Research updates on resveratrol.
As if wine lovers needed another reason to uncork, the French paradox supplied ample inspiration for toasts when scientists first elucidated it in the late 1980s. But the seemingly contradictory observation that heart disease rates remain low in France despite the relatively high-fat diet-and the theory that the resveratrol in red wine might be responsible-was so compelling that even teetotalers began eyeing Cabs and Pinots in a longing new light.
But that was several decades ago, and these days a mention of resveratrol is as likely to raise consumers’ eyebrows as it is their wineglasses. Among the scientific community, however, resveratrol retains its mojo, as active inquiry into the benefits of the compound-a phenolic antioxidant produced naturally in more than 70 species of plants, including pine trees, peanuts, cocoa, blueberries, raspberries, and, yes, wine grapes-continues.
Notes Gene Adamski, national sales manager, Evolva (Reinach, Switzerland), “Any widely used ingredient like resveratrol tends to have its ups and downs in the nutritional marketplace over time.” That said, “I do feel resveratrol is mounting a comeback based on its proven benefits in the antiaging, women’s health, cardiovascular, skin, bone, and especially cognitive health categories,” he says. “Resveratrol science continues to grow with positive results. And our industry is starting to recognize the benefits again.”
It was the purported link with heart health, as evidence by the French paradox, that first put resveratrol on the public’s radar. But, says Dan Lifton, president, proprietary branded ingredients group, Maypro (Purchase, NY), the French paradox may, in fact, have done resveratrol supplementation little favor.
“The only thing we’d been hearing for years now is how we get resveratrol from wine, so if we drink red wine, we’re set,” Lifton observes. As a consequence, he says, “The value proposition for resveratrol supplementation got lost in the smoke of the ‘just drink wine to get your resveratrol’ message, which was incorrect.” After all, you’d have to toss back 41 glasses of red wine to get the 20 mg of resveratrol found in a typical supplement, Lifton notes.
On the other, says Shaheen Majeed, president, Sabinsa Worldwide (East Windsor, NJ), the science itself is partially responsible for resveratrol’s dimmed limelight. “Most of the previous findings were based on cell cultures or laboratory animal experiments,” he says, “with very few human studies demonstrating long-term benefits.” But with the latest research “trying to fill these gaps with well-planned human studies,” he says, “resveratrol is ready to bounce back.”
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Active Areas of Inquiry
And, oh, what studies there are. Hugh Welsh, president, general counsel and secretary, DSM North America (Parsippany, NJ), did a quick PubMed search on December 13, 2017, and netted over 10,000, “with more than 120 clinical trials and the total number of publications increasing year over year,” he says.
And the clinical trials on resveratrol increasingly target a variety of challenging “therapeutic indications,” Majeed adds, with respiratory infections, obesity, osteoarthritis, hepatitis, type 2 diabetes, cancer, and cardiovascular disorders among them.
But for many resveratrol watchers, the compound’s real potential lies in its relationship to health-what Adamski calls “the most relevant area of activity.” With the population aging, Adamski says, “there remains an unprecedented need for safe dietary interventions to help support and preserve optimal cognitive function.” Resveratrol, it appears, might help.
Get the Backstory
Precisely how resveratrol effects its antiaging benefits “is yet to be understood clearly,” Majeed concedes. One possibility: “Cognitive performance is a matter of flow and preservation,” Adamski explains, “and research shows resveratrol to be effective in supporting many key neurological functions in an aging population.” It may do so via its influence on mitochondria, the functioning of which diminishes with age and compromises our bodies’ systems as a result. In research that Adamski calls “well received,” resveratrol has been shown “to penetrate cells and help rejuvenate the mitochondria, thus supporting healthier aging.”
Majeed adds that some studies have shown that in certain species of yeast, roundworms, and fruit flies, as well as in human cell cultures, resveratrol appears to turn on genes that make sirtuins, which are “ancient proteins found in virtually all species.” The genes controlling situins’ expression may confer a survival advantage upon organisms during especially stressful times. “Hence,” Majeed says, “activating sirtuins is thought to give rise to a response that fights disease and prolongs life. However, extensive research is still needed to understand its mechanism better.”
The Best is Yet to Come
“We’re certainly optimistic about resveratrol’s future,” Majeed says. “It’s exciting as well as logical to unearth the exact mechanisms of action of such a life-extending molecule that is believed to modulate genes that are involved in longevity. This would provide new possibilities for understanding the process of aging in humans.”
Once we do that, perhaps the industry can rejuvenate resveratrol’s own life as a popular dietary supplement. And we might start, Lifton says, by emphasizing the case that red wine isn’t going to do the trick-“that we need supplementation if we want the associated health benefits,” he says. “Once this message is delivered effectively, then we can move on to which forms are superior." In the meantime, take a moment to bring yourself up to date on some of the latest resveratrol science…
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Go with the Flow
Global dementia data for those aged 65 and older shows that the prevalence of dementia in women is 14% to 32% higher than it is in men, and that by age 80, women make up 63% of dementia sufferers-a trend that experts expect to intensify as the population ages.
No wonder scientists are exploring how to bend that curve. As it happens, “a recently published study1 reported that postmenopausal women consuming a resveratrol supplement had increased verbal memory and overall cognitive function scores compared to placebo,” notes Hugh Welsh, president, general counsel and secretary, DSM North America (Parsippany, NJ).
In the randomized, placebo-controlled intervention trial, researchers had 80 postmenopausal women aged 45 to 85 take either 75 mg trans-resveratrol-the more bioavailable of the compound’s two isomers-twice daily or a placebo for 14 weeks, after which the researchers assessed the subjects’ cognitive performance, cerebral blood flow velocity and pulsatility index in the middle cerebral artery (an indicator of arterial stiffness), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia (carbon-dioxide retention). The subjects also completed mood questionnaires.
Relative to the placebo, resveratrol elicited 17-percent increases in CVR to both hypercapnic and cognitive stimuli, as well as significant improvements in verbal memory tasks and overall cognitive performance. Though mood improved on multiple measures in the resveratrol group, the changes weren’t significant.
In addition to showing that resveratrol supplementation can enhance cerebrovascular function and cognition in postmenopausal women, the results “suggest that some of the observed effects on brain blood flow may have real-world implications, especially in the context of aging,” Welsh says.
1. Evans HM et al., “Effects of resveratrol on cognitive performance, mood and cerebrovascular function in post-menopausal women; A 14-week randomised placebo-controlled intervention trial.” Nutrients, vol. 9, no. 27 (January 3, 2017).
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Feel Good about Getting Older
The team of scientists responsible for the previous study examined another aspect of resveratrol’s cerebrovascular effects in an intervention trial2 that began with the premise that pain common among postmenopausal women and often related to degradative joint diseases like age-related osteoarthritis may be a product of the vascular dysfunction that comes with declining estrogen levels.
So the researchers evaluated how supplementation with resveratrol might change that scenario. Once again, 80 healthy postmenopausal women took either 75 mg of resveratrol twice daily or a placebo for 14 days. The researchers measured aspects of wellbeing including pain, menopausal symptoms, sleep quality, depressive symptoms, mood, and quality of life at baseline and following treatment, with rating scales averaged to give a composite overall wellbeing score. Also, measures of cerebral vasodilator responsiveness to hypercapnia served as a marker for cerebrovascular function.
The researchers found that compared to the placebo, resveratrol supplementation yielded a significant reduction in pain and improvement in total wellbeing emerged-both of which, along with quality of life, correlated with improved cerebrovascular function. While more study is needed, the researchers write, the findings indicate resveratrol’s potential to reduce chronic pain in age-related osteoarthritis and possibly boost perceptions of wellbeing in postmenopausal women.
Adds Adamski, the same research group is conducting a bigger follow-up study to these two previous investigations wherein they plan to examine the effects of trans-resveratrol on cerebrovascular function, cognitive performance, and bone health in a longer crossover trial involving 160 postmenopausal women. “First results from this study are expected by mid-2019,” he says.
2. Wong R et al., “Resveratrol supplementation reduces pain experience by postmenopausal women.” Menopause: The Journal of the North American Menopause Society, vol. 24, no. 8 (2017): 916-922
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Resveratrol, notes Majeed, is poorly bioavailable. “Though a number of human clinical trials have been performed over the years,” he says, “conflicting findings have precluded its applicability in clinical settings, partially due to this poor bioavailability.”
Yet in a randomized, double-blind, placebo-controlled clinical trial3 published in 2016 in the journal Applied Physiology, Nutrition, and Metabolism, researchers investigating the combined effects of resveratrol supplementation plus exercise on human skeletal muscle mitochondrial capacity coincidentally demonstrated that piperine, “a natural bioenhancer from black pepper that research shows enhances bioavailability for a variety of nutritional substances,” Majeed says, appears to do the same with resveratrol.
In the trial, 16 healthy young adults underwent four weeks of supplementation with resveratrol at 1,000 mg and piperine at 20 mg. Results showed that volunteers in the resveratrol-piperine group demonstrated significant muscle oxidative capacity recovery following short bouts of exercise compared to the placebo group. Notes Majeed, “The influence of resveratrol on low-intensity stimulus during submaximal endurance training is one of the most eye-catching recent findings.” The current data, he said, “could be significant to the general population, especially to those who may be unable to perform high-intensity exercise.”
3. Polley KR et al., “Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity.” Applied Physiology, Nutrition, and Metabolism, vol. 41, no. 1 (2016): 26-32
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