-
1.
High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial.
Mitsui, J, Matsukawa, T, Uemura, Y, Kawahara, T, Chikada, A, Porto, KJL, Naruse, H, Tanaka, M, Ishiura, H, Toda, T, et al
EClinicalMedicine. 2023;:101920
Abstract
BACKGROUND Functionally impaired variants of COQ2, encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in COQ2 is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients. METHODS This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Patients with MSA were randomly assigned (1:1) to either ubiquinol (1500 mg/day) or placebo. The primary efficacy outcome was the change in the unified multiple system atrophy rating scale (UMSARS) part 2 at 48 weeks. Efficacy was assessed in all patients who completed at least one efficacy assessment (full analysis set). Safety analyses included patients who completed at least one dose of investigational drug. This trial is registered with UMIN-CTR (UMIN000031771), where the drug name of MSA-01 was used to designate ubiquinol. FINDINGS Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (-1.7 [95% CI, -3.2 to -0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]). INTERPRETATION High-dose ubiquinol was well-tolerated and led to a significantly smaller decline of UMSARS part 2 score compared with placebo. FUNDING Japan Agency for Medical Research and Development.
-
2.
Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Shiojima, Y, Takahashi, M, Takahashi, R, Moriyama, H, Bagchi, D, Bagchi, M, Akanuma, M
Journal of the American Nutrition Association. 2022;(8):796-809
Abstract
BACKGROUND Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. OBJECTIVE This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to <80 Y). METHODS 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). RESULTS A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. CONCLUSIONS Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.
-
3.
Physical performance and maximum tongue pressure associated with oral intake independence: a retrospective study on hospitalized patients with heart failure.
Yokota, J, Takahashi, R, Endo, R, Chiba, T, Sasaki, K, Matsushima, K
Scientific reports. 2022;(1):18549
Abstract
Dysphagia in patients with heart failure leads to poorer outcomes during hospitalization and after discharge. Therefore, addressing dysphagia is critical for improving patient prognosis. This retrospective observational study aimed to evaluate associations between improvements in swallowing dysfunction at the time of hospital discharge and the physical function, cognitive function, nutritional status, and maximum tongue pressure (MTP). Overall, 111 patients who underwent cardiac rehabilitation and were deemed to have oral intake impairment were included. The exclusion criteria comprised the following: pre-admission diagnosis of dysphagia, in-hospital death, and missing data. Patients were categorized based on whether they did (n = 65) or did not (n = 46) exhibit improvements in oral intake impairment, which were determined from the functional oral intake scale (FOIS) score at discharge. Associations between potential explanatory variables and the FOIS score at discharge were assessed using a linear regression model. After adjusting for covariates, such as age, sex, heart failure severity, short physical performance battery score, Mini-Mental State Examination score, transthyretin level, and provision of swallowing therapy, the FOIS score at discharge was significantly associated with the MTP (P = 0.024, confidence interval: 0.006-0.046). In conclusion, the MTP was independently associated with improvements in FOIS in patients with heart failure.
-
4.
Swallowing-induced Paroxysmal Atrial Tachycardia Causes Weight Loss and Fainting during Mealtime: A Case Report and Literature Review.
Hosoe, T, Uzu, K, Hyogo, K, Takahashi, R, Tamai, S, Nagano, T, Shimokawa, Y, Ota, S, Okubo, H, Shimizu, H
Internal medicine (Tokyo, Japan). 2022;(23):3531-3535
Abstract
Swallow or deglutition syncope is an unusual disorder. We herein report an 80-year-old man with paroxysmal atrial tachycardia induced by swallowing, causing syncope. Initially, we suspected a digestive disorder and found no significant findings. Finally, a swallowing test with monitoring of the heart rate and blood pressure helped in the diagnosis. The patient was treated with antiarrhythmic drugs and catheter ablation. The mechanism underlying swallowing-induced tachycardia presumably involves mechanical stimulation of the esophagus and autonomic nervous system effects. However, few cases have been reported, and the exact mechanism remains unclear.
-
5.
Dysphagia and malnutrition limit activities of daily living improvement in phase i cardiac rehabilitation: a prospective cohort study for acute phase heart failure patients.
Yokota, J, Endo, R, Takahashi, R, Matsukawa, Y, Matsushima, K
Heart and vessels. 2021;(9):1306-1316
Abstract
Dysphagia and malnutrition combinations in hospitalized patients with acute heart failure (AHF) may affect activities of daily living (ADL) after hospital discharge more than dysphagia or malnutrition alone. The aim of the present study to clarify the impact of the combination of dysphagia and malnutrition on ADL in hospitalized patients with acute phase heart failure who have undergone cardiac rehabilitation (CR). Prospective cohort study. Acute care hospital. Participants were 224 AHF patients undergoing CR. Barthel index (BI), functional oral intake scale (FOIS), controlling nutritional status (CONUT), short physical performance battery (SPPB), and mini-mental state examination were evaluated at baseline. We examined primary effects of predictors (CONUT) and the moderator (FOIS) and the interaction effect of FOIS and CONUT (FOIS × CONUT) using hierarchical linear regression model and simple-slope tests. The ADL independence dropped in 29.5% of the patients on hospitalization; however, 82.6% of the patients successfully regained their independence at discharge. Based on the FOIS score and nutritional status on admission, 58.5% of the patients were classified into the non-dysphagia and non-malnutrition categories, 21.0% into non-dysphagia and malnutrition, 15.2% into dysphagia and non-malnutrition, and 5.3% into dysphagia and malnutrition. Lower FOIS and SPPB scores as well as the FOIS × CONUT interaction predicted a significantly lower BI but not CONUT. Simple slope test revealed a negative association between CONUT and BI with low-level FOIS (B = - 2.917, P < .001) but not with high-level FOIS (B = .476, P = .512). Thus, patients with dysphagia and malnutrition in combination had a greater risk of failed recovery of ADL after cardiac rehabilitation than those without this combination. In hospitalized AHF patients, FOIS and CONUT had an interactive effect on BI at hospital discharge in cases with low-level FOIS. Early detection of dysphagia might improve the accurate identification of hospitalized AHF patients at higher risk of ADL dependence at discharge.
-
6.
Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients.
Toida, T, Toida, R, Ebihara, S, Takahashi, R, Komatsu, H, Uezono, S, Sato, Y, Fujimoto, S
Nutrients. 2020;(10)
Abstract
BACKGROUND The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. METHODS This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. RESULTS Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. CONCLUSION Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.
-
7.
Daily Ingestion of Eggplant Powder Improves Blood Pressure and Psychological State in Stressed Individuals: A Randomized Placebo-Controlled Study.
Nishimura, M, Suzuki, M, Takahashi, R, Yamaguchi, S, Tsubaki, K, Fujita, T, Nishihira, J, Nakamura, K
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
Prevention and management of hypertension are major public health challenges worldwide. Psychosocial factors are related to blood pressure and may lead to hypertension. The aim of this study was to examine the long-term antihypertensive, anti-stress, and psychological state-improving effects of eggplant in human participants with normal-high blood pressure and grade 1 hypertension. The study is a randomized, double-blind, placebo-controlled, parallel-group comparative study. The participants were randomized into one of two intervention groups; placebo group or eggplant group. The participants ingested four eggplant powder capsules, or four placebo capsules every day for 12 weeks. Results indicate that continuous intake of eggplant powder improved blood pressure in participants with normal-high blood pressure and grade 1 hypertension. Additionally, eggplant intake improved positive and negative psychosocial states. Authors conclude that eggplant should be utilised as a safe treatment for blood pressure and mental health.
Abstract
Eggplant (Solanum melongena) is a globally popular vegetable and its significant health effect has not been reported in randomized controlled trials. Recently, we reported that eggplant was rich in choline esters, including acetylcholine (ACh), and had an antihypertensive effect in spontaneously hypertensive rats. Here, we evaluated the effects of a continuous intake of eggplant powder on blood pressure (BP), stress, and psychological state (PS) in 100 stressed participants with normal-high BP or grade 1 hypertension in a randomized, double-blind, placebo-controlled, parallel-group comparative study. The participants were randomly assigned to the eggplant or placebo group. Participants in the eggplant group ingested capsules containing eggplant powder (1.2 g/day; 2.3 mg of ACh/day) for 12 weeks, whereas participants in the placebo group ingested placebo capsules. The primary outcome assessed was hospital BP. Secondary outcomes were stress and PS. Eggplant powder intake significantly decreased the hospital diastolic blood pressure (DBP) at week 8 overall and in the normal-high BP group, and the systolic blood pressure (SBP) and DBP at week 12 overall and in the grade 1 hypertension group, compared to those of the placebo group. It also improved negative PSs at week 8 or 12 in the normal-high BP group. This is the first evidence of the BP- and PS-improving effects of eggplant intake in humans. The functional substance responsible for the effects was estimated to be eggplant-derived choline ester, namely ACh.
-
8.
Effect of Daikenchuto (TJ-100) on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: study protocol for a randomized controlled trial.
Hoshino, N, Kawada, K, Hida, K, Wada, T, Takahashi, R, Yoshitomi, M, Sakai, Y
Trials. 2017;(1):553
Abstract
BACKGROUND Postoperative paralytic ileus can be a difficult complication for both surgeons and patients. Causes and treatments have been discussed for more than two centuries, but have not yet been fully resolved. Daikenchuto (TJ-100, DKT) is a traditional Japanese herbal medicine. Recently, some beneficial mechanisms of DKT to relieve paralytic ileus have been reported. DKT can suppress inflammation, increase intestinal blood flow, and accelerate bowel movements. Therefore, we have designed a randomized controlled trial to investigate the effects of DKT on postoperative gastrointestinal symptoms following laparoscopic colectomy in patients with left-sided colon cancer at a single institution. METHODS/DESIGN As primary endpoints, the following outcomes will be evaluated: (i) grade of abdominal pain determined using the numeric rating scale (NRS), (ii) grade of abdominal distention determined using the NRS, and (iii) quality of life determined using the Gastrointestinal Quality Life Index (GIQLI). As secondary endpoints, the following will be evaluated: (i) postoperative nutritional status (Onodera's Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status score (CONUT score)), (ii) duration to initial flatus, (iii) duration to initial defecation, (iv) bowel gas volume, (v) character of stool (Bristol Stool Form Scale), (vi) defecation frequency per day, (vii) postoperative complications (Clavien-Dindo classification), (viii) length of postoperative hospital stay, and (ix) metabolites in the stool and blood. This trial is an open-label study, and needs to include 40 patients (20 patients per group) and is expected to span 2 years. DISCUSSION To our knowledge, this is the first randomized controlled trial to investigate the effects of DKT on postoperative subjective outcomes (i.e., postoperative quality of life) following laparoscopic colectomy as primary endpoints. Exploratory metabolomics analysis of metabolites in stool and blood will be conducted in this trial, which previously has only been performed in a few human studies. The study aims to guide a future full-scale pragmatic randomized trial to assess the overall effectiveness of DKT to improve the postoperative quality of life following laparoscopic colectomy. TRIAL REGISTRATION UMIN-CTR (Japan), UMIN000023318 . Registered on 25 July 2016.
-
9.
Phase I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine.
Ikeda, M, Sato, A, Mochizuki, N, Toyosaki, K, Miyoshi, C, Fujioka, R, Mitsunaga, S, Ohno, I, Hashimoto, Y, Takahashi, H, et al
Cancer science. 2016;(12):1818-1824
Abstract
GBS-01, an extract from the fruit of Arctium lappa L. is an orally administered drug rich in arctigenin, which has been reported to exert antitumor activity by attenuating the tolerance of cancer cells to glucose deprivation. We investigated the maximum tolerated dose of GBS-01 based on the frequency of the dose-limiting toxicities (DLTs) and pharmacokinetics in patients with advanced pancreatic cancer refractory to gemcitabine. GBS-01 was given orally at escalating doses from 3.0 g (containing 1.0 g burdock fruit extract) to 12.0 g q.d. A DLT was defined as a grade 4 hematological toxicity and grade 3 or 4 non-hematological toxicity appearing during the first 28 days of treatment. Fifteen patients (GBS-01 dose level 1 [3.0 g], three patients; dose level 2 [7.5 g], three patients; and dose level 3 [12.0 g], nine patients) were enrolled. None of the patients at any of the three dose levels showed any sign of DLTs. The main adverse events were increased serum γ-glutamyl transpeptidase, hyperglycemia, and increased serum total bilirubin; however, all the toxicities were mild. Of the 15 patients, 1 showed confirmed partial response and 4 patients had stable disease. The median progression-free and overall survival of the patients were 1.1 and 5.7 months, respectively. The pharmacokinetic study revealed a high bioavailability of arctigenin and rapid conjugation of the drug with glucuronic acid. The recommended dose of GBS-01 was 12.0 g q.d, and favorable clinical responses were obtained. This trial was registered at UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number UMIN000005787.
-
10.
Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction.
Hayashi, M, Kajioka, S, Itsumi, M, Takahashi, R, Shahab, N, Ishigami, T, Takeda, M, Masuda, N, Yamaguchi, A, Naito, S
BJU international. 2016;(1):179-91
Abstract
OBJECTIVES To clarify the effect of cAMP on the Ca(2+) -sensitized smooth muscle contraction in human detrusor, as well as the role of novel exchange protein directly activated by cAMP (Epac) in cAMP-mediated relaxation. MATERIALS AND METHODS All experimental protocols to record isometric tension force were performed using α-toxin-permeabilized human detrusor smooth muscle strips. The mechanisms of cAMP-mediated suppression of Ca(2+) sensitization activated by 10 μm carbachol (CCh) and 100 μm GTP were studied using a selective rho kinase (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF-109203X. The relaxation mechanisms were further probed using a selective protein kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2'-O-Me-cAMP. RESULTS We observed that CCh-induced Ca(2+) sensitization was inhibited by cAMP in a concentration-dependent manner. GF-109203X (10 μm) but not Y-27632 (10 μm) significantly enhanced the relaxation effect induced by cAMP (100 μm). 6-Bnz-cAMP (100 μm) predominantly decreased the tension force in comparison with 8-pCPT-2'-O-Me-cAMP (100 μm). CONCLUSIONS We showed that cAMP predominantly inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is dominant, while Epac plays a minor role in human detrusor smooth muscle Ca(2+) sensitization.