Search

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]

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. In this study, we investigate the combined effects of NTP and MCB on PHP in mice. 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. 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. 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. • Neurotropin® and methylcobalamin to postherpetic pain (PHP) were evaluated in mice. • Combined treatment with these drugs to PHP showed faster efficacy than either drug. • Methylcobalamin effected the expression of the factors on neuropathy or nerve repair. • These drugs induced the gene expression on neurotropic factors. • Combined treatment with these drugs is more effective to PHP than each drug alone. [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: Vitamin B12 deficiency can lead to serious health problems both in children and adult. Intramuscular injection therapy is applied as the gold standard in the treatment of vitamin B12 deficiency. There are also oral, nasal, and sublingual spray treatment methods. In this study, we aimed to show the efficacy of sublingual spray treatment of vitamin B12 deficiency in children. Materials and Methods: Forty-five pediatric patients (25 boys, 20 girls), aged 9-36 months with serum cobalamin concentrations less than 200 pg/mL, were treated with sublingual vitamin B12 (methylcobalamin) spray. All patients were treated for four months by giving 500 |jg oral spray daily for the first week, every other day for the next one week, two days a week for the next two weeks and then once a week for four months. Vitamin B12 levels were checked after four months. Results: Post-treatment vitamin B12 values were significantly higher than pre-treatment values (p<0.001). Vitamin B12 levels increased from 161.58±32.98 pg/mL to 427.44±148.58 pg/mL. After the treatment, the vitamin B12 level of all patients was found to be >200 pg/mL, except for only two patients. Vitamin B12 levels returned to normal in 96% of the patients with a sublingual spray treatment. Conclusions: Data from this study indicate that sublingual vitamin B12(methylcobalamin) spray (500|jg) for four months is effective for treatment of children with vitamin B12 deficiency. Sublingual spray that is easier and more practical to use can be preferred for children with vitamin B12 deficiency instead of parenteral and oral vitamin B12 therapy. [ABSTRACT FROM AUTHOR]

A stability‐indicating RP‐HPLC method for methylcobalamin determination was developed. Stress degradation under variable conditions was carried out. Methylcobalamin had pronounced susceptibility to hydrolysis under acidic, alkaline, and photolytic conditions; further study of photolytic degradation kinetics and pH rate profiling over pH range 2–11 was carried out. Photodegradation of methylcobalamin followed zero‐order kinetics with half‐life 0.99 h equivalent to 1971.53 lux. Methylcobalamin followed pseudo‐first‐order kinetics upon exposure to acidic and alkaline hydrolysis with highest stability at pH 5 and least stability at pH 2. Optimization of chromatographic conditions was performed using two level full factorial design, and chromatographic analysis was executed using Inertsil column (250 × 4.6 mm, 5 μm) maintained at 25◦C. Elution was carried out using 25 mM potassium dihydrogen phosphate (pH adjusted with phosphoric acid to 3.8): methanol:acetonitrile (55:35:10, v/v) as mobile phase. The flow rate was 1.0 ml/min. Detection was carried out at 220 nm using diode array detector. The method was validated as per ICH guidelines; the linearity was over concentration range 2–160 μg/ml with coefficient of determination 0.9995. The method was effectively applied for determination of methylcobalamin in Cobalvex ampoule, Cobal tablet, Cobal‐F tablet, and Methyltechon oral dissolvable film without interfering from excipients within run time 6 min. [ABSTRACT FROM AUTHOR]

(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]

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.)

(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.

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 .

[Display omitted] • Confirmation of controlling factors affecting polycyclic macromolecular drug solid stability for methylcobalamin. • Stable preparation of three methylcobalamin hydrate powders with isolated site and channel water structures. • Inter-conversion and corresponding structural variation relations of methylcobalamin hydrates were established. • Preferable morphology and particle size distribution control of methylcobalamin crystal product. As one of derivatives of Vitamin B 12 , methylcobalamin (MeCbl) is an indispensable "Life Element" and plays an essential role in maintaining human normal physiology function and clinical medicine application. Because of the intricate molecular structure, strong hygroscopicity and optical instability, maintaining its solid stability is a great challenge in pharmaceutical preparation. Based on the structure features of MeCbl hydrates, this study explored the drug solid stability by designing solid-solid phase transformation (SSPT) experiments. Three hydrate powders of MeCbl that had special structure with isolated site and channel water molecules were discovered. It was found that drying condition and surrounding humidity were controlling factors influencing the final solid form. The inter-conversion relations relevant to heating-induced and humidity-induced structure changes were established among the three hydrate powders. Powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, high performance liquid chromatography and dynamic vapor sorption were used to characterize the differences and related properties of stably prepared MeCbl hydrate powders. The particle size of product could be regulated and controlled by optimizing operating conditions of crystallization process, where ultrasound-assisted and seeding-introduced were applied as promising strategies to enhance solution crystallization process. This study opens up the possibility for the stable preparation and large-scale production of polycyclic macromolecular bulk drugs like methylcobalamin. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is the most common metabolic disease worldwide. Hence, the prevalence of the disease continues to increase across the globe. Metformin is used as a first-line oral hypoglycemic drug to keep control of type-2 DM (T2DM) in adults. Diabetic patients on metformin have been largely seen to be suffering from a deficiency of vitamin B12. It is a water-soluble vitamin mainly obtained from animal food like meat. At the basic cell level, it acts as a cofactor for enzymes essential for DNA synthesis and neuroprotection. As a result, vitamin B12 deficiency can show clinical effects such as progressive demyelination, peripheral neuropathy and haematological abnormalities (such as macrocytic anaemia and neutrophil hypersegmentation). Various studies also show a relation between vitamin B12 insufficiency and metformin-treated T2DM patients as decreased absorption of vitamin B12. There could be a severe complication of vitamin B12 deficiency in T2DM patients. The use of proton pump inhibitors, gastric bypass surgery, older patients and patients with a higher red blood cell turnover are factors that hasten the depletion of vitamin B12 reserves in the liver. Methylmalonic acid and homocysteine levels can be measured to identify vitamin B12 insufficiency at its early stage if blood vitamin B12 levels are borderline. The action of metformin on vitamin B12 absorption and its potential mechanisms of inhibition will be the main topics of discussion in this review. The review will also discuss how vitamin B12 deficiencies in T2DM patients using metformin affect their clinical results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Tiwari et al.)

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. 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. 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. Our procedure reveals a high content of MeCbl in rat liver. This result challenges previous data and pinpoints the need for new studies to characterize the endogenous Cbl-forms in health and disease. [Display omitted] • Low methylcobalamin (MeCbl) in liver tissues is an artifact of extraction. • The artificial decrease in MeCbl is caused by its conversion to hydroxocobalamin. • A harsh heating of a tissue sample at pH < 4 or pH > 7 accelerates this conversion. • Thiols are possible agents that demethylate MeCbl during its harsh extraction. • Milder extraction methods reveal a high level of MeCbl in rat liver. [ABSTRACT FROM AUTHOR]