Maybe, just maybe ... an end to the debate over resveratrol bioavailability?

No one in science disputes the potential of resveratrol to fight afflictions ranging from cancers to diabetes to Parkinson’s Disease. And everywhere, evidence grows that resveratrol can be used to trigger longer, healthier lives for people.

Yet since Harvard’s David Sinclair discovered some of the hidden powers of this molecule in 2003, there has been much debate about its bioavailability. (Bioavailablity = the ability of the molecule to be absorbed by the body and distributed efficiently within it.)

For an overview article on bioavailability, we contacted Bill Sardi, long-time health journalist and founder of Longevinex. Our research shows that Sardi’s firm is the first to use an independent, recognized lab to test and affirm the bioavailability of the resveratrol supplement in Longevinex. (We urge other resveratrol supplement makers to do the same.) Sardi’s Longevinex company packages its fragile resveratrol molecule in a patented, light-free, oxygen-free capsule, the only company to do so thus far. And to boost bioavailability, Sardi’s formula adds quercetin and lecithin to the resveratrol itself.

We invited Bill to compose an article for us on some new and some surprising findings on bioavailability of resveratrol supplements.

Stand by for controversy: Those who’ve contended resveratrol is not effectively bioavailable ought to get ready to order their crow entreé.

Some of the magic of resveratrol revealed
By Bill Sardi

Historical evidence and recent scientific studies attest to the almost magical properties of red wine molecules, namely resveratrol. The paradoxical health effects of red wine, despite the intake of high calorie meals among the French, have drawn considerable attention. More recently, MIT and Harvard researchers have uncovered a genetic mechanism whereby red wine molecules, such as resveratrol, mimics calorie restriction. Therefore, resveratrol may be able to produce the same beneficial health effects as a limited-calorie diet, namely life extension, elevation of HDL “good” cholesterol, and normalization of blood sugar and blood pressure.

Like other polyphenols found in plants, resveratrol, as a small molecule, is readily absorbed and is able to pass through cell walls, enters the nucleus of a living cell and favorably manipulates genetic mechanisms. Resveratrol’s ability to activate DNA repair enzymes under the control of the Sirtuin 1 gene has recently been reported, with considerable attention from the scientific community. [Nature 425:191-6, 2003]

Chart: Biomol. Activation of Sirtuin 1 controlled enzymes by various plant molecules (polyphenols). Reported in Nature 425:191-6, 2003.

One of the nagging obstacles for resveratrol has been its seeming lack of oral bioavailability. At least four times in 2004 news stories emanating from newly published research papers declared red wine pills are not orally bioavailable and therefore of no potential benefit. Since red wine molecules like resveratrol and quercetin in red wine are efficiently attached to sulfur and sugar-like molecules (a process called sulphation and glucuronidation) on their first pass through the liver, there is little free resveratrol available thereafter. Many consumers threw away their resveratrol pills with the publication of these news reports. Researchers indicate resveratrol may have some benefit in the lining of the digestive tract but cannot exert systemic health benefits because of liver metabolism.

For example, Thomas Walle and colleagues at the University of South Carolina confirm that a minimum of 70 percent of oral resveratrol, as a small molecule, is absorbed in the human digestive tract, but thereafter most resveratrol in blood plasma is conjugated with (complexed with) sulfur and glucuronic acid as it passes through the liver. [Drug Metabolism Disposition 32:1377-82, 2004] Other studies also indicate that gastric absorption of resveratrol in-vivo may be high but there is limited bioavailability due to efficient sulfate conjugation. [J Pharmacy Pharmacology 55:307-12, 2003] Researchers in Britain also maintain that oral resveratrol is not bio-available and that an aerosol delivery system would be required to treat lung diseases. [Am J Physiology Lung Cell Molecular Physiology 287:L774-83, 2004]

More recently, Italian researchers studied resveratrol from red wine and found, 30 minutes after ingestion, only a small amount of free (unsulfated, unglucuronidated) resveratrol was present in the blood circulation. There were large variances in absorption from individual to individual, and researchers concluded that this “raises some doubts about the health effects of dietary resveratrol consumption.” [Molecular Nutrition Food Research 2005 Apr 14] But don’t throw away your red wine pills just yet.

Even though very small amounts of free resveratrol are measured in the blood circulation and living tissues of humans following oral consumption of resveratrol, it should be noted that miniscule concentrations of resveratrol, only ~500 nanomolar (billionth of a gram), are required to protect nerve cells. [Nature Genetics 37: 349-50, 2005]

Moreover, three studies indicate the inclusion of quercetin with resveratrol inhibits sulfation in the liver and improves bioavailability. [Xenobiotica 30: 609-17, 2000; 30: 857-66, 2000; 30:1047-54, 2000] Additionally, lecithin has been found to enhance the oral absorption of polyphenols like quercetin and resveratrol. [J Agriculture Food Chemistry 13; 50:1706-12, 2002] Following this science, LongevinexÔ, a proprietary red wine pill, was the first to provide quercetin and lecithin with resveratrol in an airtight-sealed dietary supplement. (Patent Applied For)

But an important biochemical aspect of why resveratrol exerts seemingly magical properties has been overlooked. The metabolic process of glucuronidation in the liver actually appears to protect resveratrol from degradation, extending its half life and maintaining its biological properties. [Biochemistry Journal 374 (Pt 1):157-63, 2003]

Researchers at the Institute of Human Virology, University of Maryland Biotechnology Institute, have written an extensive report describing the biological aspects of liver metabolism and resveratrol. Here is an excerpt paraphrased from their paper:

What is the biological function of glucuronidation of resveratrol in humans? What is the real bioactive form of resveratrol in living organisms? …There are examples showing that liver metabolism (glucuronidation) has a role in drug disposition and drug targeting in humans. It is known that beta-glucuronidase, the enzyme that breaks down glucuronide, is widely expressed in organs, tissues, and body fluids in humans. Therefore, this enzyme may release a drug or bound molecule like resveratrol locally or systemically from a glucuronide conjugate (such as resveratrol glucuronide). In fact, many glucuronide prodrugs have been designed and are under development which bind a synthetic drug molecule to glucuronide which subsequently depends upon the beta-glucuronidase enzyme to release it into living tissues.

Therefore, it is likely that at least a portion of resveratrol is unzipped from its protective carrier by the glucuronidase enzyme and could be converted back to free resveratrol. Since tissue or serum beta-glucuronidase enzyme activity is elevated in certain diseased tissues, such as cancer, liver diseases, and AIDS, resveratrol would be targeted and released more so in these tissues than in healthy ones. Researchers state that “these observations… raise the possibility that glucuronidation of resveratrol may have a role in detoxification, disposition, and prolongation of the effectiveness of resveratrol in humans.” [J Pharm Science 93:2448–2457, 2004] Wow, that’s magical. What was thought to make resveratrol actually unavailable actually protects it from degradation, prolongs its circulation and then targets it for release in the very tissues that need it most. This process delivers resveratrol to the right tissues at the right time.

Oral doses of resveratrol have been found in organs beyond the intestines, liver and kidneys. For example, Italian researchers have shown that resveratrol from red wine exerts “significant cardiac bioavailability” in rodents. [Drugs Experimental Clinical Research 24: 51-55, 1998] Other researchers conclude that “resveratrol is bio-available following oral administration and remains mostly in an intact form. The results also suggest a wide range of target organs for cancer chemoprevention by wine polyphenols in humans.” [Life Science 72: 2219-33, 2003]

Yes, science is uncovering the reasons why red wine molecules exert seemingly magical properties. The metabolism of the red wine molecule resveratrol in the liver appears to be an essential part of the process that results in its extraordinary health benefits.

Bill Sardi is President of Resveratrol Partners LLC, makes of Longevinex, the world’s first red wine pill encapsulated in an airtight capsule.

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Some of the magic of resveratrol revealedBy Bill Sardi

Articles, papers, arguments & opinions, thoughts, all welcome. Email to: admin@resveratrolnews.comOur FORUM operates 24/7 ... LIVE.

Some of the magic of resveratrol revealed
By Bill Sardi

Articles, papers, arguments & opinions, thoughts, all welcome.
Email to: admin@resveratrolnews.com
Our FORUM operates 24/7 ... LIVE.