The effect of caffeine on tinnitus: Randomized triple-blind placebo-controlled clinical trial

Objective To test the hypothesis that caffeine can influence tinnitus, we recruited 80 patients with chronic tinnitus and randomly allocated them into two groups (caffeine and placebo) to analyze the self-perception of tinnitus symptoms after caffeine consumption, assuming that this is an adequate sample for generalization. Methods The participants were randomized into two groups: one group was administered a 300-mg capsule of caffeine, and the other group was given a placebo capsule (cornstarch). A diet that restricted caffeine consumption for 24 hours was implemented. The participants answered questionnaires (the Tinnitus Handicap Inventory—THI, the Visual Analog Scale—VAS, the profile of mood state—POMS) and underwent examinations (tonal and high frequency audiometry, acufenometry (frequency measure; intensity measure and the minimum level of tinnitus masking), transient otoacoustic emissions—TEOAE and distortion product otoacoustic emissions—DPOAE assessments) at two timepoints: at baseline and after capsule ingestion. Results There was a significant change in mood (measured by the POMS) after caffeine consumption. The THI and VAS scores were improved at the second timepoint in both groups. The audiometry assessment showed a significant difference in some frequencies between baseline and follow-up measurements in both groups, but these differences were not clinically relevant. Similar findings were observed for the amplitude and signal-to-noise ratio in the TEOAE and DPOAE measurements. Conclusions Caffeine (300 mg) did not significantly alter the psychoacoustic measures, electroacoustic measures or the tinnitus-related degree of discomfort.

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Excessive alcohol consumption is one of the significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. This study involves supplementation of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number ofheterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde in the ALDH2 heterozygote group were significantly downregulated in the probiotic-supplemented group with no changes in hangover score symptoms than the placebo group. No clinically significant changes were observed in safety parameters. These results suggest that probiotic has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

A PLACEBO CONTROLLED COMPARATIVE CLINICAL STUDY TO EVALUATE THE EFFICACY OF JEERAKADYA GHRITA PRAYOGA IN AMLAPITTA WITH SPECIAL REFERENCE TO URDHVAGA AMLAPITTA

Amlapitta is a disease of Annavaha srotas which is characterized by the symptoms like Avipaka, Klama, Utklesha, Tikta Amlodghara, etc. explained by Acharyas. It is the most disturbing and irritable condition. As the Nidana leading to impairment of Pachakagni causes many diseases like Ajeerna, Aruchi, Agnimandya, Amlapitta etc. Agni is responsible for digestion of food. Amlapitta is Pittapradhana Tridoshaja Vyadhi. Because of the vitiation of Pitta there is Mandagni. Ghrita which is claimed to be Pittashamaka, Dahashamaka and Agnideepaka. So, in the present study the Jeerakadhya Ghrita was taken to treat the Mandagni and vitiated Pittadosha. Jeerakadhya Ghrita, mentioned in Bhaishjya Ratnavali and Chakradatta by the virtue of its Rasa, Guna, Veerya, Vipaka and Samyoga helps in Pitta Shamana, Daha Shamana, Agni Deepana, and Ama Pachana. In the present study, 30 patients diagnosed with Urdhvagha Amlapitta were selected randomly and allocated to Group A and Group B. Group A received Placebo capsule and Group B Jeerakadhya Ghrita. Group A with placebo was studied to compare the efficacy of Jeerakadhya Ghrita was done. Results were analyzed statistically. The study proves that Jeerakadhya Ghrita has a significant effect in Urdhvagha Amlapitta and Non-Digestible Cellulose used as a placebo has no significant effect in Urdhvagha Amlapitta.

A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia

Background Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients. Methods The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer’s Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements. Results Comparing with the placebo group (n = 83, change − 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was − 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was − 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%. Conclusions GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study. Trial registration ClinicalTrials.gov, NCT01453569. Registered on October 18, 2011.

The Effect of Ginger and Ondansetron on Post-Operative Nausea and Vomiting in Patients Undergoing Eye Surgery: A Triple-Blind Clinical Trial

Background: Postoperative nausea and vomiting (PONV) is still a common complication that occurs frequently at the time of recovery from eye surgery. Objectives: The present study aimed to compare the effect of oral Ondansetron and Ginger on the frequency and severity of postoperative nausea and vomiting in patients undergoing eye surgery. Methods: A total of 148 patients were randomly assigned to Ginger, Ondansetron, and placebo groups. Group A received a Ginger capsule (1,000 mg), group B Ondansetron capsule (16 mg), and group C placebo capsule with 30 ml water, one hour before surgery. The frequency of nausea and vomiting and the severity of nausea were recorded immediately after recovery, 1, 2, and 4 hours after recovery. Also, some side effects following prescription such as headache, stomach ache, dizziness, and cardiac arrhythmias were recorded. Results: Of the 148 participants, 54% were men, and 46% were women. The average age was in group Ginger (36.14 ± 2.17), group Ondansetron (36.24 ± 2.49), and group placebo (36.24 ± 2.20). There was no significant difference in the frequency of vomiting between the three groups immediately after recovery (P = 0.19) and 4 hours after surgery (P = 0.18). However, the frequency of vomiting in Ginger and Ondansetron groups 1 and 2 hours after the surgery was significantly lower than that in the control group (P = 0.003). No significant difference was observed in the severity of nausea between the three groups at certain times (P > 0.05). There was no significant difference in terms of the need for injection antiemetic drugs after surgery (P = 0.2). Conclusions: Ginger and Ondansetron can reduce the frequency of vomiting. However, Ginger was more effective, safer, and less expensive than Ondansetron; therefore, it may be a better substitute for Ondansetron to prevent PONV.

A phase II randomized trial of sodium oligomannate in Alzheimer's dementia

Background: Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients.Methods: The 24-week multi-center, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer's Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL and NPI at 24 weeks after treatment compared with baseline. A sub-group study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements.Results: Comparing with placebo group (n=83, change -1.45), the ADAS-Cog12 score change in GV-971 600mg group (n=76) was -1.39 (p=0.89), GV-971 900mg group (n=83) was -2.58 (p=0.30). The treatment responders according to CIBIC-plus assessment was significantly higher in GV-971 900mg group than placebo group (92.77% vs 79.52%, p<0.05). GV-971 900mg subgroup showed a significantly lower cerebral metabolic rate for glucose decline than the placebo subgroup at the left precuneus, right posterior cingulate, and right hippocampus. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%.Conclusions: GV-971 was safe and well tolerated. GV-971 900mg was chosen for phase III clinical study.Trial registration: ClinicalTrials.gov, NCT01453569. Registered 18 October, 2011, https://clinicaltrials.gov/ct2/show/NCT01453569?term=NCT01453569&draw=2&rank=1.

Efficacy and Safety of New Lactobacilli Probiotics for Unconstipated Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Irritable bowel syndrome (IBS) is a common and chronic gastrointestinal disorder. Probiotics may have the potential to impact the management of IBS; however, the results of trials are conflicting. This study aimed to investigate whether a mixture of lactobacilli probiotics could improve abdominal symptoms in patients with unconstipated IBS. Fifty Vietnamese patients with unconstipated IBS were randomly assigned to either the probiotics or placebo groups. During the intervention, participants took the probiotic supplement, named Foodis Lactobacillus, or placebo capsule once a day. Patients recorded their subject global assessment (SGA) weekly and were assessed with the visual analogue scale (VAS) during the 4-week study period. Patients with SGA score of 2 points or more or a decrease of more than 30% in VAS score were considered responders. Patients who responded weekly for more than 2 of the 4 weeks were considered overall responders. There was no significant difference in demographic characteristics between the groups. Overall responder rates of improvement of global IBS symptoms assessed by SGA score were significantly higher in the probiotics group (80.8%) than in the placebo group (45.8%) (p = 0.009). The overall responder rates assessed by VAS score were also higher in the probiotics group (69.2%, 41.7%, p = 0.048). There were no adverse events in either group during the study period. Our findings suggest that the new combination of Lactobacilli appears to be promising in the relief of abdominal symptoms in Vietnamese patients with unconstipated IBS.

The Effect of Caffeine Ingestion and Carbohydrate Mouth Rinse on High-Intensity Running Performance

The aim of the current study was to investigate whether carbohydrate mouth rinsing works synergistically with caffeine to augment high-intensity running in a fed state. Eight participants completed a total of three trials; (1) placebo (PLA) trial (placebo capsule + placebo mouth rinse), (2) caffeine (CAF) trial (400 mg caffeine + placebo mouth rinse) and (3) carbohydrate mouth rinse + caffeine (CMR + CAF) trial (400 mg caffeine + 6% carbohydrate mouth rinse). Each trial consisted of a 45 min steady-state run at 65% VO2max, followed by 90% VO2max high-intensity intervals (HIIT) at 1 min and subsequently by a 1 min recovery walking at 6 km·h−1, until exhaustion. Both CAF (46.8 ± 20.1 min) and CMR + CAF (46.9 ± 18.4 min) time to exhaustion were significantly greater than the PLA group (36.2 ± 14.8 min, p < 0.001). Post hoc analysis revealed that there was a significant increase in time to exhaustion between PLA and CMR + CAF (p = 0.006) and PLA and CAF (p = 0.017) but not between CAF and CMR + CAF (p = 0.99). In conclusion, we provide novel data that suggest that caffeine alone would likely suffice as an ergogenic aid during high-intensity running while in a fed state.

Clinical evaluation of the effect of Khanda Kushmanda Avaleha in Rakta Pradara (Abnormal uterine bleeding)

Background: Raktapradara manifesting as excessive bleeding per vagina is seen to be an age old disease known to mankind since the era of Veda and Purana. Excessive and irregular menstrual bleeding condition is similar to Raktapradara a gynaecological condition mentioned in Ayurvedic classics. Rakta Pradara is one among the Rakta Pradoshaja Vikara and characterized by Artava Ati Pravrutti, Deerga Kala Pravrutti, Anruta Kala Pravrutti, Daha in Adho Vankshana Pradesha, Sroni, Prushta and Kukshi, Shoola in Garbhashaya, Angamardha etc. Objectives: To clinically evaluate the effect of Khanda Kushmanda Avaleha in Raktapradara. Materials and Methods: The patients attending the O.P.D. and I.P.D. of S.V.M Ayurvedic Medical College and PG Centre, Ilkal, were randomly divided into 2 groups, Group A was treated with Khanda Kusmanda Avaleha and Group B was treated with Placebo Capsule. Results: Khanda Kushmanda Avaleha cured 12 patients i.e. 85.71% followed by markedly improvement in 2 patients i.e. 14.28%. Placebo capsule mildly improved 61.54% i.e. 8 patients followed by no improvement to 38.46% i.e. 5 patients. Discussion: The effect of therapy on chief complaints in Group A is better than Group B. Percentage wise Khanda Kusmanda Avaleha gave 86.3% relief on duration of blood loss, 85.7% on Interval between two cycles and 58.3% on Amount of total blood loss during one period while Placebo capsule gave 27.2% relief on Duration of blood loss, 20% on Interval between cycle, and 21.05% relief on Amount of blood loss. So, more relief was observed on chief complaints in Group - A i.e. Khanda Kusmanda Avaleha.