Thread by @drkohilathas

Resveratrol

The anti-inflammatory; anti-cancer; anti-ageing; anti-diabetic; immunomodulatory; immune-enhancing; cardioprotective; neuroprotective; antiviral; and anti-prion compound found in red wine.

But there's a catch...

A THREAD 🧵

Resveratrol is a naturally occurring non-flavonoid polyphenol that is produced by several plants in response to injury. It naturally occurs in numerous foods, such as blueberries and peanuts, as well as grapes and their derived products like red wine.

Resveratrol was first isolated in 1939 from the roots of the white hellebore (Veratrum grandiflorum), a poisonous medicinal plant mainly found in China and Japan.

In traditional Chinese medicine, the dried roots and the part of the hellebore that runs underground horizontally are known as “li lu” and are indicated for jaundice, malaria, diarrhoea, and headache.

The highest concentrations of resveratrol are found in the Japanese knotweed, Polygonum japonicum, which is also used in traditional Chinese medicine in diverse tea products.

Resveratrol became popular within the scientific community after it was found to have radical-scavenging, antioxidant, and anti-cancer properties.

pubmed.ncbi.nlm.nih.gov/9395251/

It was thought that resveratrol may have a role to play in the so-called "French paradox," originally formulated in 1981 by French epidemiologists who observed a lower mortality incidence of coronary heart disease in France despite high levels of dietary sat fat and smoking.

But recent evidence suggests that the amount of resveratrol in red wine is so low that you’d have to consume 505–2762 litres of it to attain 1 g of it, the estimated therapeutic dose.

ncbi.nlm.nih.gov/pmc/articles/P…

Drinking that much outweigh any potential benefits!

Resveratrol protects against oxidative stress in numerous ways, including by reducing ROS generation, directly scavenging free radicals, improving our own natural antioxidant defences, helping to express genes involved in mitochondrial energy production, and inducing autophagy.

With regards to inflammation, resveratrol has been shown to regulate the pro- and anti-inflammatory cytokines mainly by upregulating SIRT1, suppressing NF-κB, as well as inhibiting NLRP3 inflammasome activation.

ncbi.nlm.nih.gov/pmc/articles/P…

NLRP3 is a component of the immune system that detects damaged parts of cells and triggers immune inflammation as a result. Mutations in the NLRP3 gene are associated with a number of organ-specific autoimmune diseases.

ncbi.nlm.nih.gov/pmc/articles/P…

Focusing on the cardiovascular system, resveratrol has shown to aid with endothelial health; reduce vessel thickness inflammation, fibrosis, and oxidative stress in aged mice.

pubmed.ncbi.nlm.nih.gov/29951747/

Resveratrol has also shown antithrombotic effects via decreasing the tissue factors like TNF-α; be able to reduce the ‘rusting’ of red blood cells; and mitigate toxin-related heart reshaping and dysfunctions in pumping.

ncbi.nlm.nih.gov/pmc/articles/P…

Neurologically, resveratrol has been shown to inhibit the aggregation of amyloid β and remove prion accumulation.

pubmed.ncbi.nlm.nih.gov/26440667/

Resveratrol has also been shown in animal studies to improve learning, memory, and mood functions via increasing the growth of brain cells and the blood vessel network in the brain.

pubmed.ncbi.nlm.nih.gov/25627672/

Animal studies have also reported that resveratrol reversed an age-dependent decline in cognitive functions through enhancing the secretion of neurotransmitters, including serotonin, noradrenaline, and dopamine.

ncbi.nlm.nih.gov/pmc/articles/P…

Many studies have also shown resveratrol to be effective in the prevention and treatment of cancers.

These have all been in vitro and in vivo studies, however.

ncbi.nlm.nih.gov/pmc/articles/P…

Resveratrol has exerted immunomodulating effects in various studies.

In one study, resveratrol upregulated immune responses, reduced the death of immune cells, and improved the growth of young chickens receiving conventional vaccinations.

pubmed.ncbi.nlm.nih.gov/25061707/

The polyphenol has also shown to reduced the activity of respiratory syncytial virus; reduce the virus-induced elevated IL-6 and TNF-α secretion; enhance immune activity in immunosuppressive mice; and reverse the imbalanced Th17/Treg.

pubmed.ncbi.nlm.nih.gov/31102993/

For these reasons and more, resveratrol has been put forward as a potential therapeutic against SARS-CoV-2.

pubmed.ncbi.nlm.nih.gov/32985211/

But in a very small study of those with mild COVID-19, the use of resveratrol did not show a significant benefit compared to controls.

nature.com/articles/s4159…

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With regards to fertility, resveratrol has shown some promise in improving ovarian function as well as having a positive effect on sperm motility.

ncbi.nlm.nih.gov/pmc/articles/P…

ncbi.nlm.nih.gov/pmc/articles/P…

However, while resveratrol has been advanced as a potential fertility drug, it has also been shown to negatively interfere with the process of embryo implantation.

pubmed.ncbi.nlm.nih.gov/30894514/

Furthermore, it is structurally similar to various forms of oestrogen and modulates oestrogen-response systems, which has led to it being classified as a phytoestrogen.

ncbi.nlm.nih.gov/pmc/articles/P…

Resveratrol is popular in the anti-aging scientific community as it is the most potent natural compound activator of sirtuin 1.

ncbi.nlm.nih.gov/pmc/articles/P…

Sirt1 expression is thought a protective mechanism against disease-related conditions and is involved in cog function, and mitochondrial biogenesis.

frontiersin.org/articles/10.33…

But though promising on paper, human trials using resveratrol are limited and have shown mixed results.

In 23 healthy overweight older adults who took 200 mg/day, resveratrol was shown enhanced memory performance accompanied with improved glucose metabolism and improved functional connectivity in areas of the brain related to memory formation.

ncbi.nlm.nih.gov/pmc/articles/P…

In another study, where participants took 350 mg of resveratrol-enriched grape extract for 6 months, those who supplemented it showed improvements in cholesterol quality.

pubmed.ncbi.nlm.nih.gov/22648627/

Plus, resveratrol prevented bone density loss (500 mg/day for 6 months) in type-2 diabetic patients in another study.

ncbi.nlm.nih.gov/pmc/articles/P…

But not all studies have shown effectiveness and have, in fact, shown various negative effects.

For instance, resveratrol intake (250 mg/day for 8 weeks) did not increase SIRT1 nor improve many cardiovascular risk factors in healthy aged men.

And supplementation actually reduced the positive effect of exercise training on blood pressure, blood cholesterol, and maximal oxygen uptake and did not affect the reduction of atherosclerosis.

ncbi.nlm.nih.gov/pmc/articles/P…

Other studies have documented that resveratrol may also behave as a pro-oxidizing agent, increase DNA damage, and interact with several other drugs.

ncbi.nlm.nih.gov/pmc/articles/P…

Additionally, long-term intake of resveratrol may act as a thyroid disruptor and even induce cancer growth.

pubmed.ncbi.nlm.nih.gov/28668442/

The background health of the individual, when it is taken, the dose taken, and for how long all play a part in resveratrol’s risk and effectiveness.

It has been suggested that in lower doses, resveratrol acts as a potent antioxidant, while at higher doses, it acts as a pro-oxidant.

ncbi.nlm.nih.gov/pmc/articles/P…

This has also been described for melatonin, quercetin, and epigallocatechin.

pubmed.ncbi.nlm.nih.gov/11205889/
pubmed.ncbi.nlm.nih.gov/17583542/
pubmed.ncbi.nlm.nih.gov/17392095/

In a rat study, it was documented that resveratrol behaved as an antioxidant during the dark period and as a pro-oxidant during the light period, possibly reflecting the putative changing ratio between pro- and antioxidant activities in various organs during the 24-h cycle.

pubmed.ncbi.nlm.nih.gov/19695122/

In another study authors found that resveratrol improved insulin sensitivity in old mice fed standard diet, while did not improve insulin resistance status in old mice receiving high-protein diets.

pubmed.ncbi.nlm.nih.gov/23793060/

Healthy mice given resveratrol in fact exhibited increased inflammation, demonstrating that resveratrol seemed to be beneficial to malnourished states of physiological ageing.

pubmed.ncbi.nlm.nih.gov/23793060/

The lower end of supplementation in those who are otherwise unhealthy is 5–10 mg daily, while dosages between 150–445 mg have been used in those who are otherwise healthy.

examine.com/supplements/re…

Doses greater than 1000 mg per day may increase the likelihood of side-effects and drug interactions.

ncbi.nlm.nih.gov/pmc/articles/P…