Resveratrol is not an "antioxidant"
Resveratrol is a well-known anti-ageing plant molecule, contained in grapes, berries and red wine, among other foods. Resveratrol works by increasing a protein called SIRT1, which improves lifespan and overall health and fights fat accumulation. But most importantly, resveratrol was thought to work as an "antioxidant".
However, this new study published this week shows that resveratrol does not act as an antioxidant. Instead it acts in quite the opposite way, as a pro-oxidant. The researchers have found that by being slightly poor-oxidant, resveratrol stimulates the body to boost it's antioxidant defences and produce more glutathione, one of the body's own powerful antioxidants.
Resveratrol is "hormetic"
Resveratrol achieves this effect by stimulating a protein called Nrf2, which is known to stimulate the body's own antioxidant defences. In fact, more and more papers, published the last few months, show that previously thought antioxidant molecules actually act as pro oxidants, by stimulating the same process, mediated by the protein Nrf2. nudge
The process by which a little bit of negative stimulation leads to positive changes in the body is called hormesis, a Greek work which means "gaining momentum". So by getting a bit of negative stimulation (mild free radical damage) that body is gently nudged, it gains momentum, to get much more efficient in fighting free radical damage.
- Paper: Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress.
- Abstract: Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general <50µM), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61mVmmol GSH per g protein. After induction of oxidative stress by using 0.78% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress.