A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study). Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. A multicentre trial of the aldose-reductase inhibitor tolrestat, in patients with symptomatic diabetic peripheral neuropathy. North European Tolrestat Study Group. Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study. The influence of pyridoxine in diabetic peripheral neuropathy. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results.
In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy. A three-armed, randomized, multicentre, placebo-controlled double-blind study was used to examine the efficacy of benfotiamine vs a combination containing benfotiamine and vitamins B6 and B12 in out-patients with severe symptoms of alcoholic polyneuropathy (Benfotiamine in treatment of Alcoholic Polyneuropathy, BAP I). The study period was 8 weeks and 84 patients fulfilled all the prerequisite criteria and completed the study as planned. Benfotiamine led to significant improvement of alcoholic polyneuropathy. Vibration perception (measured at the tip of the great toe) significantly improved in the course of the study, as did motor function. and the overall score reflecting the entire range of symptoms of alcoholic polyneuropathy. A tendency toward improvement was evident for pain and co-ordination; no therapy-specific adverse effects were seen. The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c < 8.0%) were randomly assigned to three groups, each of them comprising 12 participants. Neuropathy was assessed by five parameters: the pain sensation (evaluated by a modified analogue visual scale), the vibration sensation (measured with a tuning fork using the Riedel-Seyfert method) and the current perception threshold (CPT) on the peroneal nerve at 3 frequencies: 5, 250 and 2000 Hz). Parameters were registered at the beginning of the study and at the end of the 3rd and 6th week of therapy. An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy (p < 0.01). The greatest change occurred in the group of patients receiving the high dose of benfotiamine (p < 0.01 and 0.05, resp., compared to the othr groups). Metabolic control did not change over the study. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective. One hundred and ninety patients with symptomatic diabetic peripheral neuropathy took part in a double blind multicentre trial of either placebo or tolrestat 200 mg once daily for 6 months. Painful and paraesthetic symptoms, vibration sensory threshold, and nerve conduction velocity (NCV) were assessed as efficacy end-points during the trial. There was an equally marked improvement of painful symptoms during the trial in the tolrestat and placebo groups. A difference in the improvement of paraesthetic symptoms was found however in favour of the placebo group at 24 weeks (p less than 0.02). The deterioration in mean vibration threshold of the tolrestat group was less than placebo at 24 weeks at all 3 sites measured, and reached significance at the carpal site (p less than 0.05). Significant improvements in median motor NCV and in the mean NCV of the four motor nerves were also seen in tolrestat treated patients at 24 weeks compared to placebo (p less than 0.05). In addition, significant changes in favour of tolrestat were seen when the number of motor nerves per patient with NCV increased during the trial was analysed (p less than 0.001). Concordance analysis of patients with increased mean motor NCV and improvement in painful symptoms demonstrated a positive effect for tolrestat compared to placebo (p less than 0.02). Mild reversible elevations of hepatic transaminases were seen in a few patients treated with tolrestat, with no other significant adverse effects. Tolrestat may therefore be helpful in diabetic peripheral neuropathy, where there is little opportunity for therapeutic intervention apart from effort to achieve normoglycaemic control. The objective of this double-blind randomised, placebo-controlled study was to examine the efficacy and safety intramuscular vitamin B12 (Tricortin 1000) in the treatment of low back pain in patients with mechanical or irritative lumbago.
                60 patients aged between 18 and 65 years with lumbago or sciatic neuritis of mechanical origin without need for surgical procedures were enrolled. Patients had to present with a proven medical history for back pain (lasting from 6 months to 5 years) and a pain intensity [as evaluated with a Visual Analogic Scale (VAS)] equal or greater than 60 mm. Efficacy primary end-point was evaluated by means of a visual analogic scale (VAS) and a Disability Questionnaire (DQ). Consumption of paracetamol during the study period was the secondary efficacy end-point.
                Both treatment groups experienced a sharp decrease in pain and disability. However, comparison between groups at the end of the treatment period showed a statistically significant difference in favour of the active treatment both for VAS and DQ (p < 0.0001 and p < 0.0002, respectively). Consumption of paracetamol proved significantly higher in the placebo group than in the active treatment (p < 0.0001).
                The efficacy and safety of parenteral Vitamin B12 in alleviating low back pain and related disability and in decreasing the consumption of paracetamol was confirmed in patients with no signs of nutritional deficiency. To determine the role of pyridoxine in the treatment of diabetic peripheral neuropathy, 18 symptomatic diabetic patients were treated with vitamin B6 or placebo in a double-blind controlled study. Only one patient had a low plasma pyridoxal phosphate level at the start of the study. After 4 mo of treatment with pyridoxine hydrochloride (50 mg three times daily) 6 of 9 pyridoxine-treated and 4 of 9 placebo-treated patients noted significant relief from their neuropathic symptoms. There was no difference between the two groups with regard to fasting plasma glucose, motor nerve conduction velocity, or ophthalmologic examination at the beginning or at the conclusion of the study. Our results suggest that vitamin B6 deficiency is not a factor in the etiology of diabetic peripheral neuropathy. Furthermore, treating diabetic peripheral neuropathy with high dose vitamin B6 or placebo results in a similar frequency of symptomatic improvement. The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy.
                A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms.
                Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group.
                The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy. Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost.
                This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency.
                This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection.
                Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30.
                In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment. A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN).
                A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score.
                The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation.
                Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.
There are only limited data in randomised trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful. One small trial in alcoholic peripheral neuropathy reported slightly greater improvement in vibration perception threshold with oral benfotiamine for eight weeks than placebo. In another small study, a higher dose of oral vitamin B complex for four weeks was more efficacious than a lower dose in reducing symptoms and signs. Vitamin B administered by various routes for two to eight weeks was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve conduction study outcomes. Vitamin B is generally well-tolerated.