Increases telomere length in human cells, indirectly activates the “longevity” sirtuin enzyme SIRT1.
What is resveratrol?
Resveratrol (molecular formula: C14H12O3, CAS number: 501-36-0, also known as 3,5,4′-trihydroxy-trans-stilbene) is a substance naturally found in common foods, such as wine, grapes and several types of berries in tiny amounts [1].
Resveratrol has been present in medicinal preparations such as darakchasava or manakka, for more than 2000 years [2], as well as the Polygonum cuspidatum herb, which has been used in Japanese and Chinese traditional medicine such as ko-jo-kon, that is used in the treatment of several cardiovascular diseases[3]. Resveratrol is also present in Veratrum formosanum, which has been traditionally used in east Asia to treat hypertension[4].
Levels of resveratrol in red wine were studied in 1992, and speculation arose that red wine could have cardio-protective properties due to the resveratrol content [10].
In 1997, resveratrol was shown to work as a chemo-preventive agent, after it was found to inhibit carcinogenesis at multiple stages in lab tests [11]. It has also been found to indirectly activate the “anti-ageing” sirtuin enzyme SIRT1[15].
Studies on humans found resveratrol to have cardio-protective benefits, as well as improved anti-inflammatory and glucose metabolism markers [9].
Resveratrol gained increased interest as a nutritional supplement in 2006 [5], after a study conducted by Harvard scientists (who discovered in 2003 that resveratrol increased cell survival and slowed ageing in yeast[27]) found that resveratrol produced changes associated with longer lifespan in middle-aged mice on a high-calorie diet, shifting their physiology towards that of mice on a standard diet[6]. Sections of the press reported this news in relation to wine, speculating that red wine could have health benefits, as resveratrol is present in small amounts in most red wines[7,1].
How does resveratrol work?
Resveratrol exerts a wide range of beneficial effects across species and disease models, but the exact mechanisms through which it functions is currently unclear [17]. Resveratrol has relatively low bioavailability, but still exerts high activity, a problem that has been referred to as the “Resveratrol Paradox”. This makes the identification of the specific mechanisms causing the effects exerted by resveratrol challenging, as well as identifying the correct or optimal dosage [9].
It has been theorised that resveratrol exerts its major effects on the intestinal tissue, affecting the rest of the body through secondary effects that are indispensable of the plasma levels reached by the compound [17].
Due to its chemical and physical features, resveratrol can either cross cell membranes passively, or interact with membrane receptors. Therefore, it may interact with extracellular and intracellular molecules.
For this reason, its mechanism of action at the cellular level may be triggered by either activating signalling pathways when binding to cell membrane receptors, activating intracellular mechanisms, or even developing its effects inside the nucleus [8].
It has been suggested that resveratrol recruits molecular mechanisms that act both globally in muscle fibres and specifically on the postsynaptic region of the neuromuscular junctions [12].
One study indicates that while resveratrol may not directly activate the “anti-ageing” sirtuin enzyme SIRT1, it directly activates the enzyme NMNAT1 and increases intracellular NAD+ levels, which likely influences downstream SIRT1 activity, as SIRT1 requires NAD+ [15].
The same study concludes that their results are consistent with resveratrol acting as a heterotropic allosteric modulator of NMNAD1, at an as yet unidentified site [15].
A lab study on human cells treated with resveratrol found that independent of SIRT1, resveratrol was able to rejuvenate inactive senescent cells [28]. Within hours, the older cells started to divide, and had longer telomeres (the “caps” on the chromosomes which shorten as we age), and demonstrated restored splicing factor expression (a class of genes that are progressively switched off as we age).
The cells treated with resveratrol not only looked younger, but started to behave more like young cells.
What are the benefits of resveratrol?
There have been at least 30 published clinical trials on humans reporting the effects of resveratrol on human health [9]. It is becoming evident that resveratrol exerts cardio-protective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function[9]. These effects have been observed using both high and low doses of resveratrol and both in healthy volunteers and medicated patients[9].
Resveratrol has been shown to indirectly activate the sirtuin enzyme SIRT1 and therefore is predicted to benefit diseases affected by abnormal metabolic control, inflammation, and cell cycle defects. [15,18,19]
Activation of SIRT1 by polyphenols such as resveratrol has beneficial effects on regulation of calorie restriction, oxidative stress, inflammation, adipogenesis, cellular senescence, autophagy, apoptosis, circadian rhythm, autoimmunity, skeletal muscle function, metabolism, mitochondria biogenesis and endothelial dysfunction [20].
Resveratrol has been shown to rejuvenate human cells, restoring splicing factor expression and increasing telomere length [28].
Resveratrol affects the nuclear factor κB (NF-κB) signaling pathway which regulates inflammation, immune response to infection, and cellular response to stimuli [29], and can inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway to regulate cell differentiation, growth, proliferation, and several other activities[30,31,32].
Resveratrol also inhibits cyclooxygenases (COX), which are responsible for the conversion of arachidonic acid into prostaglandins. The suppression of this pathway reduces inflammation [29].
In a human study on obese individuals who were administered 150 mg/day of resveratrol for 30 days, it induced similar metabolic changes as those achieved with calorie restriction, such as a reduction in sleeping and resting metabolic rate and an increase of AMPK, Sirt1, PGC-1α, and citrate synthase activity [34].
Resveratrol has also been shown to protect primary hepatocytes in culture against oxidative stress damage by increasing the activities of catalase, superoxide dismutase, glutathione peroxidase, NADPH quinone oxidoreductase, and glutathione-S-transferase. Furthermore, it increases the level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and induces its translocation to the nucleus. This factor can activate genes with antioxidant responsive elements (ARE) [35].
Resveratrol seems to act as a neuroprotective agent [36], has an antiallergenic effect[40], has beneficial effects on bone regeneration[39], and appears to protect against muscle and bone alterations after disuse, and seems to act as a physical exercise mimetic[37].
Resveratrol binds to calcium channels producing inhibition of thrombin [38]. This is beneficial for the cardiovascular system, due to its interference in the formation of blood clots.
In humans, a recent study reported an improvement of insulin sensitivity in plasma glucose in subjects with impaired glucose tolerance, after four weeks of daily resveratrol administration [41].
Optimum diet and exercise can protect neuromuscular junction synapses from the wear and tear of ageing [42], these synapses are essential for voluntary movement because they relay motor commands that flow from neurons in the spinal cord to muscles.
A study conducted on old mice treated with resveratrol for a year, found that resveratrol slowed ageing of neuromuscular junctions and muscle fibers [42].
A study on rats in 2012 found resveratrol to enhance exercise performance over not supplementing with resveratrol, whether training or not.
The study split rats into four groups; one with no exercise, one with no exercise and supplementing with resveratrol, one with exercise training and one with exercise training and supplementing with resveratrol.
The study found that exercise performance in the rats that didn’t do any exercise training was 25% better in the group that supplemented with resveratrol. In the groups that did exercise training, the group that supplemented with resveratrol resulted in a 20% increase in exercise performance [13].
A study on male rabbits in 2008 found that resveratrol increased blood testosterone concentration, and improved sperm quality [14].
While there are several published clinical trials on humans reporting a wide range of positive effects of resveratrol on human health [9], the complex ways in which it works are not fully understood yet[17]. Correct or optimal dosage hasn’t been established[9], and gut bacteria may be responsible for high inter-individual variability in resveratrol bioavailability[33].
Many of the studies quoted here are for reference only; until the results of studies on fish, yeast, worms, flies, mice, rats or rabbits are replicated in human studies or trials, similar results or benefits in humans can’t be expected.
Why PlantPills resveratrol?
We provide high purity, pharmaceutical grade, independently verified micronized trans-resveratrol, for sale in the UK with delivery worldwide, at fair and reasonable prices.
Resveratrol is naturally found co-existing in two chemical structures; trans-resveratrol and cis-resveratrol [43]. Trans-resveratrol is the molecule that is most stable and bioavailable, and is the version extensively studied and known to be beneficial[8]. Cis-resveratrol is unstable and worthless as a nutritional supplement.
Reducing the particle size of trans-resveratrol (known as micronizing), increases the surface area, and has shown to substantially increase the amount of trans-resveratrol to make it into the blood; roughly doubling peak plasma levels [44].
This is why PlantPills resveratrol is trans-resveratrol, and is micronized. In fact, PlantPills trans-resveratrol is micronized to have an average particle size of less than 1.5 microns (less than 0.0015mm), compared to a size of at least 50 micron (0.05mm) for standard resveratrol.
Nobody should consider taking any resveratrol supplement if the retailer can’t provide test results from a third party laboratory.
The test results should be from a reputable laboratory that isn’t associated with the manufacturer or the retailer, and should confirm that the product is at least 99% pure trans-resveratrol, and doesn’t contain any dangerous levels of heavy metals or micro-organisms.
Without third party testing, it’s completely unknown whether the product is what it claims to be, and whether it’s safe for human consumption. Unfortunately the market is rife with fake and low-grade resveratrol due to the high price.
Every batch of PlantPills micronized trans-resveratrol powder is independently verified to have a purity of at least 99%, with no dangerous levels of heavy metals or micro-organisms. The certifications for the current batch are viewable below. The current batch of our trans-resveratrol powder has a purity of 99.4%.
Pack sizes are 5 grams, 10 grams, 25 grams, 50 grams, 100 grams, 250 grams, 500 grams, 1 kilogram and 2 kilograms.
Different pack sizes are selectable in the basket.
PlantPills Trans-Resveratrol Certifications
Please see our independent third-party laboratory certification bellow.
