Resveratrol Supplements: Benefits, Dosage, and Side Effects

Resveratrol is a compound that can be found in red grapes and its derivates, especially red wine. In recent years, it has gained popularity due to its proposed antioxidant, anti-inflammatory, anti-cancer, anti-aging, and many other potential beneficial properties. This, along with almost no widely reported side effects, has currently placed resveratrol amongst the favorite supplements in the market.

However, resveratrol is not completely flawless, as most research on this compound has been conducted in cells and animals, with few studies done on humans. Furthermore, there is no established dosage for humans, and its effects can vary depending on several factors.

So, is resveratrol really as good and harmless as it seems? Let's find out.

What is resveratrol?

Resveratrol is a naturally occurring polyphenol, a compound synthesized by plants in response to environmental stress or injury.

This compound can be found in more than 70 foods including blueberries, cranberries, mulberries, raspberries, apples, black olives, peanuts, and dark chocolate. But it is especially abundant in the skin and seeds of red grapes and its derivatives, including grape juice and wine.

The fermentation process of the grapes increases the concentration of resveratrol, which is why red wine is the most well-known source of this compound.

Another main source of resveratrol is a plant known as Polygonum cuspidatum, or Japanese knotweed, which is commonly used in traditional medicine in Asiatic countries.

In recent years, resveratrol has gained significant attention due to its potential anti-inflammatory, neuroprotective, cardioprotective, anti-aging, anti-cancer, and antioxidant properties, which show promising results in helping prevent or manage several diseases and conditions.

Resveratrol's mechanism of action

The exact mechanisms through which resveratrol acts in the body are complex and have yet to be fully elucidated. However, evidence has shown that resveratrol targets several molecules and exerts its effects through several cellular pathways that involve multiple systems in the body.

For instance, resveratrol activates sirtuin-1 (SIRT1), a type of protein that can have anti-inflammatory effects and is involved in regulating cellular health, aging, and metabolism.

It can also downregulate two inflammatory enzymes known as cyclooxygenase 1 and cyclooxygenase 2 (COX-1 and COX-2) and inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, one of the key regulators of inflammation.

Resveratrol also acts as an antioxidant by scavenging free radicals, upregulating the expression of antioxidant enzymes, and helping reduce oxidative stress, potentially preventing damage to the cells of the body.

Additionally, resveratrol can activate an enzyme adenosine 5′ monophosphate-activated protein kinase (AMPK), which may enhance glucose (sugar) uptake and fatty acid oxidation, potentially improving insulin sensitivity and reducing the risk of metabolic disorders, including diabetes.

In cancer cells, resveratrol can induce apoptosis (programmed cell death) by modulating the expression of apoptotic proteins and affecting various cell cycle regulators and signaling pathways, which is proposed to provide some protection against cancer.

So, depending on the effect it exerts (e.g., antioxidant, anti-inflammatory, anti-cancer, neuroprotective, etc.), the exact mechanism of action of resveratrol can vary. And, while its benefits are promising, ongoing research is needed to comprehend these mechanisms fully.

Should you take resveratrol supplements?

When ingested, resveratrol is absorbed and metabolized (broken down) by the cells in the intestinal lining, further metabolized in the liver, and excreted through urine. However, just a small amount ends up reaching the bloodstream and body tissues, meaning its bioavailability is low. This, along with its poor water solubility, results in limitations in therapeutic potential from the use of resveratrol in its natural form.

Even though resveratrol can be ingested from natural sources, studies have shown that most benefits may be obtained when consuming high doses of this compound. Higher than you could typically get by eating berries, for instance.

And, while you might be able to get therapeutic doses of resveratrol by drinking red wine, this is not recommended because the benefits of resveratrol are overshadowed by the risks of taking large amounts of alcohol. In this regard, according to the Dietary Guidelines for Americans 2020-2025 published by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture, the recommended amount of wine per day is up to 1 glass for women and 2 glasses for men.

Therefore, supplements have been developed to increase the bioavailability of resveratrol, as well as concentrate the amount of resveratrol that can be consumed in a single dosage.

Nevertheless, due to the limitations of current evidence, it is advisable to approach resveratrol supplements with caution. Ask your healthcare provider whether it is safe for you to take resveratrol supplements.

Are resveratrol supplements effective?

Because of their concentrated dosage, resveratrol supplements might be more effective than having resveratrol in its natural form.

Furthermore, some manufacturers formulate their supplements using different techniques and biomaterials, like nanoparticles, aimed to improve the bioavailability of resveratrol, thus potentially enhancing its absorption and effectiveness.

However, since the quality of resveratrol supplements can vary widely between manufacturers, their efficacy may be compromised due to inaccurate amounts of resveratrol or cross-contamination with other particles. Therefore, getting a supplement that has been certified and tested by a third party may help verify its quality.

Despite all this, there is still not enough data to firmly confirm whether one type of resveratrol is superior to another in terms of efficacy.

Science-backed resveratrol supplement benefits

The research on resveratrol and its benefits has been extensive. Several studies have been conducted both in vivo (in organisms) and in vitro (in the lab), and, although some studies have been performed on humans, most have been done on animals.

Furthermore, many variables affect how resveratrol is used by the body, which makes it difficult to determine the exact extent of benefits and possible health complications derived from its use.

Nevertheless, at the time, the research suggests several benefits that can be attributed to resveratrol:

Antioxidant properties

Antioxidants protect you against free radicals, which are substances that can harm the cells of your body and have been linked to aging and several chronic (long-term) diseases and conditions.

Resveratrol has antioxidant properties. It may protect the cells of the body against oxidative stress through several pathways: scavenging free radicals, improving existing antioxidant enzymes, and promoting the production of other antioxidant molecules in the tissues.

Thus, resveratrol is proposed to be helpful in the prevention and treatment of several chronic diseases and conditions, such as cardiovascular diseases (CVDs), diabetes, neurological disorders, kidney diseases, lung diseases, and cancer.

Anti-inflammatory effects

Research has shown that resveratrol has strong anti-inflammatory effects. This compound is believed to contribute to inflammation management by increasing the activity of several anti-inflammatory proteins while suppressing the activation of pro-inflammatory pathways in the body.

The resulting effects may help manage chronic inflammatory conditions and are proposed to help reduce the risk of inflammatory diseases such as arthritis.

Furthermore, several studies have shown that resveratrol may also help decrease and prevent airway inflammation, thus potentially resulting in beneficial impacts on respiratory diseases, like asthma.

Immunity regulation

Several studies conducted in animals and humans revealed that resveratrol may help regulate the immune system, thus helping protect the body against bacteria, viruses, fungi, and other pathogens.

Furthermore, this compound may also inhibit the growth of some potentially harmful microorganisms, which could aid and help reduce the risk of certain infectious diseases.

In this regard, further research is needed to fully elucidate the mechanism by which resveratrol can help prevent some infections and aid in managing certain viral, fungic, and bacterial diseases.

Anti-aging activity

Repeated UV (ultraviolet) exposure from sunlight produces skin damage and photoaging and is also the main risk factor for skin cancer. Due to its antioxidant and anti-inflammatory properties, resveratrol has been proposed to have many skin benefits.

This compound has been shown to confer some protection against photoaging and provide some relief in inflammatory skin diseases like psoriasis, dermatitis, and rosacea.

Additionally, it may support skin repair and regeneration, which can potentially improve the appearance of the skin and reduce premature signs of aging.

Furthermore, resveratrol has also been shown to act as a skin-lightening agent, thus, it can be useful to help treat scarring and hyperpigmentation of the skin for both therapeutic and cosmetic purposes.

Cardiovascular protection

Due to its antioxidant and anti-inflammatory properties, resveratrol is proposed to exert protective effects on the heart and blood vessels.

This compound has been shown to reduce inflammation, prevent the progression of atherosclerosis (stiffening of the arteries due to a buildup of plaque), inhibit platelet aggregation, and improve the function of the endothelium (inner lining of blood vessels), thus potentially enhancing vasodilation and blood flow.

Therefore, resveratrol is believed to help prevent and manage some cardiovascular diseases (CVDs), including hypertension (high blood pressure).

Neuroprotection

Due to its antioxidant and anti-inflammatory properties, resveratrol may help reduce inflammation in the nervous system and maintain neuronal health and function by protecting neurons (brain cells) from oxidative stress and apoptosis.

Because of these effects, resveratrol is proposed to help prevent or slow down cognitive deterioration, and may also play a role in managing neurodegenerative conditions like Parkinson’s, Alzheimer’s, Huntington’s, and amyotrophic lateral sclerosis (ALS).

Furthermore, this compound may also protect against cerebral ischemia (reduced blood flow to the brain) and aid in the treatment of epilepsy and chronic-progressive multiple sclerosis.

However, research is ongoing to fully elucidate the mechanisms by which resveratrol supplements may aid in protecting the neurological system from damage. Most studies were done on cells and animals, while human evidence is sparse and not conclusive.

Glucose metabolism and weight regulation

Resveratrol may help regulate glucose metabolism and improve insulin resistance, a condition where the cells of the body become less sensitive to the blood glucose-lowering hormone called insulin. These effects are believed to aid in preventing and managing type 2 diabetes and other related complications like diabetic kidney disease.

Furthermore, multiple studies performed on mice concluded that resveratrol influences the metabolism of fats, promoting the breakdown of fat cells and inhibiting the formation of new ones.

Hence, resveratrol may help decrease body weight and fat mass, and may also play a role in preventing and treating obesity. However, more research is necessary to fully evaluate its therapeutic potential and safety.

Anti-cancer properties

Resveratrol may inhibit the growth and proliferation of cancer cells. It is also possible that this compound can induce cancer cell apoptosis and prevent the early migration and invasion of cancer cells across the body through several pathways and mechanisms.

These beneficial effects have been noticed in several types of cancer, including lung cancer, liver cancer, cervical cancer, gastric cancer, colorectal cancer, prostate cancer, and ovarian cancer in vitro studies.

Resveratrol is also proposed to improve the effectiveness of certain chemotherapy drugs while protecting normal cells from damage. Because of all this, resveratrol may be useful to prevent and treat several types of cancer. However, research is still ongoing to confirm these results, and more human research is needed.

Hormone effects

Resveratrol is a phytoestrogen, meaning it has estrogen-like properties. Estrogen is a sex hormone that plays a crucial role in the development of the reproductive system and secondary sex characteristics in people designated female at birth. Estrogen has also been associated with the development of certain types of hormone-dependent cancers, such as breast cancer.

Research on the effect of resveratrol on breast cancer has been inconclusive. While some studies suggest resveratrol may be effective in preventing and treating breast cancer, other studies suggest resveratrol may promote tumor growth and proliferation. Therefore, more research is necessary to determine the effectiveness of resveratrol on breast cancer.

On the other hand, studies have shown that resveratrol also has androgen-lowering effects. Androgens are the principal sex hormone in people designated male at birth. Some diseases and conditions, like polycystic ovary syndrome (PCOS), are characterized by increased levels of androgens in people designated female at birth, which leads to irregular periods, infertility, and other health problems. Therefore, resveratrol may be useful in helping manage these conditions, including PCOS.

Additionally, resveratrol may increase ovarian follicular reserve and extend ovarian life span, which may aid in the prevention and treatment of infertility. However, currently, these potential effects have not been evaluated in humans, and more research is necessary.

Possible risks when taking resveratrol supplements

Resveratrol is generally considered safe and is usually well tolerated by most people when ingested from natural sources or supplements at the recommended doses.

Despite this, some mild side effects may occur when taking large amounts of this compound. Most side effects were reported when taking doses over 2.5 grams per day.

The most common side effects include:

• Nausea
• Vomiting
• Diarrhea
• Flatulence
• Abdominal discomfort or pain

Furthermore, people with blood clotting disorders and those who take blood thinners should avoid taking resveratrol supplements as it may increase the risk of bleeding.

Since resveratrol has estrogen-like properties, people who have a high risk of breast cancer should take precautions and consult with a healthcare practitioner before taking these supplements.

Additionally, long-term use of resveratrol may affect the thyroid gland, disrupting the production of thyroid hormones.

Due to the limited evidence regarding its safety in these populations, resveratrol supplements should also be avoided during pregnancy, breastfeeding, and in children.

Regulation of resveratrol supplements

In the United States, resveratrol supplements are not regulated by the Food and Drug Administration (FDA) as drugs. Instead, they are regulated as dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA).

Since resveratrol supplements are not classified as drugs, the FDA does not require pre-market approval or for manufacturers to state the actual concentration of the compound or have a standardized dosage recommendation. This means consumers may not know exactly what they are getting and whether the product is effective for its intended use.

Nevertheless, the FDA does establish that supplements must comply with specific manufacturing standards and labeling requirements, designed to ensure the safety and quality of the product.

Dosage of resveratrol supplements

The optimal dosage of resveratrol for humans is not well-established. Therefore, there is no one-size-fits-all dose when it comes to resveratrol supplements and dosage can vary depending on several factors, such as the formulation of the supplement, the intended health benefits, and the person’s health status.

Common dosages usually range from 100 to 500 mg per day for general health benefits. However, higher doses of up to 5 g per day have been safely used in specific research contexts.

In general terms, it is always recommended to start with a lower dose while monitoring for any side effects.

Nevertheless, you should always consult with a healthcare practitioner before starting resveratrol or modifying its dosage to ensure its safety and suitability based on the medications you take and your overall health state.

How to take resveratrol supplements

Resveratrol supplements are available in the form of capsules, tablets, powder, gummies, liquid, and transdermal patches.

Each manufacturer establishes the recommended dosage and frequency by which you should take the supplement. Normally, resveratrol is taken once per day. Make sure to take it at the same time each day to keep a routine and maintain consistent levels of the supplement in your body.

You can take your supplement either while fasting or with a meal. Research has shown that taking the supplement with a fatty meal can delay its absorption rate, but not its extent.

In any case, you must always follow the dosage and frequency recommended by the manufacturer and talk to your healthcare provider to make sure you are taking your resveratrol supplement as indicated.

Can you take resveratrol with other supplements or drugs?

Resveratrol may interact with other drugs and supplements. Therefore, you should always consult with your healthcare practitioner to make sure you can take this supplement safely.

You need to take precautions and consult with your doctor before taking resveratrol supplements if you are using the following medications:

• Drugs to treat chest pain (angina) or high blood pressure, (e.g., nicardipine, losartan). Resveratrol supplements can enhance the effect of these drugs.
• Disease-modifying anti-rheumatic drugs (DMARD) like methotrexate. Resveratrol can increase its absorption and decrease its elimination, thus increasing the risk of liver damage.
• Anticoagulants (blood thinners) such as warfarin or heparin, and nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, naproxen, and aspirin. Resveratrol has blood-thinning properties, so people who take anticoagulants or NSAIDs may have an increased risk of bruising and bleeding.
• Human immunodeficiency virus (HIV) protease inhibitors, including saquinavir, nelfinavir, ritonavir, and indinavir, among others. Resveratrol decreases the effect of these drugs.
• Statins, such as atorvastatin, lovastatin, rosuvastatin, and simvastatin, etc. Resveratrol can enhance the effects of these drugs.
• Antidepressants and anxiolytic drugs, such as buspirone. Resveratrol can increase the effects of these medications.

Likewise, resveratrol may also interact with and change the effect of the following supplements:

• NMN (nicotinamide mononucleotide)
• Quercetin
• Curcumin
• CoQ10
• Vitamin C
• Vitamin D
• Collagen

Additionally, further precaution must be taken when ingesting resveratrol alongside other supplements that may interfere with blood clotting, such as garlic, Ginkgo biloba, ginseng, and ginger.

Further reading on resveratrol supplements

Resveratrol is a versatile compound with many potential health benefits that multiple studies have widely supported. For instance, recent research has shed more light on how resveratrol interacts with immune cells and with the gut microbiota to enhance overall health and induce protective effects in the body, which may also aid as adjunctive therapy in COVID-19 management and its complications.

Additionally, studies suggest that resveratrol may also play an important role as a circadian rhythm modulator, which is the internal mechanism that regulates the daily cycles of various biological processes, including sleep-wake cycles, hormone secretion, metabolism, and cellular repair.

At present, further research is being carried out to explore the potential cosmetic benefits of this compound when applied topically as a skincare ingredient.

Nevertheless, it is important to note that even though some results have shown promising results, more clinical trials in humans are needed to fully understand the efficacy and optimal dosing of resveratrol for various health conditions.

Furthermore, since the effectiveness of resveratrol is influenced by several factors, it is advisable to approach these supplements cautiously, considering both the potential benefits and the limitations of current evidence.

How to choose the best resveratrol supplement

There are many resveratrol supplements on the market. So, to make sure you are getting a high-quality and safe product, you should always look for the following things:

• A complete list of ingredients which includes any excipients or fillers.
• A supplement facts panel where the amount of resveratrol per serving and the serving size should be listed.
• The name and place of business of the manufacturer, packer, or distributor.
• A statement of identity, such as 'Dietary Supplement.'
• The label must not include any drug claims like 'treats,' 'cures,' or 'prevents.'
• Any claim must be truthful and not misleading. For instance 'supports cardiovascular health.'

Besides this, look for products that have been third-party tested for quality and purity. Trusted third-party organizations include NSF International, USP (United States Pharmacopeia), and ConsumerLab.

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Final words

While it is undeniable that resveratrol has many potential health benefits, it is important to note that most of the research has been conducted in vitro or in animal models. And, even though several human studies have been carried out, these have been more limited due to the low bioavailability of this compound, which affects its efficacy and has led to inconclusive results in some studies.

Hence, while resveratrol is a promising compound with a wide range of potential therapeutic effects, more research is still needed to understand its mechanisms of action and optimal dosages fully.

Currently, it is best to consume resveratrol as part of a balanced diet rich in fruits, vegetables, and whole grains, rather than relying solely on supplements.

If you have any doubts about how to take resveratrol or whether supplements are a good choice for you, consult with your healthcare practitioner.