Trans-resveratrol vs. Resveratrol and How Different Forms Could Impact the Results You See

It turns out some of the more promising leads in the science of aging are hiding in plain sight — like in the skin of a grape or the shell of a peanut. And one of those leads happens to be resveratrol, a plant compound that's now the subject of developing longevity research.

Resveratrol’s antioxidant profile has drawn more and more attention in research, with early evidence linking it with potential health benefits for cardiovascular, metabolic, and cognitive health. And as findings continue to build, so too does the technical detail, particularly around resveratrol supplementation and whether one molecular form may be more effective than another.

Only two forms of resveratrol occur naturally in plants: cis-resveratrol and trans-resveratrol. The form you’re getting can make a big difference in how your body absorbs it — and ultimately, how much of its potential benefit you actually see. That’s what I will be looking at in this article: how cis- and trans-resveratrol differ and why those differences could matter more than they seem at first glance.

What is resveratrol, exactly?

Resveratrol is a polyphenolic compound naturally synthesized by certain plants and is crucial for the response to stress, damage, or fungal infection. You’ll find it in modest amounts in the skin of red grapes, blueberries, peanuts, and a few other foods, though in relatively small amounts and not in levels that are likely to make a clinical impact through diet alone.

What makes resveratrol particularly interesting in the context of human health is its classification as a stilbenoid, a type of compound known for its antioxidant and anti-inflammatory potential. That’s what first brought it into the public eye years ago, particularly in studies exploring the ‘French paradox’ — the idea that moderate red wine consumption might contribute to heart health.

Since then, resveratrol has been explored for its potential health‐promoting properties. But the way it behaves in the body — and how much benefit you might actually get from it — may depend on its chemical form. And that’s where the distinction between cis- and trans-resveratrol starts to matter.

Trans-resveratrol, the biologically active isomer

Among the different structural variants of resveratrol, trans-resveratrol is the one most often highlighted in scientific literature. It's what’s known as an isomer — a molecule that shares the same atoms as another, but is arranged differently in space. In this case, the ‘other’ isomer is cis-resveratrol, and the arrangement is the difference.

Trans-resveratrol is considered the more biologically active form, meaning the one your body can absorb, circulate, and potentially use to carry out its effects better. Once absorbed, trans-resveratrol is proposed to interact with a variety of molecular targets, including pathways involved in oxidative stress, inflammation, and even gene expression related to cellular aging.

Most of the studies linking resveratrol to health benefits — some relevant ones I will go over later — are actually studies of trans-resveratrol specifically. That’s why many dietary supplement brands go out of their way to specify the inclusion of this form.

So if you’ve heard about the benefits of resveratrol, chances are you’ve already been hearing about the effects of trans-resveratrol, whether it was stated outright or not.

Cis-resveratrol, the less biologically active isomer

While trans-resveratrol has been the focus of most supplement formulations and research, its lesser-studied opposite, cis-resveratrol, also occurs naturally in plants.

Interestingly, plants aren’t the only source of naturally produced cis-resveratrol — it can also gain form through isomerization when the trans form is exposed to UV irradiation.

Cis-resveratrol was originally thought to be biologically inactive, but later, newer research has shown that both isoforms actually exhibit biological activity. Nevertheless, comparative studies consistently report that trans-resveratrol is the more potent form.

Because of this, cis-resveratrol is typically considered the ‘inactive’ one, or, at least, the less biologically active of the pair.

And so, in most resveratrol-based dietary products, cis-resveratrol is present only in trace amounts. It’s rarely, if ever, the form intentionally delivered in a clinical or supplemental setting.

Trans-resveratrol and cis-resveratrol head-to-head

Where are trans-resveratrol and cis-resveratrol found?

Both trans-resveratrol and cis-resveratrol occur in nature, but their sources — and the conditions that influence their concentration — are worth a closer look.

Trans-resveratrol is the primary form produced by plants, used in a defense response process to stressors like fungal infection or UV radiation. It’s found most abundantly in the skin of red grapes, but also in peanuts, blueberries, and Japanese knotweed, the latter being a common source for supplements due to its high trans-resveratrol content.

Cis-resveratrol, on the other hand, is much less common in freshly harvested plant materials. It typically forms through the isomerization of trans-resveratrol under exposure to light, heat, or certain pH conditions. That’s also why trace amounts can sometimes appear in processed grape products, like wine.

Potential health benefits of resveratrol

Resveratrol has been studied in relation to various aspects of human health, including cardiovascular function, cognitive performance, metabolism, and even cancer biology. Though many of the findings are still early, the emerging science points to a compound with relatively broad biological activity. Here’s a look at some of the benefits being investigated.

Antioxidant and anti-inflammatory activity

Evidence from both clinical and in vitro studies supports the idea that resveratrol has potent antioxidant potential. Given this potential, resveratrol may be able to scavenge free radicals and reduce oxidative stress, which is a key driver in aging and many chronic diseases.

On top of its antioxidant profile, many studies have also reported that resveratrol helps regulate inflammatory response through a variety of signaling pathways, such as the AA pathway, nuclear factor kappa B (NF-κb), Mitogen-activated protein kinase (MAPK), and activator protein-1.

Again, much of this work and much of the existing literature have focused on trans-resveratrol, given its greater stability and biological activity. Although cis-resveratrol may share some of these effects in theory, the limited research makes it hard to draw firm conclusions.

Potential impact on aging and longevity

Resveratrol has often been discussed in the context of longevity research — not because it’s some newfound drug with proven effectiveness, but more so because it appears to interact with some of the same cellular pathways associated with extended lifespan in model organisms.

One of the key targets here is SIRT1, the so-called founding member of the sirtuin family. SIRT1 is primarily located in the nucleus of cells, where it helps regulate certain gene expression and, hence, protein synthesis and their function. It has also been linked to modulating metabolism, promoting DNA repair, exerting anti-inflammatory effects, and enhancing genomic stability.

In animal and in vitro studies, trans-resveratrol has been shown to activate SIRT1, mimicking some effects of calorie restriction, a well-established intervention for lifespan extension in several species. These findings have sparked even more interest in resveratrol as a potential longevity-supporting compound. However, it’s important to note that translating these effects into humans is still an open question, and human clinical trials have shown mixed outcomes so far.

Cis-resveratrol, again, has been much less studied in this area and simply lacks the same pool of studies and data to really present a robust account of its effects.

Cognitive function and brain health

Resveratrol has also been investigated for its potential effects on brain health, particularly due to its ability to cross the blood-brain barrier and its antioxidant and anti-inflammatory properties, which are relevant in the context of neurodegenerative diseases and age-related cognitive decline.

One human study — a double-blind, placebo-controlled crossover investigation — found that single doses of resveratrol led to dose-dependent increases in cerebral blood flow during task performance. The increases were evident in markers like total hemoglobin and deoxyhemoglobin, suggesting enhanced oxygen extraction in the brain.

However, this same study did not observe any measurable improvement in cognitive function itself. In other words, while resveratrol may influence physiological markers associated with brain activity, there’s little evidence so far that this translates into real-world cognitive benefits.

Longer-term studies in humans are needed to determine whether these early physiological changes could support cognitive function and brain health over time.

Metabolic health and weight management

Another area of research on resveratrol has also focused on its potential effects on metabolic function, including weight management. Some early studies have shown that resveratrol may improve insulin sensitivity. These effects are thought to be linked to resveratrol’s activation of cell signaling pathways like SIRT1, which is involved in regulating energy metabolism, mitochondrial function, and cellular health.

There’s also some evidence supporting the idea that resveratrol may exert anti-obesity effects by inhibiting adipogenesis, promoting apoptosis in mature adipocytes, reducing lipid accumulation, and increasing thermogenesis.

One clinical trial worth noting analyzed the effects of resveratrol administration at a dose of 500 mg taken three times daily over a 90-day period in 24 patients with metabolic syndrome. The randomized, double-blind, placebo-controlled study reported significant reductions in total weight, BMI, fat mass, and waist circumference compared to placebo.

But even though promising, findings like these remain relatively limited in humans and don’t yet match the volume or consistency seen in animal studies. Larger and better-controlled human trials are still needed to clarify resveratrol’s therapeutic potential for obesity and metabolic health.

That said, overall results from human trials have been somewhat inconsistent. A 2022 review of randomized controlled trials assessing resveratrol for weight loss in obesity highlighted major variability in study designs and concluded that weight-loss-related outcomes are difficult to interpret and cross-validate.

In short, while the biological rationale is compelling, and some early data point to potential benefits, the clinical evidence supporting resveratrol’s role in weight management and broader metabolic health remains too limited and variable to draw firm conclusions.

Is trans-resveratrol more effective than cis-resveratrol?

As we look at dietary supplements, trans-resveratrol is the form that’s preferred by most, not necessarily because it’s proven to be superior, but because it’s the form that’s been studied most extensively. In fact, most of the potential health benefits attributed to resveratrol in clinical and preclinical research are based almost exclusively on trials using the trans isomer.

This has led to a perception that trans-resveratrol is the ‘active’ or more effective form. However, that may be more a reflection of the research gap than a hard scientific truth. Cis-resveratrol simply hasn’t received the same level of scientific attention, which, in theory, leaves open the possibility that its potential is underexplored rather than underwhelming.

That said, trans-resveratrol does appear to be more chemically stable and has shown higher biological activity, which could partly explain its popularity in formulations. But the bigger issue with resveratrol overall isn’t the isomer — it’s the bioavailability. Despite an oral absorption rate of around 75%, resveratrol undergoes rapid metabolism in the intestine and liver, leaving its actual bioavailability very low.

To address this, manufacturers often pair trans-resveratrol with so-called absorption enhancers like BioPerine® (black pepper extract) or even turn to more advanced delivery systems, such as liposomal encapsulation, cyclodextrins, or nanoparticle carriers, to increase its bioefficacy. These innovations are intended to make sure more of the compound is used by the body, but results are likely to vary and are still being evaluated in human studies.

All things taken into account, while trans-resveratrol is the better-researched and more commonly used isomer, it’s difficult to make a fair comparison with cis-resveratrol given the data imbalance. What’s clearer is that enhancing bioavailability may be just as important — if not more — than the isomer in use.

Resveratrol from food vs. supplements: what’s more practical?

We now know that resveratrol naturally occurs in a variety of plant-based foods — red grapes, peanuts, berries, and even dark chocolate. Although these are healthy choices in their own right, the amount of resveratrol they provide is relatively modest. For example, while grapes may contain more resveratrol than some micronutrients like vitamin A in raw quantity, these levels are still far below those used in clinical research exploring therapeutic effects.

A common misconception is that red wine provides a meaningful dose of resveratrol, particularly its biologically active trans form. But as Dr Rhonda Patrick, a biomedical scientist and host of the FoundMyFitness podcast, explained in one of her episodes: “People often talk about the beneficial effects of red wine due to its resveratrol content. It’s important to know that a 5-oz glass of red wine contains approximately 1.8 milligrams of resveratrol, while therapeutic doses typically range from approximately 100 milligrams to 1 gram.” Her insight makes it clear that relying on red wine for resveratrol’s potential benefits is impractical — even a full bottle falls far short of the amounts studied in research.

And since resveratrol has notoriously low bioavailability, with less than 1% absorbed when taken orally, supplements have emerged as a practical workaround. Even though they don’t bypass the absorption challenge entirely, many are now formulated with those enhanced delivery systems. So, for people seriously interested in resveratrol’s potential health benefits, dietary supplements can potentially be a more efficient and consistent route to take than relying on diet alone.

Potential downsides and safety considerations

Resveratrol is considered safe for most people when used in reasonable amounts, but like many supplements, the risk of side effects increases with higher doses. Studies have suggested that higher doses of resveratrol, typically in the range of 2–5 grams per day, may lead to gastrointestinal issues such as hypersensitivity, nausea, or mild diarrhea. And for certain groups, even lower doses may warrant caution.

People who are pregnant or breastfeeding are often advised to avoid resveratrol supplements altogether, simply because there’s not enough research to confirm safety. The same caution applies to children and adolescents whose bodies are still developing. Additionally, individuals with hormone-sensitive conditions may want to steer clear, too, as resveratrol can mimic estrogen in the body.

Those taking blood thinners or managing bleeding disorders should speak with their doctor before using resveratrol, as it may enhance the effects of these medications and increase bleeding risk and bruising. Similarly, people with liver disease or taking medications processed through the liver should also approach resveratrol with caution.

In all cases, a healthcare professional’s input isn’t just a formality and shouldn’t be neglected. It’s essential, in particular for people on long-term medications or managing chronic conditions, where even a natural compound like resveratrol can tip the balance.

Final thoughts

Resveratrol continues to draw attention for its potential health benefits, from supporting cardiovascular and metabolic health to possibly influencing aging and cognitive function. While both cis- and trans-resveratrol are naturally occurring isomers, trans-resveratrol is proposed to be the more effective form that is also generally used in resveratrol supplements.

Having said that, it’s important to stay realistic. Many of the proposed health benefits are still being studied, and bioavailability remains a limitation — one that manufacturers sometimes try to address through their formulations. Now, if you’re someone who’s considering supplementation, consulting with a healthcare provider is an essential first step, especially should you have any existing or pre-existing health conditions or take medication.