Resveratrol is one of the most studied natural polyphenol compounds and is found in the skins and seeds of red and purple grapes, berries, peanuts, and pistachios.
When plants face constant environmental stress, such as from fungus, drought, ultraviolet radiation, and insect infestation, their intrinsic defence mechanism is to produce polyphenols.
Resveratrol was isolated by a Japanese scientist in 1939 from the roots of the white hellebore plant. It gained attention in 1992 when researchers suggested that this component found in red wine had cardioprotective qualities that might explain the “French paradox,” the observation that the French drink a lot of red wine and have low rates of heart disease despite a high-fat diet.
Since then, resveratrol has been studied more broadly and has shown tremendous protective potential at the cellular level.
“The in vitro and in vivo studies point to the exact mechanisms of how it works in terms of being cardioprotective, cancer preventative, cancer therapeutic, neuroprotective, helpful in people who are obese, [helpful for] glucose metabolism, anti-inflammatory, and an antioxidant,” Dr. Nathan Goodyear, a medical doctor and integrative cancer expert, told sources.
Longevity and Disease PreventionResearch has shown that calorie restriction can delay or prevent many age-related diseases and extend lifespan, and resveratrol can mimic the action of calorie restriction.
Although calorie restriction has many benefits, including increased insulin sensitivity and improved overall metabolic health, most people don’t want to spend the day counting calories or fasting.
Resveratrol mimics calorie restriction by activating signalling proteins called sirtuins, which can regulate inflammation, repair DNA, promote insulin sensitivity, and help form neurons in the brain. These proteins are also associated with healthy ageing and longevity.
“The sirtuin system is a complex regulatory process involving seven sirtuin genes expressed in multiple tissues,” registered dietician and nutritionist Kelsey Costa told sources by email.
Silent information regulator 1 (SIRT1) is one of the seven sirtuin genes activated by resveratrol. It promotes longevity through metabolic processes such as insulin release, lipid mobilisation, and a healthy stress response. A review published in the Annals of the New York Academy of Sciences found that people who had fasted for one week had a twofold increase in the SIRT1 gene in their fat cells.
The review also mentioned studies involving resveratrol and the activation of SIRT1 that showed a 70 percent increase in yeast lifespan, life-extending potential in worms and flies, and an increase in the survival of obese middle-aged mice.
“SIRT1 is abundant in the blood vessel system, plays a crucial role in creating and growing new blood vessels, and is significantly stimulated by resveratrol,” Ms. Costa said. “Ultimately, sirtuin genes create proteins that affect heart-related functions like growing new blood vessels, decreasing hypertension, and preventing atherosclerosis, which provides a plausible explanation for resveratrol’s diverse health benefits.”
Cardiovascular BenefitsCardiovascular disease is primarily the result of a chronic, low-grade inflammatory condition that can cause atherosclerosis, high blood pressure, heart attacks, and heart failure.
A 2022 systematic review and meta-analysis of six randomised controlled studies concluded that “resveratrol can be used as a potential treatment in patients with [cardiovascular disease] by reducing inflammatory conditions.” It is also a potent vasodilator that releases nitric oxide and lowers blood pressure.
According to Ms. Costa, “resveratrol decreases the serum concentrations of pro-inflammatory cytokines, which are critical compounds involved in the body’s inflammatory response, suggesting resveratrol may be beneficial as an adjuvant therapy for chronic inflammation and cardiovascular disease.”
Most studies have been performed in the lab or on animals and show the positive effects of resveratrol on the heart, prompting several randomised controlled trials in humans over the past decade to determine if the same benefits apply to both healthy and chronically ill humans. The results in humans have been variable, possibly due to inconsistent protocols and doses of resveratrol. Yet many studies have shown positive effects on coronary artery disease, including decreased arterial stiffness, hypertension, inflammation, and cholesterol.
Dr. Goodyear believes resveratrol can also protect the heart from certain types of chemotherapy that may damage it. “Although we primarily use natural and holistic treatments for cancer, we will use some conventional therapies, including chemotherapy,” he said. “If we ever use a low-dose form of chemotherapy with a potential impact on the heart or kidneys, resveratrol can be added in to protect these patients.”
May Regulate the Gut MicrobiomeThe gut microbiome, a community of trillions of microorganisms living in the digestive tract, is believed by many to be the most critical factor in overall health. It consists of bacteria, viruses, fungi, and other microbes; when they live in harmony in the gut, all body systems work harmoniously. But when those microorganisms are unhealthy and unbalanced, it can lead to several acute and chronic illnesses, including gastrointestinal problems, obesity, type 2 diabetes, cancer, and autoimmune diseases.
Recent research suggests that resveratrol’s antioxidant, anti-inflammatory, and other beneficial properties can help regulate the microbiome and protect the intestinal tract from inflammation and impending disease. While researchers are still investigating resveratrol and its role in regulating overall health through the gut microbiome, they believe it can protect the intestines by strengthening the tight junctions of the intestinal wall. A strong intestinal barrier helps with nutrient absorption and prevents a “leaky gut,” which allows bacteria, toxins, and undigested food particles to pass through and enter the bloodstream.
Resveratrol’s antioxidant and anti-inflammatory properties can also prevent pathogenic bacteria and fungi from growing inside the intestine and increase immune cells to ward off possible diseases further, including many types of cancer.
May Suppress Cancer CellsIn 1997, researchers found that resveratrol prevented cancer cell growth on the skin of mice. Since then, an overwhelming number of studies have focused on resveratrol’s anti-cancer properties.
Resveratrol affects cancer at different stages, from initiation to progression, through various signalling pathways regulating cell growth, cell destruction, inflammation, metastasis, and the development of new blood vessels. An interesting aspect of resveratrol is that it can protect normal cells while causing cancer cell death. Researchers have also found that lower concentrations of resveratrol can increase the expression of cell survival proteins, while higher concentrations stimulate cancer cell death.
A 2015 study suggests that resveratrol may inhibit the growth of gastric cancer cells and induce the programmed death of potentially cancerous cells. Human gastric cancer cells were injected into mice, and resveratrol was injected near the tumour cells, significantly inhibiting their growth. The researchers suggested that even though resveratrol’s bioavailability is low in humans and it’s quickly processed and excreted by the body, it has metabolites, or byproducts, that may continue to have beneficial effects.
Another study found that resveratrol may help treat actinic keratosis—rough, scaly patches of skin that are potentially cancerous.
Studies have shown that resveratrol can target the p53-mediated pathway to induce apoptosis, inhibiting the growth of colorectal cancer cells. The tumour suppressor p53 is a crucial protein involved in DNA repair and apoptosis (cancer cell death). Even in tumor-suppressor p53 mutations where cancers don’t respond well to chemotherapy, resveratrol treatment was found to stop cell growth in cervical cancer. It was also shown to inhibit prostate cancer cell growth and induce apoptosis by inhibiting a major protein signalling pathway.
Clinical trials involving resveratrol and other cancers, including colon and liver cancers, are ongoing and continue to have encouraging results.
Resveratrol may also be chemoprotective, meaning that it may protect healthy cells from damage during chemotherapy treatment.
In lab studies, resveratrol demonstrates several mechanisms that induce programmed cell death in several cancer lines and shows clear anti-cancer effects. Since natural resveratrol has clear drawbacks because of its limited bioavailability, there is interest in the development of resveratrol derivatives.
Dr. Goodyear told sources that despite the limited studies, there are advances in solving resveratrol’s problems with administration and bioavailability. Still, more studies are needed that look specifically at women with breast cancer, men with prostate cancer, people with cardiovascular disease, or those who have had a stroke.
“The problem with that is that it takes time and money,” he said. “Most people who have a lot of interest in these natural therapies unfortunately don’t have the money to put into the large clinical trials we need to solve the limitations.”
May Protect Against Alzheimer’s and Parkinson’sUnlike other antioxidants, resveratrol has the unique ability to cross the blood-brain barrier. Studies are ongoing, and researchers believe there is tremendous potential for resveratrol to become a viable therapy for Alzheimer’s disease and Parkinson’s disease through its antioxidant and anti-inflammatory actions.
Five of the primary causes of Alzheimer’s disease progression have shown potential for control with targeted resveratrol treatment. These include protein misfolding, cellular metabolism, inflammation, mitochondrial dysfunction, and telomere shortening.
