Resveratrol

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Resveratrol:

A flavonoid-like molecule found in grapes, mulberries, and other plants, resveratrol mimics the healthy aging effects of calorie restriction.

A significant decrease in the harmful effects of a high-fat, high-calorie diet was observed in mice, most likely due to increased fat metabolism from the up-regulation of the SIRT-1 enzyme, which acts as a cellular switch by both increasing the number of mitochondria and supporting their function. SIRT-1 also has a positive impact on blood glucose metabolism, insulin sensitivity, and cell survival.

Resveratrol – Pain

Inhibition of Cox Enzymes

It has been proposed that resveratrol reduces pain via multiple mechansms. It decreases the production of prostaglandin E2 (PGE2) by inhibiting Cox-1 and Cox-2 activity. PGE2 is well-known as a proinflammatory mediator and sensitizer of peripheral and central pain receptors (nociceptors ). The Cox enzymes, cyclooxygenase-1 and cyclooxygenase-2 (Cox-1 and Cox-2) are key players in the development of  inflammation and pain.  The mechanism by which NSAIDs such as ibuprofen and naproxen alleviate pain is by inhibiting Cox-1 and Cox-2 enzymes.

Animal studies suggest that chronic administration of resveratrol reduces inflammation-induced mechanical inflammatory pain and hyperalgesia, the magnified experience of pain associated with chronic pain.

[20,24,25].

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Resveratrol – Calorie Restriction

Resveratrol – Cardiovascular

 

Cardiovascular disease (CVD) consists of many disorders that affect the heart and the blood vessels including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, heart failure, cardiomyopathies, and rheumatic and congenital heart disease. This group of CVD disorders is associated with multiple risk factors that have complex interactions between them. One of the main targets for reduction of cardiovascular risk, from lifestyle changes to pharmacological treatments, is reduction in oxidative stress.

 

Oxidative Stress

“Oxidative stress” is an imbalance in the body of excessive “oxidants” (oxidizing or chemically active, agents, including free radicals obtained from the diet or produced by the body) and insufficient “antioxidants” (chemically active agents that are also obtained from the diet or produced by the body) and neutralize oxidants. This overabundance of oxidants causes damage to biomolecules, (lipids, proteins, DNA), cells and tissue, eventually contributing to aging and chronic diseases including chronic inflammation, arthritis and pain, atherosclerosis, cancer, diabetes, heart diseases and stroke.

 

Free radicals

Free radicals are molecules with unpaired electron in their outer orbit. This unpaired electron makes the free radical highly reactive with molecules in cells and tissues. While free radicals  have beneficial roles in some biochemical activities, excessive levels of free radicals leads to tissue damage.  People are constantly exposed to free radicals in their environment created by electromagnetic radiation, pollutants and cigarette smoke and natural sources such as radon and cosmic radiation. In addition, the human body produces free radicals and other reactive species as byproducts of numerous physiological, metabolic and biochemical processes. The most common cellular free radicals are hydroxyl (OH·), superoxide (O –·) and nitric monoxide (NO·). Other molecules like hydrogen peroxide (H2O2) and peroxynitrite (ONOO–) generate free radicals through various biochemical reactions.

Antioxidants

Antioxidants are produced in the mitochondria within cells throughout the body and serve to detoxify free radicals and protect tissues from such damage. Another important source of antioxidants is the diet, and diets rich in antioxidants are protective against the disease processes noted above. Fruits and vegetables are especially rich in antioxidants including . vitamin E, vitamin C, vitamin A, curcumin, resveratrol, glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, and polyphenols found in tea. .Diets rich in fruits and vegetables result in high blood antioxidant capacity and reduced oxidative stress. Antioxidant activity is further supported by antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase that exert synergistic actions in removing free radicals.

 

Dietary Supplementation with Antioxidants

The cardioprotective effect of eating foods rich in antioxidants is well known – see Diets  In contrast, studies on the use of antioxidant supplements, both short- and long-term, have provided inconsistent support for their cardioprotective effects.

 

Reference Publications

Resveratrol –  Overview

  1. Grape seed | University of Maryland Medical CenterResveratrol – a supplementation for men or for mice? – 2014
  2. Resveratrol in metabolic health: an overview of the current evidence and perspectives. – PubMed – NCBI
  3. Antioxidants in Translational Medicine – 2015

 

Resveratrol – Aging

  1. Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells – 2011
  2. Resveratrol delays age-related deterioration – 2008
  3. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan – 2008
  4. The molecular targets of resveratrol. – PubMed – NCBI

Resveratrol – Bioavailability

  1. Bioavailability and activity of phytosome complexes from botanical polyphenols – the silymarin, curcumin, green tea, and grape seed extracts – 2009
  2. Bioavailability and Metabolism of Resveratrol – 2010

 

Resveratrol – Cardiovascular

  1. Resveratrol in cardiovascular disease: what is known from current research? – PubMed – NCBI – 2012
  2. Phytochemical Compounds and Protection from Cardiovascular Diseases – A State of the Art – 2015
  3. Impaired Oxidative Status Is Strongly Associated with Cardiovascular Risk Factors – 2017
  4. Antioxidants and Cardiovascular Risk Factors – 2018

 

Resveratrol – Diabetes

  1. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. – PubMed – NCBI
  2. Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits? – PubMed – NCBI

 

Resveratrol – Endometriosis

  1. The Combination of N-Acetyl Cysteine, Alpha-Lipoic Acid, and Bromelain Shows High Anti-Inflammatory Properties in Novel In Vivo and In Vitro Models of Endometriosis – 2015
  2. New insights on the pathogenesis of endometriosis and novel non-surgical therapies – 2018
  3. Can Herbal Medicines Improve Cellular Immunity Patterns in Endometriosis? – 2015
  4. Endometriosis, a disease of the macrophage. – 2013
  5. Pharmacologic therapies in endometriosis: a systematic review. – PubMed – NCBI – 2012
  6. Medical therapy for endometriosis: a literature review – 2015
  7. Pharmacologic therapies in endometriosis: a systematic review – ScienceDirect – 2012
  8. Chinese herbal medicine for endometriosis. – PubMed – NCBI – 2012
  9. Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway. – PubMed – NCBI – 2014
  10. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain – 2012
  11. Therapeutic Approaches of Resveratrol on Endometriosis via Anti-Inflammatory and Anti-Angiogenic Pathways – 2019
  12. The Use of Resveratrol as an Adjuvant Treatment of Pain in Endometriosis – A Randomized Clinical Trial – 2017
  13. Natural therapies assessment for the treatment of endometriosis. – PubMed – NCBI – 2013
  14. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota. – PubMed – NCBI 2019

 

Resveratrol – Liver Disease

  1. Antioxidants in liver health – 2015
  2. Critical review of resveratrol in xenobiotic-induced hepatotoxicity. – PubMed – NCBI 2015

 

Resveratrol – Mitochondria

  1. Dosis Facit Sanitatem – Concentration-Dependent Effects of Resveratrol on Mitochondria – 2017

 Resveratrol – Nanoformulations

  1. Administration of resveratrol: What formulation solutions to bioavailability limitations? – PubMed – NCBI
  2. Bioavailability and Activity of Phytosome Complexes from Botanical Polyphenols – e Silymarin, Curcumin, Green Tea, and Grape Seed Extracts – 2009
  3. Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol. – PubMed – NCBI
  4. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability – 2013
  5. Resveratrol nanoformulation for cancer prevention and therapy. – PubMed – NCBI
  6. Resveratrol nanoformulations: challenges and opportunities. – PubMed – NCBI
  7. Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents – 2017
  8. Bioavailability and activity of phytosome complexes from botanical polyphenols – the silymarin, curcumin, green tea, and grape seed extracts. – 2009


Resveratrol – Neuroinflammation

  1.  Repeated resveratrol administration confers lasting protection against neuronal damage but induces dose-related alterations of behavioral impairments after global ischemia – 2011
  2. Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK – 2016
  3. The molecular targets of resveratrol. – PubMed – NCBI
  4. Repeated resveratrol administration confers lasting protection against neuronal damage but induces dose-related alterations of behavioral impairments after global ischemia – 2011
  5. Resveratrol regulates N-methyl-D-aspartate receptor expression and suppresses neuroinflammation in morphine-tolerant rats. – PubMed – NCBI
  6. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression – 2016
  7. Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK – 2016
  8. Reviewing the Role of Resveratrol as a Natural Modulator of Microglial Activities. – PubMed – NCBI

 

Resveratrol – NMDA Antagonism

  1. The dietary constituent resveratrol suppresses nociceptive neurotransmission via the NMDA receptor – 2017

 

Resveratrol – Obesity

  1. Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans – 2011
  2. Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? – PubMed – NCBI
  3. Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits? – PubMed – NCBI 2013

 

Resveratrol – Opioid Tolerance

  1. Resveratrol reduces morphine tolerance by inhibiting microglial activation via AMPK signalling. – PubMed – NCBI

 

Resveratrol – Oxidative Stress

  1. Impaired Oxidative Status Is Strongly Associated with Cardiovascular Risk Factors – 2017
  2. Antioxidants and Cardiovascular Risk Factors – 2018
  3. Oxidative Stress and Neurodegenerative Diseases – A Review of Upstream and Downstream Antioxidant Therapeutic Options – 2009

 

Resveratrol – Pain

  1. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol – 2016
  2. Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats. – PubMed – NCBI
  3. The dietary constituent resveratrol suppresses nociceptive neurotransmission via the NMDA receptor – 2017

 

Resveratrol – Safety

  1. Safety of resveratrol with examples for high purity, trans-resveratrol, resVida(®). – PubMed – NCBI

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

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Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

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