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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. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effect of methylcobalamin combined with holistic copper acupuncture and scraping technique in ameliorating tinnitus symptoms in patients with sudden sensorineural hearing loss. Methods: 80 patients with sudden sensorineural hearing loss from Department of Otolaryngology, The Hefei First People's Hospital, Hefei, China were selected as subjects for this study. They were divided into control and study groups, respectively, with 40 patients in each group, based on the different treatment interventions received by the patients. Conventional interventions included the use of Ginkgo biloba extract, Tianmasu injection, dexamethasone pharmacological treatments. The control group received methylphenidate tablets in addition to the conventional treatment, while the study group received further intervention comprising the combination of holistic copper acupuncture and scraping technique on the ear, in addition to the treatment received by the control group. The evaluated outcomes included efficacy, auditory threshold levels, and Pittsburgh Sleep Quality Index (PSQI) score. Results: The overall efficacy of the treatment in the control group was 77.5 %, whereas, it was significantly higher in the study group at 97.5 % (p < 0.05). Prior to treatment, there were no significant differences in pure tone audiometry thresholds between the two groups (p > 0.05). However, post-treatment, the study group exhibited significantly lower pure tone audiometry thresholds compared to the control group (p < 0.05). Before PSQI scores were similar for the two groups (p > 0.05). However, after treatment, the PSQI scores in the study group were significantly lower than those in the control group (p < 0.05). Conclusion: The combined application of methylcobalamin, holistic copper acupuncture, and scraping technique is effective for the treatment of patients with sudden sensorineural hearing loss. This integrated treatment approach significantly alleviates tinnitus and improves sleep-related symptoms in patients with sudden sensorineural hearing loss. Furthermore, it promotes the recovery of pure tone audiometry thresholds and other related parameters. [ABSTRACT FROM AUTHOR]

Abstract Background Thrombophilia is characterised by an abnormality of blood coagulation that increases thrombosis. Homocystinuria encompasses a group of disorders marked by increased levels of homocysteine and other amino acids detectable in the bloodstream and urine. Conversely, homocystinuria due to methylenetetrahydrofolatereductase (MTHFR) deficiency, a rarer disorder, stems from impaired folate metabolism due to deficient MTHFR enzyme. Case presentation A 16-year-old boy presented with walking difficulties, headaches, and thrombotic events, thrombophilia workup led to a diagnosis of homocystinuria due to a novel mutation in MTHFR gene. Anticoagulant therapy was initiated which showed clinical improvement, but financial constraints hindered follow-up. Conclusions This case highlights the complexities of diagnosing and treating paediatric thrombophilia, particularly in resource-limited settings. Notably, the identified homozygous autosomal recessive (AR) missense variation in the MTHFR gene (Exon 4—c582C>G) represents a novel mutation, suggesting the ongoing significance of genetic research in elucidating the underlying mechanisms of thrombotic disorders.

Purpose: Teratological potential of oxyfluorfen and the antioxidant role of Methylcobalamin was studied in the golden black variety of domestic chicken Gallus domesticus. Methods: The study was conducted on 200 fresh fertilized eggs collected and divided into 4 groups as follows: (1) Control injected with 0.1 µL of 5% DMSO in corn oil (2) Oxy, injected with 0.1µL of 0.01µg/g oxyfluorfen solution in 5% DMSO and corn oil (3) MeCbl, injected with 0.1µL of 0.01µg/g methylcobalamin solution (4) OxyMeCbl, injected with 0.1µL of 0.01µg/g oxyfluorfen solution in 5% DMSO and corn oil and 0.1µL of 0.01µg/g methylcobalamin solution. In-ovo treatment was given on zero day and embryos were incubated & on 14th day of incubation, the embryos were recovered from eggs and fixed in fixative (90% alcohol and 10% formaldehyde) for further studies. Results: The morphological observations showed a significant increase in mortality rate among the oxyfluorfen treated embryos against control group. Morphological analysis revealed various adverse effects, including reduced weight, crown-rump size, axial and appendicular skeleton size. Moreover, deformities were noted in the beak, eye, and neck formation. Cataracts were frequently observed in the eyes, and some embryos showed reduced head size with a prominent decrease in the beak size. Development of feathers was also affected, and several cases exhibited umbilical cord hernias. However, when the embryos were treated with methylcobalamin after oxyfluorfen exposure, there was a noticeable improvement in developmental effects. Conclusions: Oxyfluorfen, containing fluorine causes birth defects in chick embryo that might be due to oxidative stress. Methylcobalamin has showed potential to act as antioxidant by countering oxyfluorfen's harmful effects. [ABSTRACT FROM AUTHOR]

Methylmalonic aciduria and homocystinuria type C protein (MMACHC) is required by the body to metabolize cobalamin (Cbl). Due to its complex structure and cofactor forms, Cbl passes through an extensive series of absorptive and processing steps before being delivered to mitochondrial methyl malonyl-CoA mutase and cytosolic methionine synthase. Depending on the cofactor attached, MMACHC performs either flavin-dependent reductive decyanation or glutathione (GSH)-dependent dealkylation. The alkyl groups of Cbl have to be removed in the presence of GSH to produce intermediates that can later be converted into active cofactor forms. Pathogenic mutations in the GSH binding site, such as R161Q, R161G, R206P, R206W, and R206Q, have been reported to cause Cbl diseases. The impact of these variations on MMACHC's structure and how it affects GSH and Cbl binding at the molecular level is poorly understood. To better understand the molecular basis of this interaction, mutant structures involving the MMACHC-MeCbl-GSH complex were generated using in silico site-directed point mutations and explored using molecular dynamics (MD) simulations. The results revealed that mutations in the key arginine residues disrupt GSH binding by breaking the interactions and reducing the free energy of binding of GSH. Specifically, variations at position 206 appeared to produce weaker GSH binding. The lowered binding affinity for GSH in the variant structures could impact metabolic pathways involving Cbl and its trafficking. [ABSTRACT FROM AUTHOR]

Background: The literature data is scarce concerning the efficacy of various routes for administering vitamin B12 in child subjects with macrocytic-megaloblastic anemia and vitamin B12 deficiency. Aim: The present study aimed to comparatively assess the efficacy of Oral vitamin B 12 to parenteral vitamin B12 in treating child subjects with nutritional macrocytic anemia. Methods: The study assessed 160 child subjects in the age range of 3 months to 18 years with laboratory and clinical findings suggestive of megaloblastic macrocytic anemia. All subjects were given 1000μg vitamin B12 in a single parenteral dose. The subjects were then divided into 2 groups randomly where Group I was given oral vitamin B12 daily for 3 months in 1500μg dose (500μg in subjects aged < 2 years) and Group II was given intramuscular 1000μg B12 in 3 and 5 doses alternate days for <10 and >10 years respectively followed by 2 doses of 1000μg. Iron and folic acid were given to both groups. Hemoglobin and serum vitamin B12 were compared after 3 months. Results: A significant improvement was seen in levels of vitamin B12 in group II with p=0.01. Also, a significant improvement in Group II was seen for hemoglobin levels with p=0.001. Conclusion: The study concluded that a significant improvement in hemoglobin and serum vitamin B12 levels is seen in child subjects with macrocytic anemia with parenteral vitamin B12 compared to oral Vitamin B12. [ABSTRACT FROM AUTHOR]

Craig Brown,1,&ast; Jianhua Wang,2,&ast; Hong Jiang,3,&ast; Merrill F Elias4,&ast; 1Department of Ophthalmology, College of Medicine, University of Arkansas for Medical Sciences, Fayetteville, AR, USA; 2Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA; 3Bascom Palmer Eye institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; 4Department of Psychology, University of Maine and Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA&ast;These authors contributed equally to this workCorrespondence: Craig Brown, 208 E Jason Dr, Fayetteville, AR, 72703, USA, Email cjbrown2@uams.eduAbstract: Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.Graphical Abstract: Plain Language Summary: The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack is incomplete. Reduction of secondary ischemic stroke risk following an initial stroke or TIA is achievable through medication, lifestyle, and nutritional interventions detailed in the Guideline.The common patient subgroups with renal failure and/or MTHFR C677T polymorphisms are at higher risk for homocysteine elevation, ischemic stroke, and toxicity from excessive folic acid and cyanocobalamin.The natural forms, L-methylfolate and methylcobalamin, are recommended for these high-risk subpopulations with renal failure and common polymorphisms of the MTHFR and DHFR.Non-invasive imaging of retinal vessels offers real-time monitoring of small vessel ischemia in stroke patients. A recent study has shown improved retinal perfusion using a cocktail of antioxidants, L-methylfolate, and methylcobalamin. This supports the use of L-methylfolate and methylcobalamin to lower homocysteine and improve CNS perfusion, which would be beneficial for stroke prevention.We recommend revision of the 2021 Guideline to include homocysteine reduction with low dose folic acid, or better, L-methylfolate and B12 as methylcobalamin.Keywords: homocysteine, ischemic stroke, l-methylfolate, methylcobalamin, n-acetyl cysteine, renal failure

Background: Thrombophilia is characterised by an abnormality of blood coagulation that increases thrombosis. Homocystinuria encompasses a group of disorders marked by increased levels of homocysteine and other amino acids detectable in the bloodstream and urine. Conversely, homocystinuria due to methylenetetrahydrofolatereductase (MTHFR) deficiency, a rarer disorder, stems from impaired folate metabolism due to deficient MTHFR enzyme. Case presentation: A 16-year-old boy presented with walking difficulties, headaches, and thrombotic events, thrombophilia workup led to a diagnosis of homocystinuria due to a novel mutation in MTHFR gene. Anticoagulant therapy was initiated which showed clinical improvement, but financial constraints hindered follow-up. Conclusions: This case highlights the complexities of diagnosing and treating paediatric thrombophilia, particularly in resource-limited settings. Notably, the identified homozygous autosomal recessive (AR) missense variation in the MTHFR gene (Exon 4—c582C>G) represents a novel mutation, suggesting the ongoing significance of genetic research in elucidating the underlying mechanisms of thrombotic disorders. [ABSTRACT FROM AUTHOR]

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.

ABSTRACTFine particulate matter (PM2.5) in the atmosphere is easily accompanied by toxic and harmful substances, causing serious harm to human health, including cognitive impairment. Vitamin B12 (VitB12) is an essential micronutrient that is synthesized by bacteria and contributes to neurotransmitter synthesis as a nutrition and signaling molecule. However, the relationship between VitB12 attenuation of cognitive impairment and intestinal microbiota regulation in PM2.5 exposure has not been elucidated. In this study, we demonstrated that PM2.5 caused behavioral defects and neuronal damage in Caenorhabditis elegans (C. elegans), along with significant gene expression changes in neurotransmitter receptors and a decrease in VitB12 content, causing behavioral defects and neuronal damage in C. elegans. Methylcobalamin (MeCbl), a VitB12 analog, alleviated PM2.5-induced neurotoxicity in C. elegans. Moreover, using in vivo and in vitro models, we discovered that long-term exposure to PM2.5 led to changes in the structure of the gut microbiota, resulting in an imbalance of the VitB12-associated metabolic pathway followed by cognitive impairment. MeCbl supplementation could increase the diversity of the bacteria, reduce harmful substance contents, and restore the concentration of short-chain fatty acids (SCFAs) and neurotransmitters to the level of the control group to some degree. Here, a new target to mitigate the harm caused by PM2.5 was discovered, supplying MeCbl for relieving intestinal and intracellular neurotransmitter disorders. Our results also provide a reference for the use of VitB12 to target the adjustment of the human intestinal microbiota to improve metabolic disorders in people exposed to PM2.5.

This study evaluated and compared the functional recovery and histopathological outcomes of treatment involving low-intensity pulsed ultrasound (LIPUS) and methylcobalamin (B12) on brachial plexus injury (BPI) in an experimental rat model. Three days after BPI, the rats were assigned to receive either LIPUS or methylcobalamin alone or in combination consecutively for 12 days. Serial changes in sensory and motor behavioral responses, as well as morphological and immunohistochemical changes for substance P (SP), ionized calcium-binding adapter molecule 1 (iba1), brain-derived neurotrophic factor (BDNF), and S100 were examined 28 days after BPI as the outcome measurements. Early intervention of LIPUS and methylcobalamin, whether alone or in combination, augmented the sensory and motor behavioral recovery as well as modulated SP and iba1 expression in spinal dorsal horns, BDNF, and S100 in the injured nerve. Moreover, the combined therapy with its synergistic effect gave the most beneficial effect in accelerating functional recovery. In view of the effective initiation of early recovery of sensory and motor functions, treatment with LIPUS and methylcobalamin in combination has a potential role in the clinical management of early-phase BPI. [ABSTRACT FROM AUTHOR]

Gang Xu,1 Weizhen Tang,1 Chaosheng Zhou,1 Jie Xu,1 Chao Cheng,1 Weiwei Gong,2,3 Shihong Dong,2 Yu Zhang1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +8621-66306496, Fax +8621-66301051, Email sykfsci@126.comPurpose: To evaluate the efficacy and pain fluctuations of methylcobalamin in combination with lidocaine local injection treatment for subacute herpetic neuralgia (SHN).Methods: Seventy-nine women (60.4 ± 2.7 years) with thoracic SHN were enrolled and randomized to receive a combination of methylcobalamin and lidocaine local injection (MI, N=40), or a combination of lidocaine patch 5% and oral methylcobalamin (PO, N=39) for four weeks. Repeated-measures analyses of variance were used to evaluate the effect on pain levels. Generalized estimation equations were used to analyze the cause-effect relationship between pain fluctuations and influencing factors.Results: At the treatment endpoint, the group, treatment time, and group interacted with treatment time effects of the pain scores and area were statistically significant (P< 0.001), The pain scores were 2.9 ± 0.9 (MI) and 4.3 ± 1.5 (PO). 80.00% (MI) or 28.21% (PO) of patients had pain scores ≤ 3, the odds ratio was 2.84 (95% CI: 1.68 to 4.79). The incidence of postherpetic neuralgia was 5.0% (2/40) at 3 months. Pain fluctuated repeatedly during treatment. The pain fluctuation increased from 8.75 log folds in the afternoon, to 79.85 log folds at night. With the ADLs level increasing from 1 to 3, the pain fluctuated from 4.28 to 17.70 log folds. Allodynia, itching, sleep quality, and ADLs were the significant influencing factors (P< 0.05).Conclusion: This study validated the efficacy of methylcobalamin combined with lidocaine for SHN, and confirmed that pain levels in patients with SHN had an obvious circadian rhythm. ADLs were an important cause of pain fluctuations.Keywords: subacute herpetic neuralgia, methylcobalamin, lidocaine, pain fluctuation, activities of daily living

Abstract Background Fibromyalgia (FM) as a prototypical nociplastic pain condition displays a difficult therapeutic situation in many cases. Given the promising data on the effect of vitamin B12 in improving pain and cognitive functions in various nociplastic pain conditions, we aimed to determine the efficacy of 1000 mcg daily dose of oral vitamin B12 on the symptom severity and psychological profile of FM patients. Methods This open-label, pre-post study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Patients were instructed to take a daily dose of 1000mcg vitamin B12 for fifty days. Outcome measures including the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item Short-Form health survey (SF-12), and pain Visual Analog Scale (pain-VAS) were fulfilled by patients before and after the treatment. Results Of 30 eligible patients, 28 patients completed the study protocol. Patients were female with a mean age of 47.50 ± 8.47 years. FIQR scores in all domains improved significantly after treatment (total FIQR: 49.8 ± 21.86 vs 40.00 ± 18.36, p value

The oral availability of many drugs is problematic due to the pH of the stomach, enzymes, and first-pass effects through the liver. However, especially geriatric, pediatric, bedridden, or mentally handicapped patients and those with dysphagia have difficulty swallowing or chewing solid dosage forms. Oral Thin Films (OTFs) are one of the new drug delivery systems that can solve these problems. Pregabalin (PG) and Methylcobalamin (MC), which are frequently preferred for pain originating in the central nervous system, were brought together for the first time using OTF technology in this study. In this study, a quantification method for PG and MC was developed and validated simultaneously. Optimum formulations were selected with organoleptic and morphological controls, moisture absorption capacity, swelling capacity, percent elongation, foldability, pH, weight variability, thickness, disintegration time, and transparency tests on OTFs prepared by the solvent pouring method. Content uniformity, dissolution rate, determination of release kinetics, SEM, XRD, FT-IR, DSC, long-term stability, and cytotoxicity studies on the tongue epithelial cell line (SCC-9) were performed on selected OTFs. As a result, OTFs containing PG-MC, which are non-toxic, highly flexible, transparent, compatible with intraoral pH, with fast disintegration time (<30 s), and acceptable in taste and appearance, have been developed successfully. [ABSTRACT FROM AUTHOR]

Methylmalonic aciduria and homocystinuria type C protein (MMACHC) is required by the body to metabolize cobalamin (Cbl). Due to its complex structure and cofactor forms, Cbl passes through an extensive series of absorptive and processing steps before being delivered to mitochondrial methyl malonyl-CoA mutase and cytosolic methionine synthase. Depending on the cofactor attached, MMACHC performs either flavin-dependent reductive decyanation or glutathione (GSH)-dependent dealkylation. The alkyl groups of Cbl have to be removed in the presence of GSH to produce intermediates that can later be converted into active cofactor forms. Pathogenic mutations in the GSH binding site, such as R161Q, R161G, R206P, R206W, and R206Q, have been reported to cause Cbl diseases. The impact of these variations on MMACHC’s structure and how it affects GSH and Cbl binding at the molecular level is poorly understood. To better understand the molecular basis of this interaction, mutant structures involving the MMACHC-MeCbl-GSH complex were generated using in silico site-directed point mutations and explored using molecular dynamics (MD) simulations. The results revealed that mutations in the key arginine residues disrupt GSH binding by breaking the interactions and reducing the free energy of binding of GSH. Specifically, variations at position 206 appeared to produce weaker GSH binding. The lowered binding affinity for GSH in the variant structures could impact metabolic pathways involving Cbl and its trafficking.

Vitamin B12, 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 B12 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 B12 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 B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 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 B12 products. [ABSTRACT FROM AUTHOR]

Individuals with brachial plexus injury (BPI) require upper limb function restoration, but the treatment remains controversial. Vitamin B12 may aid in pain control and nerve regeneration. We present the technical aspects of ultrasound-guided perineural vitamin B12 injection for BPI. The demonstrative case is a 50-year-old man with BPI resulting from a traffic accident. Under ultrasound guidance, vitamin B12 was injected precisely into the brachial plexus compartment around the swollen neuroma of the C6 root. Motor and sensory functions of the left upper extremity improved over 6 months. Ultrasound-guided perineural vitamin B12 injection may be an efficient and personalized intervention in cases of post-ganglionic BPI that failed to improve in the first 3 months. [ABSTRACT FROM AUTHOR]

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. • Methylcobalamin (MBL) assay in rat plasma was developed by LC-MS/MS. • The MBL assay used only 10 μL of plasma and quantified MBL from 20 ng/mL. • The assay was successfully validated with acceptable criteria of validation parameters. • Pharmacokinetics (PK) of MBL in rats was assessed after multiple drug administration routes. • Bioavailability of MBL was almost complete in rats after subcutaneous and intramuscular administration. [ABSTRACT FROM AUTHOR]

This study evaluated and compared the functional recovery and histopathological outcomes of treatment involving low-intensity pulsed ultrasound (LIPUS) and methylcobalamin (B12) on brachial plexus injury (BPI) in an experimental rat model. Three days after BPI, the rats were assigned to receive either LIPUS or methylcobalamin alone or in combination consecutively for 12 days. Serial changes in sensory and motor behavioral responses, as well as morphological and immunohistochemical changes for substance P (SP), ionized calcium-binding adapter molecule 1 (iba1), brain-derived neurotrophic factor (BDNF), and S100 were examined 28 days after BPI as the outcome measurements. Early intervention of LIPUS and methylcobalamin, whether alone or in combination, augmented the sensory and motor behavioral recovery as well as modulated SP and iba1 expression in spinal dorsal horns, BDNF, and S100 in the injured nerve. Moreover, the combined therapy with its synergistic effect gave the most beneficial effect in accelerating functional recovery. In view of the effective initiation of early recovery of sensory and motor functions, treatment with LIPUS and methylcobalamin in combination has a potential role in the clinical management of early-phase BPI.

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

Objective: To compare the reduction in mean pain score with local Methylcobalamin injection versus local Bupivacaine injection in patients with acute herpetic neuralgia. Study Design: Quasi experimental study. Place and Duration of Study: Dermatology Outpatient Department, Pak Emirates Military Hospital, Rawalpindi, from Jun to Dec 2019. Methodology: Total 100 patients, having pain score more than 3, fulfilling the selection criteria were divided into two groups. Group A was treated with daily subcutaneous injection Bupivacaine, whereas Group B was treated with daily subcutaneous injection Methycobalamin at the site of neuralgia. Patients were followed up for 4 weeks. The pain score was noted. All the data was entered and analyzed on SPSS version 21. Results: In this study mean age of patients in group A was 43.82 ± 15.76 years and in group B was 44.76 ± 16.92 years. The mean visual analogue pain score at 4th week in the group A patients was 1.14 ± 0.32 and in group B was 1.90 ± 0.97. Statistically significant difference was found in group A (local Bupivacaine) with visual analogue score (VAS) at 4th week (pvalue=0.002). Conclusion: The local Bupivacaine injection showed significant reduction in mean pain score than local Methylcobalamin injection in patients with acute herpetic neuralgia.

Ran An,1,2 Dong Li,1 Yingying Dong,1 Qiuyun She,1 Ting Zhou,1 Xiaoqi Nie,1 Ronghua Pan,1 Yunhua Deng1 1Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Dermatology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Yunhua DengDepartment of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Qiaokou, Wuhan, Hubei, People’s Republic of ChinaTel +86 027 83663370Fax +86 027 83663625Email 820331158@qq.comPurpose: 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 (H2O2)-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 H2O2-induced oxidative stress in melanocytes by activating the Nrf2/HO-1 pathway, this suggests that MeCbl may be an effective treatment against vitiligo.Keywords: methylcobalamin, vitiligo, oxidative stress, melanocytes, NF-E2-related factor 2

Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Intractable facial paralysis has a poor prognosis, and new treatments are required. Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Reactive oxygen species can inhibit peripheral nerve regeneration after injury. Therefore, the administration of an appropriate antioxidant can promote nerve regeneration. Silicon (Si)-based agents can react with water to generate antioxidant hydrogen. Oral administration of Si-based agents can effectively alleviate symptoms of disease models associated with oxidative stress. Thus, we orally administered a Si-based agent to a facial paralysis model mice to investigate whether promotion of nerve regeneration occurred. The combined administration of methylcobalamin (MeCbl) with the Si-based agent was also investigated. The Si-based agent improved the clinical score evaluation of facial paralysis. Electroneuronography and immunostaining showed that the Si-based agent promoted myelination and recovery of facial nerve function. Furthermore, in the drug-administered group, oxidative stress associated with facial nerve injury was reduced more than that in the non-administered group. The clinical score evaluation, neuroregeneration effect, and reduction of oxidative stress were improved in the combination group compared to the single administration group. The Si-based agent could rapidly improve the disappearance of facial expressions by promoting myelin sheath formation and alleviating oxidative stress. Combination therapy with a Si-based agent and MeCbl should improve the prognosis and treatment of intractable facial paralysis.

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

Objective. Painful diabetic neuropathy (PDN) is a prevalent debilitating consequence of diabetes mellitus with lack of satisfactory therapeutic options. Methylcobalamin (MeCbl) is one of vitamin B12 analogs with known neurotrophic effects. We aimed to determine if MeCbl can relieve PDN. Materials and methods. This was a randomized (1:1) double-blind placebo-controlled trial involving PDN patients. Treatment and control group received daily 12.5 mg oral amitryptiline bid with either 500 µg of intravenous MeCbl or saline injection given on alternating days, respectively, for a 9-consecutive day period. PDN was assessed with douleur neuropathique 4 (DN4) questionnaire. Numeric pain rating scale (NPRS) was used to monitor pain intensity and treatment response. All investigators and patients were kept blinded throughout the study period. Outcomes. 42 patients, 21 on each arm had completed the study. The NPRS reduction can already be observed as early as day 2 post-intervention. Both the treatment and control group demonstrated sustained reduction of NPRS by almost one point per each time point of evaluation in the first three days (p

(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. [ABSTRACT FROM AUTHOR]

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

Objective: In attempt to conquer the major concerns of oral duloxetine hydrochloride (like low bioavailability, intolerable side-effects and no regeneration of demyelinated nerve fibres) for the management of chemotherapy-induced peripheral neuropathy (CIPN), an alternative delivery of duloxetine hydrochloride was aimed for in-vivo optimization. Methods: A film forming dermal gel consisting of duloxetine hydrochloride was formulated and enriched with methylcobalamin and geranium oil. The formulated gel successfully qualified the various pharmaceutical characteristics of gel. Administration of paclitaxel (8 mg/kg/i.p. in four divided doses) for 4 alternate days induced the symptoms of peripheral neuropathy in rats. On 14th day, the responses to noxious stimulus (mechanical hyperalgesia, cold allodynia, and heat hyperalgesia) were increased and reached to its maximum. Thereafter, drug treatment with formulated dermal gel and oral duloxetine hydrochloride (30 mg/kg, once daily) was initiated for 2 weeks in different group of animals. On the 28th day animals were sacrificed to isolate sciatic nerve, to assess biochemical changes (TBARS, reduced GSH, total protein, TNF-α, IL-6) and for histopathological examinations of nerve sections using Hematoxylin-Eosin and Toludine blue staining methods. Results: Application of formulated dermal gel to paclitaxel-treated rats significantly improved paw-withdrawal latency responses during noxious stimulus testing, reduced the levels of TBARS, TNF-α, IL-6 and elevated the levels of reduced GSH as compared to paclitaxel treated rats. Histographs also indicated marked regeneration of the damaged nerve fibers. Topical delivery of duloxetine hydrochloride produced similar results in disparity to oral route. However, no significant disparity in responses was obtained with twice application of formulated dermal gel when compared to once daily application. Conclusion: Tremendous recovery from nociception, oxidation and inflammation in addition to nerve degeneration was achieved through dermal application of duloxetine hydrochloride in peripheral neuropathy.

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. 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). 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). 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. [ABSTRACT FROM AUTHOR]

Objective: To compare the reduction in mean pain score with local Methylcobalamin injection versus local Bupivacaine injection in patients with acute herpetic neuralgia. Study Design: Quasi experimental study. Place and Duration of Study: Dermatology Outpatient Department, Pak Emirates Military Hospital, Rawalpindi, from Jun to Dec 2019. Methodology: Total 100 patients, having pain score more than 3, fulfilling the selection criteria were divided into two groups. Group A was treated with daily subcutaneous injection Bupivacaine, whereas Group B was treated with daily subcutaneous injection Methycobalamin at the site of neuralgia. Patients were followed up for 4 weeks. The pain score was noted. All the data was entered and analyzed on SPSS version 21. Results: In this study mean age of patients in group A was 43.82 ± 15.76 years and in group B was 44.76 ± 16.92 years. The mean visual analogue pain score at 4th week in the group A patients was 1.14 ± 0.32 and in group B was 1.90 ± 0.97. Statistically significant difference was found in group A (local Bupivacaine) with visual analogue score (VAS) at 4th week (pvalue= 0.002). Conclusion: The local Bupivacaine injection showed significant reduction in mean pain score than local Methylcobalamin injection in patients with acute herpetic neuralgia. [ABSTRACT FROM AUTHOR]

The sources of bioavailable vitamin B12 are limited, and most of them are animal-derived. Chlorella vulgaris, a freshwater microalga, is known for immune system boosting, nutraceutical properties and presence of a natural form of vitamin B12. The present study focused on the in vivo evaluation of the Chlorella biomass as a source of bioavailable vitamin B12 to alleviate the vitamin B12 deficiency status of Wistar rats. Experimental animals were evaluated for the vitamin B12 deficiency-related circulatory marker (serum vitamin B12) and functional markers (plasma homocysteine and urinary methylmalonic acid), haematological and histological changes. The results showed that an increase of 2.4-fold in urinary methylmalonic acid (13.01 ± 0.89 µmoles moles of creatinine−1), 2.6-fold in plasma homocysteine (17.18 ± 3.57 µmole L−1), and 48% decrease in serum vitamin B12 levels (252.69 ± 1.46 pg mL−1) in vitamin B12 deficient group compared to control animals. The Chlorella biomass supplementation in the diet led to the restoration of the functional and circulatory markers, hematological parameters, and vitamin B12 content of kidney and liver to control levels. The Chlorella biomass supplementation increased the erythrocyte precursors and MAST cells in the bone marrow and also normalized the histological features of kidney, liver, and lung tissues. The results suggest that the vitamin B12 from the Chlorella biomass was bioavailable and facilitated the improvement of vitamin B12 status in deficient rats. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) and autoimmune gastritis (AIG) are both autoimmune diseases (ADs) that have a low prevalence in China. Both conditions involve the immune system mistakenly attacking the body's own tissues. GBS primarily affects the peripheral nervous system, leading to muscle weakness and paralysis, while AIG targets the stomach lining, causing inflammation and reduced absorption of vital nutrients. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. As of yet, there have been no reported cases of patients with GBS and complications of AIG including SCD. We report a case of a 54-year-old male patient who had been experiencing progressive numbness and weakness in his extremities, burning and tingling sensations, a cotton-stepping sensation, and difficulty walking for three weeks. He was admitted to the hospital and underwent an extensive medical workup. Magnetic resonance imaging (MRI) of the cervical spine cord showed abnormal spinal cord signal intensity consistent with typical manifestations of vitamin B12 deficiency. Gastric endoscopy revealed local atrophy of the gastric corpus, and gastric tissue biopsy indicated atrophic gastritis with intestinal metaplasia, consistent with a diagnosis of AIG. Lumbar puncture of cerebrospinal fluid (CSF) results showed albumincytological dissociation, further confirming the diagnosis of GBS. He was treated with intravenous immunoglobulin and methylcobalamin therapy for these conditions and showed significant clinical improvement upon discharge., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Xiang et al.)

CONTEXT: Diabetic neuropathy affects 10.5%–32.2% of diabetic population posing clinical burden onto society. AIMS: We aimed to study the efficacy, safety, and tolerability of methylcobalamin, methylcobalamin plus pregabalin, and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy. SETTINGS AND DESIGN: It is a prospective, randomized, open-label, interventional, and parallel-group study done in patients of painful diabetic neuropathy. MATERIALS AND METHODS: A total of 100 patients were recruited and randomized to three study groups A, B, and C on methylcobalamin, methylcobalamin and pregabalin, and methylcobalamin and duloxetine, respectively. Patients were assessed at day 0 and 4, 8, and 12 weeks. The tuning fork test, monofilament test, Thermal Sensitivity testing, and Visual Analog Scale (VAS) were used to analyze vibration, pressure, thermal sensitivity, and pain. STATISTICAL ANALYSIS USED: The results are expressed as mean ± standard deviation. Appropriate statistical methods were used to calculate P value (<0.05 – significant). RESULTS: The increase in number of patients with vibration perception is 11.6%, 37.9%, and 41.4%; pressure sensation is 7.6%, 37.9%, and 37.9%; and thermal sensitivity is 15.4%, 31.1%, and 37.9% in Groups A, B, and C, respectively. The decrease in VAS scores is 0.58 ± 0.14, 3.82 ± 0.05, and 4.17 ± 0.48 in Groups A, B, and C correspondingly. The adverse effects reported in Groups A, B, and C are 0%, 6.9%, and 10.3%, respectively. CONCLUSIONS: Group C is more efficacious when compared to Groups A and B while Group B is safer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. Painful diabetic neuropathy (PDN) is a prevalent debilitating consequence of diabetes mellitus with lack of satisfactory therapeutic options. Methylcobalamin (MeCbl) is one of vitamin B12 analogs with known neurotrophic effects. We aimed to determine if MeCbl can relieve PDN. Materials and methods. This was a randomized (1:1) double-blind placebo-controlled trial involving PDN patients. Treatment and control group received daily 12.5 mg oral amitriptyline bid with either 500 μg of intravenous MeCbl or saline injection given on alternating days, respectively, for a 9-consecutive day period. PDN was assessed with douleur neuropathique 4 (DN4) questionnaire. Numeric pain rating scale (NPRS) was used to monitor pain intensity and treatment response. All investigators and patients were kept blinded throughout the study period. Outcomes. 42 patients, 21 on each arm had completed the study. The NPRS reduction can already be observed as early as day 2 post-intervention. Both the treatment and control group demonstrated sustained reduction of NPRS by almost one point per each time point of evaluation in the first three days (p<0.001). NPRS reduction remained until the end of the study period. The treatment group had a significantly lower NPRS score by 1.29 than that of the control group during the entire study period (95% CI -1.84 – -0.75; p < 0.001). Treatment group experienced significantly higher NPRS reduction when compared with control (4.19±1.54 vs. 2.1± 0.83; 95% CI 1.32-2.87; p < 0.001), i.e. 62.6% from baseline. Conclusions. MeCbl significantly and safely relieved PDN in a relatively rapid onset. [ABSTRACT FROM AUTHOR]

Background. Adverse side effect of metformin is disturbance in vitamin B12 metabolism associated with low serum vitamin B12 level. B12 hypovitaminosis is accompanied by peripheral neuropathy. The aim of the study was to determine the effectiveness of methylcobalamin (Diacobal preparation manufactured by Kusum Pharm LLC, Ukraine) in correcting vitamin B12 deficiency in diabetic patients with metformin­associated vitamin B12 deficiency, and to establish its effect on manifestations of diabetic neuropathy. Materials and methods. Thirty patients with type 2 diabetes mellitus and metformin­associated vitamin B12 deficiency (< 190 pg/ml) were examined. Duration of metformin administration was 6.1 years on average, the average dose was 2100 mg/day. Methylcobalamin was administered at a dose of 500 mg three times a day for three months. Determination of vitamin B12 content and assessment of neuropathy manifestations was carried out before and after the course of treatment. Results. After the course of treatment, it was found that the average content of vitamin B12 in the blood serum reached the reference values (312.4 ± 39.8 pg/ml). The positive effect of therapy on the severity of clinical manifestations of peripheral sensory motor neuropathy in the examined patients was revealed: in 17 (56.7 %) patients, the severity of numbness in feet significantly decreased, in 6 (20 %) persons, there was a complete disappearance of numbness. The intensity of the pain syndrome decreased in 19 (63.3 %) patients, the pain syndrome was completely removed in 3 (10 %) persons. Conclusions. The relationship between metformin and B12 hypovitaminosis has been confirmed. Diacobal is an effective and safe drug for the prevention and treatment of metformin­induced vitamin B12 deficiency and diabetic neuropathy.

(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.

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. [ABSTRACT FROM AUTHOR]

Aim: To know the effect of adding methylcobalamin to pregabalin in patients of postherpetic neuralgia (PHN) and also to compare the side effects of pregabalin alone and fixed-drug combination (FDC) of pregabalin and methylcobalamin. Materials and Methods: This was a multicenter randomized 10-month prospective study. A total of 90 patients with PHN (age and sex matched) were included. Baseline pain intensity was measured on a 10-point visual analog scale (VAS) score. Patients were randomized into two groups. Group A patients received pregabalin (75 mg) 12th hourly, whereas Group B patients were given FDC of pregabalin (75 mg) along with methylcobalamin (750 μg) 12th hourly. Thereafter, patients were assessed for the pain score at 4, 8, and 12 weeks after initiation of the treatment. The frequency and severity of adverse events were assessed. Results: Before starting medication, the average VAS score of Group A and Group B was 6.86 and 6.97, respectively. Post-medication average VAS score of Group A and Group B was found out to be 2.95 and 3.11, respectively. A significant reduction in VAS scores of both the groups was observed when compared to their respective baseline VAS scores (P < 0.001). But post-medication VAS scores of both the groups were not statistically significant (P = 0.58). Side effects such as dizziness and somnolence were observed in both the groups. This was also found out to be not statistically significant when side effects of both the groups were compared (P = 0.52). Conclusion: The result of our study shows minimal statistical difference between pregabalin alone and the FDC of pregabalin with methylcobalamin for the treatment of PHN. Patients showed improvement in pain with minimal side effects such as somnolence and dizziness in both the groups.

Fine particulate matter (PM 2.5 ) in the atmosphere is easily accompanied by toxic and harmful substances, causing serious harm to human health, including cognitive impairment. Vitamin B12 (VitB12) is an essential micronutrient that is synthesized by bacteria and contributes to neurotransmitter synthesis as a nutrition and signaling molecule. However, the relationship between VitB12 attenuation of cognitive impairment and intestinal microbiota regulation in PM 2.5 exposure has not been elucidated. In this study, we demonstrated that PM 2.5 caused behavioral defects and neuronal damage in Caenorhabditis elegans ( C. elegans ), along with significant gene expression changes in neurotransmitter receptors and a decrease in VitB12 content, causing behavioral defects and neuronal damage in C. elegans . Methylcobalamin (MeCbl), a VitB12 analog, alleviated PM 2.5 -induced neurotoxicity in C. elegans . Moreover, using in vivo and in vitro models, we discovered that long-term exposure to PM 2.5 led to changes in the structure of the gut microbiota, resulting in an imbalance of the VitB12-associated metabolic pathway followed by cognitive impairment. MeCbl supplementation could increase the diversity of the bacteria, reduce harmful substance contents, and restore the concentration of short-chain fatty acids (SCFAs) and neurotransmitters to the level of the control group to some degree. Here, a new target to mitigate the harm caused by PM 2.5 was discovered, supplying MeCbl for relieving intestinal and intracellular neurotransmitter disorders. Our results also provide a reference for the use of VitB12 to target the adjustment of the human intestinal microbiota to improve metabolic disorders in people exposed to PM 2.5 .

Several studies associate autism spectrum disorder (ASD) pathophysiology with metabolic abnormalities related to DNA methylation and intracellular redox homeostasis. In this regard, three completed clinical trials are reexamined in this work: treatment with (i) methylcobalamin (MeCbl) in combination with low-dose folinic acid (LDFA), (ii) tetrahydrobiopterin, and (iii) high-dose folinic acid (HDFA) for counteracting abnormalities in the folate-dependent one-carbon metabolism (FOCM) and transsulfuration (TS) pathways and also for improving ASD-related symptoms and behaviors. Although effects of treatment on individual metabolites and behavioral measures have previously been investigated, this study is the first to consider the effect of interventions on a set of metabolites of the FOCM/TS pathways and to correlate FOCM/TS metabolic changes with behavioral improvements across several studies. To do so, this work uses data from one case–control study and the three clinical trials to develop multivariate models for considering these aspects of treatment. Fisher discriminant analysis (FDA) is first used to establish a model for distinguishing individuals with ASD from typically developing (TD) controls, which is subsequently evaluated on the three treatment data sets, along with one data set for a placebo, to characterize the shift of FOCM/TS metabolism toward that of the TD population. Treatment with MeCbl plus LDFA and, separately, treatment with tetrahydrobiopterin significantly shifted the metabolites toward the values of the control group. Contrary to this, treatment with HDFA had a lesser, though still noticeable, effect whilst the placebo group showed marginal, but not insignificant, variations in metabolites. A second analysis is then performed with non-linear kernel partial least squares (KPLS) regression to predict changes in adaptive behavior, quantified by the Vineland Adaptive Behavior Composite, from changes in FOCM/TS biochemical measurements provided by treatment. Incorporating the 74 samples receiving any treatment, including placebo, into the regression analysis yields an R2 of 0.471 after cross-validation when using changes in six metabolic measurements as predictors. These results are suggestive of an ability to effectively improve pathway-wide FOCM/TS metabolic and behavioral abnormalities in ASD with clinical treatment.

Cobalamin deficiency is believed to be related to disturbances in cell division, neuropathy, nervous system disease and pernicious anemia. Elderly people are usually advised to supplement their diets with cobalamin. As cobalamin has several forms, the effects of different forms of cobalamin on gut microbiota were investigated in this study. After 7 days of supplementation, methylcobalamin had reduced the diversity of gut microbiota compared to that in the control and cyanocobalamin groups. After supplementation with methylcobalamin, the percentage of Acinetobacter spp. had increased to 45.54%, while the percentages of Bacteroides spp., Enterobacteriaceae spp. and Ruminococcaceae spp. had declined to 11.15, 9.34, and 2.69%, respectively. However, cyanocobalamin had different influences on these bacteria. Both cobalamins increased the amount of short-chain fatty acids, particularly butyrate and propionic acid. The cyanocobalamin group showed increased activity of cellulase compared with that in the other two groups. According to CCA and PICRUSt analysis, methylcobalamin had a positive correlation with Pseudomonas bacteria, propionic acid, and butyrate. Methylcobalamin promoted lipid, terpenoid, and polyketide metabolism by gut bacteria, promoted the degradation of exogenous substances, and inhibited the synthesis of transcription factors and secondary metabolites. Our results indicate that the various forms of cobalamin in the food industry should be monitored and regulated, because the two types of cobalamin had different effects on the gut microbiome and on microbial metabolism, although they have equal bio-activity in humans. Given the effects of methylcobalamin on gut microbiota and microbial metabolism, methylcobalamin supplementation should be suggested as the first option.

Objective • To observe the clinical effect of Wenjing-Quyu-Juanbi Prescription combined with methylcobalamin on chemotherapy-induced peripheral neuropathy (CIPN). Methods • A total of 133 CIPN patients were divided by random number table method into two groups, i.e. treatment group (n=67) and control group (n=66). Control group received oral methylcobalamin therapy, and treatment group received water decoction of Wenjing-Quyu-Juanbi Prescription on the basis of oral methylcobalamin therapy every day. After 4 weeks of treatment, the patients' symptom scores in traditional Chinese medicine and peripheral nerve injury grades in two groups were observed and total effective rates were calculated. The peripheral nerve conductive velocities between the two groups were compared. Results• The study was completed in 123 patients, 63 in the treatment group and 60 in the control group. After treatment, symptom scores of numbness of the extremities, pain, inconvenient flexion, mental fatigue, pale appearance and cold limbs were significantly lower than those before treatment (all P<0.05). And the symptom scores of treatment group after treatment were significantly lower than those of control group (all P<0.05). The total effective rate of treatment for peripheral nerve injury in treatment group was also higher than that in control group (P<0.05). Sensory nerve conduction velocity and motor nerve conduction velocity of median nerves and common peroneal nerves after treatment were all significantly faster than those before treatment (all P<0.05). And between the two groups they were faster in treatment group after treatment (P<0.05). Conclusion • The therapeutic effect of Wenjing-Quyu-Juanbi Prescription combined with methylcobalamin on CIPN is better than that of methylcobalamin only. [ABSTRACT FROM AUTHOR]

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A simple, selective, linear, precise, and accurate RP-HPLC method was developed and validated for the simultaneous estimation of Gabapentin & Methylcobalamin from bulk and formulation. Chromatographic separation was achieved Isocratically on an Inertsil C18 column (150x4.6, 5μ particle size) using a mobile phase Buffer: Acetonitrile in the ratio of 60:40 v/v. The flow rate was 1.0 ml/min, effluents were detected at 264 nm and 10μl of sample was injected. Retention time of Gabapentin & Methylcobalamin was found to be 2.7 and 4.13 min respectively. Linearity of the method was in the concentration range of 25-150 μg for Gabapentin & 0.125-0.750 μg for Methylcobalamin. Percent recoveries obtained for both the drugs were 100.00%. The percentage RSD for precision of the method was found to be less than 2%. The method was validated according to the ICH guidelines. The method developed was successfully applied for the analysis of simultaneous estimation of Gabapentin & Methylcobalamin tablets and was fairly good in comparison with other methods. [ABSTRACT FROM AUTHOR]

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).