There should be little or no concern of toxicity among the many thousands of resveratrol supplement users as the drug used in the trial was just that; SRT501 is a drug synthesized by Sirtris Pharmaceuticals a division of Glaxo Smithkline. And though modeled after the resveratrol molecule because of the broad based therapeutic potential that organic resveratrol has exhibited, it is a chemically synthesized compound and not a natural plant substance.

Furthermore, the drug SRT501 was formulated at a strength exceeding 1,000 times that of typical resveratrol supplement doses, a level which is nearly impossible to attain through natural supplementation.
Resveratrol alone is known to exhibit profound anti-cancer properties and has been specifically proposed for treatment of myeloma because it exhibits multiple ways to block this form of cancer, including inhibition of new undesirable new blood vessels (angiogenesis), inhibition of tumor cell invasion, and works synergistically in bone tissue with vitamin D.

Additionally, evidence from numerous in vitro and in vivo studies involving many other forms of cancer including breast, colon, prostate, pancreatic and lung has confirmed resveratrol’s ability to inhibit cancer at all three stages of development (initiation, promotion (growth) and progression (spread); something no existing anti-cancer drug does.

Resveratrol is also known to have potent anti-inflammatory and antioxidant effects, to inhibit platelet aggregation and counter insulin resistance.
The anti-cancer effects of resveratrol at low doses have been demonstrated recently in studies concerning breast cancer conducted at the University of Nebraska and colon cancer at the University of California, Irvine.

The RESVANTAGE® brand resveratrol supplements are a low dose resveratrol supplement that has become the leading choice of MDs and Naturopaths for use in their practices due to its safety (low dose) and stability (ability to retain potency).
Although considered very safe and well tolerated, the long term effects of high dose resveratrol supplementation are unknown at this time and many practitioners prefer a conservative approach since there is now abundant evidence of efficacy at low doses.

Data concerning the bioavailability of resveratrol in people is necessary and crucial since most of the studies on resveratrol have been done on cultured cells in pietre dishes in the lab which are exposed to resveratrol which has been unmatabolized and in concentrations that are usually ten to a hundred times in excess of the highest concentrations measured in human plasma after been orally consumed. Even though the digestive tract cells are exposed to unmetabolized resveratrol, research in humans suggests that other organs and cellular tissues are exposed mainly to metabolized resveratrol. Not much is understood about the biological activity of metabolized resveratrol , and it has not been conclusively determined if some cells are able to convert resveratrol metabolites back to resveratrol.

Therefore, ingesting resveratrol supplements that deliver a more effective bioactive resveratrol dose is an important factor in the manufacturing of these resveratrol products. There are several methods being utilized by the major resveratrol manufacturers to improve bioavailability.

One of the main strategies is the encapsulation process of resveratrol. Not only is it critical to process resveratrol in a nitrogen enviroment – free of oxygen – to avoid the rapid breakdown from oxidation, it is equally important to seal the contents in an airtight capsule that prevents disintegration of the molecule once packaged. That is why sealed capsules are preferable over tablet or powder forms. Some companies even produce an encapsulated resveratrol supplement in a liquid form as well because it is easier to absorb than powder forms (Resvantage Brand).

Another prominent strategy to increase the bioactive nature of the supplement is called micronization. This is a process where fine grinding mills – either jar mills or fluid energy mills – are used to reduce powder forms of Resveratrol or any other supplement into a smaller size(typically under 10 microns) particle that has been demonstrated to be more readily absorbed in the blood stream (Revgenetics Brand).

Finally, taking a liquid Resveratrol dose sublingually(under the tongue) may end up being the most effective method of taking Resveratrol because it is so easily absorbed and avoids the potential breakdown and disposal from the digestive process. There are a few manufacturers offering beverage dietary supplements which include Resveratrol.(Resversitall Plus by Neocell) Just like swirling a gulp of red wine around in your mouth, this approach may improve the amount of bioactive Resveratrol making into the body’s cells and organs.

More research into the delivery of the Resveratrol molecule will likely lead to improved methods of augmenting bioavailability. At present, the more attention paid to the manufacturing process and delivery of resveratrol, the more impactful the dose will be and the lower the dosage requirements will be needed because absorption will be much higher.

Resveratrol is extremely prone to oxidation, so both the manufacturing process as well as the end product need to be contained in an enviroment that inhibits oxygen. In addition, enhancing absorption in the body, once ingested, is is important so that you receive the full value of the supplements dose. Powders and tablets are less soluable and absorbable that liquid capsules for example. The overall goal is to maintain the potency of the supplement and enhance its bioavailability (absorption).

One Resveratrol brand, Resvantage, accomplishes this by combining the resveratrol with a lipid and an emulsifier to improve absorption by forming the micelles that will be able to pass the water layer that lines the human gastrointestinal tract. Other dosage forms like tablets and powder filled capsules are inefficient and are low in bioavailability because they pass through the body with very little being absorbed.

Another method used to improve absorption is to increase the surface area of the resveratrol crystal. This is done through a milling process called micronization, which reduces the particle size of the crystal. Several companies/brands employ the micronization process including Resvantage and Revgenetics. The resveratrol in the Resvantage supplement is reduced through this process to a particle size of below 600 nanometers which improves dissolution and absorption in the body. This is synonymous with greater bioavailability, smaller dose requirements and improved therapeutic effect. This is what makes the resveratrol supplements so effective at low doses while avoiding the potential long term negatives of high dose resveratrol supplementation.

Some of the other resveratrol supplement manufacturers employ micronization in their preparation, but they use dry powder and the problem with micronization with any dry powder is the static forces along with heat and moisture presence cause instability of the compound during the process and almost immediate agglomeration of the now micronized particle back to a larger, lower surface area particle. Liquids are the most effective way with the use of surface stabilizers or emulsifiers coupled with a high-shear, wet-milling process.

The micronization process is more efficient when combined with lipids as the resveratrol is prepared prior to encapsulation. The active resveratrol is thus preserved due to lower frictional forces-lower heat, no static forces and a protection from oxidation which improves stability.

It is important to understand and know how a resveratrol supplement is produced to understand the effectiveness of the resveratrol dose that the supplement offers. A Large resveratrol dosage doesn’t necessarily mean you are getting more biologically active resveratrol in your body.

A compelling study on gene arrays, by William S. Middleton Memorial Veterans Hospital and Lifegen Technologies researchers in Madison, Wisconsin, demonstrated that dosages of approximately 350 mgs/day of resveratrol (4.9 mg per kg of body weight) creates a gene activation profile close to a calorie inhibited diet. Super high resveratrol doses (greater than 500 milligrams) are not necessary to activate the gene and potentially produce side effects.

Both caloric reduction and resveratrol have displayed the ability to extend the life of all life forms, ranging from single-cell organisms (yeast cells) to more complex forms of life (fruit flies, roundworms) and warm-blooded mammals (laboratory rats).

Potential Resveratrol side effects of high resveratrol dosage supplements are numerous.
“Once mega-doses of resveratrol (more than 500 mg) began to be employed, side effects like anemia, Achilles heel tendonitis, anxiety reactions, numbness in the fingers, began to be reported,” says Bill Sardi, spokesperson for Longevinex “This is probably because resveratrol is a copper chelator and excessive chelation will impair the availability of copper which is needed for collagen formation and nerve regeneration,” he says. “Resveratrol is relatively safe, but not absolutely safe at any dosage. There are drawbacks,” he adds.

Some internet Resveratrol supplement sellers , who have no medical background or scientific research supporting their Resveratrol products, recklessly offer capsules with mega Resveratrol doses well above 350mg/day. There is also research showing that super high resveratrol doses restrict the absorption of folic acid (vitamin B9), an important nutrient required for DNA repair. [European Journal Nutrition. It is important to note that large resveratrol dosages have not been examined in humans for extended consumption.
Marketing claims by resveratrol supplement manufacturers that their capsules produce greater activation of the Sirt 1 gene(the DNA-repair gene) should also be questioned because an animal study demonstrated over-activation (greater than 7.5 fold) of this gene encourages heart failure in animals. [Circulation Research 2007] In addition, many studies have shown that activation of the Sirt1 gene requires only a nominal amount of Resveratrol – 10 – 15mg.

The health and longevity benefits of Resveratrol seem to numerous from all the research, but the most efficacious Resveratrol dosage is still unclear. Taking the “More is Better” attitude that is fomented by aggressive marketers may lead consumers to additional problems from the over dosing side effects that are potentially prevalent. There is one company, Resvantage , that offers a low dose resveratrol of 15 mg that they say allows people to get a resveratrol dose more in line with a lot of the research, that suggests this is the amount needed to activate the Sert 1 proteins in the DNA, without the concern of potential side effects from large dosage resveratrol supplements.

If you have had any personal issues with side effects from taking large dosages of Resveratrol feel free to post a comment below.