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How the world got lost on
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June 11, 2010: by Bill Sardi
Say again? Pterostilbene? (pronounced “tero-STILL-bean”) If you take resveratrol pills you probably have never heard of pterostilbene, but it is a naturally-occurring, molecular look-alike of resveratrol.
Pterostilbene is alleged to be superior to resveratrol and the commercial availability of a pure form of pterostilbene (pTeroPure) is creating some manufacturer-driven hype that consumers should opt for it over resveratrol.
The actual development of pterostilbene as a raw material for dietary supplements began with research conducted by US Department of Agriculture scientists. Pterostilbene is derived from blueberries. It’s being imported from India as a nearly pure extract.
Technically, pterostilbene is methylated resveratrol and another molecular cousin, piceatannol, is hydroxylated resveratrol. This means that a methyl group or hydroxyl group is added to the molecule. Methylated resveratrol (pterostilbene) is said to be better absorbed and more “bioavailable.”
The research surrounding pterostilbene is promising, however, like resveratrol, human studies have yet to be launched and while some studies indicate pterostilbene may reduce elevated cholesterol and blood sugar levels, it has been demonstrated to do so only at very high doses – 2800 milligrams for blood sugar and 1750 mg to lower cholesterol. Both of these doses may be potentially harmful. It is possible that lower doses of pterostilbene will work. Better dosing studies are needed. (This is problem that the Federal Trade Commission has with dietary supplement makers – they often quote published studies that employed far higher doses than offered by their products.)
As we are all learning about resveratrol, higher dosage may not be optimal. Lower, not higher-dose resveratrol has been found to exert biological action similar to a calorie restricted diet, and lower, not higher doses protect the heart. So there may be diminishing returns in any attempt to build a more potent form of resveratrol.
The impetus to bring pterostilbene to the nutriceutical marketplace is based upon some widely disseminated misconceptions — that resveratrol is not readily absorbed and very little of it is biologically available (bioavailable) for use by the body.
Pterostilbene advocates claim resveratrol is poorly absorbed, but the research they cite in that regard says otherwise. Researchers have previously shown that more than 70% of plain resveratrol is absorbed in the digestive tract. So any increase in absorption brought about by pterostilbene would only improve absorption by a marginal amount.
For example, if pterostilbene improves oral absorption from let’s say 70% to 85%, then 115-125 milligrams of plain resveratrol would equal 100 milligrams of pterostilbene, absorption-wise.
Pterostilbene is lipophilic, that is, it dissolves in fats and oils better than in water. Since the lining of the intestinal tract is composed of tightly-packed lipids (fats) and proteins, lipophilic molecules like pterostilbene penetrate this barrier better. But this doesn’t mean plain resveratrol is not well absorbed. It is a small molecule (228 Daltons molecular weight) and is readily absorbed.
Some makers of resveratrol pills have micronized their products (reduced the average diameter of a solid material’s particles) and folded resveratrol into plant starches or dextrins (microencapsulation) to improve absorption. So methylation is not the only way to improve absorption.
Bioavailability refers to the passage of resveratrol or pterostilbene through the liver. As these small molecules navigate through the liver they are detoxified in different ways. One way is to attach them to detox molecules, namely sulfate and glucuronate. Once bound to these other molecules, resveratrol is unable to pass through cell walls and interact independently. So it has been temporarily rendered “non bio-available.”
Methylated resveratrol makes more passes through the liver before it is attached or complexed with sulfate and glucuronate, making it more immediately bioavailable. This can also be accomplished by delivering quercetin, another red wine molecule, with resveratrol.
The problem is that resveratrol has a relatively short half-life, ~1-3 hours, circulating the body on its own, as a free unbound molecule. Methylated resveratrol is said to have a longer half life. However, as resveratrol naturally attaches to glucuronate, this will extend its half-life to ~9 hours. So nature does for resveratrol what pterostilbene is advertised to do.
Whether methylated or glucuronidated or sulfated, resveratrol must become a free, unbound molecule to pass through cells walls and exert influence over intracellular genetic machinery. This is demonstrated in the following chart.
The above chart shows various concentrations of resveratrol, MET-1 and MET-2 being resveratrol plus liver metabolites (glucuronate or sulfate) and RES as unbound, free resveratrol. The height of the bars indicates viral-infected cell viability. Only at higher concentrations and in its unbound form did resveratrol demonstrate an ability to kill viruses (cytotoxic) in combination with an antiviral drug.
Nature takes care of the problem of bioavailability by producing glucuronidase enzyme, which is 16-times more abundant at sites of inflammation, infection and malignancy, which in turn unzips or releases resveratrol from glucuronate, therefore facilitating the delivery of resveratrol at the right time and place.
The same holds true for resveratrol when has been conjugated (attached) to sulfate in the liver. Sulfatase enzyme activity unlocks resveratrol from sulfate, making it bioavailable.
This is nature’s drug delivery system. Some drug molecules are pre-glucuronidated to facilitate delivery. So it is a mistaken idea that resveratrol, once metabolized in the liver, is not bioavailable.
Most certainly, resveratrol by itself has been documented to produce a profound biological effect throughout the body – brain, eyes, heart, liver, kidneys – not just in the digestive tract where it is deposited via oral intake. Just why it has been said that resveratrol is not bioavailable is inexplicable. Pterostilbene is attempting to solve an imagined problem. Researchers are creating science to fit their own commercial interests.
Another alleged health benefit for pterostilbene is that it exhibits ability to lower cholesterol in a superior manner to fenofibrate drugs. While this has been demonstrated in animals, this research chases another long-standing falsehood – that cholesterol reduction saves lives. Cholesterol-lowering drugs have never been shown to reduce coronary artery disease mortality rates and cholesterol is not the primary plaque that occludes arteries – calcium is. Fenofibrate drugs reduce cholesterol absorption from the diet, but the diet provides less than 20% of circulating cholesterol while the liver naturally produces the other 80%. Cholesterol reduction is a straw man argument. So this health benefit ascribed to pterostilbene is specious. ### © 2010 Bill Sardi