Resveratrol vs. Pterostilbene 

A Comparison of Bioavailability and Health Benefits

Nearly two decades ago, it was discovered that resveratrol slowed the process of cellular aging in yeast. In 2003, Harvard Medical School Professor David Sinclair, PhD, found that resveratrol activated a longevity gene called SIRT1 and the resultant class of sirtuin proteins. 

 

Then, the same mechanism was studied and found to be true in mice. Investigations into resveratrol then turned toward its effects on human health. Resveratrol was found to support cardiovascular health, antioxidant defenses, glucose metabolism, healthy inflammatory balance, and more. As results of these studies were reported, people became more interested in drinking resveratrol-rich red wine and taking resveratrol supplements. 

 

However, some of the biggest hurdles for reaping the benefits of resveratrol in humans appear to be its limited bioavailability and rapid elimination from the body. But those hurdles might be overcome by a compound that has more recently gained some notice. 

 

About 10 years after the discovery that resveratrol activated a longevity gene, researchers began to take interest in its molecular cousin, pterostilbene. Although it is present in a higher concentration in blueberries than in red wine, pterostilbene is nearly identical in chemical structure to resveratrol. 

 

The first human-safety study of pterostilbene was published in 2013, and investigations have intensified since then. Pterostilbene is now championed as a more potent form of resveratrol. It’s said to offer all of the previously known benefits of resveratrol but with superior bioavailability. Are these claims true? Read on for a detailed comparison of these two cousin compounds. 

 

STRUCTURAL DIFFERENCES 

 

Resveratrol and pterostilbene are both naturally occurring plant compounds. Resveratrol is concentrated in grape skins and red wine, but it has also been isolated from the roots of Japanese knotweed. Pterostilbene is concentrated primarily in blueberries, but it has also been found in small amounts in peanuts, grapes and cocoa. 

 

Resveratrol and pterostilbene fall into a class of compounds called stilbenes. These phenolic compounds consist of two aromatic rings with hydroxyl groups (-OH). Resveratrol and pterostilbene are very similar in structure, but with one minute—yet critical—difference. Resveratrol has three hydroxyl groups, whereas pterostilbene has only one. The other two hydroxyl groups are replaced by methoxy groups (O-CH3) in pterostilbene.

 

The difference in the number of hydroxyl groups is crucial because it influences how quickly the compound is metabolized and eliminated from the body. The three hydroxyl groups in resveratrol hasten the molecule’s removal, which makes it challenging to reach and maintain appreciable levels of resveratrol in the bloodstream.

With only one hydroxyl group per molecule, pterostilbene is able to persist in circulation for a longer time. The slight difference in structure also makes pterostilbene more lipophilic. Pterostilbene can more readily pass through cell membranes—making it more available to support cellular pathways.

 

Both resveratrol and pterostilbene are naturally occurring in two forms: cis and trans. The trans forms are more stable and more abundant in nature. Studies suggest that for both resveratrol and pterostilbene, the trans forms are superior to the cis forms in terms of biological activity.

 

BIOAVAILABILITY AND HALF-LIFE 

 

The good news about resveratrol and pterostilbene is that they’re both readily absorbed after oral intake, and are even capable of crossing the blood-brain barrier. The bad news is that they’re rapidly metabolized. Their time in circulation is fleeting.

 

The absorption rate of resveratrol from the intestinal lumen is about 75 percent, but its rapid metabolism in the liver results in oral bioavailability of only about 1 percent. That’s because the liver produces resveratrol conjugates—primarily glucuronides and sulfates. In a human bioavailability study, 15 healthy volunteers each took a 500 mg capsule of trans-resveratrol. Blood samples taken after dosing showed that free resveratrol only represented 0.28 percent of total resveratrol in circulation, with the rest consisting of conjugated glucuronides or sulfates.

 

The study also showed that resveratrol was short-lived— its concentration peaked at only about one hour after intake. That result was similar to an earlier study, which found that the half-life of trans-resveratrol was one to three hours following a single dose.

 

When a compound has such low bioavailability and such a short half-life, it’s difficult to maintain a concentration in circulation. One study found that even when people took 150 mg of trans-resveratrol six times per day, they still had low plasma concentrations.

 

One of the most commonly cited comparisons of resveratrol and pterostilbene is that the oral bioavailability of resveratrol is only 20 percent, while pterostilbene reaches 80 percent. But it’s important to note that these percentages refer to the combined total of resveratrol plus resveratrol sulfate, and pterostilbene plus pterostilbene sulfate. It’s even more important to note that these percentages came from a study that was conducted in rats rather than humans.

 

The other oft-cited comparison is that the half-life of pterostilbene is seven times longer than that of resveratrol. This statistic comes from two studies: One reported that resveratrol had a half-life of 14 minutes,and the other reported that pterostilbene had a half-life of 105 minutes. Again, these were preclinical studies that were conducted not in humans but in rabbits, rats, and mice.

 

Several unanswered questions remain. We don’t know whether the conjugated metabolites of resveratrol and pterostilbene have biological activity at the tissue level (there is some evidence of activity, albeit less than free resveratrol). Also, it’s unknown whether the bioavailability data on pterostilbene from animal studies can be translated to humans.

 

Many researchers and clinicians are taking the limited data we have so far about the bioavailability of pterostilbene and running with it. Based on the studies mentioned above, pterostilbene has gained a reputation for being a more potent and bioavailable form of resveratrol.

 

COMPARISON OF HEALTH BENEFITS

 

Resveratrol has been extensively researched. Experimental studies show that resveratrol modulates numerous molecular mechanisms at the cellular level. It interacts, for example, with cellular pathways related to healthy inflammatory balance, apoptosis, and autophagy. It also interacts with pathways associated with aging and longevity, such as telomeres and cell senescence.

 

Despite its low bioavailability, there is abundant evidence for resveratrol’s ability to promote health in humans. Randomized, controlled trials have shown that resveratrol supplementation supports healthy weight management, blood-sugar metabolism, cardiovascular function, mood, healthy inflammatory balance and oxidative stress. Resveratrol’s health benefits have also been shown in many other studies, and even meta-analyses.

 

When it comes to pterostilbene, the evidence is much sparser. Aside from a safety study published in 2013, there have been very few trials conducted in humans. There was one study, conducted at the University of Mississippi in 80 adults, which found that pterostilbene supported healthy blood pressure and lipid metabolism.

 

The vast majority of research on pterostilbene is in the experimental and preclinical phase. Researchers have found that pterostilbene supports many of the same cellular pathways as resveratrol—including supporting antioxidant defenses and modulating pathways involved in healthy inflammatory balance, apoptosis, and autophagy. Most experts agree that the molecular mechanisms of pterostilbene should be considered equivalent to those of resveratrol.

 

WHICH SHOULD YOU CHOOSE?

 

PubMed has indexed more than 12,000 research studies on resveratrol, but only 500 on pterostilbene. However, the sheer number of scientific studies on a compound doesn’t necessarily mean the compound is superior. It’s also important to note that pterostilbene research lags about 10 years behind resveratrol research.

 

The slight difference in molecular structure between resveratrol and pterostilbene provides a sound rationale for the superiority of pterostilbene. Pterostilbene should be more stable and bioavailable in theory, and preclinical studies so far validate the assumption.

 

We look forward to more research on pterostilbene in the years to come. For now, many experts believe that what we’ve already learned about resveratrol regarding its ability to support cardiovascular health, cellular health, and metabolism is also true for pterostilbene. Researchers are hedging their bets that pterostilbene will prove to be all the things resveratrol is— but in a super-potent form.

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