Resveratrol: Benefits, Side Effects, Best Time to Take It & More

Resveratrol

(Red Wine Extract, Trans-Resveratrol)

Evidence: High
Possible Benefits: Reasonable
Safety: Reasonable

What is resveratrol?

Resveratrol is a popular dietary supplement often extracted from Japanese knotweed and the skin of grapes. Contrary to popular belief, resveratrol doesn’t seem to increase lifespan in most people and may even lower it by hindering exercise performance. However, there are some good reasons to consider taking the supplement as the benefits may still outweigh the negatives, especially when one takes low doses. This article is about the main benefits of resveratrol, its potential side effects, the best time to take it, and more.

Possible benefits

All of the potential benefits mentioned below are dose-dependent. As with other adaptogens, there is a sweet-spot dose that allows you to get most of the benefits without causing meaningful side effects or tolerance buildup in the body. We will discuss the best dosing protocol later in this article.

Improved longevity – This benefit does not apply to everyone. In some cases, resveratrol can do the opposite by diminishing the benefits of exercise. If you are active, high doses of resveratrol can indirectly speed up the aging process through this side effect. If you are inactive, the supplement can promote healthy aging and longevity by supporting SIRT1, telomerase activity, stem cells, mTOR signaling, and more. One study on mice on a high-calorie diet directly shows healthspan extension.
Reduced inflammation – Even low doses can significantly lower NF-kB activity and other markers of inflammation.
Improved immune health – Resveratrol was shown in many studies to support innate, adaptive, and mucosal immunity. It can improve cellular intrinsic immune defenses, immune tolerance, immune signaling, and natural killer cell function.
Improved blood flow – Low doses of resveratrol were shown to improve blood flow by increasing nitric oxide levels. When higher doses (250+ mg) are taken, this benefit also applies to cerebral blood flow (blood supply to the brain).
Improved blood pressure – Resveratrol can reduce blood pressure in people with hypertension. Blood pressure in healthy people should stay unaffected.
Improved brain function – Resveratrol was shown by multiple studies to increase brain-derived neurotrophic factor (BDNF) and improve neural stem cell functions, neurogenesis, HPA axis signaling, executive function, learning and memory, neuroimmune signaling, and more. Whether or not one needs to take higher doses to achieve these effects is not yet known. However, it is certainly possible because increases in cerebral blood flow only seem to apply to doses above 250 mg. The neuroprotective effects also only seem to occur at 20 mg/kg or more.
Improved insulin sensitivity – Even very small doses can improve insulin sensitivity to some extent, especially in obese and unhealthy individuals. A small decrease in fasting insulin and blood glucose was also found in one study.
Reduced oxidation – The supplement seems to have antioxidant properties in the brain and elsewhere. More evidence is needed to determine the potency and the degree of this effect.
Improved cholesterol levels – Resveratrol can improve cholesterol levels but only slightly. It can lower LDL cholesterol but doesn’t impact HDL cholesterol levels much if at all.
Reduced acne – Topical application of resveratrol reduced acne by an average of more than 50%.

Possible side effects

The side effects below are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

Lower exercise adaptations – Resveratrol can lower and sometimes diminish the benefits of exercise, such as increased oxygen capacity and improved cholesterol levels. This is likely caused by mTOR inhibition, which can inhibit muscle protein synthesis. The supplement can also worsen VO2 max, which is a very important marker for longevity.
Reduced anaerobic running capacity – 150 mg taken after a workout was shown to hinder the improvements in anaerobic physical performance in one study. Whether or not this inhibition occurs when one takes resveratrol at other times is not yet clear.
Allergic reaction – Some people are allergic to this compound and may experience an allergic reaction after they start taking it. Allergic reactions typically don’t disappear until one stops taking the supplement.
Nausea – This side effect is most common when people take the supplement on an empty stomach.
Diarrhea – You can usually prevent diarrhea or stomach discomfort by taking this supplement with a meal.
Toxicity – As an adaptogen, resveratrol acts as a mild stressor on the body. That is usually a great thing as it allows your body to adapt to specific forms of stress and become more resilient. However, stressing the body too much can be counter-productive and cause multiple side effects, including toxicity. While acute toxicity is extremely rare, taking high amounts of this compound could lead to chronic toxicity and cause health problems over time. To prevent chronic toxicity as all as the side effects related to exercise benefit inhibition, staying below 40 mg daily is best unless you have a great reason to take more.
Contamination – If growing or storing conditions are not adequately controlled, Japanese knotweed, red grapes, or other sources of resveratrol can be contaminated with bacteria, molds, and other potentially harmful microorganisms. Some growers also use pesticides and herbicides that can be unsafe. Another issue is that herbal supplements can get contaminated with other supplements and chemicals during the manufacturing process. Choose the brand you get herbal supplements from wisely. It is often best to use websites like Amazon, where thousands of users have reviewed and rated the products. You are less likely to buy something of lower quality there.

Who should not take resveratrol?

You should probably avoid taking the supplement if you:

exercise a lot (resveratrol can greatly inhibit the benefits of exercise, especially when taken close to a workout session)
are allergic to this compound
experience a severe adverse reaction after taking the supplement (though a mild adverse reaction is usually a great thing as it is a sign that the supplement is working and causing a hormetic response that allows the body to adapt and become more resilient)
are pregnant or breastfeeding (while it can be safe to take this adaptogen during pregnancy or breastfeeding, it acts as a mild stressor and can put some unnecessary risk to the child)

Who will benefit the most?

You should consider taking the supplement if you:

are inactive
are planning to take small doses (40 mg of resveratrol or less) that don’t have many side effects

How much resveratrol should you take?

Because resveratrol is an adaptogen, it acts as a mild hormetic stressor on the body, which allows your body to adapt and become more resilient to certain kinds of stressors in the long term.

A higher dose does not necessarily lead to more notable benefits. Instead, there appears to be an inverted U-shaped dose-response pattern. In other words, you want to find a sweet-spot dose that allows you to get the benefits of resveratrol without putting too much pressure on the body or quickly causing the body to develop tolerance to the compound.

As little as 10 mg of resveratrol can be effective in some areas, such as for improving insulin sensitivity and cardiovascular health in unhealthy people. Immune signaling can also be improved by low doses.

Higher doses (250-1000 mg) are better at increasing blood flow, inhibiting aromatase, and supporting brain function, but these extra benefits are usually not worth the side effects.

All things considered, 10-40 mg seems to be the best daily dose for most people.

Doses higher than this can be more beneficial in some areas but they are also more likely to lower or diminish the benefits of exercise.

It’s usually not a good idea to take more than 40 mg unless you are inactive and have a very good reason to take a higher dose.

The higher end of the 10-40 mg range usually provides slightly more benefits in the short term. If you plan to take this supplement for a longer time (multiple months or years), the lower end is probably a better way to go since you would develop tolerance faster if you were to take higher doses.

While resveratrol could theoretically cause acute toxicity, you’d need to take an extremely high dose that would be way beyond what even the most potent supplements contain.

Like most other adaptogens, it is best to cycle resveratrol and take about two days off weekly to reset your tolerance. That will allow you to keep getting the benefits in the long term.

Keep in mind that the effects of this supplement are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the supplement and not taking it at least twice a week is necessary to prevent tolerance in the long term.

Best time to take resveratrol

Resveratrol is a fat-soluble compound and gets absorbed much better when you take it with food.

Whether you take this supplement in the morning or the evening typically does not make much difference. Both options are fine so feel free to experiment.

Food sources of resveratrol

Here are some of the riches food sources of resveratrol and how much they contain per 100 grams:

Dark chocolate: 0.022-0.430 mg
Red wine: 0.05-12.59 mg
Peanuts: 0.01-1.28 mg
Blueberries: 0.02-0.06 mg
Bilberries: 0.12-0.62 mg
Cranberries: 0.01-0.12 mg
Grapes: 0.05-1.68 mg
Pomegranate: 0.03-1.28 mg
Mulberries: 0.02-3.54 mg
Pistachios: 0.06-0.48 mg

As you can see, no foods contain a good amount of resveratrol. Red wine is the only food/beverage that could provide a dose of this compound that would impact the body in at least some minor way.

Even when it comes to red wines, most of them do not contain enough resveratrol to make any meaningful difference, and the possible benefits are outweighed by the health problems associated with ethanol.

Interactions

Apigenin
Resveratrol can enhance the effects of apigenin.
Piperine
Piperine from black pepper or other related types of pepper can increase the absorption of resveratrol by about 229% and the maximum serum resveratrol concentration by as much as 1544%. It does so by inhibiting glucuronidation, a process in the liver that signals to the body that it should secrete resveratrol.
Soy isoflavones
Genistein, one of the main soy isoflavones, is highly synergistic with resveratrol for reducing adipose tissue.
Quercetin
This combination is even more effective for preventing adipogenesis than the combination of resveratrol with Genistein. You can also combine all three supplements to achieve the highest effects.
Leucine
SIRT1 and SIRT3 activity was increased synergistically in adipocytes and skeletal muscle in people who took this combination. Leucine can also prevent or lower the side effect of inhibiting muscle protein synthesis to at least some extent.
Turmeric
Resveratrol and curcumin from turmeric were shown to reduce lung cancer in animal studies when taken together. This is likely because of their anti-inflammatory effects.
Grape Seed Extract
Grape seed extract is significantly more potent in destroying cancer cells via the p53 pathway when taken with resveratrol.
Melatonin
Resveratrol can increase the effects of melatonin.

Where to buy resveratrol?

In most countries, Ama z on is the best option for ordering resveratrol and plant-derived supplements. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

Resveratrol vs pterostilbene

Pterostilbene is a dimethylated derivative of resveratrol. These two compounds are structurally very similar but some of their effects can differ greatly.

Pterostilbene is often called better resveratrol as it is more potent in some mechanisms and absorbs much better. It also doesn’t impair exercise performance and adaptations in the same way resveratrol can.

On the other hand, pterostilbene can worsen one’s cholesterol levels while resveratrol can slightly improve them. Resveratrol is also a more studied compound with more proven benefits.

One is not necessarily better than the other. If you have a high budget for supplements and you don’t fall into any of the categories of people that should avoid these, you can experiment with both of them to find which one works better for you. If you have a small budget for supplements, it is probably better to go for something completely different as neither resveratrol nor pterostilbene have the highest return on investment for most people.

FAQ

As with most other adaptogenic supplements, it is best to cycle resveratrol and take a break from it for about two days per week to reset your tolerance back to baseline. That will keep your body sensitive to the supplement and allow you to keep getting the benefits in the long term.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes time which can add up over months or years. The disadvantage of capsules is that they are often made of bovine gelatine, which rarely comes from ethical sources.

Yes, you can. This supplement should not impact your sleep in any negative way. Whether you take it in the morning or the evening typically doesn’t make much difference. Both options are fine so feel free to experiment. The most important thing to keep in mind is that resveratrol is fat-soluble so you should take it with food to absorb it well.

Yes, this compound can expire. When you buy a resveratrol supplement that has a yellow or brown color, chances are it has already expired, in which case it could do more harm than good.

Yes. The main problem with taking too much of this compound is that it may hinder the benefits of exercise.

While you could safely take higher doses, there is usually no point in taking more than 40 mg of resveratrol daily. This amount should give you most of the benefits without meaningful side effects. Paradoxically, taking a higher dose would likely lead to fewer benefits as the body would quickly become accustomed to the compound and you would experience more side effects related to the hindering of exercise performance.

The half-life of resveratrol in the body is anywhere from 1-3 hours. This compound should get metabolized and utilized within 12 hours of consuming it. However, most of the effects of this supplement are cumulative, so they mostly happen in the long term rather than acutely. Therefore, the half-life of this herb isn’t very relevant in practice.

The effects of this supplement are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the supplement and not taking it at least twice a week is necessary to prevent tolerance in the long term.

Yes, resveratrol is vegan-friendly. If you buy this compound in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.

No, it does not. The supplement does not interfere with fasting in any significant way. However, it is still much better to take resveratrol with food as it is a fat-soluble compound.

References

Most of the information in this guide is based on scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything you read in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

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