Metabolomic Study on Vitamins B_1, B_2, and PP Supplementation to Improve Serum Metabolic Profiles in Mice under Acute Hypoxia Based on ~1H NMR Analysis

Objective To explore metabolic changes after acute hypoxia and modulating effect of vitamins B1, B2, and PP supplementation in mice exposed to acute hypoxia. Methods Fifty male Kunming mice were randomly divided into 5 groups： normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time- vitamins B1, B2, and PP supplementation . All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6 000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles. Results There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B1, B2, and PP supplementation, all these metabolic changes gradually recovered. Conclusion Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B1, B2, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B1, B2, and PP should be increased under hypoxia condition.

Genome-wide association mapping of vitamins B1 and B2 in common wheat

Vitamin B is essential for maintaining normal life activities in humans and animals who have to intake the microelement from the outside, especially from cereal products. In the present study 166 Chinese and foreign wheat cultivars planted in two environments were characterized for variation in vitamin B1 and B2 contents. A genome-wide association study(GWAS) using the wheat 90 K SNP assay identified 17 loci for vitamin B1 and 7 for vitamin B2 contents. Linear regression analysis showed a significantly positive correlation of the number of favorable alleles with vitamin B1 and B2 contents. Marker-trait associations(MTAs) at IWB43809(6AS, 0cM) and IWB69903(6AS, 13cM) were new and stable, and significantly associated with vitamin B1 content across two environments. The loci identified in this study and associated SNP markers could be used for improvement of vitamin B1 and B2 contents to obtain superior quality along with grain yield in wheat.

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. .

Assessment of the Effects of Supplemental Rumen Protected B Vitamins and Choline for Periparturient Cows: A Meta-Analysis of 28 Feeding Studies

There are currently no prescribed requirements for B vitamins or choline for dairy cows during the transition period, but many recent studies have shown a variety of benefits from supplying these nutrients to periparturient cows. The purpose of this research effort was to determine the potential benefit of including a rumen protected blend composed of B vitamins (riboflavin, folic acid, vitamin B12) and choline (RPBlend, Jefo Nutrition Inc., St. Hyacinthe, QC, Canada) for dairy cows during the transition period, based on results from 28 on-farm feeding studies (USA-12, Mexico-7, Canada-4, Chile-3, Australia-1, Brazil-1) conducted between 2011 and 2018. All farms participated in monthly herd management record keeping systems and were selected to participate in studies due to their excellent management. Meta-analyses in which risk differences were determined were used to assess the effects of the supplemental RPBlend on health parameters and reproduction. The effect size was used as the determinant of the possible contribution of RPblend on the yields of milk, energy corrected milk (ECM), fat and protein yields during the first four weeks of lactation. Results showed that the inclusion of RPblend reduced (P < 0.05) involuntary culling and mastitis by cows during the first 30 days after calving. There was a tendency (P < 0.10) for reduced retained placenta and metritis. The meta-analyses revealed that the risk of the displaced abomasum and milk fever did not diminish (P > 0.10) with the inclusion of the BPBlend. The incidence rate of subclinical ketosis, determined as blood beta hydroxy butyric acid greater than 1.2 mM was lower (P (than those not supplemented. The proportion of cows confirmed pregnant by 100 days in milk was greater for cows given the BPBlend (P < 0.05). Milk yield and ECM were greater for cows receiving the RPBlend (1.13 and 0.93 kg/cow respectively, P < 0.05). There was no change in fat yield (P > 0.10) while the yield of milk protein was greater (P < 0.05) when the cows received the blend. These results suggest that the inclusion of rumen protected B vitamins and choline can assist cow health, reproduction and production at the start of lactation.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

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.

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets

Objective:To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase(TK)expression and activity.Methods:To test this,we separated 50 rats into five groups that were either fed a standard chow diet(controls)or a high-fat diet(experimental groups HO,HI,H2,and H3).HO group animals received no additional dietary supplementation,while H1 group animals were administered 100 mg/kg body weight(BW)thiamine,100 mg/kg BW riboflavin,and 250 mg/kg BW niacin each day,and group H2 animals received daily doses of 100 mg/kg BW pyridoxine,100 mg/kg BW cobalamin,and 5 mg/kg BW folate.Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day.Results:Over time,group HO exhibited greater increases in BW and fat mass relative to other groups.When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion(CTA)and Morris Water Maze(MWM),we found B vitamin treatment was associated with significant improvements relative to untreated HO controls.Similarly,B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in HO(P<0.05).Conclusion:Together,these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity.As such,B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.

B Vitamins Can Reduce Body Weight Gain by Increasing Metabolism-related Enzyme Activities in Rats Fed on a High-Fat Diet

B vitamins are enzyme cofactors that play an important role in energy metabolism.The aim of this study was to elucidate whether B vitamin administration can reduce body weight（BW） gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet.Fifty rats were randomly assigned to one of the following five groups：control group（C）,including rats fed on standard rat chow;four treatment groups（H0,H1,H2,and H3）,in which rats were fed on a high-fat diet.Rats in the H1 group were treated daily with 100 mg/kg BW thiamine（VB1）,100 mg/kg BW riboflavin（VB2）,and 250 mg/kg BW niacin（VPP）;rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine（VB6）,100 mg/kg BW cobalamin（VB12）,and 5 mg/kg BW folate（FA）;and rats in the H3 group were treated daily with all of the B vitamins administered to the H1 and H2 groups.After 12 weeks,the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the H1 and C groups,respectively,which were significantly less than the changes in the H0 group（285.2±14.8 g,P〈0.05）.In the H0 group,the plasma total cholesterol（CHO） and triglyceride（TG） levels were 1.59±0.30 mmol/L and 1.55±0.40 mmol/L,respectively,which were significantly greater than those in the H1 group（1.19±0.18 mmol/L and 0.76±0.34 mmol/L,respectively,P〈0.05）.The activities of transketolase（TK）,glutathione reductase,and Na^＋/K^＋ adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the H0 group（P〈0.05）.Furthermore,the glucose-6-phosphate dehydrogenase,pyruvic acid kinase,and succinate dehydrogenase activities also were increased after treatment with B vitamins.Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats,thus possibly providing potential benefits to humans.

Vitamin B3 inhibits apoptosis and promotes autophagy of isletβcells under high glucose stress

Background:Hyperglycemia is a typical symptom of diabetes.High glucose induces apoptosis of isletβcells.While autophagy functions in cytoprotection and autophagic cell death.The interaction between autophagy and apoptosis is important in the modulation of the function of isletβcells.Vitamin B3 can induce autophagy and inhibit isletβapoptosis.Method:The mechanism of vitamin B3-mediated protective effect on the function of isletβcells was explored by the method of western blot,immunofluorescence and flow cytometry.Results:In the present study,high glucose stress increased the apoptosis rate,while vitamin B3 reduced the apoptosis rate.The effect of vitamin B3 on autophagy flux under normal and high glucose stress was also investigated.Vitamin B3 increased the number of autophagosomes and increased the light chain(LC)3-II/LC3-I ratio.In contrast,vitamin B3 decreased sequestosome 1(SQSTM1)/p62 protein expression and inhibited the phosphorylation of mammalian ribosomal protein S6 kinaseβ-1(p70S6K/S6K1),which was a substrate of mammalian target of rapamycin(mTOR)under normal and high glucose stress.To further verify the protective effect of vitamin B3 on apoptosis,we treated isletβcell RIN-m5F with autophagy inhibitor 3-methyladenine(3-MA).Vitamin B3 decreased the apoptosis rate under high glucose stress,while the inhibition of apoptosis by vitamin B3 was blocked after adding 3-MA.Conclusion:Our data suggested that vitamin B3 reduced the apoptosis rate ofβcells,possibly through inducing autophagy under high glucose stress.

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.

Effects of ethanol and sex on propionate metabolism evaluated via a faster ^(13)C-propionate breath test in rats

BACKGROUND Alcoholism is regarded as a risk factor for vitamin B_(12)(VB_(12))deficiency.Because V B_(12) serves as a coenzyme of methylmalonyl-CoA mutase,a key enzyme in propionate metabolism,the ^(13)C-propionate breath test(PBT)has been studied as a non-invasive diagnostic modality for VB_(12) deficiency.However,the conventional PBT requires 2 h,which is inconvenient in clinical practice.We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice.AIM To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats(ERs).METHODS ERs were obtained by replacing standard drinking water(for control rats,CRs)with 16%ethanol solution in descendants of F344/DuCrj rats.Faster PBT was performed by administering ^(13)C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach;exhaled gas was collected in a bag to measure its ^(13)CO_(2)/12CO_(2) isotope ratio via infrared isotope spectrometry.Serum VB_(12) and alanine transaminase(ALT)levels were measured via chemiluminescence immunoassay and the lactate dehydrogenaseultraviolet method,respectively.We evaluated statistical differences in mean body weight,change in ^(13)CO_(2)(Δ^(13)CO_(2)‰),peakΔ^(13)CO_(2)‰,and serum VB_(12) and ALT,between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables,respectively.RESULTS Males weighed significantly more than females(P<0.001);CRs weighed significantly more than ERs(P<0.008).Δ^(13)CO_(2) reached a peak(C_(max))at 20 min and 30 min in females and males,respectively,decreasing after 20-30 min without rebound in all groups.Males had significantly higher C_(max) andΔ^(13)CO_(2) at 15-45 min than females(P<0.05;for all pairs).Propionate metabolism was enhanced in male ERs relative to male CRs,whereas metabolism did not differ markedly between ERs and CRs for females.Males had higher serum VB_(12) levels than females,without prominent differences between the ER and CR groups.Male CRs had notably higher ALT levels than male ERs.Thus,chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition.CONCLUSION Faster PBT shows that 16%ethanol consumption promotes propionate metabolism without inducing liver injury.This PBT may be used clinically to evaluate gut flora status.

Intron Retention Fine-Tunes the Resistance of the Rice Mutant pls4 to Rice Sheath Blight(Rhizotonia solani AG I.1a)

OsPLS4 encodes aβ-ketoacyl carrier protein reductase(KAR).The role of OsPLS4 in rice sheath blight(Rhizoctonia solani)remains unclear.Our preliminary studies showed that premature leaf senescence mutants(pls4)were highly susceptive to sheath blight in the early stage of rice development.To explore the role of this gene in the development of rice sheath blight,the transcriptome profiles of the rice pls4 mutant and wild type were compared by RNA-seq.The results revealed 2,569 differentially expressed genes(DEGs).The down-regulated genes were significantly enriched in the defense response-related biological processes.These down-regulated genes included the chitinase genes and WRKY genes,which were significantly changed in pls4 mutants.Furthermore,467 genes induced significant alternative splicing(AS)events.Among them,intron retention(IR)affected gene expression levels and functions of the vitamin B6(VB6)metabolism pathway related to sheath blight.This result suggests that IR plays an important role in the sheath blight resistance of mutant pls4.Together,these results indicate that pls4 could be involved in the biological process of sheath blight via DEGs and the fine-tuning of IR.The present study provides a molecular basis for further investigation of the resistance of rice to sheath blight.

The Role of Pyridoxine in the Prevention and Treatment of Neuropathy and Neurotoxicity Associated with Rifampicin-Resistant Tuberculosis Treatment Regimens: A Topic Review

Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.

Iron versus Iron and Vitamin B6 Supplementation in Treatment of Iron Deficiency Anemia during Second Trimester of Pregnancy: Quasi Experimental Trial

Background: Anemia is one of the most prevalent complications during pregnancy. It is commonly considered a risk factor for poor pregnancy outcomes and can result in complications that threaten the life of both mother and fetus, such as preterm birth, and low birth weight. There is clear evidence to support prompt treatment in all patients with iron deficiency anemia because it is known that treatment improves quality of life and physical condition as well as alleviates fatigue and cognitive deficits. Objective: The aim of the study was to evaluate the value of addition of vitamin B6 to iron in treatment of iron deficiency anemia in pregnant women during the second trimester. Patients and Methods: The study was done by giving anemia pregnant women iron therapy and vitamin B6 which represent group A and iron therapy alone which represents group B. For each pregnant woman, age, parity and gestational history were taken before treatment. All pregnant women took their allocated treatment regularly for three weeks after diagnosis of iron deficiency anemia with complete blood picture and followed up after three weeks. Results: Results of the study revealed that there was no statistically significant difference between the two groups of therapy according to the hemoglobin level before treatment (p-value = 0.734), statistically significant higher mean value in after treatment than before treatment (p-value = 0.048), there was a significant difference in the rate of change of hemoglobin (p-value = 0.011) and body mass index (p-value 0.001). Conclusion: Iron and vitamin B6 seems to increase hemoglobin level more than iron only. Thus, in pregnant women with iron deficiency anemia iron plus vitamin B6 may be considered as a more effective alternative treatment than iron only.

Restorative effect and mechanism of mecobalamin on sciatic nerve crush injury in mice

Mecobalamin, a form of vitamin B12 containing a central metal element （cobalt）, is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administra-tion of mecobalamin （65 μg/kg or 130 μg/kg） or saline （negative control）. Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin signiifcantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve ifbers, and increased the cross-sectional area of target muscle cells. Further-more, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors （nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor） in the L4–6 dorsal root ganglia. Our ifndings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes.

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.

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.

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.

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.

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.