Efficacy and safety of ultra-high dose Methylcobalamin vs Placebo among patients with early-stage Amyotrophic Lateral Sclerosis (ALS): A systematic review

Background@#Amyotrophic lateral sclerosis is one of the neurodegenerative disorders with very limited treatment options owing to its progressive course and diverse pathophysiology. Majority of patients succumb to death within three to five years after the onset of symptoms, mostly due to respiratory failure. This study aimed to determine the efficacy and safety of ultra-high dose methylcobalamin versus placebo among patients with early-stage amyotrophic lateral sclerosis in terms of slowing down functional decline.@*Methods@#MEDLINE, CENTRAL, and Google Scholar databases were searched from inception up to September 23, 2023. The impact of treatments was measured by risk ratios with 95% confidence interval. The overall certainty of the evidence was evaluated using GRADE. @*Results@#No significant difference was detected for the outcome median change in the ALSFRS-R score for the whole cohort. Post-hoc analyses showed that ultra-high-dose methylcobalamin decreased ALSFRS-R scores (p=0.003 for 50 mg and p=0.01 for all methylcobalamin groups) in a dose-responsive manner. Mean difference was 1.97 in favor of methylcobalamin (95% CI, 0.44- 3.50; P = .01).@*Conclusion@#Ultra-high dose methylcobalamin can reduce ALSFRS-R scores of patients in its early stage but the scarcity of clinical trials makes it difficult to support a robust conclusion. Ultra-high dose methylcobalamin therapy remains to be investigational.

Parenteral vs Oral Vitamin B12 in Children With Nutritional Macrocytic Anemia: A Randomized Controlled Trial

Background: There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia. Objective: To compare parenteral with oral vitamin B12 therapy in children with macrocytic-megaloblastic anemia. Study design: Single-center, open-label randomized controlled trial. Participant: 80 children aged 2 month-18 year with clinical and laboratory features of nutritional macrocytic anemia. Intervention: All children received an initial single parenteral dose of 1000 µg vitamin B12 followed by randomization to either parenteral or oral vitamin B12 for subsequent doses. Group A was given 1000 µg intramuscular (IM) vitamin B12 (3 doses on alternate days for those aged <10 year, five doses for age >10 year), followed by monthly 1000 µg IM for the subsequent two doses. Group B was given daily oral vitamin B12 1500 µg (500 µg in <2 years age) for three months. Folic acid and iron supplementation, and relevant dietary advice were given to both groups in a similar fashion. Outcome: Improvement in serum vitamin B12 levels and total hemoglobin was compared three months post-treatment. Result: The median(IQR) increase in serum vitamin B12 level was significantly higher in group A [600 (389,775) vs 399 (313, 606) pg/mL; P= 0.016]. The median (IQR) rise of hemoglobin was also more in group A [2.7 (0.4,4.6) vs 0.5 (-0.1,1.2) g/dL; P=0.001]. Conclusion: Increase in serum vitamin B12 levels and hemoglobin was better in children with nutritional macrocytic anemia receiving parenteral as compared to oral vitamin B12.

Comparison of sublingual and intramuscular administration of vitamin b12 for the treatment of vitamin b12 deficiency in children

Abstract Background: In most countries, contrary to some disadvantages, such as pain, relatively higher cost, and poor adherence to treatment, intramuscular (IM) route is still the primary treatment method for Vitamin B12 (VB12) deficiency. In recent years, because of these difficulties, new treatment methods are being sought for VB12 deficiency. Objectives: We aimed to compare sublingual (SL) and IM routes of VB12 administration in children with VB12 deficiency and to compare the efficacy of methylcobalamin and cyanocobalamin therapy in these children. Methods: This retrospective study comprised 129 patients with VB12 deficiency (serum Vitamin 12 level ≤ 200 pg/mL) aged 5-18 years. Based on the formulations of Vitamin 12, we divided the patients into three treatment groups as IM cyanocobalamin, SL cyanocobalamin, and SL methylcobalamin. Results: After Vitamin 12 therapy, serum Vitamin 12 levels increased significantly in all patients, and there was a statistically significant difference between the treatment groups (p < 0.05). Conclusions: SL cyanocobalamin and methylcobalamin were found as effective as IM cyanocobalamin for children with Vitamin 12 deficiency in correcting serum Vitamin 12 level and hematologic abnormalities.

Clinical effect of Wenjing-Quyu-Juanbi Prescription combined with methylcobalamin in treatment of chemotherapy-induced peripheral neuropathy / 上海交通大学学报（医学版）

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.

Effect of mecobalamin Zusanli acupoint injection combined with α-lipoic acid in the treatment of diabetic peripheral neuropathy / 中国基层医药

Objective To investigate the clinical efficacy of mecobalamin Zusanli acupoint injection combined with α-lipoic acid intravenous infusion in the treatment of patients with diabetic peripheral neuropathy.Methods From February 2016 to August 2017,80 patients with diabetic peripheral neuropathy in Zhoushan Hospital were divided into control group and treatment group according to different treatment methods,with 40 cases in each group.The two groups were given diet,exercise and medication.At the same time,the control group was given mecobalamin Zusanli acupoint injection,the treatment group was given α-lipoic acid intravenous infusion on the basis of the control group.After 2 weeks of treatment,the clinical curative effect was evaluated.The scores of MDNS before and after treatment were evaluated.The motor nerve conduction velocity (MNCV),sensory nerve conduction velocity (SNCV),and the shortest F wave latent period velocity of the tibial nerve were compared before and after treatment in the two groups.The adverse reactions during treatment in the two groups were recorded.Results The total effective rate of the treatment group was 87.5％,which was significantly higher than 52.5％ of the control group(x2 =12.621,P =0.001).The MDNS score of the treatment group after 2 weeks of treatment was (1.82 ±0.74)points,which was significantly lower than (2.45 ± 0.89) points of the control group (t =3.442,P =0.000).After treatment,the MNCV of the common peroneal nerve of the treatment group was (48.12 ±4.98) m/s,which was significantly higher than (42.68 ± 4.59)m/s of the control group (t =5.080,P =0.000).The median nerve MNCV of the treatment group was (53.31 ± 4.41)m/s,which was significantly higher than (49.85 ± 3.87)m/s of the control group (t =3.729,P =0.000).After treatment,the SNCV of the common peroneal nerve in the treatment group was (42.73 ± 4.28) m/s,which was significantly higher than (39.57 ± 3.65) m/s in the control group (t =3.552,P =0.000).The median nerve SNCV of the treatment group was (46.98 ± 3.47) m/s,which had no statistically significant difference compared with that of the control group [(45.79 ± 3.56) m/s] (t =1.513,P =0.134).The shortest F wave latent period velocity of the tibial nerve in the treatment group was (45.82 ±4.12) m/s,which was significantly higher than (42.68 ± 3.25) m/s in the control group(t =3.784,P =0.000).The two groups had no obvious adverse reactions during treatment.Conclusion Mecobalamin Zusanli acupoint injection combined with α-lipoic acid intravenous infusion in the treatment of patients with diabetic peripheral neuropathy is effective and safe,and it is worthy of promoting.

Clinical study of alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy / 中国基层医药

Objective To study the effect of alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy.Methods From January 2014 to June 2016,120 patients with type 2 diabetic peripheral neuropathy in the First People's Hospital of Baiyin were randomly divided into two groups according to the random number table method.64 patients of the observation group were given the treatment of alprostadil,epalrestat combined with methylcobalamin.56 patients of the control group were given the treatment of alprostadil and methylcobalamin.And the two groups were treated for 4 weeks.The blood glucose,clinical symptoms,adverse reaction,nerve conduction velocity index were compared between the two groups before and after treatment.Results The fasting blood glucose and 2-hour postprandial blood glucose of the two groups after treatment were significantly decreased (t =18.20,17.61,15.75,23.69,all P ＜ 0.05),and the conduction velocity of the common peroneal nerve,the median nerve and the ulnar nerve in the observation group were significantly higher than those in the control group (t =1.989,2.638,3.026,2.187,2.619,1.997,all P ＜ 0.05).The total effective rate of the observation group was significantly higher than that of the control group(95.3％ vs.82.1％,x2 =4.54,P ＜0.05).There were no statistically significant differences in the blood glucose and the incidence rate of adverse reactions between the two groups (t =0.267,0.176,0.695,0.658,x2 =1.356,all P ＞ 0.05).Conclusion Alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy has good effect.

Clinical study of neurotropin combined with methylcobalamin for the treatment of residual neurological symptoms after degenerative lumbar disease surgery / 复旦学报（医学版）

Objective To investigate the therapeutic effect of neurotropin (NTP) combined with methylcobalamin for the treatment of residual neurological symptoms after surgery for degenerative lumbar disease (DLD).Methods A total of 96 cases with residual neurological symptoms after surgery for DLD from Jan.,2012 to Jun.,2015 were enrolled in this study and divided into three groups,32 cases in each group.The patients in group A were treated with methylcobalamin,the patients in group B were treated with NTP,and the patients in group C were treated with NTP + methylcobalamin.All the patients were treated for 2 weeks.The visual analogue scale (VAS) and oswestry disability index (ODI) were observed and documented at the beginning of the treatment,14 days,3 months,6 months and 12 months after the treatment,respectively.Results The VAS and ODI scores at 14 days,3 months,6 months and 12 months after the treatment in each group decreased obviously comparing with the scores before the treatment (P＜0.05).At each time point the VAS and ODI scores in group C＜group B＜group A (P＜0.05).The excellent rate at each time point in group C＞group B＞group A (P ＜ 0.05).Conclusions NTP is effective in the treatment of residual neurological symptoms and its therapeutic effects is better than methylcobalamin.The combined application of NTP and methylcobalamin is superior to the single application of NTP or methylcobalamin for the treatment of residual neurological symptoms after surgery for degenerative lumbar diseases.

A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy

BACKGROUND: Vitamin B12 deficiency has been associated with peripheral neuropathy, loss of sensation in the peripheral nerves, and weakness in the lower extremities. Methylcobalamin is the most effective analogue of vitamin B12 used to treat or prevent the complications associated with vitamin B12 deficiency. The current study aimed to compare the serum cobalamin levels after administration of two different regimes of methylcobalamin in peripheral neuropathy patients. METHODS: The present study was a prospective, randomized, comparative study. The study consisted of two parallel groups, group A (methylcobalamin 500 µg injection intramuscularly three times a week) and group B (methylcobalamin 1500 µg injection intramuscularly once a week). A control group of healthy volunteers was also included. RESULTS: A total of 24 patients (12 in each group) were included in the study. Five healthy volunteers were also included as a control in each group. At the end of treatment, serum cobalamin levels were significantly (P = 0.028) higher in group A (1892.08 ± 234.50) as compared with group B (1438.5 ± 460.32). The serum cobalamin levels in Group A healthy volunteers were also two times higher than that of group B (P = 0.056). Both the LANSS scale and DN4 questionnaire reported similar results at end of treatment. CONCLUSIONS: The 500 µg methylcobalamin thrice weekly regime is more effective in increasing the serum cobalamin levels as compared to the 1500 µg methylcobalamin once weekly regime.

Study on the repair effect of mecobalamin in the treatment of spinal cord injury / 中国生化药物杂志

Objective To explore the repair effect of methylcobalamin treatment of nerve after spinal cord injury.Methods 108 cases of patients with acute spinal cord injury were selected treated in our hospital from 2010 April to 2014 April , including 60 cases of male, female 48 cases, were randomly divided into Mecobalamin group(n=56) and control group(n=52), mecobalamin group was treat with a cobalt amine, control group was given conventional treatment (dexamethasone intravenous drip note).According to American spinal cord injury score (ASIA) to set sensory function, motor function and spinal cord function score criteria, observed and record ed the sensory function, motor function, recovery of neurological function and complications the two groups of patients were treated for 6 weeks and followed up for 6 months.Results Spinal cord injury patients after 6 weeks and 6 months follow-up, the improvement of sensory and motor function of mecobalamin group were significantly better than the control group ( P 0.05).Conclusion In patients with acute spinal cord injury treated by mecobalamin treatment can improve the nerve function damage condition, improve the prognosis and quality of life.

Oral α-lipoic acid combined with methylcobalamin in treatment of diabetic peripheral neuropathy / 第二军医大学学报

Objective To observe the clinical efficacy and safety of oral α-lipoic acid combined with methylcobalamin in treatment of diabetic peripheral neuropathy (DPN). Methods Sixty-four DPN patients were selected and randomly divided into experimental group (n = 32) and control group (n = 32). All the patients were given diet control, insulin or oral hypoglycaemic agent and the blood glucose was satisfactorily controlled; the original antihypertensive and antilipemic therapies were maintained. Meanwhile, patients in the control group were also given oral methylcobalamin (three times per day and each for 0.5 mg), and those in the experimental group were given oral α-lipoic acid (once a day and each for 600 mg) and oral methylcobalamin (three times per day and each for 0. 5 mg). The total symptom scores (TSS) and the nerve conduction velocity (NCV) were evaluated in the two groups before and 12 weeks after treatment; and the adverse drug reactions were also observed. Results The TSS and NCV were significantly improved in both groups after treatment compared with before treatment (P<0. 05). After treatment, TSS was significantly lower in the experimental group than in the control group (P<0. 05), and there were significant differences in the transmissionvelocities of the median motor nerve, nervus peroneus communis motor nerve and its sensory nerve between two groups (P<0. 05). No serious side effects were found in the two groups during the treatment. Conclusion Oral crlipoic acid combined with methylcobalamin on DPN is superior to methylcobalamin used alone for treatment of DPN, and the combined treatment is simple and has better patient compliance, making it worth popularizing.

Methylcobalamin induces differentiation of rat bone mesenchymal stem cells into neuron-like cells in vitro / 中国组织工程研究

BACKGROUND:Currently, transplantation of bone marrow mesenchymal stem cel s into the spinal cord is very limited to the recovery of animals fol owing spinal cord injury. Methylcobalamin is a common drug for the treatment of neurological diseases and injuries, but its effects on bone marrow mesenchymal stem cel s are unclear. OBJECTIVE:To study the feasibility of bone marrow mesenchymal stem cel s differentiating into neuron-like cel s induced by methylcobalamin in vitro and to observe the cel viability and proliferation of differentiated cel s. Methods:Rat bone marrow mesenchymal stem cel s were isolated, cultured and purified by density gradient centrifugation and adherent culture. The fourth to fifth generation of bone marrow mesenchymal stem cel s were treated for 24, 48 and 72 hours with different concentrations (25, 50 and 100 mg/L) of methylcobalamin. The morphological changes and cel growth were continuously observed under an inverted phase constract microscope. The viability of induced cel s was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The expressions of Nestin and neuron-specific enolase were identified by reverse transcription PCR and western blot. RESULTS AND CONCLUSION:Most of bone marrow mesenchymal stem cel s could differentiate into neuron-like cel s after induction with methylcobalamin. The expressions of Nestin and neuron-specific enolase were up-regulated after 48 hours of methylcobalamin treatment at different concentrations, especial y after treatment with 100 mg/L methylcobalamin. Similarly, the expressions of Nestin and neuron-specific enolase could be increased significantly after 100 mg/L methylcobalamin treatment for 24, 48 and 72 hours, especial y for 72 hours. It is indicated that methylcobalamin can induce bone marrow mesenchymal stem cel s differentiating into neuron-like cel s, and the optimal concentration of methylcobalamin is 100 mg/L.

Clinical analysis of salvia ligustrazine combined with methylcobalamin in treatment of type 2 diabetic peripheral neuropathy / 中国医师进修杂志

Objective To observe the effect of salvia lignstrazine combined with methylcobalamin in treatment of type 2 diabetic peripheral neuropathy.Methods From May 2010 to May 2011,112 cases of type 2 diabetic peripheral neuropathy patients were classified into two groups by random digits table,control group of 56 cases were treated with methylcobalamin and observation group of 56 cases were treated with salvia lignstrazine combined with methylcobalamin.The clinical effects,motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of common peroneal nerve and tibial nerve between two groups were compared.Results The total effective rate in observation group was 87.5％(49/56),which was significantly higher than that in control group [ 57.1％( 32/56 ) ] (P ＜ 0.05 ).After treatment,the levels of MNCV and SNCV of common peroneal nerve and tibial nerve were (47.89 ± 6.93 ),(49.12 ± 5.54) m/s and (43.69 ± 4.97 ),(42.35 ± 5.14) m/s in observation group,which were significantly increased compared with those before treatment,while the levels of MNCV and SNCV of common peroneal nerve and tibial nerve were (41.15 ± 4.36),(39.89 ± 3.67 ) m/s and (37.57 ± 3.08),(36.56 ± 2.81 ) m/s in control group,which had no significant difference compared with those before treatment (P ＞ 0.05 ).Moreover,the levels of MNCV and SNCV of common peroneal nerve and tibial nerve in observation group were significantly higher than those in control group (P＜ 0.05).Conclusion Salvia ligustrazine combined with methylcobalamin in treatment of type 2 diabetic peripheral neuropathy can enhance the clinical effects,and improve neurological status,and can be applied in clinic.

Effect of methylcobalamin,gliclazide and combined application of both on sciatic nerve morphology and nerve growth factor contents in streptozotocin-induced diabetic rats / 中国药理学通报

Aim To investigate the curative effect and the mechanism of methylcobalamin,gliclazide and combined application of both on diabetic peripheral neuropathy(DPN)in streptozotocin-induced diabetic(STZ-D)rats.Methods STZ-D rats were administered with drugs orally for 8 weeks after streptozotocin treatment.Morphologies of sciatic nerve were observed with histological method.Nerve growth factor(NGF)contents in plasma or in sciatic nerve tissues were determined by ELISA kit or immunohistochemistry.Results Morphological degeneration in sciatic nerve,decrease of NGF concertration in plasma,as well as in nerve axis cylinder,in diabetic rats was all ameliorated by methylcobalamin and/or gliclazide.However,no significant differences in morphology and NGF contents were found between single drug treated groups and combined application group.Conclusions The observations suggest that methylcobalamin,gliclazide and combined application are effective in treating DPN in STZ-D rats.No significantly enhanced effect is found in combined application group as compared with methylcobalamin or gliclazide group.

Effects of Folic Acid Combined Methylcobalamin in the Treatment of the Patients that Are Uremia Ac-companied by Hyperhomocysteinemia / 中国药房

OBJECTIVE:To study the plasma total homocysteine(tHcy)level in the uremia patients and to study the therapeutic effects of folic acid combined with methylcobalamin in the intervention treatment of uremia patients with homo-cysteinemia.METHODS:Levels of plasma tHcy of60uremia patients(treatment group)and40normal subjects(control group)were determined both before treatment and8weeks after intervention treatment with folic acid combined with methylcobal-amin.RESULTS:The plasma level of tHcy in uremia patients were significantly higher than that in the normal subjects(P

The Morphometric changes of Rat Peripheral nerve after Methyl-cobalamin Treatment in Capsaicin Induced Neuropathy

BACKGROUND: Methcobalamin was known to act as a methyl donor in DNA metabolism and increase Protein synthesis for nerve regeneration. To determine whether methylcobalamin affects capsaicin induced polyneuropathy in rat sural nerves. METHODS: On their second day of life, 18 newborn rats were injected subcutaneously with capsaicin(50mg/kg). Ten rats were treated with methylcobalamin(500microgram/kg) and eight rats with normal saline 5 days a week for 12weeks after capsaicin injection. Using morphometry and computer digitization, the number and sloe distribution of myelinated and unmyelinated fibers were evaluated in sural nerves at 13 weeks. RESULTS: There was significant difference in the number of unmyelinated fibers between two groups(control group 33,321 +/- 15,539/mm2; methylcobalamin group 99,614+/-20,581/mm2. p<0.0001). Methylcobalamin did not change the number and size distribution of'myelinated fibers. The size distribution of'unmyelinated fibers was approximately the same. CONCLUSIONS: This study suggested that methylcobalamln could increase regeneration of peripheral nerve morphometrically. It appears that methylcobalamin might be one of the useful therapeutic agents in various polyneuropathies.