https://pmc.ncbi.nlm.nih.gov/articles/PMC9414442/
Resveratrol is a very promising natural molecule with enormous therapeutic potential.
Resveratrol has long been proposed as being beneficial to human health in a number of ways that can affect a wide array of symptoms and conditions yet at this time there is currently no conclusive clinical evidence to strongly support its direct use for any specific medical disorder.
Over the last 20 plus years there have been over 200 studies evaluating resveratrol for many clinical indications, including cancer, diabetes, metabolic syndrome, and cardiovascular disease. Still, there is no consensus on any treatment regimens for the practical application of resveratrol in the clinic . Research into Resveratrol has shown that it reduces inflammatory markers and improves aspects of a dysregulated metabolism. These properties and others have given researchers more and more evidence suggesting that resveratrol should be able to benefit many conditions, but more large, high-quality clinical trials are required to transition this substance from a research compound into the clinic. Although elucidating the properties of Resveratrol has been pursued in research for a wide array of clinical indications, the majority of research has been at the preclinical level in simple cellular and animal models. In the laboratory, resveratrol has been reported to exert cardioprotective, neuroprotective, antitumour, antidiabetic, antibacterial, and anti-ageing effects; common to some of these effects is an ability to modulate glucose metabolism, oxidative stress, cell death, and inflammation. However, to ascertain the potential value of resveratrol as a supplement for humans, clinical studies, and ultimately randomised controlled trials (RCTs), are essential to provide critical evidence that may justify its recommendation.
A review of the numerous studies done to obtain data was conducted accessing published studies available online across Medline, and clinicaltrials.gov.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/
Cancer is one of the main greatest causes of mortality worldwide. There have been over 13,000 publications featuring resveratrol (RSV) in the title since Jang et al. that demonstrated its potential cancer preventive effects in 1997 [1]. Research suggests that resveratrol can prevent the events linked to the initiation of tumors. It acts to prevent free radical formation. The antioxidant properties of resveratrol have been well documented. [75,76]. Resveratrol is an excellent scavenger of hydroxyls and superoxides as well as the radicals induced by metals/enzymes and generated by cells [77]. It also protects against lipid peroxidation within cell membranes and damage to DNA that can result from reactive oxygen species (ROS) [78]. Furthermore, resveratrol can function as an antimutagen[79], yet another way in which it could conceivably be helpful in cancer prevention. Resveratrol has been shown in preclinical studies to protect against cancer treatment-induced cardiovascular toxicity. It has also been reported to possess significant anticancer properties on its own, and thus enhance the efficacy of other cancer treatments. Thus, they hold significant promise to protect the cardiovascular system and fight cancer at the same time [106]. Resveratrol as a Cardioprotective Agent
Resveratrol has been demonstrated to have anti-inflammatory effects which could be cardiovascular preventative. By downregulating a wide range of inflammatory factors, RES strongly improved coronary injuries from inflammation in research models. Based on this effect, RES may be of benefit in diabetics with coronary heart disease [105].
One early suggestion that RSV might impact human health emanated from what became known as the ‘French paradox.’ This was the 1992 observation by Renaud and de Lorgeril that people in France experienced a relatively low incidence of coronary heart disease despite consuming a diet rich in saturated fats [140], and had a higher wine intake than in the US. It was felt that the wine intake of people in France might explain this finding and that RSV (resveratrol) , the antioxidant constituent of red wine, might account for this beneficial effect[141]. As far as the thought that red wine might be beneficial if used in moderation, it was an idea published many times over the years. However further research into alcohol intake has turned against this idea. The consensus on the most recent research seems to be that no amount of wine (or any alcohol) is beneficial to health. https://drsobo.com/any-alcohol-is-harmful-to-health/ . A recent news report was published asking the question”Is red wine good for your heart? https://apple.news/AZxbVXsAYReOAuGgfr2ZyZA The authors of the news item got a cardiologist to weigh in, a cardiovascular surgeon Jeremy London from Savannah, Georgia, who had a clear and strong opinion about it., “In a nutshell, red wine is not good for your heart,” he says, “The amount of red wine you would have to drink to get any benefit from resveratrol would be excessive.” He continued, “Resveratrol is found in the skins of grapes and in certain other plants, fruits and seeds.It is being studied in the prevention of cancer and heart disease. It is a type of antioxidant and a type of polyphenol.”
Red wine contains resveratrol he explains and it “has been shown that this can cause dilation of blood vessels, make platelets slippery so that you don’t get the blockages in the arteries, but this has never really been proven in humans.”
Resveratrol in Wound Healing
Numerous studies have suggested that resveratrol helps wound healing [87,90,91]. Inflammation, proliferation, maturation, and remodelling are the four phases which rebuild tissue integrity after injury. The proliferation phase, starting within a few days after injury, involves healing processes such as angiogenesis, granulation tissue formation, collagen deposition, and epithelialization [86]. Resveratrol seems to be a promising treatment as it interacts with the healing cascade at multiple levels as shown in published studies – [87,88,89].
Resveratrol-induced vascular endothelial growth factor (VEGF) regulates tissue regeneration and revascularization in wounds. It can inhibit the expression of the pro-inflammatory substance tumor necrosis factor-α (TNF-α), [92,93,94]. VEGF has other properties as well that promote wound healing such as increased cell migration, collagen deposition, capillary growth, and epithelialization [93]. In resveratrol-treated patients the inflammatory markers TNF-α, IL-1β, IL-6, MMP-2, -3, -9, and C-reactive protein (CRP) were shown in the lab studies to be reduced
[97,98,99,100]. Resveratrol has also a significant impact on the regulation of inflammation and consequently in processes of skin repair [101]. In vivo studies reported a significant improvement in wound healing properties [104].
Diabetes and the metabolic syndrome
The most common clinical application studied is in the management of type 2 diabetes mellitus, and glucose control, followed by cardiovascular disease (21). Considerable preclinical research has focused on the metabolic effects of RSV and this has led to a total of 39 investigations across a spectrum of cardio-metabolic disease, metabolic syndrome, NAFLD, and obesity.
Resveratrol For Fighting Infections
Resveratrol has been reported to affect many viruses like influenza A and Epstein Barr viruses by altering cellular pathways influencing viral replication itself. De Leo examined the antiviral activity of RES against the EBV replicative cycle. [109]
They found that RES inhibited EBV lytic gene expression and the production of viral particles in a dose-dependent manner. The molecular mechanisms involved can be divided into three actions: (1) inhibition of protein synthesis, (2) decrement of ROS levels, and (3) fast suppression of NF–kB and AP-1 activities, augmented by EBV-lytic cycle reactivation With this work, De Leo constructed the basis for evaluating the antiviral activity of RES against EBV infection, envisaging the possibility to extend it to other types of infections. [109].
Shevelev and colleagues have compared the antimicrobial activity of resveratrol , dihydroquercetin, and dihydromyricetin (two flavonols) extracted from the bark and wood of conifers against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. This study suggests high bactericidal activity of polyphenols like resveratrol [111]. It has been shown that RES can block the critical pathways involved in SARS-CoV-2 pathogenesis, and body immune activation, and downregulation of pro-inflammatory cytokine release. [112,113].
RES also blocked MERS-CoV replication in vitro by inhibiting RNA synthesis, and it inhibited viral replication and reduced the death risk in piglets infected with the duck enteritis virus [114]. Currently there is no evidence that RES has been used to treat SARS-CoV-2; however, available studies may envisage that it could be a strategic adjunctive antiviral agent to use in synergy with others.
Other potential uses
Resveratrol showed a protective role in preclinical models of osteoarthritis and rheumatoid arthritis by reducing the production of pro-inflammatory and pro-degradative soluble factors, and through modulation of cellular and humoral responses [81].
The general anti-inflammatory and antioxidant effects of RSV in humans has been studied, and its potential has led to trials for conditions such as ulcerative colitis and arthritis-related diseases. Ten studies have addressed the effects of RSV on cognitive function, and three have explored its ability to modulate biomarkers of Alzheimer’s disease, including one of the most promising larger-scale trials conducted to date in patients with mild to moderate dementia [109,110].
35% of all RSV studies recruited healthy volunteers. The near-even split between healthy individuals and patients with a diagnosed pathology reflects a focus on health maintenance and prevention, as well as using RSV as a potential treatment. [144,145,146,147,148]. Its potential has not been able to be clearly demonstrated due in part to its poor bioavailability when ingested orally. To overcome the issue of poor bioavailability it has been shown that encapsulating resveratrol into nanocarriers drastically can improve absorption compared to that with standard supplements.
RSV has been investigated in adults of all ages including elderly populations over 70 years old. https://pmc.ncbi.nlm.nih.gov/articles/PMC6317057/
One of the limitations associated with the existing clinical data is that the most have been relatively small. Few trials have involved over 100 people and most trials were of short duration. Six trials involved participants consuming RSV for 12 months [8,11,89,98,108,109] .Thus, RSV must still be considered at an early stage of development in showing any clinical efficacy. In general, studies have shown that RSV is well-tolerated at once-daily doses of ≤1 g, and one of the longest published trials in elderly Alzheimer’s patients has demonstrated an excellent safety profile in doses of up to 1 g taken twice daily for one year [109]. Side effects associated with RSV use were not serious, the most common being constipation or diarrhea,abdominal cramps, vomiting, heartburn, and bloating.
