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 of Serum Folate and Vitamin B_(12) Concentrations with Obesity in Chinese Children and Adolescents

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

Neurological Manifestations of Vitamin B12 Deficiency: About a Case

The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis was made possible by electroneuromyography which showed subclinical neurological damage associated with hematological damage (anemia). Through this observation, we recall the diagnostic criteria of the disease in a context of difficult medical practice. .

妊娠期糖尿病患者炎症因子、FA和Vit B-12水平检测及临床意义分析

目的研究分析妊娠期糖尿病患者炎症因子、叶酸(Folic Acid,FA)、维生素B12(Vitamin B-12,Vit B-12)的检测结果。方法回顾性选取2020年1月—2022年1月福清市妇幼保健院的60例妊娠期糖尿病患者的临床资料为观察组,同期60例健康孕妇的临床资料为对照组。两组均行疾病指标(空腹血糖、空腹胰岛素)、炎症因子[C反应蛋白(C-reactive Protein,CRP)、肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、白介素-6(Interleukin-6,IL-6)、同型半胱氨酸(Homocysteine,HCY)]、FA、Vit B-12检测,比较两组检测结果差异,分析上述指标的临床意义。结果观察组空腹血糖、空腹胰岛素、血清CRP、TNF-α、IL-6、HCY水平较对照组高,观察组FA、Vit B-12水平较对照组低,差异有统计学意义(P均<0.05)。高HCY亚组患者的FA、Vit B-12较低HCY亚组低,差异有统计学意义(P均<0.05)。妊娠期糖尿病患者的HCY与FA、Vit B-12呈负相关性(r=-0.598、-0.617,P均<0.05)。结论妊娠期糖尿病患者病发后有明显的炎症因子水平上升、FA和Vit B-12水平下降现象,其中患者HCY水平的上升与FA、Vit B-12水平的下降明显相关。

西瓜霜联合维生素B12溶液在小儿口腔溃疡中的应用效果

目的探讨西瓜霜联合维生素B12溶液在小儿口腔溃疡中的应用效果。方法选取2019年1月至2020年1月滨州市沾化区下洼镇卫生院收治的66例口腔溃疡患儿,按照随机数字表法分为对照组和研究组,每组各33例。对照组采用维生素B12溶液治疗,研究组在对照组基础上联合西瓜霜治疗。比较两组免疫功能、疼痛程度及复发率。结果治疗后,研究组CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平均优于对照组(P<0.05)。治疗后1、2、3d,研究组疼痛评分均低于对照组(P<0.05)。研究组复发率低于对照组(P<0.05)。结论西瓜霜联合维生素B12溶液在小儿口腔溃疡中应用可提高患儿免疫功能,减轻疼痛程度,降低复发率。

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.

Vitamin B_(12) Deficiency in Newborns and their Mothers_Novel Approaches to Early Detection,Treatment and Prevention of a Global Health Issue

Vitamin B 12 deficiency,mostly of maternal origin in newborns,is a well treatable condition but can cause severe neurologic sequelae.In women of childbearing age and pregnant women worldwide vitamin B12 deficiency has been reported with frequencies of 10%-50%.Children with vitam in B I2 deficiency are asym ptom atic at birth but may develop severe multisystemic symptoms,including irreversible developmental impairment in the second halfyear of life.Early detection of vitamin B12 deficiency allows for presymptomatic treatment.This article provides an overview over the function of vitamin B12 and discusses causes and frequency of vitamin B12 deficiency in newborns,infants,and women of childbearing age.It describes novel successful approaches to newborn screening(NBS)for vitamin B,2 deficiency and results of a pilot study which performed systematic NBS for vitamin B12 deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots.Recommendations for diagnostics in mothers of children with vitamin B12 deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B12 deficiency detected by NBS.Treatment options of vitamin B12 deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin BI2 supplementation.Recommendations for preventive approaches to vitamin Bl2 deficiency for children and mothers are stated.Many children worldwide could benefit from systematic inclusion of vitamin B12 deficiency into NBS panels.In addition,preventive approaches to maternal vitamin B12 deficiency should be implemented systematically during maternal care.

Determining the efficacy of vitamin B12 mixed oral liquid in the treatment of radiation-induced esophagitis

Objective This study aimed to investigate the effects of vitamin B12 mixed oral liquid in the treatment of radiation-induced esophagitis in patients with esophageal cancer.Methods Seventy-five patients with esophageal cancer who met the enrollment criteria were randomly divided into the vitamin B12 mixed oral liquid group(39 patients in the study group)and the gentamicin mixed oral liquid group(36 patients in the control group).The effects of the two treatment methods on esophagitis grading,pain degree,body weight loss,and Karnofsky performance status(KPS)score in patients with radiation esophagitis were observed.Results In the control group,grade 1 radiation esophagitis accounted for 27.8%of the total patients,grade 2 accounted for 41.7%,and grades 3 and 4 accounted for 30.6%.In the vitamin B12 treatment group,grade 1 radiation esophagitis accounted for 66.7%of the total patients,grade 2 accounted for 25.6%,and grades 3 and 4 accounted for 7.7%;there was a significant difference between the vitamin B12 treatment group and control group(P<0.01).Similarly,pain caused by radiation esophagitis was significantly improved in the vitamin B12 group compared with the control group(P<0.05).After treatment,the average weight loss of the control group was(2.18±0.36)kg,while that of the vitamin B12 treatment group was(0.90±0.43)kg(P<0.05).The KPS scores of the vitamin B12 group were higher than those of the control group,which were 86.2±1.2 and 85.6±1.5,respectively,but there was no statistical difference(P>0.05).Conclusion Vitamin B12 mixed oral liquid can effectively reduce the severity of radiation esophagitis,relieve pain,improve patients’quality of life,and increase treatment compliance.

血管性痴呆患者血清叶酸、Vitamin B_(12)水平变化的临床研究

目的测定血管性痴呆(VD)与非痴呆脑血管病(NDCVD)患者及健康老年者血清叶酸、Vitamin B_(12)水平,同时评估认知功能的变化,分析并探讨其在VD的可能作用。方法选择VD40人,为痴呆组;NDCVD40人,为非痴呆组;同期选定40名健康老年人作为对照组。应用MMSE对3组对象的认知功能进行评定,测定被试着血清叶酸、Vitamin B_(12)水平。初步观察补充叶酸、Vitamin B_(12)对VD认知功能的影响。结果3组血清叶酸、Vitamin B_(12)水平(以中位数M及95%的可信区间CI表示),以VD组最低为4.20ng/ml(4.07～5.50)、343.67pg/ml(296.54～413.73)。与对照组比较有显著性(P<0.01),VD与NDCVD组相比叶酸水平不同(P<0.01),而Vitamin B_(12)水平无差别(P>0.05)。3组MMSE值VD组最低(16.05±5.94),各组之间明显不同(P<0.01)。初步显示补充叶酸、Vita- min B_(12)对VD患者认知功能有一定的改善作用。结论VD患者血清叶酸、Vitamin B_(12)水平明显低于健康者,低水平叶酸、Vitamin B_(12)可能对VD的认知功能有影响。

Hcy相关酶基因MS A2756G、MTRR A66G多态性及Vitamin B12与脑梗死相关性的临床探讨

目的探讨同型半胱氨酸(Hcy)相关酶基因甲硫氨酸合成酶(methioninesynthase,MS)基因A2756G和甲硫氨酸合成酶还原酶(MTRR)基因A66G多态性对维生素B12和Hcy代谢的影响以及与脑梗死的关系,为寻找脑血管病易感基因提供理论依据。方法选取2014年2月-2016年2月在中日友好医院神经内科确诊为急性脑梗死患者100例作为病例组,选取同期的健康体检者100例为对照组,检测血浆Hcy水平和维生素B12的水平,聚合酶链反应-限制片段长度多态性(PCR-RFLP)技术分析基因型的多态性。在维生素B12干预试验中,100例急性脑梗死患者随机分为两组,每组50例,在常规治疗的基础上,试验组予以每天摄入0.5～1 mg维生素B12,而非试验组不服用,1 w后,检测患者血浆中Hcy指标。结果病例组血浆中Hcy的水平明显高于对照组;MS 2756AG、2756GG、MTRR 66AG、66GG型研究对象血浆中Hcy水平明显高于MS 2756AA、MTRR 66AA型研究对象;两组研究对象MS A2756G和MTRR A66G的基因型频率分布有显著性差异;病例组血浆中维生素B12的水平明显低于对照组,血浆中维生素B12的水平与Hcy的水平呈显著负相关;腺苷钴胺干预可明显降低脑梗死患者血浆中的Hcy水平。结论 MS基因A2756G突变和MTRR基因A66G突变是血浆中Hcy升高的重要因素,与脑梗死密切相关,可作为诊断和治疗的分子靶标;腺苷钴胺干预治疗可降低脑梗死患者血浆中Hcy水平。

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis(CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination fromSeptember 2013 to September 2016 were selected for this study. The age of these patients ranged within 18-to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori(H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration.Furthermore,CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve(R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.

Role of vitamin B12 deficiency in ischemic stroke risk and outcome

Currently,ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults.Nutrition is a modifiable risk factor for stroke.B-vitamins are part of a metabolic network that integrates nutritional signals with biosynthesis,redox homeostasis,and epigenetics.These vitamins play an essential role in the regulation of cell proliferation,stress resistance,and embryo development.A deficiency in vitamin B12 is common in older adults and has been reported to be implicated in ischemic stroke.The aim of this review was to investigate whether vitamin B12 deficiencies impact the risk and outcome of ischemic stroke.Clinical data from our literature review strongly suggest that a deficiency in vitamin B12 is a risk factor for ischemic stroke and possible outcome.Our survey of the literature has identified that there is a gap in the understanding of the mechanisms through which a vitamin B12 deficiency leads to an increased risk of stroke and outcome.A vitamin B12 deficiency can increase homocysteine levels,which are a well-established risk factor for ischemic stroke.Another potential mechanism through which vitamin B12 deficient may impact neurological function and increase risk of stroke,is changes in myelination,however this link requires further investigation.Further studies are required in model systems to understand how a vitamin B12 deficiency changes the brain.

High Prevalence and Factors Contributing to Hyperhomocysteinemia, Folate Deficiency, and Vitamin B_(12) Deficiency among Healthy Adults in Shanghai, China

Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin B12 influence homocysteine (Hcy) metabolism as a co-substrate and cofactor respectively, so that low concentrations of folate and vitamin B12 are also associated with high Hcy levels[1]. However, not much information is available describing serum tHcy, folate, and vitamin B12 status in Shanghai adults, especially in a healthy population. Therefore, we hypothesize that low serum folate and vitamin B12 is associated with high Hcy in healthy adults in Shanghai. The aim of this study was to determine the status of serum tHcy, folate, and vitamin B12, and the prevalence and factors contributing to HHcy, folate deficiency, and vitamin B12 deficiency among healthy adults in Shanghai, China.

Vitamin B complex and vitamin B12 levels after peripheral nerve injury

The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control（n = 8） and six study groups（1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury; n = 12 for each group）. Crush-induced peripheral nerve injury was performed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B12 in the injured sciatic nerve were significantly greater at 1 and 12 hours after experimental nerve injury, while they were significantly lower at 7 days than in control group. Tissue level of vitamin B_（12） in the injured sciatic nerve was significantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration.

Prostaglandin E_1 in conjunction with high doses of vitamin B_(12) improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve conduction velocity of the median nerve and the common peroneal nerve were determined using an electromyogram electronic stimulator （Neuropack-11, Nihon Kohden, Japan）. RESULTS： The motor nerve and sensory nerve conduction velocities of the median nerve and the common peroneal nerve were significantly faster after treatment compared to before treatment in all 3 groups （P 〈 0.05q）.01）. Compared with the control group, the motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 low-dose treated group and in the vitamin B12 high-dose treated group （P 〈 0.01）. The motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 high-dose treated group compared to the vitamin B12 low-dose treated group （P 〈 0.05）. CONCLUSION： Prostaglandin E1, in conjunction with vitamin B12, can improve neural functional states and speed up peripheral motor nerve and sensory nerve conduction velocity in diabetic peripheral neuropathy. In addition, better effects are achieved using prostaglandin E1 in conjunction with high doses of vitamin B 12.

A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B_(12 )on murine embryonic palatal shelf fusion in vitro

Excessive dexamethasone (Dex) administrated into pregnant mice during critical periods of palatal development can produce a high incidence of cleft palate. Its mechanisms remain unknown. Vitamin B12 has been shown to antagonize the tera- togenic effects of Dex, which, however, remains controversial. In this study, we investigated the effects of Dex and vitamin B12 on murine embryonic palatal shelf fusion using organ culture of murine embryonic shelves. The explanted palatal shelves on em- bryonic day 14 (E14) were cultured for 24, 48, 72 or 96 h in different concentrations of Dex and/or vitamin B12. The palatal shelves were examined histologically for the morphological alterations on the medial edge epithelium (MEE) and fusion rates among different groups. It was found that the palatal shelves were not fused at 72 h or less of culture in Dex group, while they were completely fused in the control and vitamin B12-treated groups at 72 and 96 h, respectively. The MEE still existed and proliferated. In Dex+vitamin B12 group the palatal shelves were fused at each time point in a similar rate to controls. These results may suggest that Dex causes teratogenesis of murine embryonic palatal shelves and vitamin B12 prevents the teratogenic effect of Dex on palatogenesis on murine embryos in vitro.

Use of packed-fiber solid-phase extraction for sample clean-up and preconcentration of vitamin B_(12) before determination

A rapid and simple preconcentration step applying packed-fiber solid-phase extraction columns has been investigated to vitamin B12. The extraction performance of the new method was investigated preliminarily on vitamin functional drink. The analysis used a reversed-phase C18 column, with a photo-diode array detector at 220 nm. The samples were preconcentrated with packed-fiber solid-phase extraction columns. Good linearity was observed in vitamin functional drink. The repeatability of extraction performance, expressed as relative standard deviations, was from 3.5% to 4.3%. The limit of detection （LOD） is 5 ng mL^-1 （S/N = 3）. Finally, the method had been applied for the determination of vitamin B12 in vitamin functional drink.

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.

Folate and vitamin B12 in idiopathic male infertility

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B12 （B12） and total homocysteine （tHcy）-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmo and Lund, Sweden. Serum folate, red cell folate （RCF）, serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/ homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase （PEMT） M 175V and TCblR rs173665 polymorphisms were significantly associated with infertility （P=0.01 and P=0.009, respectively）, but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men （12.89 vs. 14.73 nmoll^- 1 P=0.02）, but there were no significant differences in RCF, B 12 or tHcy. Folate, B 12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMTand TCbIR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility.

Influence of Different Ratios of Cobalt and Copper Supplementation on Vitamin B_(12) Status and Nutrient Utilization in Sheep

The present study is aimed to investigate the effects of different ratios of cobalt （Co） and copper （Cu） supplementation on vitamin B12 status and nutrient utilization in sheep. Twenty wether lambs with an average weight （22.9 ± 0.8） kg were randomly divided into five groups and fed with the control diet which was supplied with 0.3 mg kg^-1 DM （dry matter） of Co to the basal diet, and four supplemental diets which were supplied either 0.3 or 0.6 mg kg^-1 DM of Co and 10 or 20 mg kg^-1 DM of Cu to the basal diet, respectively for 8 wk. The supplementation of Co and Cu with different levels improved plasma vitamin B12 concentration which was increased with feeding time, but stable after 6 wk. Vitamin B12 status was accounted for Co intake with no combined effects by supplementation of different levels of Co and Cu. The plasma concentrations of methylmalonic acid, homocysteine, folic acid, and glucose did not show the consistent results with plasma vitamin B12, which was considered to be resulted from Cu action. Addition of Co and Cu with different levels had no influence on digestibility of dry matter （DM）, organic matter （OM）, crude protein （CP） and nitrogen free （NFE）, and N metabolism （P〉 0.05）, but the digestibility of fat and fibre （P〈0.01） was enhanced by supplementation of 0.3 mg kg^-1 DM of Co and 20 mg kg^-1 DM of Cu. In conclusion, the supplementation of Co and Cu with different levels has no influence on vitamin B12 status. The optimum ratio of Co and Cu in diet could enhance the nutrient utilization.