John Meyers Himself

http://www.altmedrev.com/archive/publications/7/5/389.pdf

Preface

Abstract PURPOSE: To determine the safety and the appropriate dose of intravenous l-ascorbic acid (AA) in conjunction with chemotherapy for patients with relapsed lymphoma.

PATIENTS AND METHODS: Patients with relapsed CD20-positive B-cell non-Hodgkin's lymphoma, who were going to receive the CHASER regimen as salvage therapy, were enrolled and treated with escalating doses of AA administered by drip infusion after the 2nd course of the CHASER regimen. The target plasma concentration immediately after AA administration was >15 mM (264 mg/dl).

RESULTS: A serum AA concentration of >15 mM was achieved in 3 sequentially registered patients, all of whom had received a 75 g whole body dose. No obvious adverse drug reaction was observed in the patients. The trial was therefore successfully completed.

CONCLUSION: Intravenous AA at a whole body dose of 75 g appears to be safe and sufficient to achieve an effective serum concentration. A phase II trial to evaluate the efficacy of intravenous AA in relapsed/refractory lymphoma patients will now be initiated.

Follow the money on this one

https://clinicaltrials.gov/ct2/show/NCT00921934?term=intravenous+vitamin+therapy

Vitamin C 2

Abstract BACKGROUND: Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v.

METHODS: A cohort of adult patients scheduled to receive IVC treatment for infection, cancer or fatigue, as prescribed by their treating doctor, participated at a Melbourne clinic, Australia. Ambulatory BP was assessed every 10 min over 90 min during i.v.

TREATMENT: Patients received 15-100 g of IVC alone or in addition to i.v. vitamin B, glutathione, magnesium or zinc. BP change over time adjusted for baseline BP, IVC dosage, i.v. treatment and BMI was analysed.

RESULTS: A total of 77 mostly normotensive patients participated, with a third receiving IVC alone (42±20 g), and two-thirds also received other i.v. nutrients. IVC alone (>30 g) reduced the mean BP up to 8-9 mmHg in prehypertensive patients. In contrast, concomitant intravenous vitamin B12 (IVB12) significantly increased the mean BP by 11-13 mmHg. Comparison of BP change during IVC versus IVC+IVB12 indicated a highly significant difference [systolic blood pressure: mean difference (SD)=16.6 (17.8) mmHg, P<0.001; diastolic blood pressure: mean difference (SD)=12.5 (16.7) mmHg, P=0.003].

CONCLUSION: Our study suggests an acute BP-reducing effect of high-dose IVC, particularly with dosages above 30 g, and in patients with prehypertension and normal BMI. Furthermore, our study indicated a marked and clinically relevant hypertensive effect of IVB12, suggesting routine BP monitoring during i.v. therapy in clinical practice

IV Magnesium A

Abstract BACKGROUND: Post-surgical pain is a physiological response to tissue trauma that produces unpleasant physiological effects with manifestations on various organic systems.

OBJECTIVE: According to the effect of magnesium sulfate on the N-methyl-d-aspartate (NMDA) receptor, this study examined the effect of magnesium sulfate on the reduction of pain and the mean amount of narcotics consumed by patients after abdominal hysterectomies.

METHODS: This double-blind clinical trial study was performed on 60 patients who had undergone abdominal hysterectomies in Shahid Sadoughi Hospital in Yazd, Iran, from 2013 to 2015. The patients were divided randomly into two groups of 30 members each. All of the patients received 2 mg of Midazolam and 2 mcg/kg of Fentanyl as the induction of anesthesia with propofol (2-2.5 mg/kg) and Atracurium 0.5 mg/kg was conducted. All of the patients received 5 mg of intravenous morphine 30 min after induction of anesthesia. Afterwards, the study group received 50 mg/kg of magnesium sulfate in 500 cm(3) of Ringer's serum during the 20 minutes, and 500 cm(3) of Ringer's serum was administered to the members of the placebo group. Visual analogue scale VAS scores were evaluated to reach the minimum difference of 0.8 in mean pain score.

RESULTS: The results of this study indicated that the mean pain scores immediately after surgery and at 1, 2, 6, and 12 hr after surgery were lower in the study group than in the placebo group. The mean value of narcotic consumption at all measured time points was higher in the placebo group. No significant differences were found between two groups concerning drug complications.

CONCLUSION: The results of this study indicated that the intravenous injection of magnesium sulfate can reduce pain, reduce morphine consumption, and reduce the side effects of morphine in patients after surgery.

FUNDING: This study was funded by Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

CLINICAL TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the registration ID: TCTR20160308001.

IV Magnesium

https://www.jopan.org/article/S1089-9472(16)30418-X/fulltext

(Must pay to access article)

IV Magnexium B

Abstract BACKGROUND: Post-surgical pain is a physiological response to tissue trauma that produces unpleasant physiological effects with manifestations on various organic systems.

OBJECTIVE: According to the effect of magnesium sulfate on the N-methyl-d-aspartate (NMDA) receptor, this study examined the effect of magnesium sulfate on the reduction of pain and the mean amount of narcotics consumed by patients after abdominal hysterectomies.

METHODS: This double-blind clinical trial study was performed on 60 patients who had undergone abdominal hysterectomies in Shahid Sadoughi Hospital in Yazd, Iran, from 2013 to 2015. The patients were divided randomly into two groups of 30 members each. All of the patients received 2 mg of Midazolam and 2 mcg/kg of Fentanyl as the induction of anesthesia with propofol (2-2.5 mg/kg) and Atracurium 0.5 mg/kg was conducted. All of the patients received 5 mg of intravenous morphine 30 min after induction of anesthesia. Afterwards, the study group received 50 mg/kg of magnesium sulfate in 500 cm(3) of Ringer's serum during the 20 minutes, and 500 cm(3) of Ringer's serum was administered to the members of the placebo group. Visual analogue scale VAS scores were evaluated to reach the minimum difference of 0.8 in mean pain score.

RESULTS: The results of this study indicated that the mean pain scores immediately after surgery and at 1, 2, 6, and 12 hr after surgery were lower in the study group than in the placebo group. The mean value of narcotic consumption at all measured time points was higher in the placebo group. No significant differences were found between two groups concerning drug complications.

CONCLUSION: The results of this study indicated that the intravenous injection of magnesium sulfate can reduce pain, reduce morphine consumption, and reduce the side effects of morphine in patients after surgery.

FUNDING: This study was funded by Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

CLINICAL TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the registration ID: TCTR20160308001.

IV Magnesium C

Abstract BACKGROUND: Post-surgical pain is a physiological response to tissue trauma that produces unpleasant physiological effects with manifestations on various organic systems.

OBJECTIVE: According to the effect of magnesium sulfate on the N-methyl-d-aspartate (NMDA) receptor, this study examined the effect of magnesium sulfate on the reduction of pain and the mean amount of narcotics consumed by patients after abdominal hysterectomies.

METHODS: This double-blind clinical trial study was performed on 60 patients who had undergone abdominal hysterectomies in Shahid Sadoughi Hospital in Yazd, Iran, from 2013 to 2015. The patients were divided randomly into two groups of 30 members each. All of the patients received 2 mg of Midazolam and 2 mcg/kg of Fentanyl as the induction of anesthesia with propofol (2-2.5 mg/kg) and Atracurium 0.5 mg/kg was conducted. All of the patients received 5 mg of intravenous morphine 30 min after induction of anesthesia. Afterwards, the study group received 50 mg/kg of magnesium sulfate in 500 cm(3) of Ringer's serum during the 20 minutes, and 500 cm(3) of Ringer's serum was administered to the members of the placebo group. Visual analogue scale VAS scores were evaluated to reach the minimum difference of 0.8 in mean pain score.

RESULTS: The results of this study indicated that the mean pain scores immediately after surgery and at 1, 2, 6, and 12 hr after surgery were lower in the study group than in the placebo group. The mean value of narcotic consumption at all measured time points was higher in the placebo group. No significant differences were found between two groups concerning drug complications.

CONCLUSION: The results of this study indicated that the intravenous injection of magnesium sulfate can reduce pain, reduce morphine consumption, and reduce the side effects of morphine in patients after surgery.

FUNDING: This study was funded by Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

CLINICAL TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the registration ID: TCTR20160308001.

Intravenous Glutathione 1

Abstract Magnesium, one of the essential elements in the human body, has numerous favorable effects that offer a variety of possibilities for its use in obstetric anesthesia and intensive care. Administered as a single intravenous bolus dose or a bolus followed by continuous infusion during surgery, magnesium attenuates stress response to endotracheal intubation, and reduces intraoperative anesthetic and postoperative analgesic requirements, while at the same time preserving favorable hemodynamics. Applied as part of an intrathecal or epidural anesthetic mixture, magnesium prolongs the duration of anesthesia and diminishes total postoperative analgesic consumption with no adverse maternal or neonatal effects. In obstetric intensive care, magnesium represents a first-choice medication in the treatment and prevention of eclamptic seizures. If used in recommended doses with close monitoring, magnesium is a safe and effective medication.

Intravenous Glutathione 2

Abstract BACKGROUND: Asthma is a chronic respiratory condition characterised by airways inflammation, constriction of airway smooth muscle and structural alteration of the airways that is at least partially reversible. Exacerbations of asthma can be life threatening and place a significant burden on healthcare services. Various guidelines have been published to inform management personnel in the acute setting; several include the use of a single bolus of intravenous magnesium sulfate (IV MgSO4) in cases that do not respond to first-line treatment. However, the effectiveness of this approach remains unclear, particularly in less severe cases.

OBJECTIVES: To assess the safety and efficacy of IV MgSO4 in adults treated for acute asthma in the emergency department.

SEARCH METHODS: We identified trials from the Cochrane Airways Review Group Specialised Register (CAGR) up to 2 May 2014. We also searched www.ClinicalTrials.gov and reference lists of other reviews, and we contacted trial authors to ask for additional information.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults treated in the emergency department (ED) for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo.

DATA COLLECTION AND ANALYSIS: All review authors screened titles and abstracts for inclusion, and at least two review authors independently extracted study characteristics, risk of bias and numerical data. Disagreements were resolved by consensus, and we contacted trial investigators to obtain missing information.We analysed dichotomous data as odds ratios using study participants as the unit of analysis, and we analysed continuous data as mean differences or standardised mean differences using fixed-effect models. We rated all outcomes using GRADE and presented results in Summary of findings table 1.We carried out subgroup analyses on the primary outcome for baseline severity of exacerbations and whether or not ipratropium bromide was given as a co-medication. Unpublished data and studies at high risk of bias for blinding were removed from the main analysis in sensitivity analyses.

MAIN RESULTS: Fourteen studies met the inclusion criteria, randomly assigning 2313 people with acute asthma to the comparisons of interest in this review.Most studies were double-blinded trials comparing a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes versus a matching placebo. Eleven were conducted at a single centre, and three were multi-centre trials. Participants in almost all of the studies had already been given at least oxygen, nebulised short-acting beta2-agonists and IV corticosteroids in the ED; in some studies, investigators also administered ipratropium bromide. Ten studies included only adults, and four included both adults and children; these were included because the mean age of participants was over 18 years.Intravenous MgSO4 reduced hospital admissions compared with placebo (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60 to 0.92; I(2) = 28%, P value 0.18; n = 972; high-quality evidence). In absolute terms, this odds ratio translates into a reduction of seven hospital admissions for every 100 adults treated with IV MgSO4 (95% CI two to 13 fewer). The test for subgroup differences revealed no statistical heterogeneity between the three severity subgroups (I(2) = 0%, P value 0.73) or between the four studies that administered nebulised ipratropium bromide as a co-medication and those that did not (I(2) = 0%, P value 0.82). Sensitivity analyses in which unpublished data and studies at high risk for blinding were removed from the primary analysis did not change conclusions.Within the secondary outcomes, high- and moderate-quality evidence across three spirometric indices suggests some improvement in lung function with IV MgSO4. No difference was found between IV MgSO4and placebo for most of the non-spirometric secondary outcomes, all of which were rated as low or moderate quality (intensive care admissions, ED treatment duration, length of hospital stay, readmission, respiration rate, systolic blood pressure).Adverse events were inconsistently reported and were not meta-analysed. The most commonly cited adverse events in the IV MgSO4 groups were flushing, fatigue, nausea and headache and hypotension (low blood pressure).

AUTHORS' CONCLUSIONS: This review provides evidence that a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes reduces hospital admissions and improves lung function in adults with acute asthma who have not responded sufficiently to oxygen, nebulised short-acting beta2-agonists and IV corticosteroids. Differences in the ways the trials were conducted made it difficult for the review authors to assess whether severity of the exacerbation or additional co-medications altered the treatment effect of IV MgSO4. Limited evidence was found for other measures of benefit and safety.Studies conducted in these populations should clearly define baseline severity parameters and systematically record adverse events. Studies recruiting participants with exacerbations of varying severity should consider subgrouping results on the basis of accepted severity classifications.

Vitamin D Drip

Abstract BACKGROUND: Hemodialysis patients who receive vitamin D receptor activator (VDRA) reportedly have better survival after infection than those who do not. However, the optimal route of its administration for minimizing death from infection remains unclear.

METHODS: This prospective cohort study aimed to compare the effectiveness of oral versus intravenous VDRA regarding infection-related mortality in 3372 hemodialysis patients. Eligible subjects were divided into the following three groups by route of administration of VDRA: oral (n = 1868), intravenous (n = 492) and not administered (n = 1012). The effect of VDRA on infection-related mortality was examined using a Cox regression model with propensity score-based adjustments.

RESULTS: During follow-up (median, 4.0 years), 118 study patients died of infection. There was a significantly lower incidence of death from infection in subjects who received intravenous VDRA than in those who did not receive VDRA; however, oral VDRA did not significantly reduce the risk of mortality from infection compared with those who did not receive VDRA [hazard ratio (HR) for intravenous VDRA, 0.16; 95% confidence interval (CI), 0.10-0.25, and HR for oral VDRA, 0.78; 95% CI, 0.60-1.01]. Direct comparison between the oral and intravenous VDRA groups showed that the intravenous group had significantly better survival than the oral group (HR, 0.39; 95% CI, 0.27-0.62).

CONCLUSIONS: Treatment with intravenous VDRA more effectively reduces the incidence of mortality from infection than oral VDRA in hemodialysis patients.

Vitamin B ABC

Abstract BACKGROUND: Thiamine is a vitamin that is essential for adequate aerobic metabolism. The objective of this study was to determine if thiamine administration prior to coronary artery bypass grafting would decrease post-operative lactate levels as a measure of increased aerobic metabolism.

METHODS: We performed a randomized, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass grafting. Patients were randomized to receive either intravenous thiamine (200 mg) or placebo both immediately before and again after the surgery. Our primary endpoint was post-operative lactate levels. Additional endpoints included pyruvate dehydrogenase activity, global and cellular oxygen consumption, post-operative complications, and hospital and intensive care unit length of stay.

RESULTS: Sixty-four patients were included. Thiamine levels were significantly higher in the thiamine group as compared to the placebo group immediately after surgery (1200 [683, 1200] nmol/L vs. 9 [8, 13] nmol/L, p < 0.001). There was no difference between the groups in the primary endpoint of lactate levels immediately after the surgery (2.0 [1.5, 2.6] mmol/L vs. 2.0 [1.7, 2.4], p = 0.75). Relative pyruvate dehydrogenase activity was lower immediately after the surgery in the thiamine group as compared to the placebo group (15% [11, 37] vs. 28% [15, 84], p = 0.02). Patients receiving thiamine had higher post-operative global oxygen consumption 1 hour after the surgery (difference: 0.37 mL/min/kg [95% CI: 0.03, 0.71], p = 0.03) as well as cellular oxygen consumption. We found no differences in clinical outcomes.

CONCLUSIONS: There were no differences in post-operative lactate levels or clinical outcomes between patients receiving thiamine or placebo. Post-operative oxygen consumption was significantly increased among patients receiving thiamine.

TRIAL REGISTRATION: clinicaltrials.gov NCT02322892, December 14, 2014.

Abstract OBJECTIVES: Intravenous micronutrient therapy (IVMT), and specifically the Myers' Cocktail, is a popular approach for treating fibromyalgia syndrome (FMS) among complementary and alternative medicine practitioners, but its efficacy is uncertain. This trial assessed the feasibility, safety, and provided insights into the efficacy of this therapy.

DESIGN: This was a randomized, double-blind, placebo-controlled pilot study.

LOCATIONS: The study locations were an academic research center, teaching hospital, and affiliated Integrative Medicine Center in Derby, CT.

SUBJECTS: The subjects were 34 adults with American College of Rheumatology (ACR)-defined FMS.

INTERVENTION: Subjects were randomly assigned either to treatment (weekly infusions of IVMT) or to placebo (weekly infusions of lactated Ringer's solution) for 8 weeks.

OUTCOME MEASURES: Primary outcome was change in the Tender Point Index, assessed 8 and 12 weeks after initiation. Secondary measures included a Visual Analog Scale to assess global pain, and validated measures of physical function (Fibromyalgia Impact Questionnaire), mood (Beck Depression Index), and quality of life (Health Status Questionnaire 2.0).

RESULTS: Clinically significant improvements were noted (of a magnitude similar to other effective interventions). However, in part because of the high placebo response and the small sample size, no statistically significant differences were seen between groups, in any outcome measure, at 8 and 16 weeks. Statistically significant within-group differences were seen in both the intervention and placebo groups, demonstrating a treatment effect for both IVMT and placebo. At 8 weeks, the IVMT group experienced significantly improved tender points, pain, depression, and quality of life directly following treatment (all p < or = 0.02), while the placebo group experienced significantly improved tender points only (p < or = 0.05). The treatment effects of IVMT persisted at 4 weeks postintervention for tender points, pain, and quality of life, while placebo effects persisted only for tender points. A single minor adverse event was noted in one subject in the intervention group.

CONCLUSIONS: This first controlled pilot study established the safety and feasibility of treating FMS with IVMT. Most subjects experienced relief as compared to baseline, but no statistically significant differences were seen between IVMT and placebo. The efficacy of IVMT for fibromyalgia, relative to placebo, is as yet uncertain.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00067405.

Vitamin B Drip B Abstract BACKGROUND: Stress related to surgery and critical illness depletes thiamine, essential in energy metabolism, and might result in high blood lactate concentrations and higher mortality.

OBJECTIVES: We hypothesised that thiamine supplementation would increase blood concentration of thiamine and reduce blood lactate concentration postoperatively. Moreover, we aimed to identify the prevalence of, and risk factors for, high blood lactate concentrations.

DESIGN: This was a double-blind, randomised controlled pilot study from February to July 2012 including 30 patients scheduled for cardiac surgery with cardiopulmonary bypass.

INTERVENTIONS: Patients were assigned randomly to receive thiamine (300 mg in 0.9% Normal saline solution) or placebo (0.9% Normal saline) preoperatively.

MAIN OUTCOME MEASURES: One arterial blood sample was taken preoperatively and another postoperatively to measure thiamine concentration, and multiple samples were taken during surgery and ICU stay to determine lactate concentrations. Twenty-four hour urine samples were collected to measure urinary thiamine concentration. Preoperatively, we assessed extracellular mass to body cell mass ratio (ECM/BCM).

RESULTS: The mean (SD) age of the patients was 58 (12) years, 73% were overweight, 10% were malnourished and the prevalence of thiamine deficiency was 10%. Patients in the thiamine group had significantly higher blood thiamine concentrations 2 days postoperatively [805.2 ± 289.8 ng g(-1) haemoglobin (Hb)] than those in the placebo group (591.2 ± 100.7 ng g(-1) Hb, P < 0.01). The mean blood lactate concentration changed significantly over time, but did not differ significantly between the groups. Patients with ECM/BCM more than 1 had higher lactate concentrations on admission to ICU than those with ECM/BCM less than 1 (2.1 ± 0.7 vs. 1.7 ± 0.6, P = 0.09) and were at a significantly greater risk of having a higher lactate concentration on ICU admission [odds ratio (OR) 13.5, 95% confidence interval (95% CI) 1.0 to 179.4, P < 0.05]. On the basis of these results, a sample size calculation for a larger study has been facilitated.

CONCLUSION: Thiamine supplementation caused normalisation of blood and urine concentrations postoperatively but without a significant reduction in lactate concentration or clinical outcome. Body composition played an important role in lactate formation. Further research focusing on preoperative screening and optimal treatment of high lactate concentrations in this specific population is warranted.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01524315.

Vitamin B Drip ABC

Abstract RATIONALE: Oxygen consumption may be impaired in critically ill patients.

OBJECTIVES: To evaluate the effect of intravenous thiamine on oxygen consumption ([Formula: see text]o2) in critically ill patients.

METHODS: This was a small, exploratory open-label pilot study conducted in the intensive care units at a tertiary care medical center. Critically ill adults requiring mechanical ventilation were screened for enrollment. Oxygen consumption ([Formula: see text]o2) and cardiac index (CI) were recorded continuously for 9 hours. After 3 hours of baseline data collection, 200 mg of intravenous thiamine was administered. The outcome was change in [Formula: see text]o2 after thiamine administration.

MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled and 3 were excluded because of incomplete [Formula: see text]o2 data, leaving 17 patients for analysis. There was a trend toward increase in [Formula: see text]o2 after thiamine administration (16.3 ml/min, SE 8.5; P = 0.052). After preplanned adjustment for changes in CI in case of a delivery-dependent state in some patients (with exclusion of one additional patient because of missing CI data), this became statistically significant (16.9 ml/min, SE 8.6; P = 0.047). In patients with average CI greater than our cohort's mean value of 3 L/min/m(2), [Formula: see text]o2 increased by 70.9 ml/min (±16; P < 0.0001) after thiamine. Thiamine had no effect in patients with reduced CI (< 2.4 L/min/m(2)). There was no association between initial thiamine level and change in [Formula: see text]o2 after thiamine administration.

CONCLUSIONS: The administration of a single dose of thiamine was associated with a trend toward increase in [Formula: see text]o2 in critically ill patients. There was a significant increase in [Formula: see text]o2 in those patients with preserved or elevated CI. Further study is needed to better characterize the role of thiamine in oxygen extraction. Clinical trial registered with www.clinicaltrials.gov (NCT01462279).

Abstract Spillover of fatty acids released by lipoprotein lipase hydrolysis of meal triglycerides may be a major contributor to the free fatty acid (FFA) pool. We studied lean (n = 6) and overweight and obese (n = 5) subjects during continuous feeding on two occasions: during intravenous infusion of niacin (2.8 mg/min) and saline. After establishment of steady-state chylomicronemia and suppression of adipose tissue lipolysis with a liquid meal, spillover was measured with infusions of [U-(13)C]oleate and [(3)H]triolein. Total FFA concentrations were lower during niacin infusion in both lean (50 ± 4 vs. 102 ± 7 μmol/L; P < 0.002) and obese (75 ± 6 vs. 143 ± 13 μmol/L; P < 0.01) subjects. Oleate appearance was lower during niacin infusion than during saline infusion in both lean (21 ± 2 vs. 32 ± 5 μmol/min; P = 0.07) and obese subjects (25 ± 3 vs. 46 ± 8 μmol/min; P < 0.02). Spillover was lower during niacin infusion than during saline infusion in lean (21 ± 4 vs. 29 ± 3%) and obese (21 ± 2 vs. 29 ± 5%) subjects (P < 0.03 for both). In summary, during meal absorption, niacin produces additional suppression of lipolysis and a reduction in fractional spillover compared with saline in both normal and obese subjects. Infusion of intravenous niacin provides a model for acutely improving dietary fat storage, perhaps by suppressing lipolysis in visceral adipose tissue.

Abstract OBJECTIVE: No clinically effective treatment for promoting peripheral axonal regeneration has yet been established. Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration.

METHODS: Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment. The primary endpoints were safety and improvement in the Medical Research Council (MRC) sum score in at least two muscles of the 20 muscles. This trial is registered with the University Hospital Medical Information Network (UMIN) Center in Japan under the ID: UMIN000009359.

RESULTS: There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the MRC sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients.

CONCLUSION: Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.

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