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  • The Most Promising Natural Anti-Cancer Molecule In 1997 — What Happened To It 17 Years Later?

    November 27, 2014: by Bill Sardi

    It was heralded in 1997 as the most promising anti-cancer molecule found in nature. [Science Jan 10, 10997]

    It stops cancer in all three stages of development (initiation, growth and spread), unlike any existing anti-cancer drug. [Cancer Prevention Research May 2009]

    It inhibits the development of new blood vessels that feeds tumors. [International Journal Oncology Dec 2013]

    It reduces the delivery of sugar to cancer cells that are reliant upon sugar for cell energy. [Journal Nuclear Medicine 54: 2161-67, Dec 2013; Molecular Carcinogenesis Oct 12, 2014]

    It blocks most all cancer pathways including inflammation. [Anticancer Agents Medicinal Chemistry 2014; Journal Nutritional Biochemistry Aug 2005]

    It increases the immune response (natural killer cells) against cancer. [Indian Journal Biochemistry Biophysics Feb 2013]

    It provides more time for the repair of broken (mutated) DNA by slowing the cell renewal cycle and therefore prevents pre-cancerous lesions. [Molecular Medicine Reports Jan 2015]

    It inhibits cancer stem cells. [PLoS One July 28, 2014]

    It kills cancer cells by various non-toxic mechanisms. [European Journal Cancer Prevention Nov 2013]

    It protects against cancer by activating internal antioxidant enzymes. [Carcinogenesis Aug 2014]

    It is a mild anti-estrogen and therefore inhibits growth of breast cancer. [Cancer Research Oct 15, 2001]

    It overcomes treatment resistance during chemotherapy. [Current Drug Metabolism Sept 26, 2014]

    It enhances chemotherapy and radiation therapy. [Cancer Letters Aug 8, 2007]

    It alleviates side effects of cancer treatment. [Mutation Research Genetic Toxicology Environmental Mutagenesis May 2014; Toxicology In Vitro March 2014]

    And where has it ended up 17 years later?

    The same researcher who said resveratrol is the most profound natural or synthetic anti-cancer agent in 1997 now says resveratrol “is not a good drug candidate” because it lacks potency and only addresses a narrow number of gene targets. [Annals New York Academy Science July 2013]

    But contrarily he says resveratrol “induces a whiff that induces a biologically specific tsunami.” [Cancer Biology & Therapy Sept 2004] Single gene targeted drugs have largely been a failure and the broad number of genes that resveratrol targets is a biological advantage, not a disadvantage.

    Over a dozen years ago researchers said: “resveratrol holds great promise for future development as a chemo-preventive agent that may be useful for several disorders.   Preclinical toxicity studies are underway that should be followed by human clinical trials. [Annals New York Academy Science May 2002]

    Seventeen years after it was identified as a profound anti-cancer molecule there are currently no human trials underway by the National Cancer Institute.

    The primary reason researchers give for their foot-dragging over resveratrol for cancer treatment is this: while cancer researchers extol resveratrol in a lab dish they bemoan its poor bioavailability. [Recent Results Cancer Research 2005]

    Researchers continue to say resveratrol is not biologically available and lab dish studies do not equate with human use because, after absorption in the gastric tract, it is shuttled to the liver where it is metabolized by attachment to detoxification molecules that render it almost useless. [Molecules Oct 24, 2014]

    But there are myriads of studies both in mammals and humans showing system-wide health benefits in the eyes, heart, brain, liver, etc. [Nutrients Oct 17, 2014; Nutrition Research Nov 2011; Journal Cellular Molecular Medicine Oct 2012] How could resveratrol be working in humans, even causing the outcropping of new blood vessels that feed tumors to recede in humans when other anti-cancer drugs fail? [Nutrients Oct 2014] How could resveratrol be exerting strong biological action when only trivial amounts are bioavailable?

    Stunning Discovery

    Now the answer to that question has been provided.

    When resveratrol is orally consumed about 70% of it is absorbed into the blood stream.   Resveratrol is then shuttled to the liver that acts as a detoxification station. Resveratrol is perceived as a molecular mimic of food deprivation and the liver takes action to detoxify it by binding it to larger molecules, namely sulfate and glucuronate. So after a few passes through the liver almost all of it is bound to carrier molecules and very little of resveratrol is unbound (what is called free resveratrol).   This is the primary objection that biologists use to substantiate the need for a resveratrol-like drug (called a synthetic analog that is patentable). [Annals New York Academy Science Jan 2011; Anticancer Agents Medicinal Chemistry 2014]

    However, researchers have made a stunning and unexpected discovery – resveratrol attached to sulfate exhibited a strong anti-cancer effect whereas unbound (free) resveratrol didn’t and conclude that synthetic analog forms of resveratrol “may not be necessary to deliver efficacious concentrations to target tissues.”

    The liver “metabolites (sulfate, glucuronate) of resveratrol may actually play a greater role than the unchanged parent molecule because resveratrol-sulfate achieved 10-fold greater concentration than free resveratrol! Resveratrol-sulfate inhibits replication of cancer cells better than native resveratrol itself.

    The chart above displays the ability of alleged non-bioavailable sulfated-resveratrol to reduce the number of cancer cells in vitro (in a lab dish). Sulfated resveratrol is represented in black whereas un-sulfated free unbound resveratrol (green) had little effect. [Science Translational Medicine 5: 205ra133, Oct 2013]

    HT-29 chart

    The whole charade that researchers have been using to justify the need to convert resveratrol into a patentable drug so they can cash in and produce a multi-billion dollar blockbuster drug is baseless.

    The profit motive in modern pharmacology without a free market where nutraceuticals can compete openly against synthetic drugs is not serving humanity. The pursuit of profits over performance produces drugs that are inferior to what nature has already provided. Prices for these synthetic drugs are inordinately high. These unethical practices are shameful.

    Over 70 years have past since its discovery and one of nature’s best-designed molecules is not being used by modern medicine solely because it is not a synthetically-made drug that reaps billions of dollars of profits for doctors and pharmaceutical companies.   If it can’t be patented then doctors and pharmacies don’t have control over it. Direct access to such a molecule would be the ruination of the practice of medicine as it could replace myriads of drugs. [Medicinal Chemistry May 2014]

    By definition, a nutraceutical categorically cannot prevent, treat or cure a disease. It has to be a drug to make that claim which dramatically increases its expense and it only becomes affordable via insurance plans where the cost of healthcare is shared.

    Resveratrol remains unproven in human studies by exclusion. In the only human trial attempted, 5000 milligrams of resveratrol (an overdose, administered as an experimental drug) was given to end-stage multiple myeloma patients (bone marrow cancer) and the study had to be halted due to rapid kidney failure. [The Myeloma Beacon May 3, 2010]

    ©2014 Bill Sardi,

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