Resveratrol is the polyphenol everyone has heard of because of the French paradox, hoping that drinking a bit of wine every day may indeed be healthy. Resveratrol does have 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.
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.
This compound has been nicknamed the French Paradox in a bottle since resveratrol is found in red wine that the French like to consume it in not-so-moderate quantities alongside a diet high in saturated fats. Yet, the French have very low rates of heart disease [1].
While the resveratrol in red wine is unlikely to fully account for the paradox, some scientists say it may be a contributing factor [1].
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 [2].
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 [3, 1].
Clinical studies suggest that resveratrol is likely safe. However, no long-term studies have been done with humans [1].
Resveratrol also has one major flaw: poor bioavailability. Resveratrol is absorbed into the blood from the gut a bit better than other polyphenols (such as quercetin). But it gets broken down fast, leaving little free resveratrol in the bloodstream. Scientists say that this is one reason why a lot of the findings from animals and cells might not apply to humans [1].
Additionally, resveratrol supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but dont guarantee that theyre safe or effective. Speak with your doctor before supplementing.
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 [1].
Resveratrol increased antioxidant enzymes in cellular and animal studies, including the following:
At the same time, limited studies suggest that resveratrol reduces free radicals and inflammatory substances (including iNOS, Myeloperoxidase, NADPH oxidase) [R, R, R, R].
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, resveratrols mechanism and anti-inflammatory potential hasnt been clinically confirmed [6].
Some scientists suspect that resveratrol also blocks the following inflammatory players (in animals or cells):
Resveratrol may not be the philosophers stone that will confer you immortality, but it 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 [10, 11]:
Well present some interesting aging-related resveratrol research and hypotheses below. Nonetheless, the whole anti-aging theory of resveratrol remains unproven.
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 [12].
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 [12].
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 [1, 13].
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 bodys 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 [14].
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 [14].
Glial cells, specifically astrocytes, provide support and protection to neurons and their damage or dysfunction is linked to many brain-related diseases [15].
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 [15].
In a cellular study, resveratrol increased their glutamate uptake. Theoretically, this is linked to better protection from brain degeneration and stroke. However, we cant draw this conclusion from a cell-based study [15].
In animal studies, resveratrol reduced seizures and protected the hippocampus, the brains main memory hub. It also increases IGF-1 in the hippocampus, which may improve cognition [16, 17].
One research group suggested that resveratrol may protect the brain by acting on the gut-brain axis [18].
According to this unproven theory, resveratrols 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 [18].
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 [5].
In mice with late-onset Alzheimers 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 [19, 20].
Nonetheless, clinical studies have not yet examined the effects of resveratrol on brain health. Thus, this purported benefit remains unproven.
Limited evidence suggests that red wine, in moderation, supports heart health. Additional, large-scale studies are needed to determine the specific effects of resveratrol, 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 increase nitric oxide, but less so than dealcoholized wine. A control group that only drank gin didnt see any benefits [21].
One analysis of 19 studies concluded that drinking 1 2 glasses of wine daily (150 300 ml) reduces heart disease risk [22].
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 didnt achieve these effects [23].
In cells, resveratrol increased the enzyme that makes nitric oxide (NO synthase) [24].
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 [25].
In cells, resveratrol increases the expression of the PON1 gene, which reduces inflammation and helps detox pesticides and drugs [26].
Some scientists believe that the gut microbiome can also protect against diseases of the arteries [27].
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 [27].
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 [28].
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 [29].
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 [29].
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 its low and decrease it when its too high [30].
Scientists have yet to explore resveratrols effects on insulin resistance and diabetes in humans.
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 [31].
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) [32, 33].
Additionally, resveratrol may boost weight loss by blocking several key fat-creating enzymes (called fatty acid synthase, lipoprotein lipase, and hormone-sensitive lipase) [32].
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 [34].
According to some, resveratrol may synergize with Vitamin D and vitamin K2 to protect the bones and increase their mineralization [35].
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 [36, 37, 38].
In mice, resveratrol applied to the skin before UVB exposure prevented skin cancers. Given orally, it was active against esophageal cancer in rats [39, 40].
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+) [41, 42].
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 [41].
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 [43].
Researchers are investigating the effects of resveratrol on liver disease and bile flow. In animals, it prevented and improved Nonalcoholic Fatty liver disease and improved conditions of obstructed bile flow (by blocking MMP-2 and MMP-9). It also prevents liver damage in animals with sepsis, or blood poisoning from serious infections. Clinical trials are needed [44, 45, 8].
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 [46].
In another study, resveratrol supplementation enhanced the exercise training response, upper muscle strength, and aerobic performance in rats [47].
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 [47].
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 [48].
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 [49].
In a different rat study, resveratrol prevented ear damage from the toxic chemotherapy drug cisplatin [50].
Clinical research is needed.
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 [51].
In women, resveratrol may act in a somewhat different way. In one trial of 40 postmenopausal women, resveratrol (1g/day for 12 weeks) didnt 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 [52].
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 its too high. More human studies are needed [53, 54].
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 dont degrade when kept in the fridge (at 4C/40F) [55].
Resveratrol has some virus-fighting action, according to cell-based or animal studies. It was effective against:
However, clinical studies are lacking and the effects of resveratrol on viral infections in humans remains unknown.
Resveratrol was researched against the Candida albicans yeast in a cell-based study [59].
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:
Clinical research should determine if these flavonoids have the potential to be used as part of complementary approaches in people with certain bacterial infections [64].
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 [65, 66].
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 [65].
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 [67].
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 [68, 69].
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, its unlikely that the concentrations present in most cosmetic products can have any effect [70].
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 [71].
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 [71].
Resveratrol blocks MAO-A more than MAO-B (in rat brains) [71].
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 dont 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 youre 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 Parkinsons Disease and Alzheimers. 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 [71].
You may not have heard of mTOR, but is one of the bodys key regulators behind the scenes. This enzyme controls the activity of over 800 other proteins [72]!
Read more:
21 Resveratrol Benefits + Dosage, Side Effects - SelfHacked
