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  • Scientific Reviewers Suggest It Will Take Another Decade To Determine If Resveratrol Is Beneficial; Recent Review Overlooks Science Behind Best-Tested Resveratrol Pill.

    July 7, 2016: by Bill Sardi

    A major review of the scientific evidence surrounding the miracle molecule resveratrol (rez-vair-ah-trol) begs for more studies that already exist, ignores important qualities of this molecule such as “preconditioning” that protects the brain and heart from damage should a stroke or heart attack occur, suggests humanity wait at least another decade before making a decision as to its contribution to health promotion and longevity, and ignores science surrounding the best-tested resveratrol product on the market today (Longevinex®).  [Nutrients June 2016]

    And that is the kindest of comments that can be made for this recently published report that creates more confusion than it does clarification.

    The European-based reviewers suggest a drug model to evaluate resveratrol – it’s ability to prevent or treat disease –which is the regulatory territory for prescription drugs.  Therefore, there is no application for resveratrol outside of a prescriptive Rx model in the minds of these researchers.

    The report says “preventive studies in humans… should be long-term (5-10 years) in order to see a preventive effect” and limited to miniscule low doses (2-5 mg/day) that are obtained from the diet (wine).  In other words, forget the red wine pills.

    These reviewers were, like others, misled by a study that mistakenly concluded there was no health benefit obtained from resveratrol among wine drinkers in Italy.  [JAMA Internal Medicine] They join others who missed the fact that the percentage of adults judged to be in mental decline was 32.8% in the teetotaler-low-wine consumption group versus just 16.4% among those who drank 2.6 glasses of wine a day.  [Resveratrol News May 12, 2014]  If scientists and biology-trained journalists missed this discovery, what are we left to think but that the research community is censoring the science?

    Since quite a few thousand health seekers are venturing forward in an unguided experiment to see if resveratrol actually does live up to its calling as an anti-aging pill by taking doses of daily resveratrol that far exceed what is consumed from the diet, the suggestion of long-term low-dose studies appears to be a backwards direction.  The begged-for question is, does anybody get any health benefit out of taking resveratrol pills today?

    The answer is a limited yes: “It is safe to say that resveratrol prevents the development of coronary vascular disease, improves insulin sensitivity, reduces serum glucose, and prevents the development of cancers of the skin, colon and prostate in animal models,” said the reviewers.  Here, here! There is at least evidence veterinarians should be prescribing resveratrol! But let’s not let it out of the animal lab for Big Pharma’s sake.

    Lack of bioavailability

    The reviewers also keep harping about the lack of resveratrol’s bioavailability.  However, this is a moot argument scientifically.  Bioavailability refers to the ability of resveratrol to get past the liver’s detoxification system.  The liver intercepts resveratrol and complexes it with detox molecules (glucuronate, sulfate) as it is perceived as a biological stressor that must be controlled.  Resveratrol mimics a food deprivation signal (calorie restriction).  However, the liver metabolites of resveratrol have been found to be as biologically active if not more active than free unbound resveratrol.  [; Science Translational Medicine 2013]

    Furthermore, unbound (free) resveratrol only has a half-life of ~14 minutes whereas liver metabolized resveratrol has a half-life of 9 hours.  [Drug Metabolism Disposition 2004] So creating newer versions of resveratrol that inhibit liver metabolism, such as resveratrol lozenges, etc., as mentioned by the reviewers, is counterproductive and hastens the excretion of resveratrol in urine.

    The accompaniment of quercetin or piperine with resveratrol allows more passes through the liver before it is metabolized and thus facilitates more immediately available resveratrol, but eventually it is all metabolized in the liver.  [British Journal Nutrition 2014; Xenobiotica 2000]  Various brands of resveratrol already provide these companion nutrients to enhance immediate availability.

    Furthermore, micronization (reduction of the diameter) of resveratrol has been shown to improve blood concentrations and consumers need not wait as some brands of micronized resveratrol are already offered (Longevinex®), a fact not mentioned by the reviewers.  [Canadian Journal Physiology Pharmacology 2010]

    Synergistic with other molecules

    While synergistic effects of resveratrol with other molecules like quercetin and catechin is mentioned in the report, the most demonstrable examples are not reported.  For example, in 2008 researchers reported that plain resveratrol significantly differentiates (activates or silences) 225 genes in a 12-week animal study.  When resveratrol was combined with quercetin, rice bran IP6 (Longevinex®), it activated 1711 genes!  That certainly is the most dramatic example of molecular synergism.  That is 9-fold more gene activity than plain resveratrol.  [Experimental Gerontology 2008]

    Then in 2010 researchers again demonstrated that a resveratrol complex (Longevinex®) exhibited a more demonstrable effect than plain resveratrol in reduction of damage to the heart in an experimental model of heart attack in animals.  [PLoS One 2010]

    Longevinex® activated microRNA20b that limits new blood vessel formation (angiogenesis or neovascularization) six-fold better than plain resveratrol.  Anti-angiogenesis inhibitors are used clinically and experimentally to inhibit the growth of tumors and halt destruction of the visual center of the eye in cases of wet macular degeneration.

    Longevinex® has actually been shown in published case reports to inhibit the formation of visually destructive new blood vessels at the back of human eyes.  [Nutrients 2014]  So this effect has been demonstrated in humans, not just in the animal lab.

    Furthermore, when resveratrol was put to the test to see how well it helped to activate widening (dilation) of blood vessels as the heart rate increases, Longevinex® was shown to be twice as effective than plain resveratrol.  Again, this effect was demonstrated in humans.  [Journal Cellular Molecular Medicine 2012; Dec 1, 2011]

    Lead researcher ignored

    The review also ignored the work of the most prolific resveratrol researcher, the late Dipak Das PhD, whose lifetime of work was discredited over contrived charges of scientific fraud.  Other researchers later repeated Dr. Das’ studies and validated all of his work.  [ Oct 19, 2015]

    Among the 130 scientific references listed in this published review, not a single one cited the work of Dipak Das.  A link to 50 of studies and papers authored by Dr. Das can be reviewed at the National Library of Medicine.

    It was Dipak Das PhD who was answering the questions posed by the reviewers, such as how much resveratrol should be consumed by healthy adults?  Das showed that the human equivalent of 175-350 mg of resveratrol produced a protective effect in the rodent heart but that ten times as much resveratrol (1750-3500 mg) actually induced more, not less, heart damage when a heart attack was intentionally induced in lab animals.  Furthermore, Das reported that a much lower dose of resveratrol (100 mg human equivalent) produced an even more protective effect in the rodent heart when combined with other molecules (Longevinex®).  [PLoS One 2010]

    Reviewers suggest resveratrol may be of no measurable benefit for perfectly healthy adults.  Resveratrol activates an internal antioxidant system in the body prior to a heart attack or stroke, thus limiting tissue damage should such an event occur.

    Consistent with the above animal studies, there are five anecdotal reports from Longevinex® users who have experienced heart attacks with no reported damage to their heart muscle.  Here is the incredulous account of one:

    Testimony of Don D: On May 15th, 2013 at 6:00pm at the age of 54, I had a sudden cardiac arrest.  By the time the first responders came to the house, I had been in cardiorespiratory arrest for an indeterminate amount of time, nonetheless using a defibrillator got my heart beating again.   In the ambulance on the way to the hospital, I arrested a second time.   The ambulance pulled over for a minute to apply another electroshock, but they couldn’t get a pulse.  I arrived at the ICU a few minutes later still in cardiorespiratory arrest, but another defibrillation attempt and a cocktail of drugs got the pulse back.  I was critical until around midnight when I arrested a third time, this time it took 6 electroshocks to get a pulse.  I was put in an induced coma for 4 days.  After I awoke I spent a couple more weeks in recovery.  I’ve been told that I had a 5% survival rate, but I went home and made a full recovery with no brain damage and no heart damage.  At that time, I had been taking Longevinex® daily for at least 5 years.  Anecdotal for sure, but I feel that based on what I know of the properties of Resveratrol, it had a net beneficial effect in my full recovery.

    You may be healthy.  You may not feel any better taking a resveratrol pill.  But by taking a resveratrol pill every day you may also be acquire a level of life-saving protection that is only demonstrated in time of critical need.

    Poor solubility

    The poor solubility of resveratrol was also addressed by  reviewers.  Resveratrol is a fat-soluble nutrient that binds to proteins, lipids (fats) and cholesterol.  Resveratrol delivered in wine is apparently more soluble than in water.  The inclusion of beta cyclodextrin, a plant-based sugar-like molecule, has been proposed to address solubility and is currently under development in a commercially available brand. (Longevinex®). [Bellstein Journal Organic Chemistry 2014; Critical Review Food Science Nutrition 2015]  Beta cyclodextrin + resveratrol appears to increase resveratrol’s antioxidant properties. [Journal Agriculture Food Chemistry 2008]

    Reviewers did note that efforts to increase the bioavailability of resveratrol, may increase the risk for toxicity.  However, in a dramatic study, researchers found, unlike plain resveratrol, Longevinex® did not increase toxicity in lab animals in equivalent human doses up to 2800 mg. [Experimental Clinical Cardiology 2010] At this same dose, plain resveratrol kills the rodent heart.

    A greatly enhanced resveratrol pill that overcomes alleged issues of bioavailability and toxicity and has demonstrated effectiveness in humans is commercially available, a fact overlooked by reviewers.  That scientific reviewers selectively choose the science they want to report mischaracterizes the promise of resveratrol in human health. ©2016 Bill Sardi


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