What is Resveratrol? Benefits, Dosage, and Risks
3,734 words, 20 minutes read time
Updated on March 16, 2024. Fact checked by Robert Underwood, Head of Research.
What it is:
Resveratrol is a polyphenol found in grapes and wine, known for its cellular protection and anti-ageing properties.
Mechanism of Action:
- Antioxidant Capacity: Boosts natural defences against oxidative damage by increasing antioxidant enzymes and reducing oxidative stress.
- Anti-inflammatory Potential: May reduce chronic inflammation by impacting cytokine signalling, crucial for immune regulation.
- Mitochondrial Support: May improve mitochondrial health and longevity, supporting metabolism and healthy ageing.
Health Benefits:
- Longevity: May activate pathways that enhance mitochondrial function, control inflammation, protect DNA, and extend cell life.
- Cardiovascular Health: May lower blood pressure and improve lipid profiles, potentially reducing cardiovascular risks.
- Joint Health: May alleviate arthritis symptoms by reducing inflammation and preventing cartilage breakdown.
- Metabolic Support: May prevent insulin resistance and type 2 diabetes by increasing insulin sensitivity and improving glucose metabolism.
- Cognitive Health: May slow cognitive decline and protect against Alzheimer’s by reducing inflammation and oxidative stress.
Risks and Side Effects:
Generally well-tolerated, but caution is advised for pregnant/nursing women, those with bleeding disorders, individuals avoiding oestrogen, surgical patients, and those on liver or blood clotting medications.
Supplementation Challenges:
Resveratrol has poor bioavailability; advanced forms with micronised or lipid carriers improve absorption.
Dosage:
Typical daily dose ranges from 250mg to 1,500mg; higher doses are usually safe short-term. Consult a healthcare professional if exceeding recommended amounts.
Interactions and Precautions:
Resveratrol may interact with blood clotting medications and those metabolised by the liver; it may also have oestrogenic effects. Consult a healthcare professional before starting, especially if managing health conditions or taking other medications.
As one of nature’s most-studied polyphenols, trans-resveratrol (often referred to as simply “resveratrol”) is an antioxidant all-star. Decades of research in cells, animals, and human trials provide ample evidence in support of this potent plant compound’s anti-ageing power.
What is Resveratrol?
Resveratrol is a polyphenol, or plant-based chemical, most commonly found in grapes, wine, peanuts, strawberries, and blueberries. Specifically, it is a stilbene, which is a unique subgroup of polyphenols that have increasingly been studied for their therapeutic value. Resveratrol is perhaps the best-known of all stilbenes, often cited as the special ingredient that makes red wine a superfood.
Over the past few decades, resveratrol has also steadily become one of the best-studied phytochemicals. A search for “resveratrol” returns more than 16,000 results on PubMed, the U.S. National Institutes of Health (NIH) online database of more than 34 million citations from medical journals and online books. Notably, 262 of the results are from clinical trials, illustrating how widely the effects of resveratrol have been documented in human studies.
The last point is an important one. Often, longevity science operates on the leading edge of clinical research. Identification of age-defying phytochemicals and protocols evolves quickly, making it difficult for human trials to keep pace. Plant chemicals with a long history of research and substantial clinical data are rare, yet resveratrol boasts both.
Resveratrol vs. Trans-Resveratrol: What’s the Difference?
In nature, resveratrol exists in two forms, a cis- and trans. The terms refer to the arrangement of atoms or groups in a molecule.
Each word is used as a prefix to describe the spatial relations of the atoms in the molecular structure. Cis being Latin for “this side of” and trans meaning “the other side of”.
In a cis molecule, similar atoms or groups are on the same side of a double bond or a ring structure. In contrast, in a trans molecule, similar atoms or groups are on opposite sides. This difference can significantly affect the properties and behaviour of the molecules.
Trans-resveratrol is known to be the more biologically active of the two isomers. This is due to the shapes of these molecules. Trans-resveratrol has a straight, angular structure, which enables it to fit tightly into the enzymes and receptors in the body it interacts with, very much like how a key fits into a lock. Cis-resveratrol has a bent shape that doesn’t align as well with these molecular targets. This results in a weaker bond which makes the molecule less effective at doing its job (source). Thus, trans-resveratrol is also more widely available, studied, and thought to have the most therapeutic value (source 2). Not surprisingly, research papers, websites, and supplement companies may often refer to trans-resveratrol as simply “resveratrol”.
Interestingly, resveratrol isomerisation is affected by the environment. Both ozone and UV light exposure have been shown to transform trans-resveratrol into its cis- isomer. This is perhaps best demonstrated in a 2012 study published by the Journal of Chromatographic Science. While observing resveratrol isomerisation in 30 different Romanian red wines, researchers found UV light exposure caused trans-resveratrol to shift into at least three different molecular arrangements: Cis-resveratrol, and at least two other unknown compounds.
This is significant for at least two reasons. First, it shows that ozone and light exposure may significantly reduce the therapeutic potential of resveratrol by causing it to shift from trans- to cis- form. Secondly, it highlights the complexity of getting therapeutic dosages from natural food sources like red wine. For more, see ‘What Foods Naturally Contain Resveratrol’ below.
Note: For the remainder of this article, “trans-resveratrol” will be referred to as “resveratrol”.
Overview of Potential Resveratrol Health Benefits and Risks
Disclaimer: Always consult your health care professional before making changes in your diet or exercise regimen, including the use of supplements like resveratrol. Pregnant women, women who are nursing and children especially, must always consult a physician prior to taking supplements or medications.
Overview of potential resveratrol health benefits:
- Promotes longevity
- Enhances mitochondrial function
- Reduces blood pressure
- Improves blood lipids
- Reduces arthritis symptoms
- Prevents insulin resistance and type 2 diabetes
- Slows cognitive decline
Overview of potential risks and side effects:
- Children and women who are pregnant and/or nursing are cautioned against using resveratrol supplements
- May interfere with blood clotting medications
- May have an estrogenic effect, and should be avoided by those avoiding estrogens
- Not suitable for individuals planning to have a surgical procedure
- Not suitable for anyone taking medications that are affected by the liver
How Does Resveratrol Work?
As noted above, a deep body of research and clinical data shows that resveratrol is a powerful plant compound with significant health and longevity benefits. This is due, in part, to the polyphenol’s ability to modulate several key signalling pathways in and between cells. Through this activity, resveratrol’s key mechanisms of action seem to be derived from its antioxidant, anti-inflammatory, and pro-mitochondrial health properties.
Supports Healthy Antioxidation
Many factors contribute to the ageing process. Modern longevity science has long called reactive oxygen species (ROS) one of them.
ROS are a byproduct of various cellular reactions. These oxygen-based molecules are inherently unstable because they are missing an electron. This causes ROS, also known as free radicals, to attack neighbouring cells to steal an electron and attain balance. Antioxidants are a line of defence against ROS, as antioxidant molecules naturally contain an extra electron that can diffuse ROS before they cause damage and dysfunction.
Thus, the balance between ROS and antioxidants is a significant factor in the ageing process.
When ROS vastly outnumber antioxidants, the imbalance is said to cause a state of oxidative stress that accelerates the ageing process and drives the “pathogenesis of a variety of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy”.
Resveratrol is a powerful antioxidant that helps to prevent ROS damage in a couple of ways.
First, it has been found to increase the natural production of the enzyme catalase (CAT), an enzyme that helps to break down a harmful molecule called hydrogen peroxide which can damage cells if it is left to accumulate. By converting hydrogen peroxide into water and oxygen, CAT can protect the body against oxidative stress.
By promoting both, resveratrol appears to increase the body’s capacity for antioxidant protection. Increased production and utilisation of glutathione—one of the body’s most powerful in-house antioxidants—is just one example of how resveratrol appears to accelerate the body’s natural defenses against ROS damage and ageing.
Finally, resveratrol’s antioxidant capacity seems to be further enhanced by its natural anti-inflammatory properties (see below).
Regulate Inflammation Pathways
Chronic inflammation is one of the biggest factors driving the ageing process, second only to the oxidative stress described above. The danger of inflammation is so great that longevity experts have coined the term “inflamm-aging” to describe the way low-grade, long-term inflammation propels the ageing process and increases the risk of age-related metabolic disease.
In this light, any food, supplement, or behaviour that reduces inflammation is a powerful weapon in the fight against ageing and chronic disease. Resveratrol appears to be one such tool, demonstrating the ability to positively impact the body’s own inflammation signalling networks.
This is primarily achieved through beneficial impacts on the body’s cytokine system. Cytokines are special proteins that play a role in modulating the immune system. Some are pro-inflammatory and induce inflammation, typically in response to an acute injury or infection. Others are anti-inflammatory in nature.
Not all cytokines are immune system cells, but every cytokine has an impact on how the immune system functions.
In vitro and in vivo studies show resveratrol reduces chronic inflammation by suppressing the following pro-inflammatory cytokines:
- Interleukin-1-beta (IL-1 beta)
- Interleukin-8 (IL-8)
- Tumour Necrosis Factor-alpha (TNF-alpha)
- Monocyte chemoattractant protein-1 (MCP-1)
Resveratrol also appears to reduce inflammation by regulating SIRT1 and NF-KB pathways, two signalling networks that play a crucial role in modulating the inflammation response.
Improving mitochondrial function
Mitochondria are often referred to as the powerhouses of the body. Every cell contains many of these tiny organelles, and each is responsible for converting food molecules into energy for the cells, tissues, organs and organisms to function.
However, mitochondria become dysfunctional with age. Along with oxidative stress, mitochondrial dysfunction is believed to be an age-related disease. Moreover, it’s now believed that dysfunctional mitochondria produce toxic compounds that may lead to systemic illness.In some studies, resveratrol appears to keep these vital organelles healthier, for longer—a benefit that may promote healthy metabolism and ageing. This appears to be achieved primarily through the activation of SIRT1, a critical protein known to govern fundamental cellular longevity mechanisms.
What Foods Naturally Contain Resveratrol?
Several foods contain resveratrol. However, supplements may be needed to obtain therapeutic doses and significant health benefits. For more information, see the following section, Resveratrol Dosages and Supplements.
In the 2021 book, Discovery and Development of Anti-Breast Cancer Agents from Natural Products, authors identify four of naturally occurring cis-resveratrol. They include:
- Nuts of the Arachis hypogaea family, including peanuts, groundnuts, monkey nuts, goobers, and earth nuts
- Plants of the Vitis vinifera family, specifically grapevines
- Trees and shrubs belonging to the Pinusspecies, specifically pine trees
- Berries from the Morusspecies, like mulberries
Of course, not all these plants are common food items. Moreover, the authors note that the cis-form of resveratrol in the plants listed above “is unsteady and transformed into the trans-form under UV light exposure” during daytime hours.
The authors then provide a list of more common food items that contain resveratrol:
- Grapes, specifically grape skin: 28 micrograms per gram
- Peanuts: 018-8.0 micrograms per gram
- Red wine: 32-4.44 milligrams per litre
- Blueberries: 140 picomoles per gram
- Strawberry achenes (the tiny, yellow, seed-like pods that cover the outside): 1.64 micrograms per gram of dry weight
Additional foods that are known to contain resveratrol include pistachios, cranberries, bilberries, and dark chocolate, although the authors did not include them in the publication.
It’s important to note that even expertly crafted plant-based diets may not provide therapeutic levels of naturally occurring resveratrol. That’s where supplementation may help.
Resveratrol Dosages and Supplements
Disclaimer: Always consult your health care professional before making changes in your diet or exercise regimen, including the use of supplements like resveratrol or trans-resveratrol.
Dosage
Typical resveratrol dosage ranges from 250mg to 1,500mg per day, orally.
Doses up to 3000mg for 8 weeks appear to be well-tolerated, however no safety data has been established for taking high doses for longer than 8 weeks.
Unwanted side effects, including nausea and upset stomach, may occur when higher doses are taken for prolonged periods of time.
Always first consult with your doctor if you wish to exceed the maximum recommended dose.
Bioavailability
Resveratrol is known to have poor bioavailability, which is usually improved by taking this fat-soluble molecule with a dietary fat source. Recent advances in the manufacturing process have allowed researchers to develop other forms of resveratrol, including micronised resveratrol which boasts improved absorption and uptake.
With these key insights, researchers have been able to further modify resveratrol to increase bioavailability and absorption. Specifically, the development of solid lipid nanoparticles and unique lipid carrier systems are two key achievements that increase absorption by up to 3.5x, solidifying resveratrol’s position as a powerful nutraceutical. Moreover, special encapsulations are known to further improve resveratrol’s bioavailability by increasing its water solubility a staggering 400-fold.
Potential Health Benefits of Resveratrol
Promotes longevity
One of the more interesting things about resveratrol is its ability to have a relatively wide distribution. From enzymes to cytokines and even DNA, resveratrol appears to have an impact on many key pieces of fundamental biology.
In fact, authors of a 2018 animal study described resveratrol as having a “multi-factor effect on aging” thanks to the compound’s unique ability to:
- Improve mitochondrial function
- Up-regulate the SIRT1 network, which helps to control inflammation, protect DNA, and prevent certain types of cancer
- Decrease levels of reactive oxygen species (ROS)
- Extend natural cell life
One point worth emphasising: Activation of the SIRT1 pathway is a key element to healthy ageing. Writing for the peer-reviewed journal Science, researchers name both resveratrol and other sirtuin-activating compounds “a viable therapeutic intervention strategy for many diseases associated with aging”.
Enhances mitochondrial function
In a 2017 study published by The Journal of Physiological Sciences, researchers found that resveratrol promotes mitochondrial function, improves physical endurance, and reduces oxidative stress. Notably, researchers observed increased antioxidant activity via the up-regulation of enzymes like CAT and SOD. Researchers also observed better regulation of mitochondrial function due to increased antioxidant capacity and balance.
By improving mitochondrial health and cellular detoxification, resveratrol may also help to prevent certain diseases. In a 2018 study, it was found to improve kidney function in mice with renal injury. Commenting on the study, authors credit the outcome to resveratrol’s ability to act as an anti-inflammatory and reduce oxidative stress via NRF2 activation, a pathway that when turned on or expressed, can increase the body’s levels of antioxidants like Glutathione.
Reduces blood pressure
Resveratrol supplements may help to reduce blood pressure. Scientists have identified several mechanisms of action for this, including resveratrol’s potent antioxidant capacity described above.
For example, a 2019 study published by the International Journal of Molecular Science showed resveratrol to reduce oxidative stress and improve arterial stiffness. Hardening of the arteries is a major contributing factor to high blood pressure. Therefore, foods, lifestyle practices, and supplements that promote arterial health are considered essential for healthy ageing.
Additionally, resveratrol appears to improve the health of endothelial cells, or the cells that line blood vessels. In a 2014 study published by the journal Molecules, researchers found resveratrol to increase endothelial nitric oxide (NO) production by up-regulating the enzyme eNOS. NO is known to relax blood vessels, which in turn lowers blood pressure. In addition to up-regulating NO, researchers note resveratrol’s antioxidant capacity prevents NO inactivation by reducing endothelial oxidative stress.
Beyond antioxidant capacity, resveratrol appears to reduce systolic blood pressure too. Systolic pressure is a measurement of the pressure exerted when the heart pumps blood out and into the body. As mentioned above, this number tends to increase with age and arterial stiffening. In a 2015 meta-analysis of six randomised controlled human trials, researchers found resveratrol doses of 150mg or more to reduce systolic blood pressure significantly.
Although potentially beneficial for individuals with high blood pressure, there are complications. Resveratrol may have an adverse reaction with blood pressure medications and certain other drugs. For more information, see the Potential Side Effects and Drug Interactions section below.
Improves blood lipids (“good” vs. “bad” cholesterol)
In recent studies, resveratrol has also demonstrated the ability to improve overall blood lipids. Blood lipids are fats in the bloodstream, and the two most common are HDL and LDL.
LDL, or low-density lipoproteins, are often referred to as “bad” cholesterol because they can accumulate and increase the risk of certain cardiovascular diseases.
HDL, or high-density lipoproteins, are sometimes called “good” cholesterol because they help the body get rid of LDL and decrease risk of disease.
LDL tends to accumulate over time, especially in western cultures where poor diet and sedentary lifestyles are common. However, animal studies indicate resveratrol may help. In 2016, a study published by Life Sciences showed that mice with hyperlipidemia (high LDL) experienced both weight loss and a decrease in total cholesterol following resveratrol treatments. Commenting on the results, researchers say the animal model justifies resveratrol’s potential to prevent metabolic disease.
Resveratrol’s antioxidant capabilities may also play a role in promoting healthy blood lipids. New research suggests LDL oxidation may contribute to arterial plaque buildup, and thus increased blood pressure. As noted above, resveratrol’s antioxidant capacity has been shown to reduce endothelial oxidative stress.The same seems to hold true for LDL oxidation. In a 2012 human trial, individuals who consumed resveratrol supplements showed a 4.5% decrease in LDL and a corresponding 20% decrease in oxidised LDL.
Reduces arthritis symptoms
Arthritis, a form of joint degeneration that causes pain and disability, is a common condition among ageing populations.
According to the UK’s National Health Service (NHS), arthritis:
- 8 million people live with a musculoskeletal condition in the UK
- 1 in 5 people consult a GP about a musculoskeletal problem every year
- 1 in 8 of the working population report having a condition of the bone, joints and muscles.
Over-the-counter anti-inflammatory medicines, like non-steroidal anti-inflammatories (NSAIDs), are one of the most common methods of treating arthritis pain. However, NSAIDs can be a dangerous medicine when used chronically. Most consumers are unaware that the UK Health Care cautioned the public against long-term use of NSAIDs like Motrin and Advil, warning that chronic use can cause heart attacks and intestinal bleeding.
Natural anti-inflammatories, like resveratrol, may provide substantial relief. Whereas NSAIDs may cause potentially harmful cardiac and neurological events, the studies described above illustrate how resveratrol may do the exact opposite by reducing blood pressure, improving blood lipids, and promoting cardiac health.
In one study, resveratrol injections were shown to ameliorate arthritis symptoms by preventing cartilage breakdown. And in a 2012 review of then-recent literature published by the International Journal of Molecular Sciences, resveratrol was found to “exhibit therapeutic potential” for arthritis treatment.
Prevents insulin resistance and type 2 diabetes
An astonishing 1 in 15 in the UK (totalling more than 4.5 million people) have type 2 diabetes. This condition is characterised by a progressive reduction in the body’s response to insulin, which is also known as insulin resistance.
As insulin resistance builds, the body loses its ability to extract glucose (sugar) from the bloodstream which is used energy, hydration, and tissue repair. This causes several adverse health conditions over time, including high blood pressure, excess body fat, and increased risk of cardiovascular disease.
Interestingly, insulin resistance and type 2 diabetes exist on a continuum. For example, poor diet and lifestyle choices may cause healthy young adults to develop insulin resistance as they age. Over time, the progression of insulin resistance may eventually cause type 2 diabetes and other health complications.
Studies indicate that resveratrol foods and supplements may prevent insulin resistance before it has the chance to progress toward type 2 diabetes and other serious health issues. Animal and human studies show resveratrol may:
- Increase insulin sensitivity, and thus prevent type 2 diabetes from developing
- Reduce oxidative stress, thereby attenuating symptoms of type 2 diabetes
Activate AMPK, a protein network that may prevent insulin resistance by facilitating more efficient glucose metabolism
Slows cognitive decline
Cognitive decline often appears as a gradual loss of thinking, memory, concentration, and coordination skills later in life. Research is ongoing, and it appears to be multi-faceted.
According to Mayo Clinic, cognitive decline is perpetuated by certain conditions and lifestyle factors, including diabetes, smoking, high blood pressure, and lack of physical and mental stimulation.
Cognitive decline may eventually lead to Vascular Dementia and Alzheimer’s disease, a condition that affects an estimated 1 million Britains. Alzheimer’s is characterised by amyloid-beta plaque accumulation and loss of brain function—both of which are now thought to be perpetuated by chronic inflammation and oxidative stress.
As described in the sections above, numerous animal and human studies demonstrate resveratrol’s efficacy in preventing both inflammation and oxidative stress. A host of other studies indicate that this polyphenol may help to prevent cognitive decline, and Alzheimer’s disease, specifically.
In a 2014 article published by Frontiers in Aging Neuroscience, resveratrol is named as one of several potent phytochemicals that may protect against age-related diseases like Alzheimer’s. And in animal models, resveratrol has also been shown to reduce the buildup of amyloid plaque—a critical factor in the onset and progression of Alzheimer’s.
Potential Side Effects and Drug Interactions
Like most polyphenols, resveratrol is generally well-tolerated and even has a Generally Recognized as Safe (GRAS) designation from the U.S. Food and Drug Administration. However, GRAS designation only applies to bottled water products with up to 10mg of resveratrol per litre, which is significantly lower than what is available in most supplements.
Although doses of 1,500mg or more per day are common, there are certain situations in which supplementing with resveratrol may cause unwanted complications.
Special precautions apply to the following individuals and situations:
- Pregnancy and breastfeeding: Pregnant or nursing women should always consult their physician prior to taking a resveratrol supplement. Seeking resveratrol from red wine should be avoided.
- Young children: Children are advised against taking resveratrol supplements.
- Individuals with bleeding disorders: Because it may relax capillaries and slow clotting, resveratrol should not be used by individuals with bleeding disorders.
- Individuals avoiding oestrogen exposure: Some studies indicate resveratrol may have an oestrogenic effect. For individuals who have breast, uterine, or ovarian cancer, or otherwise avoid oestrogens for health reasons, resveratrol should be avoided.
- Individuals undergoing surgical procedures: As mentioned, resveratrol may reduce blood clotting. Anyone scheduled to have a surgical procedure should speak to their physician about avoiding, or discontinuing resveratrol several weeks before their procedure.
- Anyone taking medications that are changed by the liver: Resveratrol may affect how quickly the liver breaks down such medications, creating unwanted effects.
- Blood clot medications: Resveratrol may slow blood clotting, thereby counteracting these medications.
Conclusion: Resveratrol is a Well-studied and Generally Safe Anti-Aging Nutraceutical
Few anti-ageing nutraceuticals are as well-studied and tolerated as resveratrol. Through a wide distribution, this potent plant compound appears to have a positive impact on the human body’s most important longevity networks.
High antioxidant capacity, anti-inflammatory potential and longevity effects are just a few of the most exciting findings modern research has uncovered about this ancient polyphenol.
Although certain side effects and drug interactions must be considered, resveratrol supplements are an exceptionally valuable and well-rounded addition to most health and longevity protocols.
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