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Overview

Name: Resveratrol Clinical Research Trials

Description: Alzheimer's, Colon Cancer, Diabetes, Metabolic Syndrome X, Lymphoma

Creator: Pepper_PhD

This casebook is published and has been read 3533 times.

The author of this casebook has identified the following medical topics as being highly relevant to this casebook.

• Metabolic Syndrome X -- A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
  
• Multiple Myeloma -- A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
  
• Prevention, Early Detection of Premalignant Lesions -- A procedure that includes screening, diet and behavioral adjustments to prevent and/or detect the transformation of normal cells into cancerous lesions.
  
• Diabetes Mellitus, Non-Insulin-Dependent -- subclass of diabetes mellitus that is not insulin responsive or dependent; characterized initially by insulin resistance and hyperinsulinemia and eventually by glucose intolerance, hyperglycemia, and overt diabetes; type II diabetes mellitus is no longer considered a disease exclusively found in adults; patients seldom develop ketosis but often exhibit obesity.
  
• Lymphoma, Follicular -- Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.
  
• Alzheimer's Disease -- A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
  
• Metabolism and nutrition disorders -- A class of disorders that encompasses conditions occurring as a result of metabolic dysfunction or deviation from the normal nutritional requirements. (NCI)
  
• Colon Carcinoma -- A disease in which malignant (cancer) cells are found in the tissues of the colon.
  
• Premature aging syndrome -- Changes in the organism associated with senescence, occurring at an accelerated rate.
  
• Malignant Neoplasms -- A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system to other parts of the body.
  

Notes

As of today, Wednesday 22 July 2009, I found 2841 articles in medical journals containing the word resveratrol. 1276 of these articles somehow apply to humans, with the rest involving experiments in animals. 257 of these articles (published from 1995 until the present) are either review articles (summarizing the contents and conclusions of primary articles) or meta-analyses (analyzing and reaching a consensus on the results of other studies). All of these articles were found using the word 'resveratrol' as a search term in the PubMed database at the U.S. National Library of Medicine (http://www.ncbi.nlm.nih.gov)

These articles cover a number of diseases in which resveratrol may be useful in prevention or treatment; these diseases include various types of cancer, cardiovascular disease, neurodegenerative diseases (e.g. Alzheimer's), age-related eye diseases, liver disease, inflammation and arthritis. The web site www.ClinicalTrials.gov currently lists 14 clinical research trials involving use of resveratrol in a number of diseases and are included as bookmarks with this casebook.

Below is the text of a press release from the U.S. National Institute on Aging that reports on some published work by Professor David Sinclair and others.

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Resveratrol Found to Improve Health, But Not Longevity in Aging Mice on Standard Diet

Embargoed for Release:
Thursday, July 3, 2008
12:00 PM EDT

Media Contact:
Megan Homer
301-496-1752
nianews3@mail.nih.gov

Scientists have found that the compound resveratrol slows age-related deterioration and functional decline of mice on a standard diet, but does not increase longevity when started at middle age. This study, conducted and supported in part by the National Institute on Aging (NIA), part of the National Institutes of Health, is a follow-up to 2006 findings that resveratrol improves health and longevity of overweight, aged mice. The report confirms previous results suggesting the compound, found naturally in foods like grapes and nuts, may mimic, in mice, some of the effects of dietary or calorie restriction, the most effective and reproducible way found to date to alleviate age-associated disease in mammals. 

The findings, published July 3, 2008, in Cell Metabolism, may increase interest in resveratrol as a possible intervention for age-related declines, said NIA scientists. The authors emphasized, however, that their findings are based on research in mice, not in humans, and have no immediate and direct application to people, whose health is influenced by a variety of factors beyond those which may be represented in the animal models.

 

The study is a collaborative effort between the laboratories of Rafael de Cabo, Ph.D., of the Laboratory of Experimental Gerontology at the NIA; David A. Sinclair, Ph.D., of the Glenn Laboratories for Molecular Biology of Aging at Harvard Medical School; and an international group of researchers. The investigators compared mice fed a standard diet, a high-calorie diet, or an every-other-day feeding regimen with or without high- or low-dose resveratrol to study the impact of resveratrol on aging and health. In previous studies, different forms of dietary restriction, including every-other-day feeding, have been shown to improve markers of health.

“Research is attempting to understand the process of aging and to determine how interventions can influence this process. Dietary restriction has well-documented health benefits in mammals, and the study of possible mimetics of it, such as resveratrol, are of great interest,” said NIA Director Richard J. Hodes, M.D. “Resveratrol has produced significant effects in animal models, now including mice, where it mimics some, but not all, consequences of caloric restriction. Its effects in humans remain to be studied.”

A major finding of the study reported today is that resveratrol prevented age-related and obesity-related cardiovascular functional decline in the mice as determined by several parameters. Total cholesterol was significantly reduced in 22-month-old non-obese mice after 10 months of resveratrol treatment, although triglyceride levels had only a slight, non-significant trend toward a decrease. Further, the aortas of 18-month-old obese and non-obese mice treated with resveratrol functioned significantly better than untreated mice. Resveratrol also moderated inflammation in the heart.

In addition to cardiovascular function, the scientists found resveratrol to have a variety of positive effects on other age-related problems in mice:

• Treated mice tended to have better bone health, as measured by thickness, volume, mineral content and density, and bending stiffness compared to the non-treated control group.
• At 30 months of age, resveratrol-treated mice were found to have reduced cataract formation, a condition found to increase with age in control-group mice.
• Resveratrol enhanced balance and motor coordination in aged animals. Scientists found significant improvement in performance at 21 and 24 months versus 15 months in the resveratrol-treated mice but not in the untreated mice.
• Resveratrol partially mimicked the effects of dietary restriction on the gene expression profiles of liver, skeletal muscle and adipose (fatty) tissue in mice.

Along with determining the effect of resveratrol on the health of mice, scientists also studied the effect of resveratrol on longevity.

“We found that while quality of life improved with resveratrol, the compound did not significantly affect overall survival or maximum lifespan for mice on a standard diet, compared to mice on the same diet without resveratrol,” said de Cabo.

Resveratrol did not have a significant effect on lifespan in animals fed standard chow, suggesting that the intervention did not affect all aspects of the basic aging process. Mice on a high-calorie diet without resveratrol lived the shortest length of time and mice on an every-other-day regimen lived the longest, regardless of resveratrol treatment. However, for mice on a high-calorie diet, mean and maximum lifespan increased for mice on resveratrol when compared with the control mice. Researchers found that resveratrol’s effects on longevity could be completely uncoupled from changes in body weight, meaning that mice on a high-calorie diet with resveratrol did not necessarily lose weight but did experience a longer (and healthier) life than mice on the same high-calorie diet not taking resveratrol. They speculate that improved cardiovascular health and reduced fatty changes in the liver may have contributed to the increased lifespan of resveratrol-treated mice.

Researchers still have much to learn before resveratrol can be recommended for human use. Basic questions of safety and biological effect in humans remain to be studied experimentally.

“We are learning a great deal about how resveratrol affects the health and survival of mammals,” said Sinclair. “Continued study of calorie restriction mimetics such as resveratrol may eventually point the way to new medicines to treat diseases of aging.”

In addition to scientists from the NIA and Harvard Medical School, researchers from the following institutions collaborated in this study: New York Medical College, Valhalla, N.Y.; University of Michigan, Ann Arbor; University of Sydney in Australia; Thomas Jefferson University, Philadelphia; University of California, San Diego, La Jolla; Hospital for Special Surgery, New York, N.Y.; University of Cincinnati, Ohio; University of Texas Health Science Center at San Antonio and Audie Murphy VA Hospital, San Antonio, Texas; Universidad Pablo de Olavide, Sevilla, Spain; Pennington Biomedical Research Center, Baton Rouge, La.; University of Washington, Seattle; and Sirtris Pharmaceuticals of Cambridge, Mass., a company founded by Harvard University co-lead author Sinclair

De Cabo is a scientist in the NIA’s Intramural Research Program. In addition, the research was funded by grants from the NIA, the primary supporter of the work, as well as grants from the National Institute of General Medical Sciences; the National Heart, Lung, and Blood Institute; the National Institute of Child Health and Human Development; the National Eye Institute; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH. The Ellison Medical Research Foundation, the American Heart Association, the Australian and Spanish governments and Paul F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging also provided support to members of the research team.

The NIA leads the federal government effort conducting and supporting research on the biomedical and social and behavioral aspects of aging and the problems of older people. For more information on healthy aging, aging-related research and the NIA, please visit the Institute’s website at www.nia.nih.gov

NIH—the nation’s medical research agency—includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov

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Bookmarks The following information, which has been distilled by the casebook author from this and other websites is particularly relevant to this casebook.