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A Randomized, Double-Blind, Controlled Trial Assessing If Medium-Chain Triglycerides in Combination with Moderate-Intensity Exercise Increase Muscle Strength in Healthy Middle-Aged and Older Adults.
Kojima, K, Ishikawa, H, Watanabe, S, Nosaka, N, Mutoh, T
Nutrients. 2023;(14)
Abstract
An adequate nutritional intake is recommended for the prevention of physical frailty and sarcopenia. In particular, medium-chain fatty acids (MCFAs) are reportedly important for muscle strength in nursing home residents. However, the effects of MCFAs on healthy adults at risk for frailty remain unknown. Hence, a randomized, placebo-controlled study was conducted to investigate the effects of 12 weeks of medium-chain triglycerides (MCTs) intake and walking on muscle mass and function in healthy, sedentary, middle-aged and older adults with a low body mass index. Three MCT intake groups with different amounts of octanoic and decanoic acid intake were compared with a control group. After 12 weeks, knee extension strength increased in all groups, with the increases in all MCT intake groups being significantly higher than those in the control group (p < 0.05). Grip strength significantly increased from baseline in the MCT 6 g/day intake group (p < 0.05). The combination of aerobic exercise and MCT intake may be effective in preventing decline in muscle strength and promoting increase in muscle strength as they can improve muscle energy production, thereby contributing to the maintenance of good health for middle-aged and older adults at high risk for frailty and sarcopenia.
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Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial.
Ishikawa, H, Mutoh, M, Sato, Y, Doyama, H, Tajika, M, Tanaka, S, Horimatsu, T, Takeuchi, Y, Kashida, H, Tashiro, J, et al
The lancet. Gastroenterology & hepatology. 2021;(6):474-481
Abstract
BACKGROUND The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP. METHODS This was a randomised, double-blind, placebo-controlled, multicentre trial with a two-by-two factorial design done in 11 centres in Japan. Eligible patients were aged 16-70 years and had a history of more than 100 adenomatous polyps in the large intestine, without a history of colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5·0 mm in diameter. Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status at the time of entry. Patients and researchers were masked to the treatment group. There were four groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy. The primary endpoint was the incidence of colorectal polyps of at least 5·0 mm at 8 months and was assessed in the intention-to-treat population. Safety was assessed in the ITT population. We also did a per-protocol analysis including only patients who took at least 70% of the allocated study drug. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000018736, and is complete. FINDINGS Between Sept 25, 2015, and March 13, 2017, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group. 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5·0 mm at 8 months, as did 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine. The adjusted odds ratio for polyp recurrence was 0·37 (95% CI 0·16-0·86) in the patients who received any aspirin and 0·87 (95% CI 0·38-2·00) in any who received mesalazine. The most common adverse events were grade 1-2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment. INTERPRETATION Low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5·0 mm in patients with FAP. These results suggest an effect of low-dose aspirin for FAP and could be an alternative method for preventing colorectal cancer in FAP. FUNDING Japan Agency for Medical Research and Development.
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Effectiveness of a Cancer Risk Prediction Tool on Lifestyle Habits: A Randomized Controlled Trial.
Yuwaki, K, Kuchiba, A, Otsuki, A, Odawara, M, Okuhara, T, Ishikawa, H, Inoue, M, Tsugane, S, Shimazu, T
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021;(6):1063-1071
Abstract
BACKGROUND Risk prediction models offer a promising approach to lifestyle modification. We evaluated the effect of personalized advice based on cancer risk prediction in improving five lifestyle habits (smoking, alcohol consumption, salt intake, physical activity, and body mass index) compared with standard advice without risk prediction among a Japanese general population with at least one unhealthy lifestyle habit. METHODS In a parallel-design, single-blind, randomized controlled trial between February 2018 and July 2019, 5984 participants aged 40-64 years with unhealthy lifestyle habits were recruited from persons covered under a life insurance policy. They were randomly assigned to an intervention or control group and received personalized or standard advice, respectively. They were also sent an invitation to participate in a lifestyle modification program aimed at improving lifestyle. Primary outcome was an improvement in lifestyle, defined as an increase in healthy lifestyle habits within 6 months. RESULTS The proportion of participants who improved their lifestyle within 6 months in the intervention group did not significantly differ from that in the control group (18.4% vs. 17.7%; P = 0.488). Among participants with low health literacy and two or fewer of five healthy habits, the proportion of participants subscribing to the lifestyle modification program was higher in the intervention group than in the control group. CONCLUSIONS Compared with standardized advice, personalized advice based on cancer risk prediction had no effect on improving lifestyle. IMPACT Provision of predicted cancer risk information did not induce change in unhealthy lifestyle.
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Effect of physical fitness on colorectal tumor development in patients with familial adenomatous polyposis.
Nakamura, T, Ishikawa, H, Sakai, T, Ayabe, M, Wakabayashi, K, Mutoh, M, Matsuura, N
Medicine. 2019;98(38):e17076
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Plain language summary
Familial adenomatous polyposis (FAP), is a rare genetic disease leading to a very high risk of developing colorectal cancer (CRC), with about half of all these patients developing cancer by the age of 40 years. Research has shown that exercise and physical fitness can reduce the risk of sporadic CRC. The aim of this cross-sectional study was to examine the relationship between physical fitness and CRC development in patients with FAP. 119 patients with FAP participated in the study and underwent an exercise stress test to determine physical fitness. The risk of CRC was significantly higher in those who were less physically fit. There was also a significant negative correlation between maximum polyp diameter and physical fitness. The authors conclude that physical fitness may play a role not only in the development of sporadic CRC, but also in cancer development in FAP. The mechanism by which physical fitness prevents the development of CRC and adenoma is largely unknown, but it is thought that improved insulin resistance and altered intestinal transit time may mediate the association.
Abstract
Although accumulated epidemiological evidence indicates that a good physical fitness level may prevent the development of sporadic colorectal cancer (CRC), few studies have examined the effect of physical fitness level on familial adenomatous polyposis (FAP). This cross-sectional study aimed to examine the relationship between physical fitness and CRC development in patients with FAP.A total of 119 patients (54 male; 65 female) with FAP, aged 17 to 73 years, underwent a step test to induce exercise stress. Predicted maximal oxygen uptake (VO2max) was calculated for each patient by using heart rate as an index of physical fitness. The association of VO2max with the presence or absence of CRC and polyp diameter was examined. Patients with FAP were divided into 3 categories according to their VO2max (high, medium, and low). The association between maximum polyp size and VO2max among the patients with FAP without a history of colectomy was examined.The risk of CRC was significantly higher in the low VO2max group than in the high VO2max group (odds ratio = 4.07; 95% confidence interval, 1.02-16.26). The maximum polyp diameter was significantly negatively correlated with the VO2max among the patients with FAP without a history of colectomy (r = -.44, P = .01). In the multiple linear regression analysis, maximum polyp diameter was independently correlated with VO2max.Our results suggest a preventive association between physical fitness and CRC development or colorectal adenoma growth exists in patients with FAP.
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Impact of Diarrhea after Drinking on Colorectal Tumor Risk: A Case Control Study.
Shiotani, A, Ishikawa, H, Mutoh, M, Takeshita, T, Nakamura, T, Morimoto, K, Sakai, T, Wakabayashi, K, Matsuura, N
Asian Pacific journal of cancer prevention : APJCP. 2019;(3):795-799
Abstract
Background: Recently, the number of colorectal cancer (CRC) cases in Japan has been increasing, and is strongly influenced by alcohol consumption. On the other hand, there are several reports suggesting a relationship between bowel movement (constipation and diarrhea) and CRC development. Moreover, it is generally known that diarrhea may occur after drinking. However, the mechanism by which drinking alcohol increases CRC is not fully clarified yet. We hypothesized that diarrhea after drinking may play an important role in colorectal carcinogenesis. Methods: We examined the presence of diarrhea after drinking and further evaluated the correlation of diarrhea after drinking with the incidence of colorectal tumors. To obtain the status of the feces, a self-recorded questionnaire survey was administered using the dietary-recording method. Blood samples were obtained to analyze the ALDH2 Glu504Lys and ADH1B His48Arg polymorphisms. Results: The participants were 417 patients who had undergone a total colonoscopy. The control was selected from 186 patients who underwent a medical checkup at the same hospital during the same time period. The odds ratio for all subjects was 2.1 (95% CI: 1.18 - 3.80), and that for heavy drinkers was 4.2 (1.48 - 11. 90). Conclusions: The results demonstrated that those who have diarrhea after drinking possess a high risk of developing colon tumors.
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Impact of genetic testing on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia (GenTLe-FH): a randomised waiting list controlled open-label study protocol.
Nomura, A, Tada, H, Okada, H, Nohara, A, Ishikawa, H, Yoshimura, K, Kawashiri, MA
BMJ open. 2018;(12):e023636
Abstract
INTRODUCTION Familial hypercholesterolemia (FH) is an autosomal-dominant inherited genetic disease. High-throughput sequencing quickly and comprehensively detects causative variants of FH-related genes (LDLR, PCSK9, APOB and LDLRAP1). Although the presence of causative variants in FH-related genes correlates with future cardiovascular events, it remains unclear whether detection of causative gene mutation and disclosure of its associated cardiovascular risk affects outcomes in patients with FH. Therefore, this study intends to evaluate the efficacy of counselling future cardiovascular risk based on genetic testing in addition to standard patients' education programme in patients with FH. METHODS AND ANALYSIS A randomised, waiting-list controlled, open-label, single-centre trial will be conducted. We will recruit patients with clinically diagnosed FH without previous history of coronary heart disease from March 2018 to December 2019, and we plan to follow up participants until March 2021. For the intervention group, we will perform genetic counselling and will inform an estimated future cardiovascular risk based on individuals' genetic testing results. The primary endpoint of this study is the plasma low-density lipoprotein cholesterol level at 24 weeks after randomisation. The secondary endpoints assessed at 24 and 48 weeks are as follows: blood test results; smoking status; changes of lipid-lowering agents' regimen and Patients Satisfaction Questionnaire Short Form scores among the four groups divided by the presence of genetic counselling and genetic status of FH. ETHICS AND DISSEMINATION This study will be conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects and all other applicable laws and guidelines in Japan. This study protocol was approved by the IRB at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER UMIN000029375.
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Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: a double-blind, randomised, placebo-controlled trial.
Takada, M, Nishida, K, Gondo, Y, Kikuchi-Hayakawa, H, Ishikawa, H, Suda, K, Kawai, M, Hoshi, R, Kuwano, Y, Miyazaki, K, et al
Beneficial microbes. 2017;(2):153-162
Abstract
The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.
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Coffee prevents proximal colorectal adenomas in Japanese men: a prospective cohort study.
Nakamura, T, Ishikawa, H, Mutoh, M, Wakabayashi, K, Kawano, A, Sakai, T, Matsuura, N
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2016;(5):388-94
Abstract
This prospective cohort study aimed to show that coffee prevents the recurrence of colorectal tumors (adenomas, precursors of colorectal cancer, and early-stage colorectal cancers) as well as colorectal cancer. The present study included 307 patients who participated in a clinical study that required endoscopy to remove a colorectal tumor. The amount of coffee consumed by the patients at study inclusion and the frequency of colorectal tumors, as detected by colonoscopy over the subsequent 4 years, were assessed. Coffee consumption was determined using a diet survey that included 3-consecutive-day food records. The risk of colorectal tumor recurrence was significantly lower (odds ratio=0.21; 95% confidence interval, 0.06-0.74) in patients who consumed more than three cups of coffee per day compared with those who consumed no coffee. No correlation was observed between the examined factors, including green tea and black tea intake and the amount of caffeine consumed. In subanalysis divided by the tumor location within the colorectum, the odds ratio of colorectal tumor recurrence in the proximal colon showed a tendency toward reduction as coffee consumption increased; however, increased coffee consumption significantly increased colorectal tumor recurrence in the distal colon. We showed that high coffee consumption reduced the overall occurrence of colorectal tumors, affected by the reduction in the proximal colon.
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A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study.
Kashiwagi, A, Takahashi, H, Ishikawa, H, Yoshida, S, Kazuta, K, Utsuno, A, Ueyama, E
Diabetes, obesity & metabolism. 2015;(2):152-60
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Abstract
AIMS: To assess the effects of renal impairment (RI) on the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus (T2DM). METHODS A cohort of Japanese patients with T2DM and mild to moderate RI and poor glycaemic control, despite diet/exercise therapy alone or diet/exercise therapy in combination with an oral hypoglycaemic agent (an α-glucosidase inhibitor, a sulfonylurea, or pioglitazone), were randomized in a double-blind manner to 50 mg ipragliflozin or placebo once daily for 24 weeks. The patients continued open-label ipragliflozin for a 28-week extension period (total treatment duration: 52 weeks). RESULTS Ipragliflozin significantly decreased glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels and body weight from baseline to week 24 (last observation carried forward) compared with placebo in all patients with RI. The decreases in HbA1c and FPG levels were statistically significant in patients with mild RI, but not in patients with moderate RI. Ipragliflozin significantly reduced body weight in both RI groups. The improvements in glycaemic control were maintained in the 28-week extension period. Ipragliflozin was associated with no clinically significant safety concerns, and its safety profiles were not influenced by the severity of RI. CONCLUSIONS Ipragliflozin significantly improved glycaemic control and body weight in patients with T2DM with mild RI, but did not improve glycaemic control in patients with moderate RI. Ipragliflozin is a valid treatment option for patients with mild RI but not those with moderate RI.
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The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial.
Ishikawa, H, Mutoh, M, Suzuki, S, Tokudome, S, Saida, Y, Abe, T, Okamura, S, Tajika, M, Joh, T, Tanaka, S, et al
Gut. 2014;(11):1755-9
Abstract
OBJECTIVE To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. DESIGN A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. PARTICIPANTS 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. RESULTS The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were non-smokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in non-smokers was 0.37 (CI 0.21 to 0.68, p<0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. CONCLUSIONS Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. THE CLINICAL TRIAL REGISTRY WEBSITE AND THE CLINICAL TRIAL NUMBER http://www.umin.ac.jp (number UMIN000000697).