There have been many efforts to produce an advanced resveratrol pill that stabilizes this wonder molecule, enhances its oral absorption, maximizes its immediate bioavailability (get as much unbound resveratrol past the liver's detoxification system), enhances its biological activity, delivers it in modest doses to produce a hormetic effect (hormesis = provision of a biological stressor in a mild dose to activate the body's internal antioxidant system) and deliver it safely without potential toxicity when administered intended or unintended mega-doses. [Current Drug Delivery Nov 9, 2016; Journal Controlled Release March 10, 2012]
Longevinex®, as the world's first stabilized resveratrol and best-tested resveratrol dietary supplement, produces a superior product by following the recipe below:
1. Resveratrol purity
First, the purest resveratrol is used. That would be 100% synthetically made resveratrol, produced by fermentation. That way one totally avoids emodin, an undesirable component found in Giant Knotweed, the common herbal source of resveratrol. Emodin induces loose stool in some individuals. Even 50% extracts of resveratrol from Giant Knotweed can induce loose stool. One brand of resveratrol induced loose stool in 6 of 8 subjects studied. [Clinical Pharmacokinetics July 2010] Many resveratrol pills contain an unlabeled amount of emodin. Journal Agriculture Food Chemistry June 2014]
While 100% pure resveratrol is desired, the Food & Drug Administration has in the past threatened to classify 100% herbal extracts as drugs. To avoid a future problem, resveratrol in Longevinex® is provided as an 85-92% extract from Giant Knotweed (botanical name: Polygonum cuspidatum) with reduced emodin content, which does not induce loose stool.
Next, resveratrol must be stabilized, as it is vulnerable to degradation from exposure to light, heat and oxygen.
2. Longevinex® was the first stabilized brand of resveratrol.
As background information, university-based animal laboratories conduct studies using research-grade resveratrol, which is stored at below-zero temperature in opaque vials shielded from light. Resveratrol exposed to UV-light degrades over time. [Jundishapur Journal of Natural Pharmaceutical Products 2013]
Longevinex® is the closest to research-grade resveratrol because it is microencapsulated (enfolded in plant starches and dextrins) and is shielded from light in an opaque capsule. Then it is presented in a foil blister card to further protect against heat and oxidation.
Longevinex® resveratrol has withstood a rooftop test under direct sun exposure and did not degrade following bombardment by direct mid-day summer sun in an Arizona laboratory.
3. Longevinex® enhances resveratrol/polyphenol absorption
The next step is to enhance absorption of resveratrol.
Oral absorption of resveratrol is actually very high, ~70%. [Drug Metabolism Disposition Dec 2004] However, micronization of resveratrol increases blood levels by about 3.6-fold. [Cancer Prevention Research Sept 2011] Micronization is a process of reducing the average diameter of a solid material's particles. Longevinex® is micronized.
4. Longevinex® and resveratrol solubility
Resveratrol is said to exhibit "vanishingly low water solubility." [Chembiochem June 15, 2015] Alcohol serves to naturally improve solubility of resveratrol in wine. Solubility of resveratrol in dietary supplements is not equivalent to that of wine.
Longevinex® resveratrol is provided in a matrix with beta cyclodextrin, a sugar-like molecule (saccharide) to improve solubility. [Advanced Materials Research 2012; Brazilian Journal Pharmaceutical Sciences 2011] Beta cyclodextrin further stabilizes resveratrol. [Journal Agriculture Food Chemistry March 2008]
5. Longevinex® overcomes alleged non-bioavailability
There are many mistaken claims in the scientific literature that resveratrol is not biologically available; that is, it doesn't make it past the liver's detoxification system without being bound to detox molecules. The claim of poor bioavailability of resveratrol has been dispelled.
Resveratrol is conjugated (joined) with detoxification molecules (sulfate, glucuronate) as it passes through the liver. Then this liver metabolized form of resveratrol is said to be too large to pass through cell walls and influence genetic machinery in the nucleus of cells.
However, it has been repeatedly demonstrated that metabolized resveratrol exerts biological activity, sometimes even better than unbound resveratrol. [Journal Agriculture Food Chemistry July 29, 2015; Chembiochem June 17, 2013] For example, resveratrol metabolites (sulfate, glucuronate) were shown to produce "almost complete recovery" of heart function in laboratory animals. [Nutrition Metabolism Cardiovascular Diseases April 2014]
However, there is still concern that resveratrol when bound to detoxification molecules does not exert biological activity. [Nutrition Cancer 2015]
Resveratrol passes through a liver a few times before it is fully metabolized. When resveratrol is provided with quercetin it makes more passes through the liver before it is metabolized, ensuring its immediate bioavailability. [Xenobiotica Sept 2000] Longevinex® is provided in a matrix with quercetin for this and other reasons.
It should be noted that unbound (unmetabolized) resveratrol has a very short half-life (around 14 minutes). When it is attached to detoxification molecules in the liver it has a half-life of ~9 hours, which means it is in the blood circulation most of the day. [Drug Metabolism Disposition Dec 2004]
Resveratrol is naturally unleashed from detoxification molecules by the enzyme glucuronidase that is 17 times more abundant at the site of inflammation, infection or malignancy. Therefore, the argument that liver-metabolized resveratrol is non-bioavailable a moot point. [Journal Pharmaceutical Sciences Oct 2004] Some drugs are pre-glucuronidated to improve delivery. [Current Pharmaceutical Design 2002; Current Medicinal Chemistry Anticancer Agents March 2003]
The argument that resveratrol is not bioavailable appears to be a contrived need to develop resveratrol-like drugs (analogs). Efforts to produce a resveratrol analog were set back by the realization that resveratrol, after oral absorption, reverts back to its original form by losing its synthetically added molecular tail. This makes efforts to produce a superior resveratrol-like analog almost laughable. [Molecular Pharmacology 2013]
6. Longevinex® exhibits molecular synergism
However, the biological action of resveratrol can be dramatically enhanced by provision with other red wine (polyphenolic) molecules. Studies show resveratrol when provided with quercetin and catechin from green tea exerts synergistic rather than just additive biological activity. For example, while low-dose (350 mg human equivalent) resveratrol, quercetin and catechin did not individually decrease cancer cell growth in a lab dish when all three molecules were provided the cancer-killing effect resulted synergistically. [Translational Oncology March 2008] Resveratrol + vitamin D exerts synergistic action. [Molecular Nutrition Food Research March 2014]
Longevinex® is the only resveratrol-based nutraceutical to actually demonstrate synergistic biological activity in animal testing. Longevinex® activated 9-fold more anti-aging genes (1711) than plain resveratrol (225) in a 12-week study of laboratory mice. [Experimental Gerontology Sept 2008] Resveratrol exhibited 6-fold greater ability to inhibit a gene (microRNA20b à vascular endothelial growth factor) that blocks growth of abnormal blood vessels (angiogenesis). [PLoS One Dec 2010] In a human study, Longevinex® exhibited two-fold greater ability to dilate (widen) blood vessels in humans compared to plain resveratrol. [Nutrition Research Nov 2011]
Furthermore, Longevinex® is the only resveratrol dietary supplement that has undergone successful toxicity testing. [Food Chemistry Toxicology Sept 2013]
7. Longevinex dosing
The dosage of resveratrol and other small molecules in the Longevinex matrix is formulated to provide a similar amount of antioxidant polyphenols provided in 3-5 glasses of red wine that has been demonstrated to produce optimal health benefits. One 5-oz. glass of dark aged red wine provides ~60 mg of polyphenols; 3-5 glasses provide ~180-300 mg of polyphenols such as resveratrol, quercetin and catechin. Longevinex® provides 220 mg of polyphenols and antioxidants, leaving room for dietary consumption of polyphenols from wine, coffee and tea. Brands of mega-dose resveratrol pills that claim they offer "more for your money" are mistakenly venturing towards a pro-oxidant dosage range.
Resveratrol is not a strong antioxidant. However, modest-dose resveratrol activates internal antioxidant enzymes (glutathione, catalase, superoxide dismutase) via the Nrf2 gene transcription switch. [Free Radical Biology Medicine Oct 2016]
Normally these endogenous antioxidants are activated following biological stress such as oxygen deprivation in the brain or heart. Resveratrol activates these internal antioxidant enzymes PRIOR TO any adverse event in what is called "preconditioning," which is considered the most ideal protection for living tissues. This so-called hormetic effect is only achieved by low-doses of polyphenols, in the range of 100-350 mg.
Excessively high doses of polyphenols including resveratrol are counterproductive as they release metals like copper that have been stored in the body and induce oxidation and tissue damage. [Current Molecular Medicine Dec 2011]
8. Longevinex® is not cytotoxic (cell killing) in mega doses
Additionally Longevinex® does not exhibit typical pro-oxidant cytotoxicity (cell killing) when given in mega-doses (up to 2800 mg human equivalent dose) to laboratory animals. Usually a 2800 mg dose "kills" the rodent heart in an experimental model of heart attack. [Experimental Clinical Cardiology 2010]
Polyphenols are known to exhibit a J-shaped risk curve; that is, in low dose they are protective and exhibit antioxidant activity while in mega doses they promote oxidation (pro-oxidant) and exhibit cell-killing activity (cytotoxicity).
However, for the first time in biology, Longevinex® exhibited an L-shaped risk curve where a dose ranging from 100-2800 produced a protective effect whereas mega-dose plain resveratrol – 1750-3500 mg human equivalent dose – was cytotoxic (cell killing). [Experimental Clinical Cardiology 2010]
When a heart is removed from a rodent in the animal lab but its pumping action is maintained, a modest dose of resveratrol (175-350 mg) protects the heart from damage should blood circulation to the heart be halted and then resumed (a heart attack), whereas mega-dose resveratrol (1750-3500 mg human equivalent dose) induces greater damage to heart muscle. [Journal Nutritional Biochemistry June 2009; Molecular Cellular Biochemistry 2011] In this experimental model Longevinex® at a lower 100 mg dose reduced the area of damage to the heart by an additional 40% over what plain resveratrol achieved. [PLoS One Dec 2010]
9. Longevinex®: best tested
Longevinex® is the best-tested resveratrol supplement. Its compendium of research studies is accessible at the National Library of Medicine. [PubMed; Longevinex.com] Less than 5 brands of resveratrol pills out of 510 brands listed at the Natural Medicine Comprehensive Database have undergone any published scientific study.
Longevinex® has been awarded a U.S. patent for a novel resveratrol-based formulation that includes nucleotides to enhance DNA repair. [US Patent 9226937 B2] Nucleotides (adenine, guanine, cytosine, thymine) comprise the steps on the DNA ladder. Supplemental nucleotides are provided to prematurely born infants and astronauts to enhance immunity, growth and healing. [Clinical Nutrition 2002]
The Longevinex® matrix includes vitamin D3. Resveratrol enhances sensitivity of the vitamin D receptor on the surface of cells. This molecular combination (i.e. matrix) is cited as a mood elevator via inducement of serotonin. The vitamin D receptor is said to activate a "fountain of youth" array of genes. [Vitamins & Hormones 2016] The vitamin D3 + resveratrol combo helps living tissues such as the heart and brain to withstand periods of ischemia (inadequate supply of oxygen). [International Journal Vitamin Nutrition Research 2016]
It can be unequivocally said, Longevinex® is the best resveratrol pill available. Its safety has not only been validated by toxicity tests but also by 12 years of use without report of serious side effects requiring hospitalization. Furthermore, animal and human studies confirm its superiority over the plethora of resveratrol pills offered in the marketplace today.
Opposition to resveratrol
Opposition to resveratrol is both covert and overt. Modern medicine, by falsely maintaining resveratrol is not biologically available, by falsely accusing a leading investigator of research fraud, by dragging its feet to conduct a human study on resveratrol's capacity to avert mortal heart attacks that has already been demonstrated in the animal lab and then endlessly claiming more research needs to be done, has for over a decade stalled translation of this wonder pill from the research lab to the medical clinic.
In an era of polypharmacy, where the average senior American takes 5 Rx drugs and 2 OTC drugs a day, resveratrol by virtue of its broad biological action is poised to replace an entire modern pharmacopoeia. [Annals New York Academy Sciences Jan 2011;
Public adoption of resveratrol pills has largely been unguided. Physicians haven't a clue what the proper dosage range is for resveratrol though they often warn of its interference with problematic drugs. [Drug Metabolism Reviews Aug 2012] Yet resveratrol has been shown to enhance the effect of certain prescription drugs. [Journal Molecular Cellular Cardiology March 2007; Chemical Biology & Drug Design April 2015]
Resveratrol defies classification
Pharmacologists argue in vain that a molecule like resveratrol exerts such broad biological action it can't be defined as a drug candidate (i.e. its ability to fit into a binding site on a protein to quell a disease). Resveratrol is mischaracterized as a "chemical con artist that foils drug discovery." [Nature Sept 24, 2014] Researchers even question whether the preventive effects of resveratrol can be assessed by standard experimental designs. [Nutrients June 9, 2016]
Resveratrol as omniceutical
That is because resveratrol doesn't fit into the current narrow paradigm of one molecule to target one disease. Resveratrol defies the modern definition of a drug. It is an "omniceutical." Resveratrol exhibits strong biological action as an antibiotic, antiviral, antifungal, anti-depressant, anti-cholesterol, anti-obesity, anti-diabetic, anti-brain plaque, anti-inflammatory agent that relieves pain and molecularly mimics physical exercise and a low-calorie diet while it elevates mood (as an MAO monoamine oxidase inhibitor) and improves alertness and mental function. [Biomedical Reports Nov 2016; Pharmazie Aug 2015]
Resveratrol slows the cell renewal cycle, thus facilitating DNA repair. [British Journal Pharmacology Sept 2009]
Resveratrol blocks are three stages of malignancy – initiation, growth and spread (metastasis). [Annals New York Academy Sciences Jan 2011]
Resveratrol even helps maintain the non-cellular "goo" or connective tissue that serves as a barrier to the spread of infection or malignancy. [Experimental Biology Medicine Oct 20 2016]
Resveratrol is also a prebiotic that favorably alters the bacteria in the human gut (intestines). Unhealthy gut bacteria is now linked to many maladies. Resveratrol recently was shown to alter gut bacteria, which in turn improved bile flow and abolished the buildup of atherosclerotic plaque in laboratory mice. [mBIO April 5, 2016]
Resveratrol simultaneously inhibit the formation of abnormal blood vessels that destroy the visual center (macula) of the eyes while it promotes the growth of new blood vessels in the heart to create collateral circulation when coronary arteries are blocked. [ResveratrolNews.com Oct 17, 2016]
Resveratrol and Longevinex® in particular has been shown to renew the intracellular atomic power plants (mitochondria) that produce energy for living cells. By age 80 only about 4% of mitochondria are functional. [Oxidative Medicine Cellular Longevity 2014]
The pressing question is not whether a person should be taking a resveratrol pill but why aren't they taking a resveratrol pill? After having learned here of all the false claims, mislabeling and lack of know-how in formulating a properly stabilized, dosed, absorbable, bioavailable and synergized resveratrol pill, why choose any of the unproven brands when Longevinex® exists?
For further information go to www.longevinex.com
Why are researchers at an obscure university in India lecturing western doctors over the misdirection of modern medicine in the prevention and treatment of Alzheimer's disease?
Investigators at little-known Bharathidasan University in Tiruchirappalli, Tamilnadu State, India, who labor under the motto "we will create a brave new world," (no, not Johns Hopkins Medical School or Harvard Medical School or the Mayo Clinic in the USA) boldly cite how the red wine molecule resveratrol is superior to statin drugs in addressing the buildup of beta amyloid (cholesterol-like) plaque in the aging brain that is associated with Alzheimer's disease.
There are over 275 reports published at the National Library of Medicine on the topic of statin cholesterol-lowering drugs and beta amyloid brain plaque. [Pubmed] The suggestion that statin cholesterol-lowering drugs may reduce beta amyloid plaque buildup in the brain has been in play for the past 15 years. [Proceedings National Academy Sciences 2001] Resveratrol's potential in controlling beta amyloid brain plaque dates back just as far. [Free Radical Biology Medicine 2003] Neither statins nor resveratrol have entered into common use for the purpose of preventing Alzheimer's related memory loss over that time.
Researchers at Bharathidasan University note that while statin drugs reduce the production of cholesterol in brain cells, they don't necessarily inhibit the buildup of this plaque.
In their own words
Here is an abridged version of what the Bharathidasan Unversity researchers discovered:
"Sufficient availability of cholesterol is necessary for normal neuronal (brain) function, however, several epidemiological (population) studies state that the elevated cholesterol is one of the risk factors for Alzheimer's. Although inhibition of cellular cholesterol by statins could play a beneficial role, cholesterol depletion in neurons (brain cells) … decreases neuronal activity and nerve transmission leading to degeneration. It is maintenance of cholesterol equilibrium without affecting its normal function that is beneficial in preventing disease progression, particularly in Alzheimer's disease. Resveratrol… as expected maintains cholesterol equilibrium."
Disposal, not production of beta amyloid plaque is the problem
The primary problem with accumulation of beta-amyloid plaque in the brain is not its production, which statin drugs address, but its disposal, or efflux as biologists say it, which resveratrol does facilitate. Statins strongly reduce beta amyloid production inside cells, resveratrol facilitates its clearance and removal via its ability to chelate (bind to) copper. [Journal Biological Chemistry 2005]
East Indian researchers recent entry into the field
Bharathisadan University researchers as newcomers to the field of Alzheimer's research published their first report about Alzheimer's disease in 2012. [Clin Chim Acta 2012] In 2015 they reported on the importance of the hippocampus, a component of the brain that is responsible for consolidating short and long-term memory.
They noted at the time that poor memory in aged laboratory rats is due to a defect in circuits in the hippocampus that are damaged over time. They also noted that resveratrol "culminates pathological events in the hippocampus …during aging, proving it as a potent therapeutic drug against age-associated memory loss."[Neuroscience 2015]
Earlier this year Bharathidasan University investigators reported that while several drugs moderately reduce symptoms of Alzheimer's, none of them have sufficient potency to reverse the progression towards Alzheimer's disease pathology. They went on to describe resveratrol has having "outstanding therapeutic effect on a broad spectrum of diseases."
These East Indian researchers subjected laboratory rats to ibotenic acid that impairs transmission of nerve signals in the brain and interferes with learning and memory. Resveratrol blunted the deleterious effects of ibotenic acid. [Frontiers Molecular Neuroscience 2016]
The cure cupboard is bare
According to the Alzheimers Association, none of the pharmacologic treatments (medications) available today for Alzheimer's disease slows or stops the damage and destruction of neurons that cause Alzheimer's symptoms and make the disease fatal. The six drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's temporarily improve symptoms by increasing the amount of chemicals called neurotransmitters in the brain.
In the decade 200-2012, 244 drugs for Alzheimer's disease were tested in human clinical trials as listed by the National Institutes of Health registry. Only 1 of 244 drugs successfully completed clinical trials and went on to receive FDA approval.
While Alzheimer's disease strikes just 4% of adults 65 years of age and under it is evident in 44% of Americans age 75-84 years of age and 37% age 85 years and older. About 8 in 10 people who have Alzheimer's are over the age of 75.
Too late to do anything about it
The problem in addressing Alzheimer's disease is that it begins before symptoms become evident. Beta amyloid plaque deposition in the brain may precede Alzheimer's disease symptoms by 20 years. [Discovery Medicine 2013]=
According to the Alzheimer's Association 11% of Americans age 45 and old report progressive confusion or memory loss with 76% not reporting this to a health care professional. So those who do experience symptoms are not readily identified.
Therefore, early detection by symptomology is too late to significantly affect the course of the disease. This suggests a massive preventive guess must be taken.
Intuitive answers: using the best available evidence
It was forensic investigator Jack Sprott in New Zealand who intuitively advised mothers of newborns to place their infants on their back to sleep and this practice quelled the incidence of sudden infant death. [South African Medical Journal 2006]
It is just this kind of leap that must be taken now to slow down Alzheimer's disease before half of the population of older adults is taking care of the other half that have Alzheimer's. Yes, that is the tragic course that lies ahead.
Financial burden on society is staggering
The family burden of Alzheimer's is staggering as 83% of the help provided to older adult in the U.S. comes from family members and friends. Alzheimer's disease accounts for $236 billion in healthcare costs in 2016. With 5.2 million Americans affects by Alzheimer's, that amounts to ~$45,000 per individual per year! [Alzheimer's Association 2016]
It was a report issued by researchers at Johns Hopkins University Medical School that maligned resveratrol for having no effect on the health status or mortality risk of senior adults. But resveratrol was not employed in their study, red wine was. Even then, further analysis by this investigator found that Johns Hopkins researchers intentionally overlooked the fact that the group that drank more wine experienced 50% less mental decline over the 9-year study period. [JAMA Internal Medicine 2014; ResveratrolNews.com] — ©2017 Bill Sardi, ResveratrolNews.com
Bill Sardi, managing partner
Resveratrol Partners LLC, dba Longevinex
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