Some avid supplement users are getting into trouble by mega-dosing on polyphenols, hence the publication of this advisory for educational purposes.
Longevinex® contains three potent polyphenols: resveratrol, quercetin and fisetin.
The bulk of the scientific literature regarding polyphenols points to modest doses providing optimal health benefits. This is evidence of hormesis, that a small amount of a “toxin” can activate the body’s defenses rather than the polyphenols themselves producing an effect.
Small amounts of polyphenols are antioxidant while mega-doses promote oxidation (pro-oxidant). Oxidation is the formation of species of oxygen that lack an electron and can be destructive until an electron can be donated to negate any potential tissue damage.
Fortunately, polyphenols spare any adverse effects upon healthy tissues as they target unhealthy cells, pathogenic bacteria or viruses, but not healthy cells. But still excessive doses can induce problems.
For example, polyphenols are natural enzyme inhibitors. Polyphenols inhibit enzymes like sulfotransferase, an enzyme that catalyzes (degrades) adrenal stress hormones as they are produced. Over-inhibition of sulfotransferase may allow stress hormones to run wild and produce migraine headaches, anxiety attacks, excessively fast heart rate (fibrillation) and elevated blood pressure.
Polyphenols are the most prominent class of natural molecules that promise to ward off many of the maladies associated with aging. Polyphenols are derived from plants and serve as anti-fungal agents. Polyphenols activate more genes than drugs and have broad activity throughout the body, particularly as prebiotics in the digestive tract.
The most frequently consumed polyphenols as dietary supplements are resveratrol (grapes), quercetin (apple peel, onions), catechin (tea leaves), caffeic acid and chlorogenic acid (coffee bean), cinnamaldehyde (cinnamon), and curcumin (turmeric spice).
There are more than 8000 types of polyphenols found in plants. Since they have multiple phenol units they are called poly (many) phenols. They bind to albumin that transport them throughout the human body.
Hundreds of foods provide polyphenols. The most well known as cocoa, cloves, grapes, coffee bean, tea, apple and berries.
The health effects of polyphenols depend on the amount consumed and on their bioavailability.
Polyphenols are TNF inhibitors. TNF, tumor necrosis (death) factor, is a small protein that activates the immune system, in particular white blood cells known as macrophages that literally ingest bacteria, viruses and tumor cells. Macrophages release TNF. TNF is also a pyrogen (activates fever).
Over-active TNF induces inflammation and accompanying pain.
High TNF levels can also trigger some unpleasant symptoms:
- Low blood pressure
- Fever
- Muscle aches
- Loss of appetite
- Redness and swelling (if you have an infected wound)
TNF inhibiting drugs are used to treat autoimmune disorders such as rheumatoid arthritis, psoriasis, Crohn’s disease, lupus, thyroiditis. Common TNF-inhibiting drugs are:
- Adalimumab (Humira), adalimumab-atto (Amjevita)
- Certolizumab pegol (Cimzia)
- Etanercept (Enbrel), etanercept
- Golimumab (Simponi, Simponi Aria)
- Infliximab (Remicade), infliximab
Polyphenols are strong TNF inhibitors and can be used to quell inflammation.
TNF is an essential part of the human immune system. Over-inhibition of TNF may impair normal immune functions.
Pharmaceutical TNF inhibiting drugs carry a BLACK BOX warning on their labels.
For pharmaceutical TNF INHIBITORS, two warnings have been issued:
- increased risk for developing serious infections (including tuberculosis -TB), histoplasmosis, listeriosis, Pneumocystis pneumonia) that may lead to hospitalization or death;
- increased risk of developing lymphoma and other malignancies.
Polyphenols in a certain dosage range provide health benefits. For example, teetotalers do not experience a decline in mortality for coronary artery disease due to abstention from alcohol. Modest consumption of polyphenol-rich wine reduces coronary artery disease mortality rates.
The grape-derived polyphenols in wine provide health benefits, but only in a range of 3-5 glasses of wine providing 60 milligrams of polyphenol per glass. That would be 3-5 glasses or 180-300 milligrams of polyphenols. Even then, that is to the point of inebriation. More polyphenols consumed and the health benefits vanish. In fact, excessive polyphenols may be toxic to organs such as the heart, and impair the immune system.
In my experience with resveratrol since it was first introduced as a nutraceutical in 2004 is that it is a very safe molecule. It does thin the blood but has very rarely been implicated in any bleeding episodes or over-thinning of the blood, which is desirable as one ages anyway.
I rarely had to answer questions about Longevinex® side effects until another polyphenol, curcumin (from turmeric spice) was widely marketed on the radio and many consumers began taking Longevinex® + curcumin. It is in these customers that I began to hear of side effects, the anxiety, fast heart rate, flu-like symptoms and skin rash as well as Achilles’ heel tendonitis.
Curcumin is a very potent TNF inhibitor. Most brands of curcumin are provided in excessive doses – – 500 to 1000 milligrams. The companies that market these products, working on a mistaken “more is better” idea, are oblivious to potential side effects, and over-dose consumers, especially when combined with other polyphenol supplements and/or wine drinking.
Anecdotally, a couple of cases of lymphoma vanished after I advised Longevinex® users to cease taking accompanying curcumin.
Like wine, don’t over-do polyphenol supplements. The dosing of polyphenols in Longevinex® has been carefully formulated to avoid overdosage. By combining polyphenols (resveratrol, quercetin, fisetin), molecular synergism results and lower doses actually produce a more demonstrative effect. Furthermore, unlike any other polyphenol product, even when overdosed, the human equivalent of 2800 milligrams of Longevinex® did not induce expected toxicity because of counter-balancing nutrients in the formula.
Bill Sardi, managing partner
Resveratrol Partners LLC, dba LONGEVINEX
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