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Resveratrol and health – A comprehensive review of human clinical trials - Smoliga - 2. Molecular Nutrition & Food Research. Review. Authors. James M. Smoliga,Corresponding author.
Human Physiology Laboratory, Department of Health and Physical Education, Marywood University, Scranton PA, USADepartment of Health and Physical Education, Marywood University, 2. Adams Avenue, Scranton, PA 1. USA Fax: +1- 5. 70- 9. Search for more papers by this author. Joseph A. Baur,Institute for Diabetes, Obesity, and Metabolism, and Department of Physiology, University of Pennsylvania School of Medicine, PA, USASearch for more papers by this author. The Return of Resveratrol: A Clinical Research Update. Other recent human clinical studies of resveratrol for heart health have reported that resveratrol. Titre du document / Document title Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence Auteur(s) / Author(s) TOME. Background: - Resveratrol is a compound found in the skin of red grapes. It is being tested to see if it can have positive effects on human health. Heather A. Hausenblas. Exercise Psychology Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USASearch for more papers by this author. Abstract. In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti- aging, anti- carcinogenic, anti- inflammatory, and anti- oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well- tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials. Introduction. From the years 2. United States aged 6. This rapid demographic shift will markedly increase the prevalence of age- related disorders including diabetes mellitus, cardiovascular and neurodegenerative diseases, and cancer. Unsurprisingly, the search for interventions that can prevent and alleviate age- related health problems is rapidly accelerating. Traditionally, chronic diseases have been treated through pharmaceutical interventions following a medical diagnosis. Over the past few decades, there has been an increasing emphasis on using lifestyle changes and nutritional modifications to prevent and treat chronic diseases 2, 3. Caloric restriction is an effective means of preventing chronic disease and ultimately increasing lifespan in laboratory animals 4. DOI 10.1002/mnfr.201100143. Resveratrol and health – A comprehensive review of human clinical trials James. Clinical trials of resveratrol. Patel KR(1), Scott E, Brown VA, Gescher AJ. A new study gives insight into how resveratrol—found in grapes. NIH Clinical Research Trials and You. How Resveratrol May Fight Aging. However, it is difficult to employ in actual practice, especially considering the cultural emphasis on eating that is a major contributor to many chronic diseases. As such, considerable research has been directed toward identifying substances that mimic the physiological effects of caloric restriction, and resveratrol has emerged as a leading candidate in this realm 4. Resveratrol (3,5,4. The most important dietary source of resveratrol is red wine, and it is often postulated to be an important factor in the French Paradox, a term coined to describe the observation that the French population has a very low incidence of cardiovascular disease, despite a diet high in saturated fats 6. Scientific interest in resveratrol has continually gained momentum since 1. In the intervening years, this molecule has received considerable attention for its anti- inflammatory, anti- tumorigenic, and anti- oxidant properties, as well as its ability to increase lifespan in lower organisms and improve general health in mammals 8. Recent data suggest that resveratrol does not extend lifespan in healthy mice or in a model of premature aging 9, but does appear to delay or attenuate many age- related changes and prevent early mortality in obese animals 1. Reports of significant life extension in simpler laboratory organisms, combined with thousands of in vitro and in vivo studies supporting a role for resveratrol in either the prevention or treatment of chronic diseases, suggest that resveratrol and similar nutraceuticals may have the potential to make an unprecedented impact on human health. Resveratrol has multiple mechanisms of action that may be related to its health benefits 5. Similar to most polyphenols, resveratrol has intrinsic anti- oxidant capacity, but it also induces the expression of a number of anti- oxidant enzymes, making it difficult to decipher the precise contribution of each mechanism to an overall reduction in oxidative stress 1. Resveratrol further interacts with a large number of receptors, kinases, and other enzymes that could plausibly make major contributions to its biological effects. In vivo, resveratrol treatment stimulates the activities of sirtuin 1 (SIRT1) and adenosine monophosphate- activated protein kinase (AMPK), both of which influence the regulation of metabolism in multiple tissues 8, 1. Intriguingly, some of the beneficial effects of resveratrol appear to be replicated by overexpression of SIRT1 1. SIRT1 activator 1. AMPK fail to exhibit many of the normal responses to resveratrol 1. Resveratrol further inhibits cyclooxygenases 1. An unbiased approach to select resveratrol- binding proteins revealed quinone reductase 2, which is inhibited by resveratrol, as one of the highest affinity targets, although the significance of this observation is not yet known 2. Fully defining the targets of resveratrol that are biologically relevant is an enormous task, made more difficult by questions of whether effects are either direct or indirect, and often conflicting results in different systems. A full discussion of these issues is beyond the scope of this review, and has been attempted elsewhere (e. The complexity of resveratrol's effects in cells and in animals presents a major challenge in moving forward with human studies. Although almost all the nearly 4. Fig. 1), intense media coverage highlighting its potential applications in the prevention and treatment of age- related diseases has inspired many individuals to try resveratrol supplements, and many companies to develop either resveratrol- based drugs or nutraceuticals. Indeed, a 2. 00. 7 cross- sectional study found that supplemental resveratrol is taken by 2/3 of people who routinely consume multiple dietary supplements 2. Because of the continued public interest and the explosion of resveratrol supplements on the market, an urgent need exists to summarize the available clinical literature, which is the overarching goal of the present review. We will consider research related to resveratrol's bioavailability (both from red wine and resveratrol supplementation), as well as its effects on oxidative stress, inflammation, obesity, diabetes, and cardiovascular health, and how it interacts with drug- metabolizing enzymes. Finally, we will discuss theoretical, methodological, and statistical limitations of the literature, and explore promising directions for future research in light of the current findings. Annual count of resveratrol articles indexed on Pub. Med. The results include articles with the term “resveratrol” in found in the title, abstract, or keywords. Note that “human” studies includes cell culture studies. Some studies which were not resveratrol specific (i. The absorption and metabolism of resveratrol appear to be broadly similar to that of other polyphenols such as quercetin and catechin 2. Further studies are needed to compare maximum or average concentrations of resveratrol (Cmax or Cavg, respectively) in human plasma or tissue with the concentrations necessary for achieving physiological benefit in animal and in vitro models. Although this provides researchers with a starting point, little is known about how time- dependent bioavailability variables relate to resveratrol's mechanisms of action (e. A recent review by Patel et al. Herein, we have focused on the plasma Cmax resulting from resveratrol supplementation, as this is the most easily translated variable in relating data from laboratory animals and in vitro models to humans. For the purposes of this review, all plasma concentrations have been converted to . The greatest plasma trans- resveratrol concentrations have been reported by Boocock et al. The lowest dose used in the study (0. Coefficient of variation (CV) for Cmax for the dosages used ranged from 4. Similarly, Chow et al. Cmax can be increased through multiple days of supplementation 3. Cmax more than doubled in the 2. Regardless, Cmax of the 1. The CV for Cmax was large, similar to that reported by Boocock et al., ranging from 4. Although Cmax was not reported following initial dose, data from Brown et al. Following 2. 9 days of 5 g trans- resveratrol administration, Brown et al. Cmax to be 9. 58. This Cmax is higher than that reported by Boocock et al. There is evidence that resveratrol and its metabolites accumulate within human cells in vivo in a tissue- specific manner and this is highly dependent on the dosage. Following either 0. Conversely, normal colonic tissue had considerably more trans- resveratrol (6. Despite these differences, it is uncertain if the optimal resveratrol concentration and metabolite profile differs in other tissues and further research is needed in this area. The wide variability in tissue concentration observed is consistent with that of the plasma, further emphasizing inter- individual differences in bioavailability. Bioavailability from wine and juice consumption. In considering studies using wine as a means of resveratrol administration, it is important to note that the resveratrol concentrations in wine vary widely, even within a given variety of grape or growing region 3. Resveratrol and the Metabolic Syndrome - Full Text View. Primary Outcome Measures. Reduction in Insulin resistance . The underlying causes of metabolic syndrome are obesity, being overweight, physical inactivity and genetic factors. In recent decades, the prevalence has increased dramatically in the United States. Lifestyle interventions including dietary modification, physical activity and weight loss form the basis of treatment for these patients. However, research has shown that even when people are able to incorporate these changes, they often revert back to their usual lifestyle resulting in weight gain and continued risk for diabetes and heart disease. Resveratrol, a natural plant derived compound found in grapes, peanuts and red wine, has been found to reverse some of the features of the metabolic syndrome (insulin resistance, high triglycerides, high blood pressure) in rodents. These improvements occurred without weight loss, and were proven to be a direct result of resveratrol ingestion. Other studies reveal improvement in cardiovascular health, tumor suppression, and longevity. However, there are few studies investigating these beneficial effects in humans. In a systematic review of resveratrol research, the authors conclude that . Improvement in triglycerides, blood pressure and insulin resistance were noted. Resveratrol was well tolerated without serious side effects. These studies, however, did not recruit subjects with the metabolic syndrome, nor were they tightly controlled. The investigators propose to prove that resveratrol, administered to subjects with the metabolic syndrome, under controlled conditions of weight stability, common diet, and strict compliance with the study drug, will improve the symptoms of the metabolic syndrome, thereby decreasing the chance of developing diabetes or heart disease. Pro tools 10 Rewire Reason 6.5 by Cedric la CruZz. This video shows you how to Rewire Propellerhead Reason 6.5 to Avid Pro Tools 10. Reason will functon as a slave to. Reason is a libertarian monthly. Two hundred white nationalists get more coverage than tens of thousands of pro-life. Can You Spot a Trend in New Jersey’s 10. Pro Tools 10: ReWire with Reason not working. It's running pretty solid, and my. Brand new Reason user here (v8) and fairly well-versed in Pro Tools 10 & 11. Shouldn't it be pretty straight-forward to have my MIDI tracks in PT fire live from Reason? 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Britney Spears - Wikipedia. Britney Jean Spears (born December 2, 1. American singer, dancer and actress. Born in Mc. Comb, Mississippi, and raised in Kentwood, Louisiana, she performed acting roles in stage productions and television shows as a child before signing with Jive Records in 1. Spears's first and second studio albums, .. Baby One More Time (1. Oops!. I Did It Again (2. In 2. 00. 1, Spears released her self- titled third studio album, Britney, and played the starring role in the film Crossroads (2. She assumed creative control of her fourth studio album, In the Zone (2. Her fifth studio album, Blackout, was released later that year, and spawned singles such as . Her erratic behavior and hospitalizations continued through the following year, at which point she was placed under a still ongoing conservatorship. Spears's sixth studio album, Circus (2. Her seventh studio album, Femme Fatale (2. United States. She released her eighth studio album Britney Jean in 2. Later that year, Spears began the four- year residency show, Britney: Piece of Me, at The AXIS at Planet Hollywood Resort & Casino in Las Vegas. In 2. 01. 6, Spears released her ninth studio album, Glory. Spears is regarded as a pop icon and credited with influencing the revival of teen pop during the late 1. She became the 'best- selling teenage artist of all time'. In 2. 00. 9, Billboard ranked her as the 8th overall Artist of the Decade. According to Billboard Spears has sold about 2. US and is the fourth best- selling female artist since Nielsen Sound. Scan began. Her maternal grandmother, Lillian Portell, was English (born in London), and one of Spears's maternal great- great- grandfathers was Maltese. During her childhood, she also attended gymnastics and voice lessons, and won many state- level competitions and children's talent shows. She said about her ambition as a child, . Casting director Matt Casella rejected her for being too young to join the series at the time, but introduced her to Nancy Carson, a New York City talent agent. Carson was impressed with Spears's vocals and suggested enrolling her at the Professional Performing Arts School; shortly after, Lynne and her daughters moved to a sublet apartment in New York. Spears was hired for her first professional role as the understudy for the lead role of Tina Denmark in the Off- Broadway musical Ruthless! She also appeared as a contestant on the popular television show Star Search and was cast in a number of commercials. She enrolled at Parklane Academy in Mc. Comb, Mississippi. Although she made friends with most of her classmates, she compared the school to . I was the point guard on the basketball team. I had my boyfriend, and I went to homecoming and Christmas formal. Lynne asked family friend and entertainment lawyer Larry Rudolph for his opinion and submitted a tape of Spears singing over a Whitney Houston karaoke song along with some pictures. Rudolph decided he wanted to pitch her to record labels, therefore she needed a professional demo. He sent Spears an unused song of Toni Braxton; she rehearsed for a week and recorded her vocals in a studio with a sound engineer. Spears traveled to New York with the demo and met with executives from four labels, returning to Kentwood the same day. Three of the labels rejected her, arguing that audiences wanted pop bands such as the Backstreet Boys and the Spice Girls, and . And Britney had that. Spears had originally envisioned . I Did It Again. After Spears returned to the United States, she embarked on a shopping mall promotional tour to promote her debut album. Her show was a four song set and she was accompanied by two back up dancers. Her first concert tour followed, as an opening act for NSYNC. Billboard 2. 00 and was certified two- times platinum by the Recording Industry Association of America after a month. Worldwide, the album topped the charts in fifteen countries and sold over 1. Originally, Jive Records wanted its music video to be animated; however, Spears rejected it, and suggested the final idea of a Catholic schoolgirl. It has sold more than 1. It became a top- ten hit worldwide and propelled .. Baby One More Time to sell even more. As of today, it has sold 3. It is also the best- selling first album by any artist ever. The American Family Association (AFA) referred to the shoot as ? I thought the pictures were fine. And I was tired of being compared to Debbie Gibson and all of this bubblegum pop all the time. Spears premiered songs from her upcoming second album during the show. I Did It Again, her second studio album, was released in May 2. It debuted at number one in the US, selling 1. Sound. Scan record for the highest debut sales by any solo artist.! I Did It Again Tour, which grossed $4. Britney Spears' Heart- to- Heart, co- written with her mother. Halfway through the performance, she ripped off her black suit to reveal a sequined flesh- colored bodysuit, followed by heavy dance routine. It is noted by critics as the moment that Spears showed signs of becoming a more provocative performer. While on tour, she felt inspired by hip hop artists such as Jay Z and The Neptunes and wanted to create a record with a funkier sound. It was harshly received by animal rights organization PETA, who claimed the animals were mistreated and scrapped plans for an anti- fur billboard that was to feature Spears. The show was critically praised for its technical innovations, the pi. Although the film was largely panned, some critics praised Spears's acting. In December 2. 00. Timberlake released the song . The music video featured a Spears look- alike and fueled the rumors that she had been unfaithful to him. However, Spears denied Durst's claims. In a 2. 00. 9 interview, he explained that . Halfway through they were joined by Madonna, with whom they both kissed. The incident was highly publicized. She assumed more creative control by writing and co- producing most of the material. The marriage was annulled 5. Spears . Spears underwent arthroscopic surgery. She was forced to remain six weeks with a thigh brace, followed by eight to twelve weeks of rehabilitation, which caused The Onyx Hotel Tour to be canceled. The romance received intense attention from the media, since Federline had recently broken up with actress Shar Jackson, who was still pregnant with their second child at the time. They held a wedding ceremony on September 1. October 6 due to a delay finalizing the couple's prenuptial agreement. Child advocates were horrified by the photos of her holding the wheel with one hand and Sean with the other. Spears claimed that the situation happened because of a frightening encounter with paparazzi, and that it was a mistake on her part. The picture was heavily compared to Demi Moore's August 1. Vanity Fair cover. The following night, she shaved her head with electric clippers at a hair salon in Tarzana, Los Angeles. She admitted herself to other treatment facilities during the following weeks. The reasons of the court ruling were not revealed to the public. The album debuted at the top of charts in Canada and Ireland, number two in the U. S. Billboard 2. 00, France, Japan, Mexico and the United Kingdom and the top ten in Australia, Korea, New Zealand and many European nations. In the United States, Spears became the only female artist to have her first five studio albums debut at the two top slots of the chart. The performance was panned by many critics. She was hospitalized at Cedars- Sinai Medical Center after police that arrived at her house noted she appeared to be under the influence of an illicit substance. The following day, Spears's visitation rights were suspended at an emergency court hearing, and Federline was given sole physical and legal custody of the children. She was committed to the psychiatric ward of Ronald Reagan UCLA Medical Center and put on 5. The court placed her under temporary, and later, permanent. She received positive reviews for her performance, as well as bringing the series its highest ratings ever. She won Best Female Video, Best Pop Video and Video of the Year for . Directed by Phil Griffin, For the Record was shot in Beverly Hills, Hollywood, and New York City during the third quarter of 2. It was the highest rating in its Sunday night timeslot and in the network's history. It received positive reviews from critics. The single also topped the charts in Belgium, Canada, Denmark, Finland, France, Norway and Sweden. The restraining order forbids Lutfi and Ghalib from contacting Spears or coming within 2. The album's lead and only single, . The episode drew Glee's highest ratings ever. Its peak in the United States ties Britney with Mariah Carey and Janet Jackson for the third- most number ones among women. Femme Fatale became Spears's first album in which three of its songs reached the top ten of the chart. The music video caused controversy when British politicians criticized Spears for using replica guns while filming the video in an area of London that had been badly affected by the 2. England riots. Trawick was also removed as Spears's co- conservator, restoring her father as the sole conservator. Reid and fellow new judge Demi Lovato, who replaced Paula Abdul. With a reported salary of $1. Spears did not return for the show's third season and her spot was filled by Kelly Rowland. The song later became Spears's sixth number one single on the UK Singles Chart and peaked at #3 on US Billboard Hot 1. Scream & Shout was among the best selling songs of 2. VEVO despite the video being released in 2. It began on December 2. Billboard 2. 00 with first- week sales of 1. United States. In doing so, it became Spears's lowest- charting and lowest- selling album in the country. Billboard Hot 1. 00 marking Spears's 3. It also marked Spears's 1. It also entered the top 1. U. S Billboard Hot Digital Songs chart at number 6 and debuted at number 2 on both the U. S. Billboard chart's Hot Dance Club Songs and Hot Dance/Electronic Songs. Also its debut on the U. S. Billboard Pop Songs chart at number 2. |
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