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Methylcobalamin (MBL) is a vitamin B12 coenzyme and is effective for treating peripheral neuropathies. Little is known about pharmacokinetics (PK) of MBL in animals, we have developed a simple assay for MBL by using only 0.01 mL of plasma for PK of MBL in rats. Under minimal light exposure (<5 lx), MBL was extracted by a simple protein precipitation using methanol and detected by liquid chromatography with tandem mass spectrometry. MBL in rat plasma at 20-10,000 ng/mL was quantified using only 0.01 mL of plasma. Relative error and relative standard deviation met the acceptance criteria in reproducibility assessments, indicating the robustness of the assay. PK of MBL was evaluated after intravenous, intramuscular, and subcutaneous administration. PK of MBL was dose proportional at 5-20 mg/kg in both intramuscular and subcutaneous administrations. Bioavailability after the two dosing routes was complete (ca. 100 %). The incurred sample reanalysis also supported that the assay is robust. The established assay was successfully applied to PK studies in rats to find that MBL showed high bioavailability after intramuscular and subcutaneous administrations., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( p < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, p < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, p < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, p < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.

Background: Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood., Objective: In this study, we investigate the combined effects of NTP and MCB on PHP in mice., Methods: NTP and MCB were administered from day 10-29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR., Results: Repeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells., Conclusion: These results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs., Competing Interests: Declaration of Competing Interest The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. This study was funded by Nippon Zoki Pharmaceutical Co., Ltd., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Vitamin B12 (cobalamin, Cbl) is represented by several molecular variants distinguished by the exchangeable ligand X coordinated to cobalt ion (XCbl). The most typical XCbl-forms are cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), methylcobalamin (MeCbl) and 5'-deoxydeoxyadenosylcobalamin (AdoCbl). Cells convert the "inactive" vitamins CNCbl and HOCbl to the two critically important coenzymes AdoCbl or MeCbl. Surprisingly, little or no MeCbl is usually uncovered in the tissue samples, as compared to AdoCbl and HOCbl. We hypothesized that a low level of MeCbl is an artifact of "harsh" extractions, leading to degradation of MeCbl and/or its conversion to other XCbl-forms., Methods: We designed a "mild" extraction protocol, including homogenization of rat liver in ammonium acetate (pH 4.6), dilution with EtOH (final 60%) and heating for 10 min at 70 °C. The XCbls were separated by HPLC and quantified by isotope dilution assays., Results: A "mild" extraction revealed the following composition of Cbls: 37% AdoCbl, 35% MeCbl, 15% HOCbl and 13% CNCbl. The usual "harsh" protocol (pH 7, 20 min at 80 °C) changed this balance to 33%, 5%, 43% and 17%, respectively. A model assay revealed that MeCbl underwent demethylation and conversion to HOCbl at pH 3 and pH > 7, when heated with thiols. Other changes included decyanation of CNCbl and destruction of HOCbl., Conclusions: Our procedure reveals a high content of MeCbl in rat liver., General Significance: This result challenges previous data and pinpoints the need for new studies to characterize the endogenous Cbl-forms in health and disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Vitamin B 12 , also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B 12 forms-cyanocobalamin, hydroxocobalamin, 5'-deoxyadenosylcobalamin, and methylcobalamin-are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B 12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B 12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B 12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B 12 products.

(1) Background: Autism, also known as autism-spectrum disorder, is a pervasive developmental disorder affecting social skills and psychological status in particular. The complex etiopathogenesis of autism limits efficient therapy, which leads to problems with the normal social integration of the individual and causes severe family distress. Injectable methylcobalamin was shown to improve the clinical status of patients via enhanced cell oxidative status and/or methylation capacity. Here we tested the efficiency of a syrup form of methylcobalamin in treating autism. (2) Methods: Methylcobalamin was administered daily at 500 µg dose to autistic children and young adults ( n = 25) during a 200-day period. Clinical and psychological status was evaluated by parents and psychologists and plasma levels of reduced and oxidized glutathione, vitamin B12, homocysteine, and cysteine were determined before the treatment, and at day 100 and day 200 of the treatment. (3) Results: Good patient compliance was reported. Methylcobalamin treatment gradually improved the overall clinical and psychological status, with the highest impact in the social domain, followed by the cognitive, behavioral and communication characteristics. Changes in the clinical and psychological status were strongly associated with the changes in the level of reduced glutathione and reduced/oxidized glutathione ratio. (4) Conclusion: A high dose of methylcobalamin administered in syrup form ameliorates the clinical and psychological status of autistic individuals, probably due to the improved oxidative status.

Purpose: Vitamin B12 deficiency is a cause of preventable growth and developmental retardation in children. In this respect, alternative methods such as oral and sublingual treatments are being tried. We aimed to compare the efficacy of oral, sublingual, and intramuscular vitamin B12 treatments in children aged 0-3 years., Methods: The study included 158 patients with serum vitamin B12 deficiency (serum vitamin B12 level <300 ng/L) aged 0-3 years retrospectively. According to the vitamin B12 treatment modalities, the patients were divided into three groups as oral cyanocobalamin (group 1), sublingual methylcobalamin (group 2), and intramuscular cyanocobalamin (group 3)., Results: The mean values of vitamin B12 levels increased to above 300 ng/L in all three groups. This increase was statistically significant for Group 1,2 and 3 ( p<0.05) ., Conclusion: Sublingual methylcobalamin was determined as effective as oral and intramuscular cyanocobalamin improving vitamin B12 levels aged 0-3 years., What's already known about this topic? It is already known that intramuscular and oral cyanocobalamin treatments are effective in vitamin B12 deficiency of children. What does this article add? Sublingual methylcobalamin treatment, which is a new treatment method, was found to be as effective as oral and intramuscular cyanocobalamin treatments. To our knowledge, there is no study about sublingual treatment in children and comparing oral cyanocobalamin, intramuscular cyanocobalamin, sublingual methylcobalamin.

Purpose: Oxidative stress is considered a major determinant in the pathogenesis of vitiligo. Methylcobalamin (MeCbl) is an activated form of vitamin B12 that regulates inflammatory factors, counters oxidative stress, and reduces apoptosis in many disease models. However, the specific mechanism of MeCbl repigmentation against vitiligo is unknown. In this study, we explored the effect of MeCbl on melanocytes following hydrogen peroxide (H 2 O 2 )-induced oxidative stress., Methods: We established an oxidative stress model using the immortalized human normal melanocyte cell line PIG1. We used a Cell Counting Kit-8 (CCK-8) to detect drug cytotoxicity, and we measured the melanin content of cells using the NaOH method. Intracellular oxidative damage was assessed by flow cytometry and antioxidant enzyme detection kits. In addition, we assessed the presence of apoptosis by flow cytometry and Western blots. We explored the underlying mechanisms of MeCbl during oxidative stress in melanocytes by analyzing the results of experiments based on real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and laser scanning confocal immunofluorescence microscopy. Finally, we repeated the experiments after applying an inhibitor to block the Nrf2 pathway., Results: We found that MeCbl treatment enhanced cell viability, increased melanin content, reduced intracellular reactive oxygen species (ROS) accumulation, increased the activities of antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT), reduced melanocyte apoptosis, and up-regulated the expression of the Nrf2/HO-1 pathway. Moreover, the protective effects of MeCbl were significantly weakened after inhibiting the Nrf2/HO-1 pathway., Conclusion: Our results indicate that MeCbl attenuated the H 2 O 2 -induced oxidative stress in melanocytes by activating the Nrf2/HO-1 pathway, this suggests that MeCbl may be an effective treatment against vitiligo., Competing Interests: The authors declare no conflict of interest., (© 2021 An et al.)

Despite advances in the understanding of the pathophysiology of ischemic stroke, therapeutic options remain limited. Methylcobalamin is an endogenous vitamin B12 that exhibits anti-inflammatory and antiapoptotic activities in a variety of diseases. In this study, we aimed to explore the neuroprotective effects and mechanism of action of methylcobalamin on cerebral ischemic injury in vitro and in vivo. The oxygen and glucose deprivation/reperfusion model and middle cerebral artery occlusion model were used to simulate cerebral ischemic injury in vitro and in vivo. Cell viability, inflammatory factors, cell apoptosis, and protein expression levels were determined. Further, autophagy flux and the cerebral infarction volume were measured. The modified neurological severity score, Longa score, Rotarod assay, and foot-fault test were used to evaluate behavioral changes and neurological deficits in rats. In vitro, methylcobalamin significantly increased cell viability, decreased lactate dehydrogenase release, attenuated inflammatory cytokine expression, reduced the apoptotic proportion, and enhanced autophagy flux after OGD treatment. In addition, Bcl-2 and Beclin1 expression levels and the LC3 II/I ratio were increased, whereas levels of Bax and cleaved caspase-3 were decreased. In vivo, methylcobalamin significantly reduced the cerebral infarction volume and neurological deficits in the rats. Furthermore, methylcobalamin activated the ERK1/2 pathway, whereas ERK1/2 inhibitors diminished its effects in the in vitro and in vivo models. In conclusion, methylcobalamin may exert a neuroprotective effect on cerebral ischemia and is a promising drug candidate for developing novel neuroprotective therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical effect of mouse nerve growth factor (mNGF) and methylcobalamin (MeCbl) for the treatment of lumbar disk herniation (LDH) with foot drop., Methods: A total of 46 patients suffering from LDH with foot drop who underwent transforaminal lumbar interbody fusion (TLIF) surgery in our department from January 2015 to December 2017 were retrospectively analyzed. We divided these patients into two groups according to the different postoperative treatment which independently selected by patients after signing informed consent form: one group of 25 patients was treated with MeCbl alone (Group MeCbl), the other group of 21 patients was treated with a combination of mNGF and MeCbl (Group MeCbl+mNGF). Patient demographics, the visual analogue scale (VAS) scores, sensory and muscular strength improvement statistics at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively were recorded. Motor/sensory deficits, sciatica and overall neurological outcome after treatment of MeCbl alone and combination of mNGF and MeCbl were retrospectively analyzed., Results: The follow-up ranged between 12 and 42 months (mean 20.8 months). There were no significant differences between these two groups of patients with respect to sex ratio, age, smoking, diabetes, disease course, section of protruding disc(s), muscular strength of foot dorsiflexion or preoperative visual analogue scale (VAS) score (P > 0.05). The VAS scores of Group MeCbl+mNGF were significantly lower than Group MeCbl at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively (4.32 ± 0.75 vs 5.25 ± 0.79,2.65 ± 0.48 vs 3.42 ± 0.52, 1.72 ± 0.36 vs 2.45 ± 0.39, 1.12 ± 0.22 vs 1.52 ± 0.24, P < 0.05). The effective rates of sensory improvement were significantly higher in Group MeCbl+mNGF compared with Group MeCbl at 12-week/12-month follow-up time point (90.48% vs 52.00%,95.24% vs 68.00%, P < 0.05). The effective rate of muscular strength improvement of the two groups did not differ significantly at 1 week after surgery but exhibited statistically significant differences at subsequent time points (61.90% vs 32.00%, 76.19% vs 44.00%, 80.95% vs 48.00%, P < 0.05)., Conclusions: Application of mNGF had clinical effects on promoting the recovery of neurological function in patients suffering from LDH with foot drop., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Vitamin B-12 deficiency is widespread in many parts of the world, affecting all age groups and increasing with age. It is primarily due to a low intake of animal source foods or malabsorption. The measurement of bioavailability of vitamin B-12 is etiologically important in deficiency but is limited due to the use of radioactive isotopes like [57Co]- or [14C]-cyanocobalamin., Objectives: The aim of this study was to measure the bioavailability of [13C]-cyanocobalamin in humans and to assess the effect of parenteral replenishment of vitamin B-12 on the bioavailability., Methods: We synthesized a stable isotope-labeled vitamin B-12, [13C]-cyanocobalamin, using Salmonella enterica by providing [13C2]-ethanolamine as a sole carbon source. After purification and mass spectrometry-based characterization, its oral bioavailability was measured in the fasted state with high and low oral doses, before and after parenteral replenishment of vitamin B-12 stores, from the kinetics of its plasma appearance in a 2-compartment model., Results: [13C]-cyanocobalamin was completely decyanated to [13C]-methylcobalamin describing metabolic utilization, and its plasma appearance showed early and late absorption phases. At a low dose of 2.3 µg, the mean bioavailability was 46.2 ± 12.8 (%, mean ± SD, n = 11). At a higher dose of 18.3 µg, the mean bioavailability was 7.6 ± 1.7 (%, mean ± SD, n = 4). Parenteral replenishment of the vitamin B-12 store in deficient individuals prior to the measurement resulted in a 1.9-fold increase in bioavailability., Conclusions: Vitamin B-12 bioavailability is dose dependent and at a low dose that approximates the normal daily requirement (46%). The stable isotope method described here could be used to define the etiology of deficiency and to inform the dietary requirement in different physiologic states as well as the dose required for supplementation and food fortification. This trial was registered at the Clinical Trials Registry of India as CTRI/2018/04/012957., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Objectives: To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Background: Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in improving nerve conduction and neuropathic pain symptoms. Although it is already widely used in Asia for the treatment of peripheral neuropathies, its efficacy remains unclear. Methods: Relevant electronic databases were systematically searched for randomized controlled trials investigating the efficacy and safety of mecobalamin on peripheral neuropathy, from inception through December 2019. Study selection, data extraction, and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy, pain score, neuropathic symptom score, nerve conduction velocities (NCVs), and adverse events of mecobalamin were assessed and were pooled by using a random-effects model. Heterogeneity was assessed by I 2 and chi-squared tests. Results: Fifteen studies with 1707 peripheral neuropathy patients caused by diabetic peripheral neuropathy and herpetic neuropathy were included. Based on Cochrane's risk of bias criteria, most of the included studies (11/15, 73%) were rated high risk of bias, whereas 20% and 7% were rated some concerns and low risk of bias, respectively. In terms of the proportion of patients achieving clinical therapeutic efficacy, mecobalamin alone (risk ratio [RR] = 1.17; 95% confidence interval [CI] 1.03-1.33) and mecobalamin in combination (RR = 1.32; 95% CI 1.21-1.45) are more effective than active control. For NCV outcomes, only mecobalamin combination treatment was effective. Neither mecobalamin alone nor mecobalamin in combination is effective on the pain score and neuropathic symptom outcomes. No serious adverse events associated with mecobalamin were reported during the treatment periods. Conclusion: Our findings indicate that mecobalamin in combination may be effective in improving clinical therapeutic efficacy and NCV outcomes for peripheral neuropathy patients, but the evidence is not clear for mecobalamin alone. More high-quality studies are required to confirm this finding.

Objectives: The ophthalmic branch of the trigeminal nerve is one of the most frequently involved sites of postherpetic neuralgia. A single-center randomized controlled study was conducted to evaluate the efficacy of local methylcobalamin injection for subacute ophthalmic herpetic neuralgia (SOHN)., Methods: One hundred and five patients with a pain score of 4 or greater were randomized to receive a combination of methylcobalamin and lidocaine via local injection (LM group, n = 35), intramuscular methylcobalamin and local lidocaine injection (IM group, n = 35), and oral methylcobalamin tablet and lidocaine local injection (OM group, n = 35) for 4 weeks. Multilevel mixed modeling was employed to examine treatment responses., Results: Pain scores were reduced in all groups, but this reduction was significantly greater in the LM group (6.7 at baseline vs. 2.8 at endpoint) when compared with systemic administration (IM group 6.8 vs. 4.9, OM group 6.7 vs. 5.1). Clinically relevant reduction of pain (>30%) was seen in 91% of patients in the LM group, a significantly greater proportion than in the systemic groups (66% IM group, 57% OM group). Analgesic use reduced significantly in the LM group (94% at baseline vs. 6% at endpoint) but not in systemic groups (IM group 97% vs. 86%, OM group 94% vs. 80%). Health-related quality of life was higher in the LM group than in the systemic groups. In mixed modelling, increased age was associated with a lower response to methylcobalamin., Conclusions: This study indicates that local injection of methylcobalamin produces significant pain relief from SOHN and is superior to systemic administration., (© 2020 World Institute of Pain.)

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).

The feasible fabrication of nerve guidance conduits (NGCs) with good biological performance is important for translation in clinics. In this study, poly(d,l-lactide-co-caprolactone) (PLCL) films loaded with various amounts (wt; 5%, 15%, 25%) of methylcobalamin (MeCbl) are prepared, and are further rolled and sutured to obtain MeCbl-loaded NGCs. The MeCbl can be released in a sustainable manner up to 21 days. The proliferation and elongation of Schwann cells, and the proliferation of Neuro2a cells are enhanced on these MeCbl-loaded films. The MeCbl-loaded NGCs are implanted into rats to induce the regeneration of 10 mm amputated sciatic nerve defects, showing the ability to facilitate the recovery of motor and sensory function, and to promote myelination in peripheral nerve regeneration. In particular, the 15% MeCbl-loaded PLCL conduit exhibits the most satisfactory recovery of sciatic nerves in rats with the largest diameter and thickest myelinated fibers., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vitamin B12 dietary supplement can be critical to the alleviation strategies against micronutrient malnutrition and food insecurity. An HPLC-DAD method has been developed and validated, per AOAC SMPR 2016.017 (Standard Method Performance Requirements), for the quantitation of four bioactive forms of vitamin B12 (adenosylcobalamin, cyanocobalamin, hydroxocobalamin, methylcobalamin) from dietary ingredients and supplements. The method achieves chromatographic baseline resolution of vitamin B12 forms on a modern column platform without the expensive requirement of an ultra-high pressure liquid chromatography and/or mass spectrometry. The method has a wide analytical range (0.0005%w/w-85%w/w), high precision (reproducibility relative standard deviations ranged from 1.43% to 4.67%), and high accuracy (>96% spike recovery rate for 11 out of 12 accuracy testing data points). The method detection and quantification limits are less than 0.16 and 0.52 µg/mL, respectively. To our best knowledge, it is simpler, less time-consuming, and more economical than other published methods for its intended uses., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Patients with inflammatory bowel disease (IBD) are usually advised to supplement various types of vitamin B 12 , because vitamin B 12 is generally absorbed in the colon. Thus, in the current study, the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on IBD symptoms will be investigated. Then, whether and how the application of various cobalamins would modify the taxonomic and functional composition of the gut microbiome in mice will be examined carefully. Dextran-sulfate-sodium-induced IBD mice were treated with MECBL or CNCBL; disease activity index (DAI) scores and intestinal inflammatory conditions of mice were evaluated. Fecal samples were collected; microbiota composition was determined with a 16s rRNA analysis; functional profiles were predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt); and short-chain fatty acids were measured. The consequence of higher relative abundances of Enterobacteriaceae and isomeric short-chain fatty acids by cobalamin treatment revealed that a high concentration of CNCBL but not MECBL supplementation obviously aggravated IBD. A microbial ecosystem rich in Escherichia/ Shigella and low in Lactobacillus, Blautia, and Clostridium XVIII was observed in IBD mice after a high concentration of CNCBL supplementation. In cobalamin-dependent enzymes, CNCBL was more efficient in the adenosylcobalamin system than MECBL and vice versa in the MECBL system. The distinct effects of various cobalamins were associated with the distribution and efficiency of vitamin-B 12 -dependent riboswitches. CNCBL had a strong inhibitory effect on all riboswitches, especially on btuB and pocR riboswitches from Enterobacteriaceae. CNCBL aggravated IBD via enhancing the proportion of Enterobacteriaceae organisms through riboswitch and enzyme systems. The present study provides a critical reference for offering a suitable amount and type of cobalamin during a symbiotic condition.

Inorganic arsenic (iAs) is an established environmental diabetogen. The link between iAs exposure and diabetes is supported by evidence from adult human cohorts and adult laboratory animals. The contribution of prenatal iAs exposure to the development of diabetes and underlying mechanisms are understudied. The role of factors that modulate iAs metabolism and toxicity in adults and their potential to influence diabetogenic effects of prenatal iAs exposure are also unclear. The goal of this study was to determine if prenatal exposure to iAs impairs glucose metabolism in mice and if maternal supplementation with folate and methylcobalamin (B12) can modify this outcome. C57BL/6J dams were exposed to iAs in drinking water (0, 100, and 1000 µg As/L) and fed a folate/B12 adequate or supplemented diet from before mating to birth of offspring. After birth, dams and offspring drank deionized water and were fed the folate/B12 adequate diet. The metabolic phenotype of offspring was assessed over the course of 14 weeks. Male offspring from iAs-exposed dams fed the folate/B12-adequate diet developed fasting hyperglycemia and insulin resistance. Maternal folate/B12 supplementation rescued this phenotype but had only marginal effects on iAs metabolism in dams. The diabetogenic effects of prenatal iAs exposure in male offspring were not associated with changes in global DNA methylation in the liver. Only minimal effects of prenatal iAs exposure or maternal supplementation were observed in female offspring. These results suggest that prenatal iAs exposure impairs glucose metabolism in a sex-specific manner and that maternal folate/B12 supplementation may improve the metabolic phenotype in offspring. Further studies are needed to identify the mechanisms underlying these effects.

Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors, and its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyperphosphorylation and aggregation of tau protein. Regarding the structure and function of vitamin B12 and tau protein, we assumed that vitamin B12 is also able to directly bind to tau protein. Hence, we investigated the interaction of vitamin B12 with tau protein in vitro using fluorometry and circular dichrosim. Interaction studies was followed by investigation into the effect of vitamin B12 on tau aggregation using ThT fluorescence, circular dichroism, transmission electron microscopy, and SDS-PAGE. The results indicated that vitamin B12 interacts with tau protein and prevents fibrillization of tau protein. Blocking the cysteine residues of tau confirmed the cysteine-mediated binding of vitamin B12 to tau and showed that binding to cysteine is essential for inhibitory effect of vitamin B12 on tau aggregation. SDS-PAGE analysis indicated that vitamin B12 inhibits tau aggregation and that tau oligomers formed in the presence of vitamin B12 are mostly SDS-soluble. We propose that direct binding of vitamin B12 is another mechanism underlying the inhibitory role of vitamin B12 on tau aggregation and neurodegeneration.

To demonstrate the efficacy of oral methylcobalamin in treating vitamin B12 (vitB12) deficiency anemia, our prospective observational study enrolled 28 children with both macrocytic anemia and low holotranscobalamin (HoloTC) levels. Their hematological and biochemical parameters pre- and posttreatment at 1 month were compared. Hemoglobin showed mean increase of 2.89 g/dl (P < 0.001), rising above 10 g/dl in 24 patients (85.7%). Reticulocytes peaked at 1 week. Mean fall in mean corpuscular volume of 24.83 fl (P < 0.001) and mean improvement in platelets of 122,100/μl (P = 0.001) were noted, and mean rise in HoloTC and vitB12 were 111.36 pmol/l (P < 0.001) and 918.34 pg/ml (P < 0.001), respectively. Thus, initial responses to oral methylcobalamin in children with vitB12 deficiency anemia were adequate., (© 2017 Wiley Periodicals, Inc.)

Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the capacity to regenerate, axon regeneration proceeds slowly and functional outcomes are often poor. Pharmacological enhancement of regeneration can play an important role in increasing functional recovery. In this study, we developed a novel electrospun nanofiber sheet incorporating methylcobalamin (MeCbl), one of the active forms of vitamin B12 homologues, to deliver it enough locally to the peripheral nerve injury site. We evaluated whether local administration of MeCbl at the nerve injury site was effective in promoting nerve regeneration. Electrospun nanofiber sheets gradually released MeCbl for at least 8weeks when tested in vitro. There was no adverse effect of nanofiber sheets on function in vivo of the peripheral nervous system. Local implantation of nanofiber sheets incorporating MeCbl contributed to the recovery of the motor and sensory function, the recovery of nerve conduction velocity, and the promotion of myelination after sciatic nerve injury, without affecting plasma concentration of MeCbl., Statement of Significance: Methylcobalamin (MeCbl) is a vitamin B12 analog and we previously reported its effectiveness in axonal outgrowth of neurons and differentiation of Schwann cells both in vitro and in vivo. Here we estimated the effect of local administered MeCbl with an electrospun nanofiber sheet on peripheral nerve injury. Local administration of MeCbl promoted functional recovery in a rat sciatic nerve crush injury model. These sheets are useful for nerve injury in continuity differently from artificial nerve conduits, which are useful only for nerve defects. We believe that the findings of this study are relevant to the scope of your journal and will be of interest to its readership., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) seriously affects the quality of life of patients with multiple myeloma (MM) as well as the response rate to chemotherapy. Acupuncture has a potential role in the treatment of CIPN, but at present there have been no randomized clinical research studies to analyze the effectiveness of acupuncture for the treatment of CIPN, particularly in MM patients., Methods: The MM patients (104 individuals) who met the inclusion criteria were randomly assigned into a solely methylcobalamin therapy group (500 μg intramuscular methylcobalamin injections every other day for 20 days; ten injections) followed by 2 months of 500 μg oral methylcobalamin administration, three times per day) and an acupuncture combined with methylcobalamin (Met + Acu) group (methylcobalamin used the same way as above accompanied by three cycles of acupuncture). Of the patients, 98 out of 104 completed the treatment and follow-ups. There were 49 patients in each group. The evaluating parameters included the visual analogue scale (VAS) pain score, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire scores, and electromyographic (EMG) nerve conduction velocity (NCV) determinations. We evaluated the changes of the parameters in each group before and after the therapies and made a comparison between the two groups., Results: After 84 days (three cycles) of therapy, the pain was significantly alleviated in both groups, with a significantly higher decrease in the acupuncture treated group (P < 0.01). The patients' daily activity evaluated by Fact/GOG-Ntx questionnaires significantly improved in the Met + Acu group (P < 0.001). The NCV in the Met + Acu group improved significantly while amelioration in the control group was not observed., Conclusions: The present study suggests that acupuncture combined with methylcobalamin in the treatment of CIPN showed a better outcome than methylcobalamin administration alone., Trial Registration: China Clinical Trials Register (registration no. ChiCTR-INR-16009079 , registration date August 24, 2016).

Cobalamin-dependent radical S-adenosylmethionine (SAM) methylases play vital roles in the de novo biosynthesis of many antibiotics, cofactors, and other important natural products, yet remain an understudied subclass of radical SAM enzymes. In addition to a [4Fe-4S] cluster that is ligated by three cysteine residues, these enzymes also contain an N-terminal cobalamin-binding domain. In vitro studies of these enzymes have been severely limited because many are insoluble or sparingly soluble upon their overproduction in Escherichia coli. This solubility issue has led a number of groups either to purify the protein from inclusion bodies or to purify soluble protein that often lacks proper cofactor incorporation. Herein, we use TsrM as a model to describe methods that we have used to generate soluble protein that is purified in an active form with both cobalamin and [4Fe-4S] cluster cofactors bound. Additionally, we highlight the methods that we developed to characterize the enzyme following purification., (© 2017 Elsevier Inc. All rights reserved.)

Folic acid (FA) and iron are essential supplements during pregnancy. Similarly effects of vitamin B12 (B12) inadequacy and high folate and low B12 status, on pregnancy outcome are available. However there are no mandatory recommendations for B12. There are many forms of B12 viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl), and Hydroxycobalamin (HCbl) though there is limited consensus on which form has better efficacy. In the present study we have determined effect of various forms of B12 in the presence of two FA concentrations namely normal physiological (20ng/mL; NPFA) and supra-physiological (2000ng/mL; SPFA) concentration to mimic real time situation where FA is in excess due to supplementation. We assessed trophoblastic proliferation, viability, TNFα and EGFr mRNA expression, homocysteine, β-hCG and MDA levels. Trophoblastic viability was significantly suppressed at SPFA concentration and was restored by B12 treatment with Cbl, AdCbl and combination of MeCbl+AdCbl. The mRNA expressions of TNFα were up-regulated, while EGFr were down-regulated at SPFA concentrations, as validated by RT-PCR. Treatment with MeCbl+AdCbl significantly decreased homocysteine and MDA levels at SPFA concentrations. High levels of FA alone had a detrimental effect on placental health and functions as reflected by decreased viability, EGFr expression and increased TNFα expression, homocysteine and MDA levels. Combination of B12 active forms i.e. MeCbl+AdCbl was found to be most effective in neutralising excess folate effect in-vitro., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Aims: This study investigated the efficacies of gliclazide (GLZ), methylcobalamin (MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related changes in peripheral nerve function, the polyol pathway, and oxidative stress in the sciatic nerve of streptozotocin-induced diabetic rats., Materials and Methods: The rat model of streptozotocin-induced diabetes was orally given GLZ (25mg/kg/day), MCA (175μg/kg/day), and GLZ+MCA (25mg/kg/day+175μg/kg/day) combination therapy for 8weeks, in order to observe its effects on the motor nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme activities and peroxidation products in the sciatic never tissue., Key Findings: Most of the indicators of DPN, such as delayed MNCV, altered/damaged nerve structure, inhibited Na(+),K(+)-ATPase activity, enhanced AR activity and AR mRNA expression, increased polyol contents, altered Cu,Zn-superoxide dismutase, catalase, and glutathione-peroxidase activities, and elevated malondialdehyde level in the sciatic nerves of the diabetic rats, were significantly ameliorated by treatment with either GLZ or MCA. Moreover, the combination of GLZ and MCA was found to enhance the curative effect on DPN in parts of above-mentioned parameters as compared to monotherapy., Significance: Monotherapy with GLZ or MCA, and especially the combined application of GLZ and MCA, could be efficient therapeutic strategies for combating experimental DPN in diabetic rats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To determine the therapeutic efficacy of combined methylcobalamin and lidocaine for acute ophthalmic herpetic neuralgia (AOHN)., Methods: Based on the onset, patients with AOHN (n = 98) were randomly allocated into groups A (≤ 3 days) and B (4 to 7 days) and then subdivided into control (A0, B0; received intramuscular methylcobalamin in addition to local lidocaine injection) and treatment (A1, B1; received local injection of the methylcobalamin and lidocaine combination for 14 days) groups. Treatment efficacy was assessed based on rash healing time, alteration of pain intensity, and interference with quality of life. Multilevel modeling and survival analysis were performed., Results: The time (hours) to start and full opening of the affected eye and the time (hours) to start and full crusting were significantly reduced in both treatment groups (P < 0.05 vs. controls). The mean pain scores in A1 (2.6 ± 0.7) and B1 (1.2 ± 0.8) decreased significantly compared with those in A0 (7.0 ± 1.7) and B0 (5.6 ± 1.9), and the difference between the two therapeutic strategies significantly increased over time. The median minimum intervention time was 6 days in B1 and 11 days in A1. The incidence of postherpetic neuralgia (PHN) was 2.04% at 3 months., Conclusions: Methylcobalamin combined with lidocaine mediated detumescence and improved cutaneous healing of the affected area, as well as a significant and sustained analgesic effect on AOHN. The incidence of PHN was also significantly decreased. Local methylcobalamin intervention within 4 to 7 days of onset may be an effective therapeutic option for AOHN., (© 2015 World Institute of Pain.)

Aims/introduction: To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC)., Materials and Methods: This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up., Results: A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events., Conclusions: ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To determine the efficacy of methylcobalamin combined with lidocaine for acute herpetic neuralgia., Design: Randomized controlled trial with longitudinal analysis., Subjects: The authors recruited 204 patients (>50 years) with T5-10 dermatomal acute herpetic neuralgia with rash onset within 7 days. Patients were divided into two groups based on the time of onset: immediate-early (IE, 1-3 days) and early stage (ES, 4-7 days) groups and then subdivided randomly into control (IE-Ctl, ES-Ctl) and treatment (IE-Tr, ES-Tr) groups., Methods: Control groups received intramuscular methylcobalamin in addition to local lidocaine injection, while treatment groups received local methylcobalamin combined with lidocaine injection for 14 days. Treatment efficacy was assessed based on rash healing time, alteration in pain intensity, and interference with quality of life. Multilevel mixed modeling and survival analysis were employed to examine treatment responses., Results: There was no significant difference in the rash healing time between IE and ES. The mean pain scores in IE-Tr (2.4 ± 0.7) and ES-Tr (1.3 ± 0.7) decreased significantly compared with those in the control groups. The median satisfactory response time was 6 days in ES-Tr and 11 days in IE-Tr. The benefit ratio for ES-Tr versus IE-Tr was 14.94. The subjects in IE-Tr and ES-Tr had higher quality of life scores (81.2 ± 6.9 vs 88.3 ± 8.6, respectively) than those in the control groups. The incidence of postherpetic neuralgia was 1.1% at 3 months., Conclusions: Local methylcobalamin combined with lidocaine, optimally administered within 4-7 days of onset, may be an effective therapeutic option for acute herpetic neuralgia., (© 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study was to compare the intestinal permeation of vitamin B12 and various derivatives thereof. Permeation behavior and cytotoxicity of four derivatives (coenzyme B12, hydroxocobalamin, methylcobalamin and 4-ethylphenylcobalamin) in comparison to vitamin B12 were evaluated in two different in vitro models, Caco-2 cells and freshly excised rat intestinal mucosa. Resazurin assay was used to evaluate cytotoxicity of the test substances. All test compounds were used at a concentration of 200 μg/ml. Permeation experiments were carried out for 3h and test compounds were quantified via reversed phase high performance liquid chromatography (HPLC). Cytotoxicity studies showed all test compounds are not toxic to cells. HPLC analyses of test compounds revealed the following rank order of increasing hydrophobicity: hydroxocobalamin

Objective: Current therapies for diabetic peripheral neuropathy with pain mask the painful symptoms while the underlying pathology continues to progress. This study assessed changes in symptoms and quality of life in patients taking a novel prescription medical food, L-methylfolate-methylcobalamin-pyridoxal-5-phosphate (LMF-MC-PP, Metanx ), intended to address the underlying metabolic needs of patients with diabetic peripheral neuropathy., Research Design and Methods: Between November 2010 and April 2012, patients rated their experiences before and after using LMF-MC-PP through an automated telephone system that included symptomatic items from the Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire and questions related to quality of life and medication satisfaction., Results: A total of 544 patients participated in the study. Patients reported a mean reduction of 35% in NTSS-6 scores from after 12 weeks on LMF-MC-PP. Mean (standard deviation) score was reduced by 1.5 (1.8) at 12 weeks from a baseline of 4.3 (1.5) (p < 0.05). Patients achieved significant reductions in self-reported disruptions in work/school activities, social life, and family life, respectively. Overall pain rating decreased by 32% (p < 0.05). Patients previously treated with medications reported a 52% improvement in medication satisfaction (p < 0.05)., Conclusions: In a real-world clinical setting, patients with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant improvements in total symptom score (NTSS-6) and in quality of life and functioning, together with greater medication satisfaction. A limitation of this study was the use of a survey instrument to collect data on patient outcomes.

Background: High-dose of methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS (Clinicaltrial.govNCT00444613). We attempted to study whether high-dose methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS., Methods: After initial diagnosis of the disease at the postnatal age of 3-4 weeks, wobbler mice received methylcobalamin (3 or 30 mg/kg, n=10/group) or vehicle (n=10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n=5/group)., Results: In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle., Conclusion: Our results suggest that treatment with methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used., (Copyright © 2015. Published by Elsevier B.V.)

Methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) are coenzymes for methionine synthase and methylmalonyl-CoA mutase, respectively. Hydroxylcobalamin (HOCbl) and cyanocobalamin (CNCbl) are frequently used for supplementation. MeCbl and AdoCbl have recently emerged as alternative forms in supplements. In the light of metabolic transformation of Cbl into its cofactor forms, this review discusses current evidence on efficacy and utility of different Cbl forms in preventing or treating Cbl deficiency. Cbl-transporting proteins bind and mediate the uptake of all aforementioned forms of Cbl. After internalization and lysosomal release, Cbl binds to the cytosolic chaperon MMACHC that is responsible for (i) flavin-dependent decyanation of [CN-Co(3+) Cbl to [Co(2+)]Cbl; (ii) glutathione-dependent dealkylation of MeCbl and AdoCbl to [Co(2+/1+)]Cbl; and (iii) glutathione-dependent decyanation of CNCbl or reduction of HOCbl under anaerobic conditions. MMACHC shows a broad specificity for Cbl forms and supplies the Cbl(2+) intermediate for synthesis of MeCbl and AdoCbl. Cobalamin chemistry, physiology, and biochemistry suggest that MeCbl and AdoCbl follow the same route of intracellular processing as CNCbl does. We conclude that supplementing MeCbl or AdoCbl is unlikely to be advantageous compared to CNCbl. On the other hand, there are obvious advantages of high parenteral doses (1-2 mg) of HOCbl in treating inborn errors of Cbl metabolism., (© The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This report was to evaluate the efficacy of lipoic acid, prostaglandin E1 and methylcobalamin (L+P+M) for the treatment of diabetic peripheral neuropathy (DPN) in comparison with that of prostaglandin E1 plus methylcobalamin (P+M), in order to provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of L+P+M for DPN published up to 3rd August, 2014 were searched. A random or fixed effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95% confidence interval (CI). Eighteen RCTs with 1410 participants were included. Clinical efficacy of L+P+M therapy was significantly better than P+M therapy (fifteen trials; RR 1.32, 95% CI 1.24-1.41, P<0.00001, I(2)=32%). As compared with P+M therapy, the pooled effects of L+P+M therapy on nerve conduction velocities (NCVs) were (fifteen trials; MD 4.70, 95% CI 3.77-5.63, P<0.00001, I(2)=79%) for median MNCV, (thirteen trials; MD 4.73, 95% CI 3.69-5.77, P<0.00001, I(2)=85%) for median SNCV, (sixteen trials; MD 4.22, 95% CI 3.32-5.12, P<0.00001, I(2)=83%) for peroneal MNCV, (fourteen trials; MD 3.09, 95% CI 2.04-4.14, P<0.00001, I(2)=82%) for peroneal SNCV. There was no serious adverse events associated with drugs intervention. L+P+M therapy was superior to P+M therapy for improvement of clinical efficacy and NCVs in DPN patients. These findings should be further verified by high-quality RCTs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Vitamin B12 is among the most essential biomolecules required for crucial metabolic processes in humans. Vitamin B12 was extracted from Chlorella vulgaris biomass under aqueous conditions, partially purified by passing the extract through amberlite XAD-2, Sep-Pak columns, and further purified by HPLC. The target peak eluent was subjected to characterisation by tandem mass spectrometry (MS/MS), selected ion recording (SIR) and multiple reaction monitoring (MRM) and identified as methylcobalamin (Me-Cbl). Quantification of Me-Cbl was carried out by microbiological and chemiluminescence methods, and found to be 29.87±2 μg/100 g and 26.84±2 μg/100 g dry weight, respectively. The presence of Me-Cbl was further substantiated using gold nanoparticle (AuNPs) based aptamer analysis, and found to be 28.02±2 μg/100 g dry weight. Good similarity was observed among all the methods. Methylcobalamin, a form of vitamin B12 was identified in C. vulgaris and this finding enhances its use as a nutritional supplement., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of this work was to evaluate the vitamin B12 content and profile of cobalamin bioactive forms in raw and cooked beef. The study showed that vitamin B12 distribution is unequal among beef muscles. The content of this nutrient ranges from 0.7 to 1.5 μg/100 g of tissue. In beef, three biologically active forms of vitamin B12 were determined, i.e.: methylcobalamin, adenosylcobalamin and hydroxycobalamin; the dominating form of vitamin B12 was adenosylcobalamin (68% of total cobalamins). The process of roasting and grilling had little effect on the vitamin B12 content in the final product as compared to the raw meat. The fried product was characterised by about a 32% lower content of cobalamins than in raw meat., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Methylcobalamin (MeCbl) is a vitamin B12 analog that has some positive effects on peripheral nervous disorders. Although some previous studies revealed the effects of MeCbl on neurons, its effect on the muscle, which is the final target of motoneuron axons, remains to be elucidated. This study aimed to determine the effect of MeCbl on the muscle. We found that MeCbl promoted the proliferation and migration of C2C12 myoblasts in vitro and that these effects are mediated by the Erk1/2 signaling pathway without affecting the activity of the Akt signaling pathway. We also demonstrated that MeCbl inhibits C2C12 cell apoptosis during differentiation. Our results suggest that MeCbl has beneficial effects on the muscle in vitro. MeCbl administration may provide a novel therapeutic approach for muscle injury or degenerating muscle after denervation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN)., Methods: Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity., Results: Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment., Conclusions: The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)