Can High-Dose Resveratrol Slow Dementia?

R. Scott Turner, MD, PhD Director of the Memory Disorders Program Georgetown University Medical CenterMedicalResearch.com Interview with:
R. Scott Turner, MD, PhD
Director of the Memory Disorders Program
Georgetown University Medical Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Turner: The resveratrol trial originated from the extensive scientific literature demonstrating that caloric restriction (consuming only 2/3 usual calories) prevents or delays diseases of aging – including Alzheimer’s disease (AD) in laboratory animals. The molecular mechanism is thought to involve sirtuins – a group of genes/proteins that sense energy balance to regulate gene expression. Sirtuins are activated by caloric restriction (a mild stressor) to express genes that promote resilience of the organism. Resveratrol is a potent activator of sirtuins – thus bypassing the requirement for caloric restriction. On the opposite side of the coin – caloric excess, midlife obesity, and diabetes are strong risk factors for Alzheimer’s disease. And we have long-known that resveratrol is found in red grapes, red wine, and other foods that promote general health.

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Resveratrol In Food May Help Maintain Memory and Mood Function in Old Age

Ashok K. Shetty, Ph.D. Professor and Director of Neurosciences Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine
Texas A&M Health Science Center College of Medicine, Temple, TX
Research Career Scientist, Central Texas Veterans Health Care System (CTVHCS), Temple, TXMedicalResearch.com Interview with:
Ashok K. Shetty, Ph.D.
Professor and Director of Neurosciences
Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine
Texas A&M Health Science Center College of Medicine, Temple, TX
Research Career Scientist, Central Texas Veterans Health Care System (CTVHCS), Temple, TX

Medical Research: What is the background for this study?

Prof. Shetty: Hippocampus is a region in the brain important for maintaining functions such as learning, memory and mood. However, this region is highly vulnerable to aging and brain insults. Previous research has shown that diminished function in the dentate gyrus region of the hippocampus is one of the key reasons for memory impairments seen in old age. Dentate gyrus is also one of the few regions in the brain where neural stem cells generate new neurons on a daily basis, also referred to as “adult neurogenesis”. Studies have suggested that a significant fraction of newly born neurons mature, get incorporated into the existing hippocampus circuitry and contribute to learning, formation of new memories, and normal mood. However, with aging, the dentate gyrus shows decreased function with some conspicuous structural changes, which include reduced production of new neurons, diminished microvasculature implying reduced blood flow, and occurrence of hypertrophy of astrocytes and activated microglia, signs of chronic low-level inflammation. Because alterations such as reduced neurogenesis, decreased blood flow and brain inflammation can contribute to memory and mood impairments, the idea that drugs that are efficacious for mitigating these changes may preserve memory and mood function in old age has emerged. Such drugs may be prescribed to the aging population if they are efficacious for maintaining normal cognitive and mood function in old age with no or minimal side effects.

Medical Research: What is the rationale for choosing resveratrol for preventing age-related memory dysfunction in this study?

Prof. Shetty:  Administration of resveratrol, a naturally occurring polyphenol found in the skin of red grapes, red wine, peanuts and some berries, appeared suitable for counteracting age-related detrimental changes in the hippocampus. This is because, previous studies have shown that resveratrol has ability to promote the formation of new capillaries (through pro-angiogenic effects) and to suppress oxidative stress and inflammation (via antioxidant and antiinflammatory effects) with no adverse side effects. Other studies have also reported that resveratrol can mediate extension of the life span and delayed onset of age related diseases. More importantly, a recent human study suggested that a reasonably lower dose of resveratrol intake for 26 weeks is good enough to improve memory performance as well as hippocampus functional connectivity in 23 healthy overweight older individuals (Witte et al., J. Neurosci., 34: 7862-7870, 2014).

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New Mechanism of Resveratrol Stress Response Described

Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California MedicalResearch.com Interview with:
Paul Schimmel, Ph.D. Professor
The Skaggs Institute for Chemical Biology,
The Scripps Laboratories for tRNA Synthetase Research
Department of Molecular and Cell Biology,
The Scripps Research Institute, La Jolla, California

Medical Research: What is the background for this study? What are the main findings?

Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism.
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Resveratrol May Enhance Acne Treatment With Benzoyl Peroxide

Dr. Emma Taylor MD UCLA Division of Dermatology and Department of Medicine David Geffen School of Medicine Los Angeles, CA,MedicalResearch.com Interview with:
Dr. Emma Taylor MD
UCLA Division of Dermatology and Department of Medicine
David Geffen School of Medicine
Los Angeles, CA,


Medical Research: What are the main findings of the study?

Dr. Taylor: The main findings is that resveratrol, an antioxidant has antibacterial activity against Proprionibacterium acnes, the bacteria that causes acne, and that the combination with benzoyl peroxide, the current gold standard for topical acne therapy, has enhanced and sustained antibacterial activity when compared either compound alone. Additionally resveratrol was less toxic to keratinocytes and monocytes which are cells found in the skin, and this may translate to less irritation as a topical acne therapy.

Medical Research: What was most surprising about the results?

Dr. Taylor: That the combination of an oxidant (benzoyl peroxide) and an antioxidant (resveratrol) had enhanced and sustained antibacterial activity. We initially hypothesized that the effects of both compounds would essentially cancel each other out.

Medical Research: What should clinicians and patients take away from your report?

Dr. Taylor: What is most important about this study is that antioxidants such as resveratrol, may be useful adjuvants for topical acne therapy when used in combination with benzoyl peroxide. Since topical acne therapies are traditionally irritating, leading to reduced patient compliance and treatment failures, a combination therapy using resveratrol and benzoyl peroxide may allow for enhanced activity but with reduced irritation, as lower concentrations of benzoyl peroxide could then be used.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Taylor: All our studies were done in vitro, meaning in a laboratory setting, and therefore have to be validated in human studies and clinical trials to evaluate for efficacy and tolerability.

Citation:

Resveratrol Demonstrates Antimicrobial Effects Against Propionibacterium acnes In Vitro
Dermatol Ther (Heidelb). 2014 Sep 17. [Epub ahead of print]
Taylor EJ1, Yu Y, Champer J, Kim J.

Study Cautions Against Resveratrol Supplements During Pregnancy

Antonio E. Frias, MD Associate Professor | Division of Maternal Fetal Medicine Oregon Health & Science University Director, Diabetes and Pregnancy Program Assistant Scientist | Oregon National Primate Research Center Portland, Oregon 97239MedicalResearch.com Interview with:
Antonio E. Frias, MD
Associate Professor | Division of Maternal Fetal Medicine
Oregon Health & Science University
Director, Diabetes and Pregnancy Program
Assistant Scientist | Oregon National Primate Research Center
Portland, Oregon 97239

MedicalResearch: What are the main findings of the study?

Dr. Frias: Resveratrol supplementation in pregnant nonhuman primates fed a Western-style diet improved maternal metabolism, restored placental blood flow, reduced placental inflammation and improved lipid deposition in the fetal liver.  However, there was an unexpected disruption of fetal pancreatic development that is very concerning.
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