今日の臨床サポート

サプリメント(ミネラルとビタミン以外)

著者: 青島周一 医療法人社団 徳仁会 中野病院

監修: 名郷直樹 武蔵国分寺公園クリニック

著者校正/監修レビュー済:2018/06/06
患者向け説明資料

概要・推奨   

  1. サプリメントとは「dietary supplement」の訳語であり、わが国では健康食品と同じ意味で用いられることが多い。
  1. 法律上の定義は無く、ビタミン、ミネラル、ハーブ類や生薬など健康の保持および増進に資する食品として販売・利用されるもの全般を指す。そのうち、国の制度としては、国が定めた安全性や有効性に関する基準等を満たした「保健機能食品制度」がある
  1. サプリメントの利用状況について、内閣府・消費者委員会が2012年に報告した『消費者の「健康食品」の利用に関する実態調査』によれば、消費者の約6割が健康食品(サプリメント)を利用しており、50代以上の約3割が健康食品をほぼ毎日利用している。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
青島周一 : 未申告[2021年]
監修:名郷直樹 : 特に申告事項無し[2021年]

まとめ

まとめ  
  1. サプリメントとは「dietary supplement」の訳語であり、わが国では健康食品と同じ意味で用いられることが多い。
  1. 法律上の定義は無く、ビタミン、ミネラル、ハーブ類や生薬など健康の保持および増進に資する食品として販売・利用されるもの全般を指す。そのうち、国の制度としては、国が定めた安全性や有効性に関する基準等を満たした「保健機能食品制度」がある
  1. サプリメントの利用状況について、内閣府・消費者委員会が2012年に報告した『消費者の「健康食品」の利用に関する実態調査』によれば、消費者の約6割が健康食品(サプリメント)を利用しており、50代以上の約3割が健康食品をほぼ毎日利用している。
  1. 『消費者の「健康食品」の利用に関する実態調査』によれば、健康食品利用者の約4割が2種類以上の健康食品(サプリメント)を利用しており、年齢が上がるほど、複数の健康食品(サプリメント)を利用する割合が増える傾向がある。
  1. 現状で積極的に奨められるサプリメントは抗菌薬関連下痢症および下痢症の対症療法としてのプロバイオティクスであるが、保険診療でも対応可能である(ビオフェルミン錠、もしくはビオフェルミンR錠)

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Thammanard Charemboon, Kankamol Jaisin
雑誌名: J Med Assoc Thai. 2015 May;98(5):508-13.
Abstract/Text OBJECTIVE: To determine the efficacy of Ginkgo biloba for the prevention of dementia in individuals without dementia.
MATERIAL AND METHOD: English databases including Medline, Embase, Cochrane Library and PsycINFO, were searched, and randomized double-blind controlled studies comparing Ginkgo biloba with placebo in prevention of dementia were considered. Two trials met inclusion criteria. Methodological quality was assessed using the Jadad criteria.
RESULTS: Meta-analysis of the two trials involving 5,889 participants indicated no significant difference in dementia rate between Ginkgo biloba and the placebo (347/2,951 vs. 330/2,938, odds ratio = 1.05, 95% CI 0.89-1.23) and there was no considerable heterogeneity between the trials. The two studies revealed no statistically significant differences in the rate of serious adverse effect between Ginko biloba and the placebo.
CONCLUSION: There is no convincing evidence from this review that demonstrated Ginkgo biloba in late-life can prevent the development of dementia. Using it for this indication is not suggested at present.

PMID 26058281  J Med Assoc Thai. 2015 May;98(5):508-13.
著者: Meng-Shan Tan, Jin-Tai Yu, Chen-Chen Tan, Hui-Fu Wang, Xiang-Fei Meng, Chong Wang, Teng Jiang, Xi-Chen Zhu, Lan Tan
雑誌名: J Alzheimers Dis. 2015;43(2):589-603. doi: 10.3233/JAD-140837.
Abstract/Text BACKGROUND: Research into Ginkgo biloba has been ongoing for many years, while the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive impairment and dementia has been discussed controversially.
OBJECTIVE: To discuss new evidence on the clinical and adverse effects of standardized Ginkgo biloba extract EGb761 for cognitive impairment and dementia.
METHODS: MEDLINE, EMBASE, Cochrane, and other relevant databases were searched in March 2014 for eligible randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with cognitive impairment and dementia.
RESULTS: Nine trials met our inclusion criteria. Trials were of 22-26 weeks duration and included 2,561 patients in total. In the meta-analysis, the weighted mean differences in change scores for cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18; -2.54); the standardized mean differences in change scores for activities in daily living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI -0.44; -0.28); Peto OR showed a statistically significant difference from placebo for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54; 2.29). All these benefits are mainly associated with EGb761 at a dose of 240 mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240 mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric symptoms with statistical superiority than for the whole group. For the Alzheimer's disease subgroup, the main outcomes were almost the same as the whole group of patients with no statistical superiority. Finally, safety data revealed no important safety concerns with EGb761.
CONCLUSIONS: EGb761 at 240 mg/day is able to stabilize or slow decline in cognition, function, behavior, and global change at 22-26 weeks in cognitive impairment and dementia, especially for patients with neuropsychiatric symptoms.

PMID 25114079  J Alzheimers Dis. 2015;43(2):589-603. doi: 10.3233/JAD-・・・
著者: Guoyan Yang, Yuyi Wang, Jin Sun, Kang Zhang, Jianping Liu
雑誌名: Curr Top Med Chem. 2016;16(5):520-8.
Abstract/Text BACKGROUND: Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer's disease. The objective of this review is to explore the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease.
METHODS: Electronic search was conducted from PubMed, Cochrane Library, and four major Chinese databases from their inception up to 1(st) December, 2014 for randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer's disease. Meta-analyses were performed by RevMan 5.2 software.
RESULTS: 21 trials with 2608 patients met the inclusion criteria. The general methodological quality of included trials was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer's disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer's disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild.
CONCLUSION: Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease.

PMID 26268332  Curr Top Med Chem. 2016;16(5):520-8.
著者: Young Ho Lee, Jin-Hyun Woo, Seong Jae Choi, Jong Dae Ji, Gwan Gyu Song
雑誌名: Rheumatol Int. 2010 Jan;30(3):357-63. doi: 10.1007/s00296-009-0969-5. Epub 2009 Jun 21.
Abstract/Text The aim of this study was to assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee osteoarthritis (OA). The authors surveyed randomized controlled studies that examined the effects of long-term daily glucosamine sulfate and chondroitin sulfate on joint space narrowing (JSN) in knee OA patients using the Medline and the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis was performed using a fixed effect model because no between-study heterogeneity was evident. Six studies involving 1,502 cases were included in this meta-analysis, which consisted of two studies on glucosamine sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did not show a significant effect versus controls on minimum JSN over the first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429). However, after 3 years of treatment, glucosamine sulfate revealed a small to moderate protective effect on minimum JSN (SMD 0.432, 95% CI 0.235-0.628, P < 0.001). The same was observed for chondroitin sulfate, which had a small but significant protective effect on minimum JSN after 2 years (SMD 0.261, 95% CI 0.131-0.392, P < 0.001). This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological progression of OA of the knee after daily administration for over 2 or 3 years.

PMID 19544061  Rheumatol Int. 2010 Jan;30(3):357-63. doi: 10.1007/s002・・・
著者: Jos Runhaar, Rianne M Rozendaal, Marienke van Middelkoop, Hans J W Bijlsma, Michael Doherty, Krysia S Dziedzic, L Stefan Lohmander, Timothy McAlindon, Weiya Zhang, Sita Bierma Zeinstra
雑誌名: Ann Rheum Dis. 2017 Nov;76(11):1862-1869. doi: 10.1136/annrheumdis-2017-211149. Epub 2017 Jul 28.
Abstract/Text OBJECTIVE: To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data.
METHODS: After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted. As a minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed to be assessed.
RESULTS: Of 21 eligible studies, six (n=1663) shared their trial data with the OA Trial Bank. Five trials (all independent of industry, n=1625) compared glucosamine with placebo, representing 55% of the total number of participants in all published placebo-controlled RCTs. Glucosamine was no better than placebo for pain or function at short (3 months) and long-term (24 months) follow-up. Glucosamine was also no better than placebo among the predefined subgroups. Stratification for knee OA and type of glucosamine did not alter these results.
CONCLUSIONS: Although proposed and debated for several years, open trial data are not widely made available for studies of glucosamine for OA, especially those sponsored by industry. Currently, there is no good evidence to support the use of glucosamine for hip or knee OA and an absence of evidence to support specific consideration of glucosamine for any clinically relevant OA subgroup according to baseline pain severity, BMI, sex, structural abnormalities or presence of inflammation.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PMID 28754801  Ann Rheum Dis. 2017 Nov;76(11):1862-1869. doi: 10.1136/・・・
著者: Alexander G Schauss, Amy Clewell, Lajos Balogh, Ilona Pasics Szakonyi, Istvan Financsek, János Horváth, Julianna Thuroczy, Erzsébet Béres, Adél Vértesi, Gabor Hirka
雑誌名: Toxicology. 2010 Nov 28;278(1):46-54. doi: 10.1016/j.tox.2010.04.017. Epub 2010 May 7.
Abstract/Text The safety of an açai (Euterpe oleracea Mart.) pulp enriched fruit and berry juice, MonaVie Active®, fortified with the functional ingredient, glucosamine, was studied. The beverage was found not to be mutagenic, clastogenic, cytotoxic, or genotoxic, as determined by the bacterial reverse mutation assay, chromosomal aberration assay, mouse micronucleus assay, and mammalian cell gene mutation (L5178Y) assay. The single dose LD50 based on a 14-day acute oral toxicity study is greater than 20,000 mg/kg bw, the highest dose tested. In a repeat dose 90-day oral subchronic toxicity study by gavage, 220 animals were randomly assigned to a control group, an untreated group, or one of three experimental groups (10, 20 and 40 g/kg bw). No treatment-related significant changes in body weight, food and water consumption, ophthalmology, organ weights, urinanalysis, hematological and clinical chemistry, or gross pathology, were observed in surviving animals compared to the control groups. Three animals died midway through the observation period (male, 20 g/kg bw/day; male 40 g/kg bw/day; and, female, 10 g/kg bw/day). These animals died without preceding clinical symptoms, histopathological lesions, or evidence of injury to tissue or organs except for signs of suffocation/aspiration congestion, which was concluded to be due to problems with the gavage administration of the fluid test article, and not due to the test article itself. The NOEAL was determined to be 40 g/kg bw/day for male and female rats, which was the highest dose tested. Phylloquinone (vitamin K1) content averaged 21.7 μg/100 g, comparable to amounts found in iceberg lettuce. In conclusion, the results provide additional experimental evidence that MonaVie Active® juice is non-toxic.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
PMID 20452390  Toxicology. 2010 Nov 28;278(1):46-54. doi: 10.1016/j.to・・・
著者: Chih-Hung Wang, Cheng-Chung Fang, Nai-Chuan Chen, Sot Shih-Hung Liu, Ping-Hsun Yu, Tao-Yu Wu, Wei-Ting Chen, Chien-Chang Lee, Shyr-Chyr Chen
雑誌名: Arch Intern Med. 2012 Jul 9;172(13):988-96. doi: 10.1001/archinternmed.2012.3004.
Abstract/Text BACKGROUND: Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry-containing products for the prevention of UTI and to examine the factors influencing their effectiveness.
METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched from inception to November 2011 for randomized controlled trials that compared prevention of UTIs in users of cranberry-containing products vs placebo or nonplacebo controls. There were no restrictions for language, population, or publication year.
RESULTS: Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I(2) = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I(2) = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I(2) = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I(2) = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I(2) = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I(2) = 18%).
CONCLUSIONS: Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials.

PMID 22777630  Arch Intern Med. 2012 Jul 9;172(13):988-96. doi: 10.100・・・
著者: Ruth G Jepson, Gabrielle Williams, Jonathan C Craig
雑誌名: Cochrane Database Syst Rev. 2012 Oct 17;10:CD001321. doi: 10.1002/14651858.CD001321.pub5. Epub 2012 Oct 17.
Abstract/Text BACKGROUND: Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.
OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies.Date of search: July 2012
SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.
MAIN RESULTS: This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.
AUTHORS' CONCLUSIONS: Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.

PMID 23076891  Cochrane Database Syst Rev. 2012 Oct 17;10:CD001321. do・・・
著者: Monique A A Caljouw, Wilbert B van den Hout, Hein Putter, Wilco P Achterberg, Herman J M Cools, Jacobijn Gussekloo
雑誌名: J Am Geriatr Soc. 2014 Jan;62(1):103-10.
Abstract/Text OBJECTIVES: To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents.
DESIGN: Double-blind randomized placebo-controlled multicenter trial.
SETTING: Long-term care facilities (LTCFs).
PARTICIPANTS: LTCF residents (N = 928; 703 women, median age 84).
MEASUREMENTS: Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥ 1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition.
RESULTS: In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57-0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68-1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412).
CONCLUSION: In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk.

PMID 25180378  J Am Geriatr Soc. 2014 Jan;62(1):103-10.
著者: Kevin C Maki, Kerrie L Kaspar, Christina Khoo, Linda H Derrig, Arianne L Schild, Kalpana Gupta
雑誌名: Am J Clin Nutr. 2016 Jun;103(6):1434-42. doi: 10.3945/ajcn.116.130542.
Abstract/Text BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption.
OBJECTIVE: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs.
DESIGN: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time.
RESULTS: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914).
CONCLUSION: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.

© 2016 American Society for Nutrition.
PMID 27251185  Am J Clin Nutr. 2016 Jun;103(6):1434-42. doi: 10.3945/a・・・
著者: Wilbert B van den Hout, Monique A A Caljouw, Hein Putter, Herman J M Cools, Jacobijn Gussekloo
雑誌名: J Am Geriatr Soc. 2014 Jan;62(1):111-6.
Abstract/Text OBJECTIVES: To investigate whether the preventive use of cranberry capsules in long-term care facility (LTCF) residents is cost-effective depending on urinary tract infection (UTI) risk.
DESIGN: Economic evaluation with a randomized controlled trial.
SETTING: Long-term care facilities.
PARTICIPANTS: LTCF residents (N = 928, 703 female, median age 84), stratified according to UTI risk.
MEASUREMENTS: UTI incidence (clinically or strictly defined), survival, quality of life, quality-adjusted life years (QALYs), and costs.
RESULTS: In the weeks after a clinical UTI, participants showed a significant but moderate deterioration in quality of life, survival, care dependency, and costs. In high-UTI-risk participants, cranberry costs were estimated at €439 per year (1.00 euro = 1.37 U.S. dollar), which is €3,800 per prevented clinically defined UTI (95% confidence interval = €1,300-infinity). Using the strict UTI definition, the use of cranberry increased costs without preventing UTIs. Taking cranberry capsules had a 22% probability of being cost-effective compared with placebo (at a willingness to pay of €40,000 per QALY). In low-UTI-risk participants, use of cranberry capsules was only 3% likely to be cost-effective.
CONCLUSION: In high-UTI-risk residents, taking cranberry capsules may be effective in preventing UTIs but is not likely to be cost-effective in the investigated dosage, frequency, and setting. In low-UTI-risk LTCF residents, taking cranberry capsules twice daily is neither effective nor cost-effective.

PMID 25180379  J Am Geriatr Soc. 2014 Jan;62(1):111-6.
著者: Judith E Bosmans, Mariëlle A J Beerepoot, Jan M Prins, Gerben ter Riet, Suzanne E Geerlings
雑誌名: PLoS One. 2014;9(4):e91939. doi: 10.1371/journal.pone.0091939. Epub 2014 Apr 4.
Abstract/Text BACKGROUND: Urinary tract infections (UTIs) are common and result in an enormous economic burden. The increasing prevalence of antibiotic-resistant microorganisms has stimulated interest in non-antibiotic agents to prevent UTIs.
OBJECTIVE: To evaluate the cost-effectiveness of cranberry prophylaxis compared to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) over a 12 month period in premenopausal women with recurrent UTIs.
MATERIALS AND METHODS: An economic evaluation was performed alongside a randomized trial. Primary outcome was the number of UTIs during 12 months. Secondary outcomes included satisfaction and quality of life. Healthcare utilization was measured using questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to evaluate the cost-effectiveness of the treatments.
RESULTS: Cranberry prophylaxis was less effective than TMP-SMX prophylaxis, but the differences in clinical outcomes were not statistically significant. Costs after 12 months in the cranberry group were statistically significantly higher than in the TMP-SMX group (mean difference €249, 95% confidence interval 70 to 516). Cost-effectiveness planes and cost-effectiveness acceptability curves showed that cranberry prophylaxis to prevent UTIs is less effective and more expensive than (dominated by) TMP-SMX prophylaxis.
CONCLUSION: In premenopausal women with recurrent UTIs, cranberry prophylaxis is not cost-effective compared to TMP-SMX prophylaxis. However, it was not possible to take into account costs attributed to increased antibiotic resistance within the framework of this randomized trial; modeling studies are recommended to investigate these costs. Moreover, although we based the dosage of cranberry extract on available evidence, this may not be the optimal dosage. Results may change when this optimal dosage is identified.
TRIAL REGISTRATION: ISRCTN.org ISRCTN50717094.

PMID 24705418  PLoS One. 2014;9(4):e91939. doi: 10.1371/journal.pone.0・・・
著者: Samantha J Eells, Kiran Bharadwa, James A McKinnell, Loren G Miller
雑誌名: Clin Infect Dis. 2014 Jan;58(2):147-60. doi: 10.1093/cid/cit646. Epub 2013 Sep 24.
Abstract/Text BACKGROUND: Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking.
METHODS: We performed a systematic literature review of management of women experiencing ≥3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with ≥2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life.
RESULTS: Five strategies had ≥2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained.
CONCLUSIONS: Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician-patient partnership in determining a preferred method of prevention for this common clinical problem.

PMID 24065333  Clin Infect Dis. 2014 Jan;58(2):147-60. doi: 10.1093/ci・・・
著者: Afa K Palu, Brett J West, Jarakae Jensen
雑誌名: N Am J Med Sci. 2011 Dec;3(12):552-6. doi: 10.4297/najms.2011.3552.
Abstract/Text BACKGROUND: The prevalence of obesity and overweight in the Unites States has reached unprecedented levels, and so has the need for effective exercise and nutritional programs for prevention of unhealthy weight gain or safe weight loss.
AIMS: The present study was conducted in overweight men and women to assess the impact of noni-based nutritional supplementation and exercise interventions on body composition.
MATERIALS AND METHODS: Twenty two participants (16 women and 6 men), ages 18-65, were enrolled in a 12-week, open-label trial of a weight-loss program involving noni-based dietary supplements, gender-specific daily calorie restriction, and exercise interventions. Weight, percent body fat, and body mass index were measured before and after the trial.
RESULTS: All participants experienced weight loss. The average decrease in fat mass was highly significant (P < 0.0001), as were decreases in percent body fat and body mass index. Individual weight and fat mass losses were 17.55 ± 9.73 and 21.78 ± 8.34 lbs., respectively, and individual percent body fat and body mass index decreases were 8.91 ± 3.58 % and 2.6 ± 1.32, respectively.
CONCLUSION: The nutritional and exercise interventions significantly influenced body composition among participants.

PMID 22363077  N Am J Med Sci. 2011 Dec;3(12):552-6. doi: 10.4297/najm・・・
著者: B Yuce, V Gulberg, J Diebold, A L Gerbes
雑誌名: Digestion. 2006;73(2-3):167-70. doi: 10.1159/000094524. Epub 2006 Jul 11.
Abstract/Text A 24-year-old female patient presented to her community hospital with mild elevations of serum transaminase and bilirubin levels. Because of multiple sclerosis, she was treated with interferon beta-1a for 6 weeks. After exclusion of viral hepatitis due to hepatitis A-E, interferon beta-1a was withdrawn under the suspicion of drug-induced hepatitis. One week later, she was admitted again to her community hospital with severe icterus. The transaminase and bilirubin levels were highly elevated, and a beginning impairment of the liver synthesis was expressed by a reduced prothrombin time. The confinement to our department occurred with a fulminant hepatitis and the suspicion of beginning acute liver failure. There was no evidence for hepatitis due to potentially hepatotoxic viruses, alcoholic hepatitis, Budd-Chiari syndrome, hemochromatosis, and Wilson's disease. In her serum there were high titers of liver-kidney microsomal type 1 autoantibody; the serum gamma globulin levels were in the normal range. Fine-needle aspiration biopsy of the liver ruled out an autoimmune hepatitis but showed signs of drug-induced toxicity. During the interview, she admitted that for 'general immune system stimulation' she had been drinking Noni juice, a Polynesian herbal remedy made from a tropical fruit (Morinda citrifolia), during the past 4 weeks. After cessation of the Noni juice ingestion, her transaminase levels normalized quickly and were in the normal range within 1 month.

Copyright 2006 S. Karger AG, Basel.
PMID 16837801  Digestion. 2006;73(2-3):167-70. doi: 10.1159/000094524.・・・
著者: Vanessa Stadlbauer, Sabine Weiss, Franz Payer, Rudolf E Stauber
雑誌名: Am J Gastroenterol. 2008 Sep;103(9):2406-7. doi: 10.1111/j.1572-0241.2008.02010_8.x.
Abstract/Text
PMID 18844633  Am J Gastroenterol. 2008 Sep;103(9):2406-7. doi: 10.111・・・
著者: Vanessa Stadlbauer, Peter Fickert, Carolin Lackner, Jutta Schmerlaib, Peter Krisper, Michael Trauner, Rudolf E Stauber
雑誌名: World J Gastroenterol. 2005 Aug 14;11(30):4758-60.
Abstract/Text NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses. No overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. Causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice. A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acute hepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.

PMID 16094725  World J Gastroenterol. 2005 Aug 14;11(30):4758-60.
著者: Gunda Millonig, Sylvia Stadlmann, Wolfgang Vogel
雑誌名: Eur J Gastroenterol Hepatol. 2005 Apr;17(4):445-7.
Abstract/Text A 45-year-old patient was sent to our department because of highly elevated transaminases and elevated lactate dehydrogenase. His medical history was unremarkable and he took no medication on regular basis. Physical examination did not detect any abnormalities. There was no evidence for viral hepatitis, Epstein-Barr virus or cytomegalovirus, autoimmune hepatitis, Budd-Chiari syndrome, haemochromatosis or Wilson's disease. During the interview he admitted that for 'prophylactic reasons' he had been drinking the juice of Noni (Morinda citrifolia), a Polynesian herbal remedy made from a tropical fruit, during the preceding 3 weeks. This gave rise to the suspicion of herbal toxicity, which was confirmed by a liver biopsy. After ceasing the ingestion of Noni, transaminase levels normalized quickly and were within normal ranges 1 month after the first presentation. To our knowledge, this is the first report of hepatotoxicity caused by this herbal remedy, which has been highly praised in the tabloid press.

PMID 15756098  Eur J Gastroenterol Hepatol. 2005 Apr;17(4):445-7.
著者: Elizabeth L Yu, Mamata Sivagnanam, Linda Ellis, Jeannie S Huang
雑誌名: J Pediatr Gastroenterol Nutr. 2011 Feb;52(2):222-4. doi: 10.1097/MPG.0b013e3181eb69f0.
Abstract/Text We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important.

PMID 21119544  J Pediatr Gastroenterol Nutr. 2011 Feb;52(2):222-4. doi・・・
著者: Anna Mrzljak, Iva Kosuta, Anita Skrtic, Tajana Filipec Kanizaj, Radovan Vrhovac
雑誌名: Case Rep Gastroenterol. 2013 Jan;7(1):19-24. doi: 10.1159/000343651. Epub 2013 Jan 10.
Abstract/Text Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both agents were stopped and corticosteroids were initiated. Five months later the patient had fully recovered. Although in the literature the hepatotoxicity of noni juice remains speculative, sporadic but emerging cases of noni juice-associated liver injury address the need to clarify and investigate potential harmful effects associated with this supplement.

PMID 23467452  Case Rep Gastroenterol. 2013 Jan;7(1):19-24. doi: 10.11・・・
著者: Kai Liu, Rui Zhou, Bin Wang, Man-Tian Mi
雑誌名: Am J Clin Nutr. 2014 Jun;99(6):1510-9. doi: 10.3945/ajcn.113.082024. Epub 2014 Apr 2.
Abstract/Text BACKGROUND: The results of human clinical trials investigating the effects of resveratrol on glucose control and insulin sensitivity are inconsistent.
OBJECTIVE: We aimed to quantitatively evaluate the effects of resveratrol on glucose control and insulin sensitivity.
DESIGN: We performed a strategic literature search of PubMed, Embase, MEDLINE, and the Cochrane Library (updated to March 2014) for randomized controlled trials that estimated the effects of resveratrol on glucose control and insulin sensitivity. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in glycemic measures by using fixed-effects or random-effects models. We performed prespecified subgroup and sensitivity analyses to evaluate potential heterogeneity. Meta-regression analyses were conducted to investigate dose effects of resveratrol on fasting glucose and insulin concentrations in nondiabetic subjects.
RESULTS: Eleven studies comprising a total of 388 subjects were included in this meta-analysis. Resveratrol consumption significantly reduced fasting glucose, insulin, glycated hemoglobin, and insulin resistance (measured by using the homeostatic model assessment) levels in participants with diabetes. No significant effect of resveratrol on glycemic measures of nondiabetic participants was found in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects of resveratrol on fasting glucose and insulin concentrations in nondiabetic participants were not affected by body mass index, study design, resveratrol dose, study duration, or Jadad score.
CONCLUSIONS: Resveratrol significantly improves glucose control and insulin sensitivity in persons with diabetes but does not affect glycemic measures in nondiabetic persons. Additional high-quality studies are needed to further evaluate the potential benefits of resveratrol in humans.

© 2014 American Society for Nutrition.
PMID 24695890  Am J Clin Nutr. 2014 Jun;99(6):1510-9. doi: 10.3945/ajc・・・
著者: Heather A Hausenblas, Jennifer A Schoulda, James M Smoliga
雑誌名: Mol Nutr Food Res. 2015 Jan;59(1):147-59. doi: 10.1002/mnfr.201400173. Epub 2014 Oct 9.
Abstract/Text The red wine polyphenol, resveratrol, is highly effective in treating type 2 diabetes mellitus (T2DM) in animal models, but there is no consensus regarding its efficacy in humans. We conducted a systematic review, which included searches in nine scholarly databases and six clinical trial registries, and identified randomized controlled clinical trials whereby resveratrol was used as an adjunct to pharmaceutical interventions in T2DM. Meta-analysis on clinical parameters was performed for available data. Of 764 articles originally identified, data from six unique datasets, examining a total of 196 T2DM patients (104 resveratrol, 92 control/placebo) ultimately met inclusion criteria. Statistically significant (p < 0.05) positive effects, indicating that resveratrol supplementation was more effective than placebo/control, were identified for systolic blood pressure, hemoglobin A1c, and creatinine, but not for fasting glucose, homeostatic model assessment of insulin resistance, diastolic blood pressure, insulin, triglycerides, LDL, or HDL cholesterol. No major adverse events were reported and side effects of resveratrol were not different than placebo/control. Though limitations in sample size and treatment duration preclude definitive changes in clinical practice, significant improvements in multiple cardiometabolic biomarkers and an excellent safety profile support resveratrol as a leading candidate as an adjunct to pharmacological management of T2DM.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID 25138371  Mol Nutr Food Res. 2015 Jan;59(1):147-59. doi: 10.1002/・・・
著者: Richard D Semba, Luigi Ferrucci, Benedetta Bartali, Mireia Urpí-Sarda, Raul Zamora-Ros, Kai Sun, Antonio Cherubini, Stefania Bandinelli, Cristina Andres-Lacueva
雑誌名: JAMA Intern Med. 2014 Jul;174(7):1077-84. doi: 10.1001/jamainternmed.2014.1582.
Abstract/Text IMPORTANCE: Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms.
OBJECTIVE: To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans.
DESIGN: Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study ("Aging in the Chianti Region"), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older.
EXPOSURES: Twenty-four-hour urinary resveratrol metabolites.
MAIN OUTCOMES AND MEASURES: Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease.
RESULTS: Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer.
CONCLUSIONS AND RELEVANCE: In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.

PMID 24819981  JAMA Intern Med. 2014 Jul;174(7):1077-84. doi: 10.1001/・・・
著者: Giacomo Novara, Gianluca Giannarini, Antonio Alcaraz, José-M Cózar-Olmo, Aurelien Descazeaud, Francesco Montorsi, Vincenzo Ficarra
雑誌名: Eur Urol Focus. 2016 Dec;2(5):553-561. doi: 10.1016/j.euf.2016.04.002. Epub 2016 Apr 23.
Abstract/Text CONTEXT: A recent Cochrane Collaboration meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of different extracts of Serenoa repens in relieving lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) concluded that these extracts were no more effective than placebo. However, among all Serenoa repens extracts, Permixon (Pierre Fabre Medicament, Paris, France) has the highest activity and the most accurate standards of drug preparation and extraction.
OBJECTIVE: To evaluate the efficacy and safety of Permixon in the treatment of LUTS/BPH.
EVIDENCE ACQUISITION: A systematic review and meta-analysis of the literature was performed in January 2016 using the Medline, Scopus, and Web of Science databases, searching for the term Serenoa repens in all fields of the records. Only RCTs reporting on efficacy and safety of Permixon in the treatment of LUTS/BPH were selected.
EVIDENCE SYNTHESIS: The systematic search identified 12 RCTs: 7 compared Permixon with placebo; 2 compared Permixon with tamsulosin; 2 compared Permixon plus tamsulosin with, respectively, placebo plus tamsulosin and tamsulosin alone; and 1 compared Permixon with finasteride. Permixon was significantly more effective than placebo in reducing the number of nocturnal voids (weighted mean difference [WMD] -0.31; p=0.03) and increasing maximum flow rate (Qmax; WMD 3.37; p<0.0001). The rates of overall adverse events (odds ratio [OR] 1.12; p=0.92) and withdrawal (OR 1.52; p=0.60) were similar for Permixon and placebo. Permixon was as effective as tamsulosin monotherapy and short-term therapy with finasteride in improving International Prostate Symptom Score (WMD 1.15; 95% confidence interval [CI], -1.11 to 3.40; p=0.32) and Qmax (WMD -0.16; 95% CI, -0.60 to 0.28; p=0.48). The combination of Permixon and tamsulosin was more effective than Permixon alone for relieving LUTS (WMD 0.31; 95% CI, 0.13-0.48; p<0.01) but not for improving Qmax (WMD 0.10; 95% CI -0.02 to 0.21; p=0.10). Permixon had a favorable safety profile, with a very limited impact with regard to ejaculatory dysfunction compared with tamsulosin (0.5% vs 4%; p=0.007) and with regard to decreased libido and impotence compared with short-term finasteride (2.2% and 1.5% vs 3% and 2.8%, respectively).
CONCLUSIONS: The conclusions of the recent Cochrane meta-analysis on Serenoa repens in the treatment of LUTS/BPH apparently do not apply to Permixon. Our meta-analysis showed that Permixon decreased nocturnal voids and Qmax compared with placebo and had efficacy in relieving LUTS similar to tamsulosin and short-term finasteride. Moreover, Permixon had a favorable safety profile with a very limited impact on sexual function, which is significantly affected by all other drugs used to treat LUTS/BPH.
PATIENT SUMMARY: A systematic review of the literature showed that Permixon was effective for relieving urinary symptoms due to prostate enlargement and improving urinary flow compared with placebo. Permixon had efficacy similar to tamsulosin and short-term finasteride in relieving urinary symptoms. Permixon was well tolerated and had a very limited impact on sexual function.

Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 28723522  Eur Urol Focus. 2016 Dec;2(5):553-561. doi: 10.1016/j.e・・・
著者: Young Woo Ryu, Song Won Lim, Jung Hoon Kim, Seung Hyun Ahn, Jae Duck Choi
雑誌名: Urol Int. 2015;94(2):187-93. doi: 10.1159/000366521. Epub 2015 Jan 23.
Abstract/Text INTRODUCTION: In Korea, increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH. Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies. The present study was designed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH.
MATERIALS AND METHODS: One hundred forty men with symptomatic BPH (IPSS≥10) were recruited in our hospital for a 12-month, open-label, randomized trial. Patients were randomly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day (n=60) or tamsulosin 0.2 mg/day only (n=60). Prostate volume and PSA were measured at baseline and at end-point, whereas total IPSS, and its storage and voiding subscores, LUTS-related QoL, Qmax, and PVR were evaluated at baseline and later every 6 months.
RESULTS: Total 103 patients were finally available: 50 in the TAM+SR group and 53 in the TAM group. At 12 months, total IPSS decreased by 5.8 with TAM+SR and 5.5 with TAM (p=0.693); the storage symptoms improved significantly more with TAM+SR (-1.7 vs. -0.8 with TAM, p=0.024). This benefit with regard to storage symptom in the TAM+SR group lasts at 12 months (-1.9 vs. -0.9, p=0.024). The changes of voiding subscore, LUTS-related QoL, Qmax, PVR, PSA, and prostate volume showed no significant differences between the TAM+SR and TAM groups. During the treatment period, 8 patients (16.9%) with TAM and 10 (20%) with TAM+SR had drug-related adverse reactions, which included ejaculatory disorders, postural hypotension, dizziness, headache, gastro-intestinal disorders, rhinitis, fatigue and asthenia.
CONCLUSIONS: The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment.

© 2015 S. Karger AG, Basel.
PMID 25614155  Urol Int. 2015;94(2):187-93. doi: 10.1159/000366521. Ep・・・
著者: Ismaila Jibrin, Ayodele Erinle, Abdulfattah Saidi, Zakari Y Aliyu
雑誌名: South Med J. 2006 Jun;99(6):611-2. doi: 10.1097/01.smj.0000215642.76198.44.
Abstract/Text Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

PMID 16800417  South Med J. 2006 Jun;99(6):611-2. doi: 10.1097/01.smj.・・・
著者: Kurt A Wargo, Elena Allman, Farrah Ibrahim
雑誌名: South Med J. 2010 Jul;103(7):683-5. doi: 10.1097/SMJ.0b013e3181e1e3ee.
Abstract/Text A 65-year-old male with a history of diabetes, hypertension, hyperlipidemia, gout, Barrett esophagitis, and chronic gastritis developed acute pancreatitis after taking one week of the herbal medicine, saw palmetto, for symptoms related to benign prostatic hyperplasia (BPH). Ultrasound and computed tomography ruled out cholelithiasis and obstruction, triglycerides were normal, and he had no recent infection or trauma. He had a history of occasional alcohol consumption, though there was no recent increased intake. The most likely cause of pancreatitis in this case was saw palmetto. Saw palmetto (Serenoa repens) is an herbal medication used primarily in the treatment of symptoms related to BPH. It has a high content of fatty acids and phytosterols which are thought to exert their effects by inhibiting the enzyme 5-alpha-reductase, thereby preventing the conversion of testosterone into dihydrotestosterone (DHT). It has been postulated that saw palmetto directly stimulates estrogenic receptors and inhibits progesterone receptors in the prostate tissue. A previous report implicated the estrogen/antiandrogen properties of saw palmetto as inducing hepatotoxicity in a patient. Additionally, it has also been postulated that stimulation of the estrogenic receptors may lead to increased triglyceride levels or induction of a hypercoagulable state that leads to pancreatic necrosis. Finally, inhibition of cyclooxygenase, a property of saw palmetto, may be linked to acute pancreatitis. Acute pancreatitis, a serious and sometimes fatal disorder may occur secondary to medications. Although the mechanism is not fully known, this is the second case of acute pancreatitis that has been documented secondary to the herbal medication saw palmetto. It is important for clinicians to obtain detailed medication histories, including over-the-counter and herbal medications, in order to prevent further complications from occurring.

PMID 20531057  South Med J. 2010 Jul;103(7):683-5. doi: 10.1097/SMJ.0b・・・
著者: Jackrapong Bruminhent, Perliveh Carrera, Zhongzhen Li, Raymond Amankona, Ingram M Roberts
雑誌名: J Med Case Rep. 2011 Aug 25;5:414. doi: 10.1186/1752-1947-5-414. Epub 2011 Aug 25.
Abstract/Text INTRODUCTION: Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto.
CASE PRESENTATION: A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto.
CONCLUSION: It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions.

PMID 21867545  J Med Case Rep. 2011 Aug 25;5:414. doi: 10.1186/1752-19・・・
著者: Francesco Lapi, Eugenia Gallo, Elisa Giocaliere, Michele Vietri, Roberto Baronti, Giuseppe Pieraccini, Alessandro Tafi, Francesca Menniti-Ippolito, Alessandro Mugelli, Fabio Firenzuoli, Alfredo Vannacci
雑誌名: Br J Clin Pharmacol. 2010 May;69(5):558-60. doi: 10.1111/j.1365-2125.2010.03618.x.
Abstract/Text
PMID 20573093  Br J Clin Pharmacol. 2010 May;69(5):558-60. doi: 10.111・・・
著者: Minako Hanaka, Chiharu Yoshii, Kazuhiro Yatera, Chiyo Ito, Yasuo Chojin, Shuya Nagata, Kei Yamasaki, Chinatsu Nishida, Toshinori Kawanami, Yukiko Kawanami, Hiroshi Ishimoto, Hiroshi Mukae
雑誌名: J UOEH. 2012 Jun 1;34(2):193-9.
Abstract/Text An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

PMID 22768426  J UOEH. 2012 Jun 1;34(2):193-9.
著者: Marco Miroddi, Antonio Carnì, Carmen Mannucci, Mariacarla Moleti, Michele Navarra, Gioacchino Calapai
雑誌名: Pediatrics. 2012 Nov;130(5):e1374-6. doi: 10.1542/peds.2011-2679. Epub 2012 Oct 1.
Abstract/Text Extracts of the plant Serenoa repens are widely used in male adults for the treatment of benign prostatic hyperplasia. Recently, therapy with S repens has been proposed as a "natural" alternative to conventional treatments for male androgenetic alopecia as well as for other hair disorders. Telogen effluvium is a form of alopecia characterized by abnormality of hair cycling, resulting in excessive loss of telogen hair. We report the case of an 11-year-old girl presenting hot flashes that appeared after treatment of telogen effluvium with a food supplement containing S repens that lasted for ~2 months. When use of the product was discontinued, the hot flashes no longer occurred. Four months after the start of S repens intake and 45 days from the cessation of therapy, the girl experienced menarche at the age of 11 years. The Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the appearance of hot flashes and the intake of S repens. A correlation between exposure to S repens and the onset of menarche is not certain, but it cannot be excluded. Medicinal products or food supplements containing S repens are generally well tolerated in male adults, but we believe that their use in pediatric patients should be better evaluated.

PMID 23027164  Pediatrics. 2012 Nov;130(5):e1374-6. doi: 10.1542/peds.・・・
著者: Paolo Morabito, Marco Miroddi, Salvatore Giovinazzo, Edoardo Spina, Gioacchino Calapai
雑誌名: Pharmacology. 2015;96(1-2):41-3. doi: 10.1159/000431327. Epub 2015 Jun 2.
Abstract/Text Serenoa repens, commonly known as saw palmetto, is the sole species currently classified in the genus Serenoa. The plant is a low shrubby palm that is native of West Indies, and it grows in the coastal lands of North America and other European mediterranean countries. Its fruits contain high concentrations of fatty acids and phytosterols. S. repens extracts have been studied for the symptomatic treatment of benign prostatic hyperplasia. Recently, they have been proposed to treat androgenic alopecia and other hair disorders. We report a new case of hot flashes in a 10-year-old girl using a food supplement containing the extract of S. repens for the treatment of hirsutism. When the girl discontinued the treatment, the hot flashes stopped. A 'rechallenge' of the supplement was tried and symptoms reappeared. About 4 months after starting therapy, the girl experienced menarche. Exposure to the plant-derived product could be responsible for the appearance of menarche. In our opinion, use of phytotherapeutic agents in pediatric patients should be associated to a better evaluation of benefit/risk profile taking in account the physiological changes that occurs at different ages in this subgroup of population.

© 2015 S. Karger AG, Basel.
PMID 26043832  Pharmacology. 2015;96(1-2):41-3. doi: 10.1159/000431327・・・
著者: Yuko Kurosawa, Shinsuke Nirengi, Toshiyuki Homma, Kazuki Esaki, Mitsuhiro Ohta, Joseph F Clark, Takafumi Hamaoka
雑誌名: Sci Rep. 2015 Jun 25;5:11601. doi: 10.1038/srep11601. Epub 2015 Jun 25.
Abstract/Text Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

PMID 26109079  Sci Rep. 2015 Jun 25;5:11601. doi: 10.1038/srep11601. E・・・
著者: Ji Young Kim, Si Nae Gum, Jean Kyung Paik, Hyo Hee Lim, Kyong-Chol Kim, Kazuya Ogasawara, Kenichi Inoue, Sungha Park, Yangsoo Jang, Jong Ho Lee
雑誌名: Hypertens Res. 2008 Aug;31(8):1583-8. doi: 10.1291/hypres.31.1583.
Abstract/Text The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. In a randomized, double-blind, placebo-controlled trial, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for 8 weeks. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg (95% confidence interval [CI], -10.5 to -0.57 mmHg; p<0.05) and -2.84 mmHg (CI, -5.33 to -0.33 mmHg; p<0.05), respectively, after the 8-week intervention. The corresponding net change in renin activity was -1.17 ng/mL/h for the nattokinase group compared with the control group (p<0.05). In conclusion, nattokinase supplementation resulted in a reduction in SBP and DBP. These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.

PMID 18971533  Hypertens Res. 2008 Aug;31(8):1583-8. doi: 10.1291/hypr・・・
著者: N N Ren, H J Chen, Y Li, G W Mcgowan, Y G Lin
雑誌名: Zhonghua Yi Xue Za Zhi. 2017 Jul 11;97(26):2038-2042.
Abstract/Text Objective: To evaluate the efficacy of oral nattokinase (NK) in the reduction of common carotid artery intimal medial thickness (CCA-IMT) and carotid artery plaque size and in lowering blood lipids, and to explore the underlying mechanism of actions of NK and its potential clinical use. Methods: All enrolled patients were from the Out-Patient Clinic of the Department of TCM at the 3(rd) Affiliated Hospital of Sun Yat-sen University. Using randomised picking method, all patients were randomly assigned to one of two groups, NK and Statin (ST) group. NK Group-patients were given NK at a daily dose of 6 000 FU and ST Group-patients were treated with statin (simvastatin 20 mg) daily. The treatment course was 26 weeks. CCA-IMT, carotid plaque size and blood lipid profile of the patients were measured before and after treatment. Results: A total of 82 patients were enrolled in the study and 76 patients (NK 39, ST 37) completed the study. Following the treatments for 26 weeks, there was a significant reduction in CCA-IMT and carotid plaque size in both groups compared with the baseline before treatment. The carotid plaque size and CCA-IMT reduced from(0.25±0.12)cm(2) to (0.16±0.10)cm(2) and from (1.13±0.12)mm to (1.01±0.11)mm, repectively. The reduction in the NK group was significantly profound (P<0.01, 36.6% reduction in plaque size in NK group versus 11.5% change in ST group). Both treatments reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). While the reduction in both groups was shown to be statistically significant (P<0.01), the reduction of TC, LDL-C and TG in ST group was significantly greater (P<0.05). In addition, NK significantly increased the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), in contrast, HDL-C in the ST group did not change. The lipid lowering effect observed in the NK group was not correlated to the reduction of CCA-IMT and carotid artery plaque size (r=0.35, P=0.09). Conclusions: Our findings from this pioneer clinical study suggests that daily NK supplementation is an effective way to manage the progression of atherosclerosis and potentially may be a better alternative to statins which are commonly used to reduce atherosclerosis and further to prevent cardiovascular attack and stroke in patients. The mechanism underlying the reduction of carotid atherosclerosis by NK may be independent from its lipid-lowering effect, which is different from that of statins.

PMID 28763875  Zhonghua Yi Xue Za Zhi. 2017 Jul 11;97(26):2038-2042.
著者: Yung-Yee Chang, Jia-Shou Liu, Shung-Lon Lai, Hsiu-Shan Wu, Min-Yu Lan
雑誌名: Intern Med. 2008;47(5):467-9. Epub 2008 Mar 3.
Abstract/Text Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

PMID 18310985  Intern Med. 2008;47(5):467-9. Epub 2008 Mar 3.
著者: Tomohiro Sugino, Tomoko Shirai, Yoshitaka Kajimoto, Osami Kajimoto
雑誌名: Nutr Res. 2008 Nov;28(11):738-43. doi: 10.1016/j.nutres.2008.08.008.
Abstract/Text We examined the effects of L-ornithine administration on physical fatigue. In a double-blind, placebo-controlled, 2-way crossover study, 17 healthy volunteers were randomized to L-ornithine (2000 mg/d for 7 days and 6000 mg/d for 1 day as L-ornithine hydrochloride) or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 hours on 2 occasions. We found that oral L-ornithine administration promoted lipid metabolism and activated the urea cycle from serum triacylglycerol, ketone bodies, free fatty acids, and blood ammonia level changing. L-ornithine significantly attenuated the subjective feeling of fatigue (measured by visual analog scale at postrecovery) compared with postload (P < .01). Moreover, in female subjects, the subjective feeling of fatigue was significantly lower compared with the placebo group (P < .05). In the physical performance test in female subjects, the decrease in mean speed for 10 seconds maximum pedaling from 0.5- to 3.5-hour trials in the group receiving L-ornithine was smaller than that in the group receiving placebo (P < .05). These results suggest that L-ornithine has an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia. L-ornithine is a free amino acid and is not rich in meats or fish, so it is difficult to obtain amounts of L-ornithine from ordinary meals that would be sufficient to promote the antifatigue effect. We recommend L-ornithine intake as a nutritional supplement in cases of physical fatigue.

PMID 19083482  Nutr Res. 2008 Nov;28(11):738-43. doi: 10.1016/j.nutres・・・
著者: Mika Miyake, Takayoshi Kirisako, Takeshi Kokubo, Yutaka Miura, Koji Morishita, Hisayoshi Okamura, Akira Tsuda
雑誌名: Nutr J. 2014 Jun 3;13:53. doi: 10.1186/1475-2891-13-53. Epub 2014 Jun 3.
Abstract/Text BACKGROUND: L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small.Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals.From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers.
METHOD: Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA).
RESULTS: Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group.
CONCLUSION: L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.

PMID 24889392  Nutr J. 2014 Jun 3;13:53. doi: 10.1186/1475-2891-13-53.・・・
著者: Takeshi Kokubo, Emiko Ikeshima, Takayoshi Kirisako, Yutaka Miura, Masahisa Horiuchi, Akira Tsuda
雑誌名: Biopsychosoc Med. 2013 Feb 18;7(1):6. doi: 10.1186/1751-0759-7-6. Epub 2013 Feb 18.
Abstract/Text UNLABELLED:
BACKGROUND: Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism.
METHODS: This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the 'flusher' phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption.
RESULTS: There were significant decreases in "awareness", "feeling of fatigue" and "lassitude" VAS scores and in "anger-hostility" and "confusion" POMS scores and a significant increase in "sleep length" in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism.
CONCLUSIONS: Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.

PMID 23414576  Biopsychosoc Med. 2013 Feb 18;7(1):6. doi: 10.1186/1751・・・
著者: Stephan Reichenbach, Rebekka Sterchi, Martin Scherer, Sven Trelle, Elizabeth Bürgi, Ulrich Bürgi, Paul A Dieppe, Peter Jüni
雑誌名: Ann Intern Med. 2007 Apr 17;146(8):580-90.
Abstract/Text BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect.
PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis.
DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006.
STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions.
DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis.
DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event.
LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable.
CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

PMID 17438317  Ann Intern Med. 2007 Apr 17;146(8):580-90.
著者: Jean-Yves Reginster, Jean Dudler, Tomasz Blicharski, Karel Pavelka
雑誌名: Ann Rheum Dis. 2017 Sep;76(9):1537-1543. doi: 10.1136/annrheumdis-2016-210860. Epub 2017 May 22.
Abstract/Text OBJECTIVES: Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline.
METHODS: A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints.
RESULTS: 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (-42.6 mm) and in celecoxib group (-39.5 mm) was significantly greater than the placebo group (-33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (-4.7) and celecoxib group (-4.6) was significantly greater than the placebo group (-3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles.
CONCLUSION: A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PMID 28533290  Ann Rheum Dis. 2017 Sep;76(9):1537-1543. doi: 10.1136/a・・・
著者: Jorge A Roman-Blas, Santos Castañeda, Olga Sánchez-Pernaute, Raquel Largo, Gabriel Herrero-Beaumont, CS/GS Combined Therapy Study Group
雑誌名: Arthritis Rheumatol. 2017 Jan;69(1):77-85. doi: 10.1002/art.39819.
Abstract/Text OBJECTIVE: To assess the efficacy and safety of combination therapy with chondroitin sulfate (CS) and glucosamine sulfate (GS) compared to placebo in patients with symptomatic knee osteoarthritis (OA).
METHODS: A multicenter, randomized, double-blind, placebo-controlled study was performed in 164 patients with Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and moderate-to-severe knee pain (mean ± SD global pain score 62.1 ± 11.3 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to receive either combined treatment with CS (1,200 mg) plus GS (1,500 mg) or placebo in a single oral daily dose for 6 months. The mean change from baseline in the VAS global pain score was set as the primary end point. Secondary outcomes included the mean change in the investigator's global assessment of disease activity, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain and function subscale scores on the WOMAC, responder rates based on the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) 2004 response criteria, and rescue medication use. Adverse events were also recorded. A Data and Safety Monitoring Board was instituted to ensure patient safety and data accuracy.
RESULTS: Intriguingly, in the modified intent-to-treat (mITT) population, CS/GS combination therapy was inferior to placebo in the reduction of joint pain (mean ± SD change in VAS global pain score over 6 months -11.8 ± 2.4 mm [19% reduction] in patients receiving CS plus GS versus -20.5 ± 2.4 mm [33% reduction] in patients receiving placebo; peak between-group difference in global pain score at 6 months 8.7 mm [14.2%], P < 0.03), but no between-group differences were seen in the per-protocol completers. Both placebo treatment and CS/GS combination treatment improved to a similar extent the total WOMAC score as well as the pain and function WOMAC subscale scores, both in the mITT population and in the per-protocol completers. Neither the OMERACT-OARSI responder rate nor the frequency of rescue medication use differed between the treatment groups. Severe adverse events were uncommon and equally distributed.
CONCLUSION: The results of this trial demonstrate a lack of superiority of CS/GS combination therapy over placebo in terms of reducing joint pain and functional impairment in patients with symptomatic knee OA over 6 months. Further research might fully elucidate the suitability of CS/GS combination therapy in patients with OA.

© 2016, American College of Rheumatology.
PMID 27477804  Arthritis Rheumatol. 2017 Jan;69(1):77-85. doi: 10.1002・・・
著者: Svend A Mortensen, Franklin Rosenfeldt, Adarsh Kumar, Peter Dolliner, Krzysztof J Filipiak, Daniel Pella, Urban Alehagen, Günter Steurer, Gian P Littarru, Q-SYMBIO Study Investigators
雑誌名: JACC Heart Fail. 2014 Dec;2(6):641-9. doi: 10.1016/j.jchf.2014.06.008. Epub 2014 Oct 1.
Abstract/Text OBJECTIVES: This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF).
BACKGROUND: CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints.
METHODS: Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.
RESULTS: A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028).
CONCLUSIONS: Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 25282031  JACC Heart Fail. 2014 Dec;2(6):641-9. doi: 10.1016/j.jc・・・
著者: Ahmed Negida, Ahmed Menshawy, Gehad El Ashal, Yasmin Elfouly, Yasmein Hani, Yasmin Hegazy, Samar El Ghonimy, Samar Fouda, Yomna Rashad
雑誌名: CNS Neurol Disord Drug Targets. 2016;15(1):45-53.
Abstract/Text INTRODUCTION: Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated CoQ10 for neuroprotection against Parkinson's disease (PD). The aim of this study is to synthesize evidence from published randomized controlled trials (RCTs) about the benefit of CoQ10 supplementation for patients with Parkinson's disease.
METHODS: We followed the PRISMA statement guidelines during the preparation of this systematic review and metaanalysis. A computer literature search for (PubMed, EBSCO, Web of science and Ovid Midline) was carried out. We included RCTs comparing CoQ10 with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III and Schwab and England scores were pooled as standardized mean difference (SMD) between two groups from baseline to the endpoint.
RESULTS: Five RCTs (981 patients) were included in this study. The overall effect did not favor either of the two groups in terms of: total UPDRS score (SMD -0.05, 95%CI [-0.10, 0.15]), UPDRS I (SMD -0.03, 95% CI [-0.23, 0.17]), UPDRS II (SMD -0.10, 95%CI [-0.35, 0.15]), UPDRS III (SMD -0.05, 95%CI [-0.07, 0.17]) or Schwab and England score (SMD 0.08, 95%CI [-0.13, 0.29]).
CONCLUSION: CoQ10 supplementation does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease.

PMID 26553164  CNS Neurol Disord Drug Targets. 2016;15(1):45-53.
著者: Zhen-Guo Zhu, Miao-Xuan Sun, Wan-Li Zhang, Wen-Wen Wang, Yi-Mei Jin, Cheng-Long Xie
雑誌名: Neurol Sci. 2017 Feb;38(2):215-224. doi: 10.1007/s10072-016-2757-9. Epub 2016 Nov 9.
Abstract/Text The objective of this meta-analysis was to evaluate the effects of coenzyme Q10 (CoQ10) for the treatment of Parkinson's disease (PD) patients in order to arrive at qualitative and quantitative conclusions about the efficacy of CoQ10. Databases searched included PubMed, Google scholar, CNKI, Wan-Fang, and the Cochrane Library from inception to March 2016. We only included sham-controlled, randomized clinical trials of CoQ10 intervention for motor dysfunction in patients with PD. Relevant measures were extracted independently by two investigators. Weighted mean differences (WMD) were calculated with random-effects models. Eight studies with a total of 899 patients were included. Random-effects analysis revealed a pooled WMD of 1.02, indicating no significant difference when CoQ10 treatment compared with placebo in terms of UPDRS part 3 (p = 0.54). Meanwhile, the effect size of UPDRS part 1, UPDRS part 2, and total UPDRS scores were similar in CoQ10 group with in placebo group (p > 0.05). Moreover, we found CoQ10 was well tolerated compared with placebo group. Subgroup analysis showed that the effect size of CoQ10 in monocentric studies was larger than in multicenter studies. Using the GRADE criteria, we characterized the quality of evidence presented in this meta-analysis as moderate to high level. The current meta-analysis provided evidence that CoQ10 was safe and well tolerated in participants with PD and no superior to placebo in terms of motor symptoms. According to these results, we cannot recommend CoQ10 for the routine treatment of PD right now.

PMID 27830343  Neurol Sci. 2017 Feb;38(2):215-224. doi: 10.1007/s10072・・・
著者: Dominik D Alexander, Paige E Miller, Mary E Van Elswyk, Connye N Kuratko, Lauren C Bylsma
雑誌名: Mayo Clin Proc. 2017 Jan;92(1):15-29. doi: 10.1016/j.mayocp.2016.10.018.
Abstract/Text OBJECTIVE: To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk.
METHODS: A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed.
RESULTS: Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event.
CONCLUSION: Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.

Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
PMID 28062061  Mayo Clin Proc. 2017 Jan;92(1):15-29. doi: 10.1016/j.ma・・・
著者: Kevin C Maki, Orsolya M Palacios, Marjorie Bell, Peter P Toth
雑誌名: J Clin Lipidol. 2017 Sep - Oct;11(5):1152-1160.e2. doi: 10.1016/j.jacl.2017.07.010. Epub 2017 Aug 2.
Abstract/Text BACKGROUND: Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results.
OBJECTIVE: The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk.
METHODS: A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses.
RESULTS: Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I(2) ≤ 15.5%, P > .05) for the primary and subset analyses.
CONCLUSION: LC-OM3 supplementation is associated with a modest reduction in cardiac death.

Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.
PMID 28818347  J Clin Lipidol. 2017 Sep - Oct;11(5):1152-1160.e2. doi:・・・
著者: Débora Finger, Fernanda Reistenbach Goltz, Daniel Umpierre, Elisabeth Meyer, Luis Henrique Telles Rosa, Cláudia Dornelles Schneider
雑誌名: Sports Med. 2015 Feb;45(2):245-55. doi: 10.1007/s40279-014-0269-4.
Abstract/Text BACKGROUND: Older individuals present reductions in muscle mass and physical function, as well as a blunted muscle protein synthesis response to amino acid administration and physical activity. Although resistance training is an effective intervention to slow down muscle impairments in the elderly, there is no consensus whether a combination with protein supplementation could offer additional benefits to an older population.
OBJECTIVE: We aimed to systematically summarize and quantify whether protein supplementation could optimize the effects of resistance training on muscle mass and strength in an aged population.
DESIGN: A structured literature search was conducted on MEDLINE (PubMed), Cochrane, EMBASE and LILACS databases. The search had no period or language restrictions. Inclusion criteria comprised study design (randomized controlled trials-RCTs), sample mean age (60 years and over) and intervention (a resistance training program for a period of 6 weeks or longer combined with protein or amino acids supplementation). Two independent reviewers performed the study selection and data extraction. Continuous data on fat-free mass, muscle mass and muscle strength were pooled using a random-effects model.
RESULTS: Of the 540 articles reviewed, 29 eligible articles underwent full-text evaluation. Nine RCTs (462 subjects) met the inclusion criteria and were included in the study. The mean age of the participants ranged from 61 to 79 years old. Protein supplementation protocols varied widely throughout the studies. Three studies used quantities related to the body mass of the participants and the other six trials provided supplements in daily amounts, independently of subjects' body masses. Overall, protein supplementation in combination with resistance training was associated with gains in fat-free mass, resulting in a standardized mean difference (SMD) of 0.23 [95% confidence interval (CI), 0.05-0.42]. However, protein supplementation was not associated with changes in muscle mass (0.14, 95% CI -0.05 to 0.32) or muscle strength (0.13, 95% CI -0.06 to 0.32).
LIMITATIONS: Studies among the very elderly population are scarce. The variation regarding the supplementation protocol, namely the different protein sources, amounts and timing of ingestion, also made it harder to compare the results. The general quality of the studies was low, reflecting increased risk of bias in some studies. Despite these limitations, this systematic review provides a general overview of the role of protein supplementation with no other added macronutrients to augment muscle mass and strength during resistance training in older adults.
CONCLUSION: Combining protein supplementation with resistance training is effective for eliciting gains in fat-free mass among older adults, but does not seem to increase muscle mass or strength.

PMID 25355074  Sports Med. 2015 Feb;45(2):245-55. doi: 10.1007/s40279-・・・
著者: Fernando Naclerio, Eneko Larumbe-Zabala
雑誌名: Sports Med. 2016 Jan;46(1):125-37. doi: 10.1007/s40279-015-0403-y.
Abstract/Text BACKGROUND: Even though the positive effects of whey protein-containing supplements for optimizing the anabolic responses and adaptations process in resistance-trained individuals have been supported by several investigations, their use continues to be controversial. Additionally, the administration of different multi-ingredient formulations where whey proteins are combined with carbohydrates, other protein sources, creatine, and amino acids or derivatives, has been extensively proposed as an effective strategy to maximize strength and muscle mass gains in athletes.
OBJECTIVE: We aimed to systematically summarize and quantify whether whey protein-containing supplements, administered alone or as a part of a multi-ingredient, could improve the effects of resistance training on fat-free mass or lean body mass, and strength in resistance-trained individuals when compared with other iso-energetic supplements containing carbohydrates or other sources of proteins.
METHODS: A structured literature search was conducted on PubMed, Science Direct, Web of Science, Cochrane Libraries, US National Institutes of Health clinicaltrials.gov, SPORTDiscus, and Google Scholar databases. Main inclusion criteria comprised randomized controlled trial study design, adults (aged 18 years and over), resistance-trained individuals, interventions (a resistance training program for a period of 6 weeks or longer, combined with whey protein supplementation administered alone or as a part of a multi-ingredient), and a calorie equivalent contrast supplement from carbohydrates or other non-whey protein sources. Continuous data on fat-free mass and lean body mass, and maximal strength were pooled using a random-effects model.
RESULTS: Data from nine randomized controlled trials were included, involving 11 treatments and 192 participants. Overall, with respect to the ingestion of contrast supplements, whey protein supplementation, administered alone or as part of a multi-ingredient, in combination with resistance training, was associated with small extra gains in fat-free mass or lean body mass, resulting in an effect size of g = 0.301, 95% confidence interval (CI) 0.032-0.571. Subgroup analyses showed less clear positive trends resulting in small to moderate effect size g = 0.217 (95% CI -0.113 to 0.547) and g = 0.468 (95% CI 0.003-0.934) in favor of whey and multi-ingredient, respectively. Additionally, a positive overall extra effect was also observed to maximize lower (g = 0.316, 95% CI 0.045-0.588) and upper body maximal strength (g = 0.458, 95% CI 0.161-0.755). Subgroup analyses showed smaller superiority to maximize strength gains with respect to the contrast groups for lower body (whey protein: g = 0.343, 95% CI -0.016 to 0.702, multi-ingredient: g = 0.281, 95% CI -0.135 to 0.697) while in the upper body, multi-ingredient (g = 0.612, 95% CI 0.157-1.068) seemed to produce more clear effects than whey protein alone (g = 0.343, 95% CI -0.048 to 0.735).
LIMITATIONS: Studies involving interventions of more than 6 weeks on resistance-training individuals are scarce and account for a small number of participants. Furthermore, no studies with an intervention longer than 12 weeks have been found. The variation regarding the supplementation protocol, namely the different doses criteria or timing of ingestion also add some concerns to the studies comparison.
CONCLUSIONS: Whey protein alone or as a part of a multi-ingredient appears to maximize lean body mass or fat-free mass gain, as well as upper and lower body strength improvement with respect to the ingestion of an iso-energetic equivalent carbohydrate or non-whey protein supplement in resistance-training individuals. This enhancement effect seems to be more evident when whey proteins are consumed within a multi-ingredient containing creatine.

PMID 26403469  Sports Med. 2016 Jan;46(1):125-37. doi: 10.1007/s40279-・・・
著者:
雑誌名: JAMA. 2012 May 9;307(18):1959-69. doi: 10.1001/jama.2012.3507.
Abstract/Text
PMID 22570464  JAMA. 2012 May 9;307(18):1959-69. doi: 10.1001/jama.201・・・
著者: Joshua Z Goldenberg, Lyubov Lytvyn, Justin Steurich, Patricia Parkin, Sanjay Mahant, Bradley C Johnston
雑誌名: Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. doi: 10.1002/14651858.CD004827.pub4. Epub 2015 Dec 22.
Abstract/Text BACKGROUND: Antibiotics are frequently prescribed in children. They alter the microbial balance within the gastrointestinal tract, commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via restoration of the gut microflora.
OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children.
SEARCH METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to November 2014) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutraceutical and pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched.
SELECTION CRITERIA: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea, mean daily stool frequency) as mean difference (MD), along with their corresponding 95% confidence interval (95% CI). For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, as well as risk of bias. We also conducted post hoc subgroup analyses by patient diagnosis, single versus multi-strain, industry sponsorship, and inpatient status. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria.
MAIN RESULTS: Twenty-three studies (3938 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. Eleven studies used a single strain probiotic, four combined two probiotic strains, three combined three probiotic strains, one combined four probiotic strains, two combined seven probiotic strains, one included ten probiotic strains, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high or unclear in 13 studies and low in 10 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 22/23 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 8% (163/1992) compared to 19% (364/1906) in the control group (RR 0.46, 95% CI 0.35 to 0.61; I(2) = 55%, 3898 participants). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate. This benefit remained statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) sensitivity analysis, where the incidence of AAD in the probiotic group was 14% (330/2294) compared to 19% (426/2235) in the control group (RR 0.69; 95% CI 0.54 to 0.89; I(2) = 63%, 4529 participants). None of the 16 trials (n = 2455) that reported on adverse events documented any serious adverse events attributable to probiotics. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.01). The majority of adverse events were in placebo, standard care or no treatment group. Adverse events reported in the studies include rash, nausea, gas, flatulence, abdominal bloating, abdominal pain, vomiting, increased phlegm, chest pain, constipation, taste disturbance, and low appetite.
AUTHORS' CONCLUSIONS: Moderate quality evidence suggests a protective effect of probiotics in preventing AAD. Our pooled estimate suggests a precise (RR 0.46; 95% CI 0.35 to 0.61) probiotic effect with a NNT of 10. Among the various probiotics evaluated, Lactobacillus rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony forming units/day may be appropriate given the modest NNT and the likelihood that adverse events are very rare. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Although no serious adverse events were observed among otherwise healthy children, serious adverse events have been observed in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation. Until further research has been conducted, probiotic use should be avoided in pediatric populations at risk for adverse events. Future trials would benefit from a standard and valid outcomes to measure AAD.

PMID 26695080  Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. ・・・
著者: Stephen J Allen, Elizabeth G Martinez, Germana V Gregorio, Leonila F Dans
雑誌名: Cochrane Database Syst Rev. 2010 Nov 10;(11):CD003048. doi: 10.1002/14651858.CD003048.pub3. Epub 2010 Nov 10.
Abstract/Text BACKGROUND: Probiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness.
OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea.
SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (July 2010), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to July 2010), and reference lists from studies and reviews. We also contacted organizations and individuals working in the field, and pharmaceutical companies manufacturing probiotic agents.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trial and extracted data. Primary outcomes were the mean duration of diarrhoea, stool frequency on day 2 after intervention and ongoing diarrhoea on day 4. A random-effects model was used.
MAIN RESULTS: Sixty-three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention.Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies.The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555, trials=35) diarrhoea lasting ≥4 days (risk ratio 0.41; 0.32 to 0.53; n=2853, trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n=2751, trials=20).The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries.
AUTHORS' CONCLUSIONS: Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.

PMID 21069673  Cochrane Database Syst Rev. 2010 Nov 10;(11):CD003048. ・・・
著者: Qiukui Hao, Bi Rong Dong, Taixiang Wu
雑誌名: Cochrane Database Syst Rev. 2015 Feb 3;(2):CD006895. doi: 10.1002/14651858.CD006895.pub3. Epub 2015 Feb 3.
Abstract/Text BACKGROUND: Probiotics may improve a person's health by regulating their immune function. Some trials have shown that probiotic strains can prevent respiratory infections. Even though the previous version of our review showed benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published.
OBJECTIVES: To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs.
SEARCH METHODS: We searched CENTRAL (2014, Issue 6), MEDLINE (1950 to July week 3, 2014), EMBASE (1974 to July 2014), Web of Science (1900 to July 2014), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to July 2014), the Chinese Medicine Popular Science Literature Database (from 2000 to July 2014) and the Masters Degree Dissertation of Beijing Union Medical College Database (from 1981 to July 2014). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for completed and ongoing trials on 31 July 2014.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics with placebo to prevent acute URTIs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and quality of trials, and extracted data using the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS: We included 13 RCTs, although we could only extract data to meta-analyse 12 trials, which involved 3720 participants including children, adults (aged around 40 years) and older people. We found that probiotics were better than placebo when measuring the number of participants experiencing episodes of acute URTI (at least one episode: odds ratio (OR) 0.53; 95% confidence interval (CI) 0.37 to 0.76, P value < 0.001, low quality evidence; at least three episodes: OR 0.53; 95% CI 0.36 to 0.80, P value = 0.002, low quality evidence); the mean duration of an episode of acute URTI (mean difference (MD) -1.89; 95% CI -2.03 to -1.75, P value < 0.001, low quality evidence); reduced antibiotic prescription rates for acute URTIs (OR 0.65; 95% CI 0.45 to 0.94, moderate quality evidence) and cold-related school absence (OR 0.10; 95% CI 0.02 to 0.47, very low quality evidence). Probiotics and placebo were similar when measuring the rate ratio of episodes of acute URTI (rate ratio 0.83; 95% CI 0.66 to 1.05, P value = 0.12, very low quality evidence) and adverse events (OR 0.88; 95% CI 0.65 to 1.19, P value = 0.40, low quality evidence). Side effects of probiotics were minor and gastrointestinal symptoms were the most common. We found that some subgroups had a high level of heterogeneity when we conducted pooled analyses and the evidence level was low or very low quality.
AUTHORS' CONCLUSIONS: Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTI, the mean duration of an episode of acute URTI, antibiotic use and cold-related school absence. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the quality of the evidence was low or very low.

PMID 25927096  Cochrane Database Syst Rev. 2015 Feb 3;(2):CD006895. do・・・
著者: Abirami Pararajasingam, Juliet Uwagwu
雑誌名: BMJ Case Rep. 2017 Sep 13;2017. doi: 10.1136/bcr-2016-218423. Epub 2017 Sep 13.
Abstract/Text We present a 65-year-old diabetic patient with a complex liver abscess and bacteraemia from Lactobacillus paracasei The abscess resulted in a prolonged hospital stay due to ongoing sepsis despite ultrasound-guided drainage and broad-spectrum antibiotics. Furthermore, the patient developed several secondary complications including a right-sided pleural effusion, an inferior vena cava thrombus and septic lung emboli. The abscess was eventually managed successfully with a prolonged course of antibiotics and multiple ultrasound-guided drainage procedures.To our knowledge, this is the first reported case of probiotic consumption, confirmed by strain identification, as the likely source of a liver abscess. Probiotic products have been widely used for many years and are advocated to the general public for their health benefits with no warning of side effects. Lactobacilli are one group of bacteria commonly used in these products. Although rare, complications have been reported. Susceptible patients, such as those who are immunocompromised, should be advised against excessive consumption.

© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PMID 28903972  BMJ Case Rep. 2017 Sep 13;2017. doi: 10.1136/bcr-2016-2・・・
著者: Michael H Land, Kelly Rouster-Stevens, Charles R Woods, Michael L Cannon, James Cnota, Avinash K Shetty
雑誌名: Pediatrics. 2005 Jan;115(1):178-81. doi: 10.1542/peds.2004-2137.
Abstract/Text Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations.

PMID 15629999  Pediatrics. 2005 Jan;115(1):178-81. doi: 10.1542/peds.2・・・
著者: Leila Haghighat, Nancy F Crum-Cianflone
雑誌名: Int J STD AIDS. 2016 Nov;27(13):1223-1230. doi: 10.1177/0956462415590725. Epub 2015 Jun 30.
Abstract/Text Lactobacillus sp. are commensal organisms that are increasingly reported to cause invasive infections among immunosuppressed persons. However, few data exist regarding the occurrence and risk factors of these infections among HIV-infected persons. Further, the safety of products that contain lactobacilli (e.g. probiotics) in certain populations, including those with HIV/AIDS, is unclear. We report a case of Lactobacillus acidophilus bacteraemia in a patient with AIDS temporally related to excessive consumption of probiotic-enriched yogurt, and provide a comprehensive review of the literature of Lactobacillus sp. infections among HIV-infected persons.

© The Author(s) 2015.
PMID 26130690  Int J STD AIDS. 2016 Nov;27(13):1223-1230. doi: 10.1177・・・
著者: Claire Bertelli, Trestan Pillonel, Anaïs Torregrossa, Guy Prod'hom, Céline Julie Fischer, Gilbert Greub, Eric Giannoni
雑誌名: Clin Infect Dis. 2015 Mar 15;60(6):924-7. doi: 10.1093/cid/ciu946. Epub 2014 Dec 3.
Abstract/Text Administration of probiotics to premature newborns has been shown to prevent necrotizing enterocolitis and reduce all-cause mortality. In our hospital, we documented 2 cases of Bifidobacterium longum subspecies infantis bacteremia in newborns receiving probiotics. By comparative genomics, we confirmed that the strains isolated from each patient originated from the probiotics.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 25472946  Clin Infect Dis. 2015 Mar 15;60(6):924-7. doi: 10.1093/・・・
著者: O Bruyere, K Pavelka, L C Rovati, J Gatterová, G Giacovelli, M Olejarová, R Deroisy, J Y Reginster
雑誌名: Osteoarthritis Cartilage. 2008 Feb;16(2):254-60. doi: 10.1016/j.joca.2007.06.011. Epub 2007 Jul 27.
Abstract/Text OBJECTIVE: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo.
METHODS: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement.
RESULTS: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20-0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up.
CONCLUSIONS: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation.

PMID 17681803  Osteoarthritis Cartilage. 2008 Feb;16(2):254-60. doi: 1・・・

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