There might not be a more controversial ingredient on the market than resveratrol. It’s been hyped about for years due to early research in animals and test-tubes suggesting it extends lifespan and attenuates many of the aging processes.
In particular, this early research suggested resveratrol acted on sirtuins and several other molecular targets to reduce oxidative stress and inflammation, promote DNA repair and autophagy, and stimulate mitochondrial biogenesis — all of which lead to improved metabolic health and extended lifespan .
Of course, at the time, there weren’t any human clinical trials around to support such effects, so its purported benefits were met with resistance from many evidence-based circles. That’s really a downside of giving something a lot of hype, often more than it needs or warrants — there will be many who throw the baby out with the bathwater.
I’ll be the first to tell you that resveratrol isn’t a panacea, and there is certainly a lot of hyperbolic language surrounding this molecule. But I’ll also be the first to tell you that, despite all the nonsense surrounding resveratrol, it still has remarkable benefits as a supplement for supporting mitochondrial function, and that’s why we’ve made it one of the ingredients in our mitochondrial energy formula, Energenesis.
For Mitochondria, More Isn’t Better
One of the big issues surrounding resveratrol is dose and bioavailability. Many of the molecular mechanisms and observed outcomes in animals require high resveratrol concentrations that simply aren’t feasible to obtain in humans unless you inject the stuff directly into your bloodstream .
At the same time, high doses aren’t always ideal. For almost every outcome that resveratrol has been tested for, there’s a hormetic relationship where too little has no effect and too much is either useless or harmful .
Thankfully, when it comes to mitochondrial function, more isn’t better and we can actually reap most of resveratrol’s benefits with pretty low doses. This was made clear in 2017 when Yuki Mizuguchi published a study where he and his colleagues from the Japanese National Center of Neurology and Psychiatry took cells from patients with genetic mitochondrial disorders and incubated them in different doses of resveratrol .
The researchers found a clear hormetic effect whereby the lowest tested dose slightly benefited cell growth and survivability, with the effect disappearing as the dose increased and ultimately entered into a toxic range where cell growth was strongly inhibited.
To help explain this cell growth benefit, the researchers then looked to the mitochondria of these cells and some healthy cells that served as controls in their experiment. Expectedly, the mitochondrial mutations reduced energy production by 50–85% compared to healthy mitochondria. Yet, in both the healthy and mutated mitochondria, low-dose resveratrol increased energy production by 40–100%!
In short, you don’t need a lot of resveratrol to experience a mitochondrial benefit, and this makes reaping the benefits of resveratrol both realistic and fairly easy. For example, just one month of supplementing with 150 mg/d of resveratrol leads to significant increases in the activation of several mitochondrial regulators, including AMPK, SIRT1, and PGC-1α, while also increasing the ability of mitochondria to oxidize fat as an energy source .
Increases in SIRT1 and AMPK were also seen in adults with type 2 diabetes after supplementing with 3000 mg/d of resveratrol for 12 weeks, which coincided with an 8% increase in energy expenditure, likely from the increase in mitochondrial function .
Lastly, it’s worth mentioning that resveratrol supplementation increases mitochondrial adaptations to exercise [7,8]. In elderly adults undergoing 12 weeks of resistance and endurance training, supplementing with 500 mg/d of resveratrol was superior to a placebo for improving aerobic fitness, muscular strength, size, and fatigue resistance, and mitochondrial density of skeletal muscle .
Resveratrol Improves Cardiometabolic Health
Both through improving mitochondrial function and reducing oxidative stress and inflammation, resveratrol also benefits numerous parameters of cardiometabolic health, such as glycemic control and blood lipids.
This was made clear in a meta-analysis of 17 randomized controlled trials, which found improvements in insulin sensitivity, fasting glucose, LDL-C, and HDL-C in those with metabolic syndrome after supplementing with an average of just 250 mg/d of resveratrol for an average of just two months .
Other individual studies have confirmed these benefits in those with several different types of metabolic dysfunction:
- In adults with type 2 diabetes, supplementing with 10–2000 mg/d of resveratrol improved insulin sensitivity, blood lipids, and antioxidant capacity while reducing blood glucose, HbA1c, and oxidative stress after 4–8 weeks [10–14]. While even just the 10 mg/d dose led to benefits , the effects were most pronounced in those taking 500–1000 mg/d [12–14], with no significant benefit from increasing further to 2000 mg/d .
- In adults with type 1 diabetes, supplementing with 500 mg/d of resveratrol lowered fasting glucose, HbA1c, and oxidative stress after two months .
- In adults with non-alcoholic fatty liver disease, supplementing with 300–500 mg/d of resveratrol reduced the extent of liver damage, fasting glucose and insulin resistance, blood lipids, and markers of inflammation after three months [16–18].
- In adults at a high risk of developing cardiovascular diseases and taking a statin preventively, supplementing with a resveratrol-enriched grape extract significantly reduced blood lipids, oxidized LDL, and several markers of inflammation after 6–12 months [19,20].
- In adults with heart disease, supplementing with just 10 mg/d of resveratrol improved heart and endothelial function after three months .
- In overweight and obese adults, supplementing with 75–400 mg/d of resveratrol improved endothelial function and reduced endothelial inflammation [22–24].
Basically, if you are someone who is trying to overcome metabolic dysfunction and improve your health, then it’s likely that resveratrol will help after a couple months of consistent supplementation.
Resveratrol Fights Neurodegeneration
Another area of research where resveratrol shows promise is in slowing age-related declines in cognitive function and the development of neurodegenerative disorders like Alzheimer’s disease.
Brain cells are highly susceptible to oxidative stress and mitochondrial dysfunction due to their high energy requirements, and several lines of evidence have shown that resveratrol protects neurons and other brain cells from both by increasing energy production, mitochondrial membrane integrity, and antioxidant status .
For example, in healthy older adults, just 200 mg/d of resveratrol increased functional connectivity of the hippocampus — a key brain region involved in memory — and improved memory scores on cognitive tests after six months . Similarly, 150 mg/d of resveratrol increased cognitive performance, particularly on memory tests, after 14 weeks of supplementation in healthy postmenopausal women .
The benefits are apparent in those with Alzheimer’s disease as well. The longest and largest study to date had over 100 adults with Alzheimer’s supplement with 500–2000 mg/d of resveratrol over the course of year [28,29]. The researchers found that resveratrol attenuated disease progression, preserved blood-brain barrier integrity, and reduced neuroinflammation compared to a placebo.
Resveratrol is a molecule whose claim to fame began with studies showing it could help extend lifespan in animals. While such data doesn’t exist in humans, clinical research has shown that it improves mitochondrial function, metabolic health, and brain health.
The science overwhelmingly shows that resveratrol is a powerful mitochondrial nutrient that can fight fatigue, memory loss, and metabolic dysfunction. That’s why we’ve made it one of the cornerstone ingredients in our mitochondrial energy formula, Energenesis.
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