Quest for the fountain of youth

Michael McBurney

Michael McBurney is part of a global quest to understand the “fountain of youth” potential of resveratrol.

by Tony Martins

Most of us are familiar with the conventional wisdom that a glass of red wine with dinner can improve our health—but not even the most advanced scientific minds have fully understood why.

Now, amidst a sensational global quest to harness resveratrol, an enigmatic substance found in red wine and a potential “fountain of youth,” Michael McBurney wants to add a little bit of scientific caution to the equation.

Professor McBurney is program director of cancer therapeutics at the Ottawa Hospital Research Institute and a professor in the Faculty of Medicine’s biochemistry, microbiology and immunology (BMI) department at the University of Ottawa. He was among some 150 people at the first-ever international meeting on resveratrol held in Copenhagen in mid-September.

“The challenge is to separate the hype of the entrepreneurs from the serious work of the scientists,” explains McBurney, referring to one of the challenges facing the multidisciplinary global researchers hoping to document resveratrol’s life-prolonging benefits in humans.

A natural substance most prevalent in fruits and vegetables, resveratrol was thrust into the public eye when the television news program 60 Minutes profiled the phenomenon in January 2009.

While McBurney reports that the remarkable and broad-ranging benefits of resveratrol are “not disputed,” he cautions that “it is still unclear whether resveratrol is of benefit to humans—all of the work has been done on experimental animals who live in controlled environments.” 

“There are folks ready to start selling [resveratrol] to the public—this is already done online— with no guidelines as to safe or effective doses,” warned McBurney.

In the Cancer Therapeutics Program, McBurney directs 14 scientists, who lead research teams of more than 100 people, as well as nearly 50 medical, surgical and radiation oncologists. Under McBurney’s leadership, the program has grown substantially and has become increasingly collaborative since it was established in 1995.

McBurney’s biochemical research aims to help crack the resveratrol mystery by determining whether the SirT1 protein in experimental mice is required in order for resveratrol to produce physiological benefits, leading to, for example, treatment of metabolic syndrome, prevention of cancer and improved recovery following a stroke.

“Our work should determine whether the pathways regulated by SirT1 are those targeted by resveratrol,” Michael McBurney explains. “If we are correct, then we ought to be able to use more quantitative methods to assess resveratrol’s effects, dosage and safety. And we might be able to design drugs that work better and at lower doses once we know what the target is.” 

Despite the resveratrol hype and the prevalence of ongoing studies involving human subjects, McBurney points to the many challenges still surrounding the potential wonder drug.

“Since the main benefit of resveratrol is disease avoidance and longer lifespan, it will take a significant length of time to formally prove its benefit in humans,” McBurney says.

There are also regulatory issues to grapple with. “Because it is a natural product, there is some uncertainty about under whose regulatory authority it will fall,” explains McBurney.“It is currently marketed as a nutriceutical, but it does not seem to be a nutrient in the normal sense of the word.” 

Speculation abounds that resveratrol may be the answer to what’s known as the French Paradox, the phenomenon whereby people from France have lower rates of heart disease despite a high-fat and dairy-rich diet. One possible explanation is the regular consumption of the resveratrol that is found in red wine.

Of primary interest to McBurney, however, is the fundamental mystery of why resveratrol does what it does. The substance has been shown to result in a change in expression of a number of genes when provided to cells in culture. “Since we don’t know the mechanism of action, we don’t know whether any of these are the primary cause of resveratrol action or secondary consequences of downstream events,” McBurney explains.

“Once we know what the primary effect of resveratrol is,” he adds, “we will be able to work out dosages, look at the kinetics and extrapolate to humans from results obtained in experimental animals.” 

Despite mounting global efforts to understand and market resveratrol, McBurney admits that he has no idea how close we are to knowing exactly how the mystery compound works.

“We know some things, but if there is a constant in biomedical science, it is that every time we think we are beginning to understand the system, we find an entire level of complexity emerging that we did not previously know about.” 

In the meantime, however, having that glass of red wine with dinner seems more and more like a good way to not just enjoy life but also prolong it. 

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