Comprehensive Library Of Resveratrol News

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3. Modest doses of natural molecules in Longevinex® activate internal antioxidant defenses

A biological phenomenon called hormesis has yet to be incorporated into the daily practice of medicine or even included into daily self-care regimens. Hormesis asserts that the human body, exposed to mild biological stressors, will respond by increasing internal antioxidant defenses. Some of these biological stressors are oxygen deprivation (high altitude), low-dose radiation (radon gas, solar rays) and food deprivation.

It has been demonstrated that the molecules that mimic calorie restriction also activate this same endogenous antioxidant defense system.

In calorie restricted animals a gene transcription factor called Nrf2 docks up next to and binds to strands of DNA which triggers the production of antioxidant enzymes glutathione, catalase and superoxide dismutase (SOD). [Antioxidant Redox Signaling April 2011] It is the activation of these internal antioxidants prior to a heart attack that results in minimal harm to heart muscle during a heart attack.

Two physicians have independently contacted me to say they prescribed an Nrf2-promoting anti-Parkinson’s drug (Deprenyl/Eldepryl: selegiline) and their mothers lived in good health and maintained mental faculties to the age of 103 and 109 years. [Toxicology Dec 18, 2011; ResveratrolNews.com Feb 11, 2013] It appears activation of internal antioxidants will accomplish far more health-wise than taking oral antioxidants.

Only mild doses produce this beneficial effect. Resveratrol pills, or any polyphenolic molecule like curcumin from turmeric spice or catechin from green tea, if provided in an excessive dose will promote oxidation and negate the Nrf2 activation of internal antioxidants. Taking mega-dose resveratrol pills that are advertised to provide more for your money may be biologically counterproductive.

The health benefits proposed by resveratrol for healthy individuals appear to be delivered by modest doses only. This fact is confirmed by a study where high-dose resveratrol inhibited the viability of natural killer cells whereas modest dose increased natural killer cell activity. [Journal Agriculture Food Chemistry Oct 2014]

In fact, biologists laud resveratrol, the red wine molecule, for its longevity effects but await further tests to determine the optimal hormetic dose that activates internal antioxidant defenses. [Human Experimental Toxicology Dec 29, 2010]

Longevinex® is formulated to match the amount of wine solids (polyphenols) provided in 3-5 glasses of red wine that has been shown to be the dosage range that produces optimal health benefits. One 5-oz. glass of dark aged red wine provides ~60 milligrams of polyphenols; 3-5 glasses provide ~180-300 milligrams of polyphenols, the primary ones being quercetin, catechin and resveratrol. Longevinex® provides 200 milligrams of resveratrol, quercetin and rice bran IP6 per capsule leaving room for a glass of red wine or two.

The only branded resveratrol-based product that has undergone dose and toxicity testing is Longevinex®. Generic resveratrol was found to exert optimal cardio-protection in lab animals at a human equivalent dosage range of 175-350 milligrams whereas Longevinex® exerted more of a protective effect at 100 mg of resveratrol and total polyphenols of just 200 milligrams overall [Canadian Journal Physiology Pharmacology Nov 2010] and never generated any toxicity at doses up to 2800 milligrams, a dose at which plain resveratrol “kills” animal hearts under experimental conditions. [Experimental Clinical Cardiology Winter 2010]

4. Longevinex® activates Sirtuin3 mitochondrial rescue gene three times better than plain resveratrol.

As the intracellular atomic power plants (the mitochondria) rust and calcify they lose their ability to produce cellular energy as measured by the production adeno triphosphate (ATP). As cells age the mitochondria increasingly generate ATP from glucose rather than oxygen. It is now suggested that the restriction of sugar rather than just raw calories may induce more youthful mitochondrial metabolism.

As mitochondria “run out of gas” the only nutrient the cell can use to produce ATP is glucose. This state of affairs describes the genesis of cancer. The discovery that cancer cells utilize sugar to produce energy thereby creating an immortal cell won two Nobel prizes for Otto Warburg in the 1930s. [Cancer March 2014]

Over a decade ago it was discovered that resveratrol (and likely other polyphenols) initially generate free radicals [Drugs Experimental Clinical Research 1999] that activate the Nrf2 switch that in turn increases the endogenous antioxidants catalase, superoxide dismutase (SOD) and glutathione. Calorie restriction is a form of biological stress that initially generates potentially destructive free radicals that triggers the production of protective antioxidant enzymes catalase, superoxide dismutase (SOD) and glutathione. [Free Radical Research Jan 2005]

But still there is progressive degeneration and malfunction of mitochondria with advancing age. The rescue agent here is the Sirtuin3 gene. Mitochondrial enzymes are inhibited in animals that have had their Sirtuin3 gene “knocked out.” [Cell Metabolism Oct 1, 2014]

Resveratrol activates the PGC-1a gene that is considered the master regulator of “mitochondrial biogenesis.” [British Journal Pharmacology April 2014] The hearts of animals that have had their Sirtuin3 gene “knocked out” are more vulnerable to damage caused by a heart attack and cannot properly repair themselves due to lack of survival of stem cells. [American Journal Physiology Heart Circulatory Physiology June 2014; PLoS One Sept 2014]

The importance of Sirtuin3 is observed in lab dish studies where it was shown to balance two forms of the antioxidant enzyme superoxide dismutase 1 & 2 (SOD1 & SOD2). SOD1 is produced from copper and zinc whereas SOD2 is synthesized from manganese. When cells switch towards SOD1 they are more prone to become abnormal. Sirtuin3 regulates SOD2. [Journal Biological Chemistry Feb 28, 2014]

A recent study sheds more light on the subject of the true longevity mechanisms behind calorie restriction. What has been learned over the past decade is that genes and gene pathways that are cell energy sensors, Sirtuin1 and AMPK, are activated by calorie-restricted diets and by molecules that mimic food deprivation such as resveratrol.

However, scientists unexpectedly found that the generation of free radicals (aka reactive oxygen species) is necessary for calorie restriction to extend lifespan in roundworms. The transient production of free radicals is essential for longevity via inhibition of a mitochondrial marker called Complex I. Calorie restriction and Complex 1 inhibition share some of the same mechanisms.

For example, use of a known natural insecticide (rotenone, found naturally in the roots of jicama) is able to generate free radicals that provoke a defensive response that is independent of AMPK and Sirtuin1.

This opens the door to the pursuit of longevity via methods that are independent of calorie restriction or calorie restriction mimicry. Resveratrol and some other natural compounds inhibit mitochondrial Complex I and prolong the life of roundworms. [Molecular Metabolism Feb 14, 2014]

So has Longevinex® specifically been tested to measure how it affects mitochondria? Yes, Longevinex® increases Sirtuin3 gene protein which is a mitochondrial rescue gene. Longevinex® increases Sirtuin3 about 295% better than plain resveratrol. [Canadian Journal Physiology Pharmacology Nov 2010]

Furthermore, in a model of experimental heart attack, resveratrol and Longevinex® activated the PINK1 gene that in turn triggers regeneration of damaged mitochondrial via a process called fission/fusion. This experiment re-confirmed Longevinex® protects and regenerates damaged heart muscle and does so via a mitochondrial regeneration which is an anti-aging pathway. [Oxidative Medicine Cell Longevity 2014]

Activation of Sirtuin3 gene in mitochondria by resveratrol and Longevinex by fluorescent imaging.