test your knowledge
How the world got lost on
the road to an anti-aging pill
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October 1, 2010: by Bill Sardi
“Resveratrol this and resveratrol that, it cures most everything in the laboratory rat.”
Resveratrol — the red wine molecule heralded for its potential to reverse biological time, to erase the ravages of human aging, to do what only could be previously imagined in science-fiction books. But the rush to commercialize resveratrol is trivializing its future. A cobweb of false advertising, pseudoscience (even in published scientific journals), misleading labeling and potential side effects posed by overdosing could provoke regulatory agencies to step in and declare this molecule a drug, robbing the public of direct access to this miracle of our time.
Resveratrol is now an additive in chewing gum, beer, nutrition bars, various and sundry beverages, and of course, myriads of dietary supplements.
If you can imagine the absurdity of thinking that you will be adding a few minutes to your lifespan for every stick of resveratrol gum you chew, you will begin to realize how this miracle molecule is being trivialized with pseudo-science and promoted by companies who simply have rushed to commercialize resveratrol before its health benefits are proven. The next thing you know, resveratrol will be added to table salt and sprinkled on popcorn.
Generally speaking, resveratrol is for the over-40 crowd. It is an antidote to aging. It has anti-growth properties that are not appropriate to growing children, pregnant women and those who are anemic.
Placing resveratrol in food bars and chewing gum in doses beyond the few micrograms provided by grapes and peanuts in the general diet, that growing kids might pick up at eat, is simply irresponsible. But one of the largest suppliers of raw materials for nutriceuticals is leading the charge to place resveratrol in foods and beverages. Resveratrol is fast becoming a pop-science ingredient that is being brandished as a cure-all. Yes, certainly, it may be, but among which segment of the population and at what dosage?
It is said that resveratrol, as a small molecule, mimics a calorie restricted diet. But is it a glutton’s delight? “Can you have your cake and eat it too?!” Can we eat as much as we like and not pay the price by downing a resveratrol pill? Well, not quite yet.
A limited calorie diet, which resveratrol is theorized to mimic, does avert age-related weight gain in animals. However, the only experiment which showed resveratrol produces leanness had to force-feed the human equivalent of 14,000 milligrams of resveratrol (that would be fourteen 1-gram pills a day) down the throats of laboratory mice. Any online shopper can quickly find makers of resveratrol who make bogus claims their red wine pills produces weight loss. As in most cases of false advertising, there is a little bit of distorted truth mixed with real fact.
Like flour dough in bread, resveratrol is fast becoming a commodity. Yet there are a lot of bread bakers, but only a few who make truly nutritious whole-grain bread (despite the misleading labels).
The verifiable health claims for resveratrol cannot be transferred to every product that contains resveratrol because of failure to provide the research-grade resveratrol used in laboratory experiments, and failure to employ the precise human equivalent dose used in animal or human clinical trials. Furthermore, the labeled dose may not be what is provided in the product.
When Longevinex® confronted the industry about this problem it was immediately burdened with two lawsuits from resveratrol pill makers who didn’t want this fact disclosed. Hundreds of thousands of dollars in legal fees later a revelation was made outside of courts of law.
This is what the dietary supplement industry does to hush up its embarrassing and even fraudulent mistakes – burden a competitor with legal fees as they hold onto their existing business.
Many brands of resveratrol brag they provide the highest amount of resveratrol for the price, but with diminishing health benefits and increased risk for side effects as the dosage rises.
Dipak Das PhD, a heart researcher at the University of Connecticut, has found the optimal human dosage range for resveratrol in the heart is less than 175 milligrams for a 160-lb (70 kilogram) adult. At 350 mg resveratrol begins to lose its protective effect in the heart. A 1750 mg dose of resveratrol actually worsens damage to heart muscle tissue in the event of a heart attack. In one experiment as little as 365 mg slightly shortened the lifespan of laboratory animals. Yet there are 500-mg and 1000-mg resveratrol pills recklessly being sold in retail stores today, accompanied by boastful advertising which mistakenly assumes more is better. Some resveratrol pill users may be putting their lives on the line by following the bad advice from novices who produce resveratrol pills.
There is now voluminous data to show that the combination of resveratrol with other small molecules magnifies its biological and genomic effect far beyond an additive effect. Plain resveratrol pills miss the mark by a mile.
Red wine produces profound health benefits while delivering small amounts of resveratrol (3-5 milligrams in 3-5 glasses) accompanied by an array of other molecules such as quercetin, catechin, ferulic acid, etc.
Plain resveratrol pills should mimic red wine in composition, as best as possible, in order to replicate the French Paradox, the fact that French wine drinkers have the similar circulating cholesterol levels as North Americans but exhibit a coronary artery disease mortality rates that is 2.7 times lower (90 per 100,000 versus 240 per 100,000). Controlled studies confirm resveratrol is far more powerful when combined with other small molecules.
The accompanying ingredients and the recipe for making resveratrol pills make the difference among the estimated 290 brands now being offered online and at retail outlets.
The French have found a way to remain lean despite a high-calorie, high-fat diet, and to produce an unprecedented number of centenarians — 20,000 of them living to 100 years or more. It’s the highest ratio of centenarians per capita among all the countries of the world.
But the health benefits of French red wine are not produced solely by resveratrol. It is an array of small molecules delivered in an alcohol base that produces red wine’s magical effects. The combined biological power of low doses of these wine solids produces a more profound effect than the highest dose of pure resveratrol alone. This fact got lost in all the hype about resveratrol. The whole is greater than its parts. The recipe of ingredients in a resveratrol pill yields greater health benefits than plain resveratrol.
This is not to say there are no health benefits from downing modest doses of a plain resveratrol pill every morning. The potential health benefits of plain resveratrol produced in the laboratory are more than striking, and include prevention of sudden-death heart attack, blockage of all cancer mechanisms, improved mood, reduced inflammation, better bone and muscle strength, elevated immunity, to name a few. But even these health benefits are largely achieved with lower rather than higher doses. In fact, low doses of resveratrol more aptly mimic the effects of a low-calorie diet. However, the optimal health benefits promised by resveratrol are only achieved when other molecules are combined with it.
One study showed when 100 milligrams of resveratrol was combined with other small molecules (Longevinex®), such as those found in red wine, the genomic effect was 9-fold greater. In a short-term study, Longevinex activated 1711 longevity genes in laboratory mice compared to just 225 genes for plain resveratrol. Furthermore, life-long calorie restriction, which is the unequivocal practice that nearly doubles the lifespan of all living organisms, activates about 832 genes. It would likely require many decades of resveratrol pill consumption to activate that many genes and truly mimic a limited calorie diet. But Longevinex® more than doubled the number of activated genes in just a short time.
If this rodent study can be extrapolated to humans (mice have a similar number and sequence of genes as humans), resveratrol pill users may be wasting their time and money and many are likely to die before they experience the full benefits of this molecule.
Certainly, consumers like to shop around for the best price. However, comparison shopping can work against many consumers because it is so difficult to compare one product against another.
For example, the cost of ingredients and microencapsulation in one product, Longevinex®, which is the best-tested brand, and was the first to provide 100 mg of stabilized trans resveratrol in a base of other red wine molecules, exceeds the retail price of many brands of resveratrol supplements now on the market. For example, one low-priced brand selling at COSTCO for $7.99 (with coupon) provides just 1 milligram of resveratrol. You have to down 100 of their tablets to get 100 mg.
Or how about resveratrol offered at Wal-Mart, but resveratrol is only advertised on the front label and the Supplement Facts box doesn’t even list resveratrol as an ingredient!
(Take that, old man who keeps calling this author to say he can purchase the equivalent of Longevinex® at Wal-Mark for $7.00 a bottle!)
Again, compare Longevinex® to a product sold at COSTCO that says it provides 100 mg of trans resveratrol, but when you read the label carefully, to get that amount you have to consume 5 caplets a day! The same company that sells these pills previously sold a liquid resveratrol product at COSTCO that was so unstable it was admittedly fermenting into vinegar in the bottle!
Yet Longevinex® (~$27/month supply) is not the high-price leader ($74.99/month supply) by a wide margin. While that $74.99 product offers 500 mg of resveratrol, but that is a mega-dose that was found to shorten the lifespan of laboratory mice.
Or how about a commercially available resveratrol pill that touts it also provides calcium, which actually accelerates human aging and runs counter to the anti-aging properties of a red wine pill! Unfortunately, many resveratrol pills today are formulated by fast-buck artists.
Then there are a bevy of resveratrol products that claim their resveratrol molecule is superior to others.
Regardless of how resveratrol is presented – stabilized, micronized, sublingual, organic, or methoxylated as pterostilbene, as it is in many dietary supplements, its molecular formula is still C14H12O3. So will any old resveratrol pill do? Well, again, that depends upon whether you want the optimal health benefits produced by resveratrol, without any drawbacks posed by over-dosage.
Dr. Dipak Das recently showed in animal studies that high-dose resveratrol is “cytotoxic,” that is, it kills healthy living cells. At 3500 mg human equivalent dose resveratrol “kills the mouse heart every time,” says Dr. Das.
Longevinex® is about to unleash a published study showing its proprietary resveratrol pill exhibits no cytotoxicity whatsoever up to 7000-mg human equivalent dose in two species of animals (rodents and rabbits). This is a world’s first! An L-shaped risk curve is what biologists call it. Wine and resveratrol produce a U-shaped or J-shaped risk curve – at modest doses risk for mortality declines but at mega-doses mortal risk rises above that of non-users. The underlying protective mechanism is being kept as a trade secret for now.
Advertising that purports organic resveratrol as being purer is almost laughable. Pesticides are not used to grow Giant Knotweed (Polygonum cuspidatum, botanical name), the source of most botanically-extracted resveratrol.
Ditto for sublingual (under the tongue) resveratrol — stomach acid does not degrade resveratrol. Being a small molecule, it is immediately absorbed in the gut.
About 70% of orally-consumed resveratrol is absorbed in humans. Micronization (reduction in particle size) may enhance absorption by another 15%, but this is no magnanimous advantage either. About 115-mg of plain resveratrol would deliver about the same amount of this molecule as 100-mg of micronized resveratrol. (There is one guy who ridiculously claims his brand of micronized resveratrol is 500% better absorbed. Just how do you increase absorption by 500% when plain resveratrol is 70% absorbed? The best you can do is increase absorption by another 30%.)
What makers of resveratrol pills ought to be working on is stabilizing resveratrol to make it as close as possible to research-grade product that is sealed in airtight vials and stored at -20° Fahrenheit, since analysis shows some degradation from trans to cis resveratrol in unprotected products.
Exposure to UV radiation degrades resveratrol from its biologically active form (trans resveratrol) to its degraded and less biologically-active form (cis resveratrol). Exposure to heat also degrades resveratrol. Its inclusion in processed foods may require special stabilization methods.
Microencapsulated resveratrol (enfolded in plant starches and dextrins) retains the molecular integrity of resveratrol even when it has been exposed to direct rooftop midday sunlight at an Arizona testing laboratory. (Data on file, Longevinex®. ) Furthermore, Longevinex® dry powder is placed in an opaque capsule to block all incoming light. Then it is foil packaged. This is as close to research-grade resveratrol as one can get.
The claim of superior bioavailability made by purveyors of pterostilbene – a methylated form of resveratrol, is particularly annoying. Despite some widespread scientific confusion about the bioavailability of resveratrol, plain resveratrol is biologically available. It produces system-wide health benefits in remote parts of the human body including the brain and kidneys.
It is true that resveratrol is temporarily made unavailable by virtue of it being attached to detoxification molecules in the liver which make it too large a molecule to pass through cell walls and penetrate the blood-brain barrier. However, this is advantageous as it prolongs the half-life (degradation rate) of resveratrol from a few minutes to many hours.
Most of the resveratrol that circulates in the blood is conjugated (attached) to detoxification molecules (glucuronate, sulfate) in the liver, since resveratrol is perceived as a potential toxin by the body. This is what turns on all the body’s defenses and produces the many health benefits attributed to resveratrol.
So how does resveratrol get un-tethered from these detox molecules so it can pass through cells walls and the blood brain barrier?
Nature has its own resveratrol delivery system. An unzipping enzyme called glucuronidase is abundantly produced at sites of inflammation, infection and malignancy. This frees resveratrol from its carrier molecule and delivers what is called “free” unbound resveratrol at the right time and place.
The claim by any entity that they have invented a more bioavailable form of resveratrol is patently false.
Yes, early on, Longevinex® was suckered into claiming its product activated the Sirtuin1 longevity gene after tests conducted at a biotech laboratory were conducted. However, quite embarrassingly, it was found the initial study published in 2003 in Nature Magazine, which claimed resveratrol is the best molecular activator of Sirtuin1 (Sir2 in yeast cells), was flawed. A fluorescent dye used in the test activated the Sirtuin1 gene, not resveratrol.
Then later researchers at MIT reported that the Sirtuin1 gene is not activated in all tissues and organs in calorie restricted animals. So Sirtuin gene activation cannot be used as a reliable measure of calorie restriction, which is the gold-standard against which all resveratrol longevity pills must be measured. So Longevinex® no longer mentions Sirtuin1 in its advertising.
Aging involves hundreds of genes, not a single gene. Makers of resveratrol pills that continue to refer to Sirtuin1 gene activation ignorantly do so without understanding this science has been discredited. (So much for consumers who call up and ask if Longevinex® activates the Sirtuin1 gene? They have fallen for mistaken science.) Most makers of resveratrol haven’t a clue that the scientific understanding of resveratrol’s gene targets has changed.
Currently, the best-tested resveratrol pill is Longevinex®. It presents a summary of its published science for all to view and evaluate below.
May other brands make impermissible claims their resveratrol products produce weight loss, eradicate wrinkles, grow hair, restore lost memory and even cure cancer, using bloggers who receive kickbacks as front men, and borrowing from existing medical literature under the false assumption their products work as well as those in the laboratory, even though their products often don’t provide resveratrol in the same dose used in controlled studies.
Here is the current list of published scientific investigation involving Longevinex®. For those savvy consumers who demand human data, be aware that some studies, such as those where animals must be sacrificed for analysis of tissue, are simply impossible or impractical to reproduce in humans.
*First time shown in biology
© 2010 Bill Sardi, Resveratrol Partners LLC, dba LONGEVINEX®