Resveratrol

Resveratrol first came to the spotlight thanks to a phenomenon known as the French paradox – its antioxidant abilities have begun to explain why the French suffer less often from cardiovascular disease than other nations, even though their diet is rich in animal fats. In recent years, however, it has also been shown to have strong epigenetic effects, so that when consumed regularly it can influence which of our genes are expressed and which are not. This may make it an effective part of the prevention and treatment of a number of serious diseases.

Description

Resveratrol is chemically a derivative of stilbene, which belongs to the polyphenols. It is found in a wide variety of fruits and vegetables, the most well-known source being the skins and pips of blue grapes, from where it is also found in red wine (some amounts are also found in white and rosé wine). However, it is also abundant in, for example, peanuts, blackcurrants, blueberries and mulberries. (5) Its role in plants is not well defined, but it probably helps protect against fungal diseases.

History

The phenomenon called the French paradox was first scientifically described by the Irish physician Samuel Black in 1819.(3, 4) It was he who first suggested that the low incidence of cardiovascular disease in the French population might be due to the regular consumption of red wine. As time went on, more and more scientists were inclined to this view. Resveratrol was first isolated in the 1940s. It was not until the 1990s that it became the subject of intensive scientific research.

Effects

Resveratrol is most thoroughly described in terms of its antioxidant action, which is very pronounced indeed (7). Gradually, however, it has become clear that the main key to its efficacy must be sought in the field of epigenetics. For example, it influences a phenomenon called histone acetylation. Histones are proteins that form complexes with DNA and are important for its correct spatial organisation. By regulating histone acetylation, resveratrol influences a process called gene transcription, in which proteins are synthesized (10). Thus, it does not directly affect our genetic information, but it co-determines which part of it is eventually expressed.

Tumour diseases

Due to its epigenetic action, resveratrol affects a process called proliferation, i.e. the rapid multiplication of cells.(11) Disorders of this process are usually found in most types of cancer. In addition, by suppressing the production of the enzyme cyclooxygenase, resveratrol reduces the production of prostaglandins, which not only promote inflammatory processes but also stimulate the growth of cancer cells (15, 16)

Resveratrol also has anti-inflammatory effects against colitis, or inflammation of the colon, including those types of colitis that are associated with the development of tumours of this organ, especially ulcerative colitis. In experiments on mice, resveratrol not only significantly reduced the indicators of ongoing inflammation, but also reduced the incidence of intestinal tumours. (1,2) Due to its ability to bind to estrogen receptors, it can also influence the development of breast cancer (6, 12).

Cardiovascular disease

Due to its antioxidant effects, resveratrol has been shown to affect fat metabolism, inhibit oxidation of low-density lipoprotein (LDL) cholesterol and platelet aggregation, processes that play an important role in the development of atherosclerosis. (13) It may also be useful in reversing the effects of a heart attack – in experiments in mice, administration of resveratrol resulted in a 36% reduction in infarct volume within 24 hours of vessel closure. (14) A preventive effect against cardiovascular disease has also been demonstrated in smokers, who are at significantly higher risk than the non-smoking population. (18)

It also affects the production of sirtuin enzymes, as well as the enzyme eNOS, which is necessary for the production of nitric oxide. At the same time, it reduces the production of a number of pro-inflammatory substances (e.g. NF-kB or TNF-α), which are important contributors to atherosclerosis, as well as the production of vasoconstrictors (i.e. vasoconstrictors that close blood vessels).

Inflammatory processes

The principle principle of the anti-inflammatory action of resveratrol is the suppression of transcription of genes responsible for the development of inflammatory processes.(10) Inflammation plays an important role in the development of many serious diseases, such as cardiovascular diseases, some types of cancer, diabetes, and obesity. Resveratol also reduces the inflammatory processes that occur in muscles after intense physical exercise and can therefore be used in athletes to speed up recovery. (19)

Resveratrol also promotes the health of the gut microbiome, which contributes to its anti-inflammatory effects, as well as its positive impact in the prevention and treatment of a number of diseases (29).

Effect on the gut microbiome

In addition to epigenetic effects, the effect on the gut microbiome may be another of the key pathways by which resveratrol affects our health. In fact, it is the imbalance of microorganisms living in our gut that can contribute significantly to a number of diseases and disorders – from inflammatory bowel disease to obesity to depression(read more here: https://www.epivyziva.cz/tajemny-svet-uvnitr-nasich-strev-bakterie-ovlivnuji-nase-zdravi-i-genetickou-informaci/).

Resveratrol can affect the gut microbiome in several ways. First, it can help change the ratio of “good” to “bad” organisms in the gut. For example, obese people generally have a different microbiome composition to lean people: for example, the proportion of Bacterioides bacteria increases and the proportion of Firmicutes bacteria decreases. And the same is true for animals. But when, for example, one study gave resveratrol to a group of obese mice on a high-fat diet for a long time, the proportions of both types of microorganisms changed to match those of lean mice. (63)

Similarly, resveratrol is likely to affect the composition of substances secreted by gut microorganisms. For example, in mice used in another study, its administration reduced the secretion of substances that contribute to atherosclerosis.(64) Finally, it also has a beneficial effect on the state of the cells of the intestinal mucosa, affecting, for example, the permeability of the vascular wall.(65)

Sports performance

Resveratol suppresses the production of aromatase, thereby reducing the rate of conversion of testosterone to estrogen, and thus helping to maintain its sufficient level at the blood. It also reduces the inflammatory processes that occur in muscles after intense physical exertion, and can therefore be used in athletes to speed recovery.(44) Veteran athletes respond very well to it.

Resveratrol also increases AMPK production in muscle tissue, which is especially important for endurance athletes. This is because the AMPK enzyme improves the absorption of glucose from the blood into the muscles and its utilization within the muscle cells, allowing for better production of energy usable after muscle work.

In combination with regular exercise, resveratrol is also effective in preventing age-related muscle loss and obesity, which is typically associated with muscle loss (50).

Asthma

The anti-inflammatory effects of resveratrol have been shown to be beneficial in conditions such as asthma and other diseases of the respiratory system. It inhibits the release of inflammatory mediators from the epithelial cells of the airways.(8, 9) Although it is slightly less effective than glucocorticoids, it is also effective in people in whom glucocorticoid treatment is not working for some reason.

Mental performance

Resveratrol improves glucose control in the hippocampus, improves so-called functional connectivity in this area and has a significant positive effect on memory. It is effective not only in healthy people, but also in people at high risk of dementia. As a phytoestrogen, it is particularly effective in post-menopausal women (38).

Interestingly, one study confirmed a beneficial effect on cognitive abilities when resveratrol and alcohol were combined in low doses. When volunteers, whose average age was 70.4 years, were asked to complete a series of tasks testing cognitive ability, they performed much better after consuming red wine (1 dcl) fortified with resveratrol (200 mg) than when they drank red wine alone before the tests. The research authors attribute the results to improved blood flow to the brain. (30)

Alzheimer’s disease

There has been little research on this topic and the principle of this action has not yet been fully elucidated, but it appears that resveratrol has a significant neuroprotective effect, i.e. it protects the cells of the nervous system from the damage that is the main manifestation of Alzheimer’s disease. (20, 39) Two studies have confirmed that high doses of resveratrol are able to stabilise the levels of amyloid-beta 40, one of the main components of the so-called amyloid plaques that appear in the brains of Alzheimer’s sufferers. (24) Long-term use also improves blood supply to the brain, long-term memory and the function of the hippocampus, the part of the brain responsible for memory.

Parkinson’s disease

It has significant antioxidant, anti-inflammatory and neuroprotective effects, and has a positive effect on ageing processes. When administered to patients with Parkinson’s disease, after only a few weeks, there was a relatively significant improvement in motor and cognitive abilities.

Longevity

Resveratrol is one of the most potent activators of sirtuin 1, an enzyme that regulates the expression of certain genes and is involved in a number of cellular regulatory processes. It deacetylates proteins that affect the ability of cells to respond to environmental stressors and thus contribute to longevity (21).

In addition, resveratrol has a significant beneficial effect on cellular organelles called mitochondria, whose damage and deterioration is another important mechanism associated with aging. Resveratrol is not only very effective in protecting mitochondria from damage, but it also promotes the formation of new ones.(60, 61) Read more about mitochondria here: https://www.epivyziva.cz/mitochondrie-klic-k-dlouhovekosti/

There is also research confirming the ability of resveratrol to regulate the visible signs of aging – in particular, the significant reduction of wrinkles with long-term use. (22) In addition, low levels of sirtuin 1 have been reported in cells with high levels of insulin resistance (23), so it is likely that resveratrol may also play a positive role in the prevention and treatment of type II diabetes.

Experiments in mice showed that resveratrol administration led to similar effects as restricting total caloric intake, a strategy whose antiaging effect has been confirmed in a number of studies. In experimental animals, resveratrol administration not only reduced the overall signs of ageing but also improved motor coordination, arterial elasticity, bone mineral density and cataract status (35).

Acne

Although acne is caused by bacteria, if they invade our skin and cause inflammatory problems, it is also largely due to epigenetic influences.

And it is resveratrol that represents one of the most effective means of treating this problem. It has a significant anti-inflammatory effect, and it also has antibacterial effects, including directly against the acne agent Propionibacterium acnes.(33) Moreover, its effectiveness has been confirmed by both internal and external administration (application of a gel containing resveratrol).(42)

Read more about acne-fighting options here: https://www.epivyziva.cz/akne-sex-nepomuze-uprava-stravy-ano/

Menopause

Resveratrol belongs to the phytoestrogens, it binds to the same receptors as estrogen and is therefore able to replace it at least partially when the ovaries stop producing this hormone. As a result, it is able to alleviate the unwanted symptoms of menopause that are caused by estrogen deficiency. This applies both to the actual symptoms of the onset of menopause (hot flushes, sweating, mood disorders, etc.) and to diseases whose risk increases significantly during this period (cardiovascular disease, osteoporosis, depression, Alzheimer’s disease, etc.).

A significant protective effect has been shown, for example, in osteoporosis, where resveratrol administration improves bone density, mineralisation and mechanical resistance. This is probably due to its positive effect on the production of sirtuin SIRT-1 and nuclear factor NF-kB (34).

In addition, in menopausal and post-menopausal women, resveratrol can help effectively manage the tendency to gain weight. This is because, by counteracting the drop in estrogen production, it also prevents a decrease in leptin sensitivity. This hormone, produced by fat tissue, induces a feeling of satiety in the brain, and a reduction in its production can lead to overeating. Resveratrol also promotes the production of the enzyme SIRT-1, which prevents the formation of new adipose tissue and inhibits angioneogenesis (i.e. the formation of new blood vessels that supply the adipose tissue with blood, allowing it to grow).

Support for blood formation

Resveratrol activates the FOXO3 gene, which is involved in the maturation process of red blood cells. This will be appreciated not only by people suffering from anaemia, but also by endurance athletes, for whom the support of blood formation will help to improve the capacity of their blood to transport oxygen to the working muscles.

The key to anaemia is, of course, a sufficient intake of iron and other nutrients needed for blood formation (vitamin B12 and C, copper and others), but if this does not help, resveratrol may be a good choice.

Diabetes

As we mentioned above, resveratrol is one of the effective activators of the AMPK enzyme, which improves glucose absorption from the blood, while also improving tissue sensitivity to insulin. (36)

Eye health

It has been known for some time that moderate consumption of red wine has a preventive effect on the development of age-related macular degeneration (retinal degenerative disease), which scientists attribute to the positive effect of resveratrol.(40) However, further research has confirmed that the effect of resveratrol on eye health is much broader. Overall, it improves vision and visual acuity, and helps with dry eye syndrome, glaucoma, macular degeneration, and diabetic retinopathy (a complication of diabetes affecting the eyes).(58, 59)

Hearing protection

But resveratrol also has a beneficial effect on another sense – hearing. In general, it slows down cellular ageing, which also affects the auditory receptors, and according to some studies, its use prevents hearing damage when exposed to excessive noise (41).

Antiviral action

Resveratrol is characterized by a relatively broad antiviral action. It helps to destroy, for example, influenza viruses, EB virus, RPSV virus, rhinovirus (the causative agent of rhinitis), and even increases the effectiveness of drugs administered for HIV infection (62).

Very effective is the use of resveratrol in the treatment of cold sores. In the case of cold sores, the tricky thing is that the causative agent, both HSV-1 and HSV-2 viruses, cannot be completely eliminated by the immune system. Those that do escape are encapsulated, thus becoming invisible to the immune system, and then patiently waiting for their opportunity to “wake up” and start reproducing. And that is when resveratrol comes in, suppressing the multiplication of herpes viruses and their awakening from the latent phase. It is particularly effective in the early stages of infection, i.e. at the very first signs of herpes. (43)

Fertility

The postponement of motherhood typical of today’s times brings with it one major problem: After the age of 30, epigenetic changes related to ageing begin to appear in our DNA, altering the activity of a number of important genes. This affects the DNA of every cell in the body, including that in eggs. And it is this that can cause problems with getting pregnant at an older age.

Resveratrol, however, slows down the aging process of all cells, not excluding eggs. It helps to increase the number of oocytes (immature eggs), which protects against free radical damage, and thus improves the quality of eggs that are already mature. As a result, the age at which a woman is able to conceive a child is prolonged. Resveratrol also increases the chance of pregnancy in women suffering from polycystic ovary syndrome and obesity, and also increases the success rate of artificial insemination (31, 32).

Prostate

Zinc is a key element for the proper development of the prostate gland.A deficiency of zinc can play a role in both the development of prostate enlargement and the risk of prostate cancer. Studies have shown that resveratrol can increase the level of zinc in prostate cells. Of course, concurrent zinc supplementation is also appropriate (46).

Use of

As we mentioned above, resveratrol is found in a number of natural sources, the most well-known of which is red wine. However, the problem is that the resveratrol content varies depending on many factors, not to mention the presence of alcohol, which makes it unacceptable to some of the population. Resveratrol can also be taken in the form of dietary supplements, and the recommended doses vary quite considerably, ranging from 20 mg to 5000 mg per day, with doses for therapeutic purposes usually ranging from 1000 mg upwards.

Resveratrol is not recommended for use in multiple sclerosis. Not only do its otherwise pronounced neuroprotective effects not apply in the case of the disease, but it may even promote the course of demyelination. It should also be avoided by pregnant women.

Combination of resveratrol with other dietary supplements

Resveratrol as a dietary supplement is very suitable for combinations with many other herbs and nutrients.

Very interesting is the combination with quercetin, which incidentally also accompanies resveratrol in red wine. Not only is it very effective, but quercetin also significantly improves the absorption of resveratrol (27). The same applies to the combination of resveratrol with curcumin. In studies, adding quercetin improved the absorption of resveratrol by 310%, adding curcumin improved absorption by 300%, and when the combination curcumin + piperine + quercetin was added to resveratrol, it improved absorption by 350% over resveratrol alone (47).

Another very effective combination is resveratrol and oligomeric proanthocyanidins (OPCs), a mixture of substances with strong antioxidant and epigenetic effects, which is also abundant in grape wine, specifically in grape seeds. Together, they act synergistically (i.e. complement each other) in a number of conditions (56).

Resveratrol can also be combined with omega-3 unsaturated fatty acids, rosemary or vitamin K2. Here are combinations suitable for some specific problems:

Heart and blood vessels: resveratrol + omega-3 (52), resveratrol + quercetin (26), resveratrol + EGCG (51), resveratrol + vitamin K2

Diabetes: resveratrol + quercetin (28), resveratrol + OPC (57), resveratrol + curcumin

Cancer: resveratrol + curcumin (45), resveratrol + EGCG (48), resveratrol + rosemary (55), resveratrol + OPC (56, 57)

Prostate: resveratrol + zinc (46), resveratrol + curcumin

Weight loss: resveratrol + quercetin (49), resveratrol + OPC

Anti-inflammatory action: resveratrol + omega-3 (52), resveratrol + OPC (57), resveratrol + rosemary

Eye health: resveratrol + omega-3 (53)

Brain function, Alzheimer’s and Parkinson’s disease: resveratrol + omega-3, resveratrol + OPC, resveratrol + vitamin K2

Sports performance: resveratrol + curcumin, resveratrol + OPC, resveratrol + quercetin

Aging: resveratrol + EGCG, resveratrol + vitamin K2

Osteoporosis: resveratrol + vitamin K2, resveratrol + vitamin D3

Acne: resveratrol + omega-3

Antiviral and antibacterial action: resveratrol + rosemary