Nov 30, 20224 min read

Resveratrol: myths and reality

Resveratrol has been a buzz for several years now, propelled to publicity by David Sinclair PhD from Harvard University. There has been some controversy surrounding this compound. So let’s dig into some details.

In this article we are going to discuss following:

What is Resveratrol?
How Resveratrol works?
Resveratrol's benefits
Resveratrol's downsides
Potential side effects
Conclusion

1. What is Resveratrol?

Resveratrol is a natural compound that is found in plants. They produce chemicals to fight pathogens, such as bacteria and fungi. These chemicals called phytoalexins and they have very unique properties like antimicrobial and antioxidative. Resveratrol is found in grapes, raspberries, blueberries, cranberries, mulberries, peanuts, cocoa.

2. How does resveratrol work in our bodies?

Human cells have a system of enzymes called Sirtuins. They are found in cell nucleus (SIRT1, SIRT6, and SIRT7), mitochondria (SIRT3, SIRT4, and SIRT5), and cytoplasm (SIRT2, rarely SIRT1). Sirtuins play multitude of roles in our cells:

Controlling gene expression
Protecting DNA from damage
Regulate the cell cycle
Facilitating DNA repair
Controlling energy production by mitochondria

3. Resveratrol's benefits

Resveratrol is a potent SIRT1 activator and has beneficial effects on cardiovascular disease, metabolic disease, longevity, neuroprotective effects, and more.

Cardiovascular disease:

Resveratrol has been shown to protect the innermost layer of blood vessels from oxidative stress. As a result, it may slow down the onset of atherosclerosis.
Resveratrol has demonstrated ability to increase nitric oxide synthesis, which is a potent vasodilator. It relaxes smooth muscles inside the arterial walls, allowing them to carry more oxygen and nutrients throughout the body. Thus, decreasing risk of hypertension.
Resveratrol has shown to inhibit activation of platelets, which can prevent clot formations. This leads to decreased risk of infarct and stroke.

Metabolic disease:

Resveratrol may have tremendous effects in people suffering from metabolic diseases. It can improve insulin sensitivity, glucose tolerance, and lipid profile in people with high BMI. Also, resveratrol has been shown to lower fasting glucose and insulin concentrations, improve HbA1c, increase good cholesterol (HDL), and reduce bad cholesterol (LDL).

Longevity:

Resveratrol is widely known by its ability to increase longevity. It has shown to increase lifespan in worms, fruit flies, and vertebrate fish. Resveratrol also extends lifespan by 70% in yeast. However, in mice, resveratrol has only increased the lifespan on calorie-rich diet, averaging life expectancy equal to normally fed mice.

Neuroprotective effects:

Resveratrol has neuroprotective effects in various neuronal diseases, such as Alzheimer′s, Huntington′s and Parkinson′s diseases, ALS and others. Resveratrol improves mitochondrial functions and biogenesis through SIRT1/AMPK/PGC1α pathways, which protects cells from

deleterious effects of oxidative stress. Resveratrol decreases cholinergic neurotransmission, brain-derived neurotrophic factor expression, and oxidative stress, promotes β-amyloid peptides clearance and anti-amyloidogenic cleavage of APP, and reduces neuronal death.

4. Resveratrol's downsides

Dosing and action controversies:

Resveratrol has been identified for it’s numerous beneficial activities, but some studies have documented that it may behave as a pro-oxidizing agent.

One study revealed that resveratrol can produce different effects depending on its concentrations or treatment time. Low resveratrol doses (0.1–1.0 μg/mL) has been documented to enhance cell growth, whereas higher doses (10.0–100.0 μg/mL) induced cell death and decreased mitotic activity on human tumors and endothelial cells. In another study, exploring resveratrol effects on colon cancer cells, at low concentrations (1 and 10 μmol/L), resveratrol increased number of cells, while at higher doses (50 or 100 μmol/L) resveratrol reduced number of cells and increased percentage of cell death.

It was also documented that resveratrol behave as an antioxidant during dark span and as a pro-oxidant during light span of the day. This potentially explains alternating activity of pro- and anti-oxidant effects during 24-h cycle. Recently, Plauth et al. proposed that resveratrol generates oxidation products at non-toxic concentrations inside cells. Cells respond by activating protection mechanism, such as gene expression and transcription factor Nrf2, making it resistant to more stress.

5. Potential Side Effects

Resveratrol does not appear to have side effects at short-term and low doses (< 1.0 g/day). At doses of > 2.5 g/day, there is a potential for side effects, such as nausea, vomiting, diarrhea and liver dysfunction in patients with non-alcoholic fatty liver disease. However, no major side effects were stated in long-term clinical trials. In fact, resveratrol has been found to be safe and well-tolerated at up to 5 g/day, either as a single dose or as fraction of multiple-day dosing schedule. It is important to note that these studies were done in healthy populations, and that risk may vary in patients with chronic health conditions. It’s important to consult with healthcare professional before taking resveratrol.

In a study on atherosclerotic development in hypercholesterolemic rabbits, Wilson et al. supplemented rabbits with oral resveratrol (in doses of 1 mg/kg), and found that resveratrol treatment promoted atherosclerosis. Atherosclerotic lesions staining in control and resveratrol-treated groups revealed that resveratrol-treated rabbits had significantly more aortic surface area covered by atherosclerotic lesions. Therefore, resveratrol promoted atherosclerotic development, rather than protected against it.

Study by Crowell et al. aimed to analyze resveratrol nephrotoxicity effects, by giving oral resveratrol to rats at doses 0, 300, 1000, and 3000 mg/kg body weight for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg/kg/day. Following clinical signs of toxicity were present: reduced final body weights and food consumption; elevation of multiple blood biomarkers (BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts). Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, have been seen. However, at doses of 1000 mg/kg/day only reduced body weight gain (females only) and elevated white blood cell count (males only) were observed. In addition, there was no adverse effects at levels of 300 mg/kg/day. This data clearly indicates at dose depended nephrotoxicity and warrant further studies.

Resveratrol has been reported to both reduce cell growth and induce death in normal cells, when administered at high doses. Additionally, resveratrol consumption at modest doses result in a life span increase in 1-year old mice. However, when mice consumed larger resveratrol doses (1800 mg/kg), animals were shown to die within 3–4 months.

5. Conclusion

Resveratrol has a lot of potential benefits but we have to carefully select the dose. At this time, it appears that resveratrol is safer at low doses. It is always prudent to discuss use of any dietary supplement with your doctor, as it could cause more harm in people with chronic health conditions.

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