years old female patient who consulted for a one month history of generalised muscle cramps, weakness and numbness of all four limbs. Physical examination was relevant for a poor gait, poor coordination of both upper and lower limbs, a positive Romberg sign, normal muscle tone in all four limbs, reduced pallesthesia and deep tendon reflexes, abolished plantar reflexes. Paraclinical investigations revealed macrocytosis without anemia, a low cyanocobalamin (vitamin B12) level with a normal folic acid level, an atrophic corporeofundic mucosa which upon pathological analysis revealed a chronic atrophic gastritis with no Helicobacter pylori infection. Anti-intrinsic factor antibodies were positive while anti parietal cells antibodies were negative. The diagnosis of Biermer disease was considered and the patient did well on vitamin B12 supplementation. Conclusion: Though a rare disease, Biermer disease should be considered in a patient who consults for polyneuropathy even in the absence of anemia.

Pernicious anemia: New insights from a gastroenterological point of view

Pernicious anemia （PA） is a macrocytic anemia that is caused by vitamin B12 deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis （ABG）, whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling＇s test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are use- ful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weak-ness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease （40%） and other autoimmune disorders, such as diabetes mellitus （10%）, as part of the autoimmune polyen-docrine syndrome. PA is the end-stage of ABG. Long- standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.

Lower folate levels in gastric cancer:Is it a cause or a result?

Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.

Effect of complex reinforcing-reducing manipulation on lower limb motion and balance disorder in patients with subacute combined degeneration of the spinal cord

Objective：To observe the effect of complex reinforcing [Shao Shan Huo （Mountain-burning Fire）] and reducing [Tou Tian Liang （Heaven-penetrating Cooling）] manipulations on motion and balance of the lower limbs in patients with subacute combined degeneration of the spinal cord （SCD）. Methods：A total of 100 SCD cases were randomly allocated into an observation group and a control group by their visit sequence, 50 cases in each group. On the basis of Western medical treatment, cases in the observation group were also treated with acupuncture therapy plus complex reinforcing-reducing manipulation; whereas cases in the control group were only treated with the same Western medical treatment as those in the observation group. Before and 2 months after treatment, kinematic parameters including muscle force, muscle tone and range of motion of the hip and knee joints were measured. In addition, balancing parameters including the path length of center of pressure （COP）, peripheral area, COP path length per unit area and rectangular area were also measured before and after treatment. Results：After treatment, there were statistical intra-group differences in COP path length, peripheral area, COP path length per unit area, left-right offset, rectangular area, coefficient of stability and coefficient of weight distribution （P〈0.01）. There were statistical inter-group differences in muscle force, muscle tone and range of motion of hip and knee joints （P〈0.01）. The total effective rate was 83.3% in the observation group, versus 60.0% in the control group, showing a statistical difference （P〈0.05）. Conclusion：Complex reinforcing-reducing manipulations can improve the lower limb motion and balance in SCD patients.