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  • Resveratrol Metabolism Explained

    April 26, 2016: by Bill Sardi

    Metabolism and Bioavailability of Resveratrol

    Misconceptions abound as to whether resveratrol is biologically available, that is, available in human body in its unbound form as “free resveratrol.” Initially it was mistakenly believed resveratrol bound to other molecules is inactive biologically. Over time it has become apparent that resveratrol bound to other molecules, its metabolites, are also biologically active. Furthermore, only recently has it been demonstrated that resveratrol exerts indirect biological activity by altering the composition and ratio of gut bacteria, making the claim resveratrol is not biologically available a moot point. So this report both graphically and textually provides an up-to-date explanation of resveratrol metabolism.

    To metabolize: to organically or chemically process or breakdown a drug, food or nutrient into a usable form in the body; sometimes metabolism involves detoxification of potential toxic molecules via liver enzymes (cytochrome p450 enzymes) that utilize iron to oxidize incoming molecules; or by conjugation (attachment) of proteins (glucuronate, sulfate) in the liver. Metabolism may also occur in the digestive tract, principally in the intestines where many types of generally neutral bacteria (examples: Bifidus, Acidophilus) produce metabolites that exert biological activity.

    The way the human body processes resveratrol is called metabolism. Resveratrol’s metabolism can be broken down into steps:

    Resveratrol Metabolism

    Step #1: gastric absorption; as a small molecule most resveratrol (~75%) is said to be absorbed into the blood circulation. Micronization of resveratrol is a way to enhance absorption of resveratrol. Some unabsorbed resveratrol is rapidly excreted via the kidneys in urine flow.

    Step #2: (a) Some un-absorbed resveratrol also makes its way from the stomach to the intestines where it favorably alters the composition of bacteria, particularly Bifidus, to enhance calorie-burning which results in leanness; or (b) once absorbed, resveratrol makes it way to the liver, which is the master metabolic organ in the body.

    Step #3: Once absorbed into the blood circulation resveratrol is shuttled to the liver. The human liver has two ways it detoxifies the body from incoming toxins:

    (1) creation of enzymes, known as cytochrome p450 enzymes that utilize iron to degrade toxins, drugs, etc. Resveratrol inhibits cytochrome p450 enzymes and thus, for example, makes drug action stronger, which may be beneficial or deleterious;

    And (2) creation of detoxification molecules glucuronate and sulfate in the liver that attach to (conjugate with) molecules newly introduced into the blood circulation like resveratrol to detoxify them.

    Once resveratrol is attached to glucuronate or sulfate it becomes a larger molecule.

    Molecular weight of resveratrol is 228 Daltons {unit of atomic mass}; molecular weight of resveratrol glucuronide is 404 Daltons; molecular weight of resveratrol sulfate is 303 Daltons.

    Essentially all resveratrol is eventually conjugated with sulfate or glucuronate as it passes through the liver but the simultaneous ingestion of quercetin or piperine delays liver conjugation and allows for more immediately available free- unbound resveratrol in the blood circulation.

    Once bound to glucuronate or sulfate, resveratrol has a half-life of ~9 hours.

    On the other hand, free/unbound resveratrol has a short half-life of ~14 minutes. (Half-life is the amount of time it takes before half of the active elements are either eliminated or broken down by the body).

    Glucuronidated resveratrol is uncoupled by the enzyme glucuronidase, which is abundant at sites of inflammation, infection and malignancy, and delivers free-unbound resveratrol at the right time and place.

    ©2016 Bill Sardi,

    Three Ways Resveratrol is Metabolized


    Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver.  Xenobiotica 2000.

    Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids.  Xenobiotica 2000.

    High absorption but very low bioavailability of oral resveratrol in humans, Drug Metabolism Disposition 2004.

    Resveratrol glucuronides as the metabolites of resveratrol in humans: characterization, synthesis, and anti-HIV activity.  Journal Pharmaceutical Sciences 2004

    Bioavailability of resveratrol, Annals New York Academy Science 2011

    Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence, Journal Translational Medicine 2013.

    Beneficial action of resveratrol: how and why? Nutrition 2016

    Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota.  MBio 2016.

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