Resveratrol, a polyphenol abundant in red wine, has some antioxidant and heart-protective properties. However, its bioavailability is poor and most of its purported benefits have not been confirmed in humans. Read this science-based review to learn more.
What is Resveratrol?
Resveratrol is a small polyphenol that came to scientific attention during the 1990s. Since then, it has been hyped by supplement manufacturers and news outlets alike.
Resveratrol is high in grape skin, as grapes produce resveratrol in defense against toxins and parasites. It is also found in various berries, peanuts, soy, and “Itadori tea” made from Japanese Knotweed [1].
Limited studies have explored its antioxidant, anti-inflammatory, anti-aging, and phytoestrogen activity. Resveratrol does hold some potential for improving chronic diseases. Researchers are also exploring its ability to mimic the effects of caloric restriction in animals, which might affect lifespan [2, 3].
Snapshot
Proponents
- Antioxidant
- May be anti-aging
- May activate detox genes
- May support brain and heart health
- May help fight infections
- Safe when consumed from wine or foods
Skeptics
- Binds to iron and may not be safe in people who are anemic
- Poor bioavailability
- Clinical studies lacking or showing no health benefits
- Interacts with some drugs and supplements
- High doses may be harmful
- Long-term safety is unknown
- May cause nausea or stomach upset
Resveratrol Purported Health Benefits
Possibly Effective for:
1) Hay Fever
According to some clinical trials, resveratrol nose sprays may improve symptoms of hay fever or allergic rhinitis. Scientists came up with nose sprays as a great way to bypass resveratrol’s poor bioavailability and get it straight to localized, problematic body areas.
In one study of 100 people, an intranasal spray containing resveratrol 0.1% reduced nasal symptoms and improved quality of life in adults with hay fever used three times daily for 4 weeks [4].
In another trial of 68 children with pollen-induced hay fever, an intranasal spray with resveratrol 0.05% and one other ingredient (beta-glucan 0.33%) improved itching, sneezing, runny nose, and nasal blockage. It was given three times daily for 2 months [5].
Possibly Ineffective for:
2) Heart Health (Unlike Red Wine)
Limited evidence suggests that red wine, in moderation, supports heart health.
On the other hand, resveratrol supplements probably don’t aid in heart disease prevention.
Therefore, scientists think that other compounds in red wine may be more important, while resveratrol may or may not contribute to this effect.
Additional, large-scale studies are needed to determine the specific effects of different components in red wine, especially in people with blood pressure and heart problems.
In 67 men at high heart disease risk, alcohol-free red wine reduced blood pressure (both diastolic and systolic) after 4 weeks. It increased nitric oxide, which relaxes blood vessels. Regular red wine (9 oz glass/day) also slightly reduced blood pressure and increased nitric oxide, but less so than dealcoholized wine. A control group that only drank gin didn’t see any benefits [6].
One analysis of 19 studies concluded that drinking 1 – 2 glasses of wine daily (150 – 300 ml) reduces heart disease risk [7].
Interestingly, based on the first study, the alcohol in red wine may actually reduce the beneficial effect of resveratrol and other polyphenols. This especially holds true for people who already have high blood pressure or those at high risk.
In healthy people, though, moderate intake of red wine may indeed improve heart health.
In a study of 80 healthy, young people, a smaller amount of red wine (100 ml/day) over 3 weeks boosted blood vessel health, nitric oxide, and the number of cells that regenerate blood vessels (endothelial progenitor cells). Drinking water, beer, or vodka didn’t achieve these effects [8].
In cells, resveratrol increased the enzyme that makes nitric oxide (NO synthase) [9].
According to animal and cellular studies, resveratrol also reduces the formation of plaques in arteries, known as atherosclerosis. It also reduces the clumping of platelets, reduces blood lipids, and lowers inflammatory substances that increase risk of atherosclerosis [10].
In cells, resveratrol increases the expression of the PON1 gene, which reduces inflammation and helps detox pesticides and drugs [11].
3) Non-Alcoholic Fatty Liver Disease
Researchers are investigating the effects of resveratrol on liver disease and bile flow.
Most clinical research suggests that resveratrol is not beneficial for non-alcoholic fatty liver disease (NAFLD). According to one analyses of four small clinical studies, resveratrol (300-3000 mg daily) taken for 3 months does not affect liver enzymes, insulin resistance, or weight in patients with NAFLD [12].
In animals, it prevented and improved conditions of obstructed bile flow (by blocking MMP-2 and MMP-9). It also prevented liver damage in animals with sepsis, or blood poisoning from serious infections. These effects remain to be explored in clinical studies [13, 14, 15].
Insufficient Evidence for:
The following purported benefits are only supported by limited, low-quality clinical studies.
There is insufficient evidence to support the use of resveratrol for any of the below-listed uses.
Remember to speak with a doctor before taking resveratrol supplements. Resveratrol should never be used as a replacement for approved medical therapies.
4) Blood Sugar Control
One study suggested that resveratrol helps with glucose metabolism. In 11 healthy but obese men, resveratrol (150 mg/day) increased insulin sensitivity and lowered blood sugar levels after 30 days [16].
However, additional clinical studies are lacking. Therefore, existing evidence does not support the use of resveratrol for lowering blood sugar.
It also raised SIRT1 and PGC-1a levels. SIRT is an enzyme crucial for “turning off” harmful genes that increase fat deposits, blood sugars, and inflammation in the body, while PGC-1a supports healthy mitochondria [16].
Resveratrol lowered blood sugars in studies on rats with diabetes. It prompts cells to take in more glucose, which reduces insulin resistance. Resveratrol also protects the insulin-secreting beta cells in the pancreas, which helps increase insulin when it’s low and decrease it when it’s too high [17].
Scientists have yet to explore resveratrol’s effects on insulin resistance and diabetes in humans.
5) Effects on Sex Hormones
According to one research team, resveratrol may help balance the response to estrogen, which affects reproductive health in both men and women.
In male rats, resveratrol increased testosterone and sperm count without any adverse effects. Scientists think it may activate the HPG – hypothalamic-pituitary-gonadal – axis that controls sex hormone release from the hypothalamus via the pituitary in the brain [18].
In women, resveratrol may act in a somewhat different way. In one trial of 40 postmenopausal women, resveratrol (1g/day for 12 weeks) didn’t affect estrogen or testosterone but increased the protein that binds sex hormones and carries them through the blood (SHBG) by 10%. It also improved estrogen metabolism, which may lower the risk of breast cancer [19].
In animals, it blocks the enzyme that makes estrogen (aromatase) and mildly activates estrogen receptors. Resveratrol binds to estrogen receptors much weaker than estrogen does, which has a balancing effect: it may help increase estrogen-like activity when this female sex hormone is low (as after menopause) or decrease it when it’s too high. More human studies are needed [20, 21].
6) Acne
In a clinical trial of 20 people with acne, a gel with resveratrol showed positive results over 2 months. It reduced acne severity by almost 70% and improved overall skin health by over 50% with no adverse effects. The team discovered that cosmetic products with resveratrol are stable and don’t degrade when kept in the fridge (at 4°C/40°F) [22].
Uses Lacking Evidence:
No clinical evidence supports the use of resveratrol for any of the conditions listed in this section.
Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
7) Antioxidant Defense
Scientists believe resveratrol may have dual antioxidant activity: as a direct antioxidant and as a compound that may increase other antioxidant enzymes, genes, and pathways.
Antioxidant claims underlie many of its purported health benefits. Based on this theory, oxidative stress and inflammation trigger or worsen numerous diseases – from heart disease and diabetes to cancer and cognitive decline [3].
Resveratrol increased antioxidant enzymes in cellular and animal studies, including the following:
- SOD and NRF2, crucial components of the detox hub and antioxidant defense [23]
- Glutathione [23]
- Heme-oxygenase 1, which breaks down hem from hemoglobin to antioxidants and iron [24]
- Catalase, which protects from oxidative damage [23]
- Sirtuins and SIRT enzymes, which turn off aging-related genes and protect proteins [3]
At the same time, limited studies suggest that resveratrol reduces free radicals and inflammatory substances (including iNOS, Myeloperoxidase, NADPH oxidase) [23].
8) Inflammation
Aside from its indirect antioxidant effects on inflammation, resveratrol is theorized to affect specific inflammatory processes.
For one, it may block inflammatory COX enzymes, which are also the main target of commonly used painkillers and anti-inflammatory drugs (NSAIDs like Motrin). However, resveratrol’s mechanism and anti-inflammatory potential hasn’t been clinically confirmed [25].
Some scientists suspect that resveratrol also blocks the following inflammatory players (in animals or cells):
- NF-kB pathway, one of the most important and deeply-rooted triggers of inflammation in the body, according to some theories [26]
- HMGB1, a protein made by immune cells that causes inflammation and tissue damage in autoimmune diseases like arthritis [15]
- STAT3, which may contribute to problems in people with chronic inflammation, autoimmune diseases such as IBD, obesity, cancer, or Th1/Th17 dominance [27]
9) Anti-Aging Potential
Resveratrol may not be the philosopher’s stone that will confer you immortality, but scientists are looking to see if it can beneficially impact some important aging-related disease pathways.
Based on animal and cellular research, they hypothesize that resveratrol may combat some age-related disorders by [28, 29]:
- Mimicking the effects of caloric restriction, which increases lifespan in animals
- Reducing oxidative stress and inflammation on multiple levels (enzymes, immune cells, gene expression)
- Activating SIRT1, which turns off genes that promote aging
We’ll present some interesting aging-related resveratrol research and hypotheses below. Nonetheless, the whole “anti-aging theory” of resveratrol remains unproven.
Senescence, Inflammation & Autophagy
One of the theories scientists use to explain aging involves so-called “cellular senescence.” With aging, cells become senescent and less resilient to stress, they lose their function and start producing inflammatory substances [30].
This loss of function and inflammation on a cellular level then extends to organs and tissues: the brain, heart, muscles, skin, and gut – and the body as a whole – also start to degenerate and lose function, especially if the body cannot or does not eliminate the dysfunctional cells through a process called autophagy [30].
SIRT1 is an enzyme that can turn off genes that trigger cellular senescence. Scientists are wondering if, by activating SIRT1, resveratrol may epigenetically hinder the aging process, at least based on cellular studies [3, 31].
Autophagy & Cellular Quality Control
Autophagy is a normal process that triggers the destruction of damaged cells, recycling the products of broken-down cells to make new and healthy ones. Autophagy is our body’s main “Quality Control Officer.”
Some theories have linked aging and age-related diseases to impaired autophagy. Though these theories are still a topic of research, they have yet to be confirmed or rejected.
Autophagy theories also led to the recent boom in caloric-restriction practices. Caloric restriction is said to promote longevity and healthy aging by activating autophagy [32].
However, caloric restriction is not safe for everyone. It may be especially tricky for older or thin people who struggle to get enough nutrients in their daily diet.
In animal studies, resveratrol confers similar benefits to caloric restriction and increases autophagy induction without the need to reduce daily calorie intake. These effects have not been investigated in humans yet [32].
Clinical studies are needed to determine whether or not resveratrol can extend lifespan in humans.
10) Brain Health
Glial cells, specifically astrocytes, provide support and protection to neurons and their damage or dysfunction is linked to many brain-related diseases [33].
One of the ways in which astrocytes protect neurons is by removing excess glutamate (a neurotransmitter) from synapses and the extracellular space that surrounds neurons. Excess glutamate in the brain can lead to excitotoxicity and ultimately neuronal damage or even death [33].
In a cellular study, resveratrol increased their glutamate uptake. Theoretically, this is linked to better protection from brain degeneration and stroke. However, we can’t draw this conclusion from a cell-based study [33].
In animal studies, resveratrol reduced seizures and protected the hippocampus, the brain’s main memory hub. It also increases IGF-1 in the hippocampus, which may improve cognition [34, 35].
One research group suggested that resveratrol may protect the brain by acting on the gut-brain axis [36].
According to this unproven theory, resveratrol’s potential benefits may not even depend on it being absorbed and passing the blood-brain barrier. In mice, resveratrol stimulated gut nerves, which passed the signal on to the hippocampus. Resveratrol was undetectable in the hippocampus, it improved cognition only by activating nerves in the gut [36].
In a study on brain cells, resveratrol increased the activity of the antioxidant gene heme-oxygenase 1, which protects the brain from damage. The effect was enhanced by melatonin [24].
In mice with late-onset Alzheimer’s disease, long-term resveratrol supplementation reduced cognitive impairment and disease biomarkers. It could also activate AMPK, which maintains energy balance in the brain under challenging conditions [37, 38].
Nonetheless, clinical studies have not yet examined the effects of resveratrol on brain health. Thus, this purported benefit remains unproven.
11) Gut Microbiome Balance and Bile Production
Some scientists believe that the gut microbiome can protect against diseases of the arteries [39].
In one study, resveratrol protected blood vessels in mice without APOE, stopped harmful bacteria in their gut from secreting harmful oxidative substances (like TMAO), and balanced their microbiome. It increased beneficial gut bacteria (such as Lactobacillus and Bifidobacterium), which raised the production of bile acids [39].
According to some, resveratrol may counter lower bile acid production and the weaker ability to eliminate cholesterol in people with heart disease. However, clinical trials are lacking to support such claims [40].
12) Obesity
No clinical evidence supports the use of resveratrol in people who struggle with obesity. The existing animal research should guide future human studies.
In mice fed a high-fat diet, resveratrol reduced oxidative stress and prevented the death of protective immune cells called Tregs [41].
Resveratrol stopped fat cells from making new fats and triggered their death, in cell-based studies. It accomplishes this by turning off genes that cause weight gain (such as PPAR gamma) while activating genes that enhance energy use and mitochondrial health (SIRT3, UCP1) [42, 43].
Additionally, resveratrol may boost weight loss by blocking several key fat-creating enzymes (called fatty acid synthase, lipoprotein lipase, and hormone-sensitive lipase) [42].
13) Bone Health
This purported benefit remains unproven.
Stem cells in the connective tissue are presented with several possibilities: to develop into fat cells, bone-building cells, joint, or muscle cells. Resveratrol activates the fat-burning pathway (SIRT1), which blocks genes that increase fat storage (PPAR gamma). This epigenetic shift causes stem cells to develop into bone-building cells, which may boost bone health [44].
According to some, resveratrol may synergize with Vitamin D and vitamin K2 to protect the bones and increase their mineralization [45].
14) Cancer Prevention Research
The effects of resveratrol on cancer prevention in humans are unknown.
Scientists are investigating resveratrol for its potential to prevent cancer, especially liver cancer and some other cancer cell types [46, 47, 48].
In mice, resveratrol applied to the skin before UVB exposure prevented skin cancers. Given orally, it was active against esophageal cancer in rats [49, 50].
Since resveratrol is an antioxidant phytoestrogen, some scientists are investigating its effects on breast cancer. In cells, it blocks the enzyme aromatase, which makes estrogen. High activity of this enzyme and high estrogen levels worsens a common type of breast cancer that has receptors for estrogen (receptor-positive or ER+) [51, 52].
In animal studies, resveratrol prevented and reduced the growth of breast cancer. Clinical studies have not yet determined its efficacy and safety in breast cancer patients [51].
Aside from its hormonal effects, scientists are wondering whether resveratrol can regulate another cancer enzyme called topoisomerase II. In cells from a deadly brain tumor (glioblastoma), resveratrol blocked the activity of this cancer enzyme, which should guide further research efforts [53].
15) Muscle Growth
According to some unproven theories, resveratrol may increase muscle-building pathways and block processes that degrade proteins (proteolysis). For example, it increased the size of fish and enhanced their muscle growth in one study [54].
In another study, resveratrol supplementation enhanced the exercise training response, upper muscle strength, and aerobic performance in rats [55].
Scientists are questioning if its effects stem from epigenetic changes like activating fat- and sugar-burning sirtuins (SIRT1) and other molecules that heighten energy levels (AMPK and PGC-a). Future studies might give us some answers [55].
16) Radiation
In mice, high-dose resveratrol had a good anti-radiation effect. It prevented the decline in bone marrow and white blood cells from radiation, helping to maintain proper immune function. It also increased the antioxidant and detox enzyme SOD without causing adverse effects. These effects remain completely unproven in humans, though [56].
17) Hearing Loss
Scientists found that noise increases free radicals, which can cause ear damage and hearing loss. In mice exposed to damaging noise, resveratrol protected against hearing loss by neutralizing free radicals and improving blood flow in the ears [57].
In a different rat study, resveratrol prevented ear damage from the toxic chemotherapy drug cisplatin [58].
Clinical research is needed.
18) Infections
Antiviral Activity
Resveratrol has some virus-fighting action, according to cell-based or animal studies. It was effective against:
- The herpes virus infection in ducks and geese as well as in cells [59, 60]
- Viruses that cause both oral herpes (HSV-1) and genital herpes (HSV-2) [61]
- The Influenza virus, which causes the common cold [61]
- The Epstein-Barr virus, which causes infectious mononucleosis (“the kissing disease”) [61]
- Viruses that cause lung infections (the Respiratory Syncytial virus) in mice and in cells (Human meta pneumonia and Human rhinovirus virus) [61]
- HIV-1 in synergism with the anti-HIV drug decitabine [60]
- The virus that causes chickenpox (Varicella zoster) [60]
- Viruses linked to gut infections (Enterovirus 71) [60]
- The African swine fever virus [60]
However, clinical studies are lacking and the effects of resveratrol on viral infections in humans remains unknown.
Antifungal Activity
Resveratrol was researched against the Candida albicans yeast in a cell-based study [62].
Antibacterial Activity
Resveratrol was active against MRSA (Methicillin-Resistant Staphylococcus aureus) in bacterial samples from infected patients. Scientists are investigating its synergy with luteolin and quercetin. In other cell-based studies, resveratrol showed antibacterial activity against:
- The ulcer-causing E.Coli, in which case its poor bioavailability may be beneficial to achieve the desired effects in the gut [63]
- Acne-causing bacteria (Propionibacterium acnes), for which it can be applied as a gel or cream [64]
- STD-causing bacteria (Haemophilus ducreyi) [65]
- Diarrhea-causing bacteria (Arcobacter butzleri and Arcobacter cryaerophilusa) [66]
Clinical research should determine if these flavonoids have the potential to be used as part of complementary approaches in people with certain bacterial infections [67].
19) Sensitivity to Vitamin D
Resveratrol alone and by SIRT1 activation might increase sensitivity to vitamin D. Resveratrol can activate the vitamin D receptor (VDR), which increases the response to vitamin D and its activity in the body [68, 69].
Resveratrol increases the binding of calcitriol (1,25-dihydroxycholecalciferol) to VDR and activates the retinoid receptors (RXR), which are crucial for the proper activity of vitamin D [68].
20) Pain Research
Resveratrol is being researched for reducing pain and inflammation. In animal studies, resveratrol given directly into the brain reduced the sensitivity of pain. Its pain-relieving effects could be to its ability to block COX-1 and COX-2 inflammatory enzymes, the same targets of commonly used NSAID painkillers [70].
Oral resveratrol also reduced pain and inflammation in mice, but injections had a stronger effect. In another study, resveratrol decreased hard-to-treat neuropathic pain in mice [71, 72].
While its oral bioavailability is still unclear, some people suggest that a way to bypass this is to use resveratrol creams locally, applied directly to painful areas such as joints or the back.
Although resveratrol can penetrate the skin, it’s unlikely that the concentrations present in most cosmetic products can have any effect [73].
21) Neurotransmitters Balance
Resveratrol blocked the enzymes that take noradrenaline and serotonin back into brain cells from neurons in rat brains, which increases their concentration in the synapse. By increasing serotonin activity in the brain, resveratrol may boost mood – at least theoretically [74].
Resveratrol also blocks MAO (MAO-A and MAO-B), an enzyme that breaks down monoamine neurotransmitters like serotonin and dopamine, which is equally important for mood [74].
Neurogenetics & the Warrior Gene (MAO-A)
Resveratrol blocks MAO-A more than MAO-B (in rat brains) [74].
MAO-A is the “warrior gene” because some of its genetic variations (2R and 3R) are linked to increased violence and aggressiveness. This gene codes for the enzyme MAOA that breaks down neurotransmitters such as noradrenaline, adrenaline, serotonin, and dopamine.
High levels of this enzyme may imply fewer neurotransmitters available in the brain. This is because more neurotransmitters are being broken down at a faster rate.
On the other hand, low levels of this enzyme imply more neurotransmitters.
MAO-A balance is key: you don’t want it to be too high or too low because both situations may have negative effects.
Based on this, some people claim that resveratrol is better-suited for those predisposed to high MAO activity, as it blocks this enzyme and can compensate for potentially low neurotransmitter levels.
If you’re curious to learn more, you can upload your genotype file to SelfDecode and look at the following SNPs:
MAO-B is similar to MAO-A but plays a more important role in the risk for Parkinson’s Disease and Alzheimer’s. Overactivity of this gene may lower levels of dopamine and other neurotransmitters in areas of the brain important for the onset of these diseases. Resveratrol also blocks MAOB, but the effect is more modest [74].
22) Autoimmunity
You may not have heard of mTOR, but is one of the body’s key regulators behind the scenes. This enzyme controls the activity of over 800 other proteins [75]!
Its expression is usually increased in times of plentiful nutrient intake and decreased in times of stress and calorie restriction. And while it does increase energy production, it also increases waste products and reduces repair processes (including autophagy), all of which can trigger autoimmune problems in the long run [75].
Resveratrol blocks mTOR signaling in a unique way, according to cell-based studies. An over-active mTOR has been linked to autoimmunity and cancer, while scientists are exploring whether reducing mTOR activity may help prevent these diseases while also promoting longevity [76].
Takeaway
Resveratrol is a polyphenol found mostly in grape skin and red wine. Some berries, legumes, and “Itadori tea” (made from Japanese Knotweed) also contain it.
Based on the available evidence, drinking red wine in moderation possibly supports cardiovascular health — but taking resveratrol supplements doesn’t.
Its most promising uses rely on applying specific formulations to localized body areas. For example, a nose spray with resveratrol may help with hay fever. Gels with resveratrol are also being developed for improving acne.
There is insufficient evidence to rate the effectiveness of resveratrol for any other purported benefit.
