Resveratrol – a buzz word in anti-aging these days – is an antioxidant that’s been credited with a range of things from reducing heart disease to preventing premature aging. Dr Haran Sivapalan examines the evidence.

Found in the skin of red grapes, blueberries, pomegranates and peanuts resveratrol first hit the headlines in 1992 when it was put up as a possible solution to “The French Paradox.” How could the French, a people with a diet high in fat, still have a relatively low rate of coronary heart disease?

The answer apparently lay in France’s famed penchant for red wine. Red wine is rich in polyphenols – compounds which are antioxidants and could protect the heart from inflammatory damage. One of these polyphenols, found in the red grape’s skin, was resveratrol. By consuming resveratrol in the form of red wine, it was proposed that the French were lowering their risk of cardiovascular disease, in spite of their high fat diet.

It hit the news again in 1997, when researchers at the University of Illinois applied resveratrol to the cancerous skin of mice. The number of skin tumours decreased by 68 to 98%. Unsurprisingly, this finding sparked further interest in resveratrol, both in the scientific community and in the wider public – could it prevent or cure certain cancers? Further studies in mice and rats showed that it could indeed prevent the development of tumours in breast, colon and prostatic tissue.

In 2003, resveratrol made the scientific headlines yet again, when it was found to prolong the lifespan of the yeast, Saccharomyces cerevisiae. Soon after, it was used to extend the lives of nematode worms, fruit flies, honeybees and, eventually, mice. In the latter species, resveratrol was shown to emulate the effects of ‘caloric restriction.’ When mice are forced to eat fewer calories than normal, it turns out that they become healthier, show less signs of ageing and living longer and resveratrol had a similar anti-ageing effect. More specifically, it was shown to activate Sirt1 – an enzyme linked to the increased survival of cells and their ability to cope with adverse conditions.

So, in mice at least, resveratrol afforded protection from heart disease, prevented cancer and now had the ability to slow down ageing. Was this the long elusive magic bullet?

Based on these animal studies, resveratrol is now marketed to people as a dietary supplement to thwart “premature ageing” and also as a key ingredient of various “anti-ageing” moisturising creams.

But, does what works in mice also work in humans and is there evidence to back up these claims?

From mice to men – what do clinical trials say?

Resveratrol is an ingredient in many anti-ageing facial creams, where it penetrates directly into the skin. Despite a huge market for such products, there are surprisingly few studies about topically applied resveratrol. It is worth noting that, of the studies showing positive results for topically applied resveratrol, some have been sponsored by product manufacturers.

One small study (Fabbrocini et al 2011) showed that a resveratrol-containing facial gel elicited a 57% decrease in acne (as assessed by a Global Acne Grading Score), compared to 6.1% for placebo (or “vehicle” as topically applied control substances are known). While these results show promise, the number of subjects was low. Furthermore, if resveratrol is to be seriously considered as a treatment for acne, there is a need to test it against established acne treatments (e.g. retinoids).

Another study by Wu et al (2012) demonstrated that resveratrol moisturising cream could protect skin from redness caused by UV light (UV-induced erythema). Again, it was a small size (15 people).

On a more promising note, there is a small amount of evidence to show that oral supplements (rather than creams or topical applications) may help skin health. A randomised controlled trial by Buonocore et al (2012) examined 50 people with signs of skin aging – wrinkles, dull complexion and brown spots. Half of the people took 8mg of resveratrol supplements over a period of 60 days. Compared to the half in the placebo group, those taking resveratrol experienced improvements in skin moisturisation, elasticity and smoothness. The depth of wrinkles also decreased, along with the intensity of age spots.

Take home message

While pre-clinical studies based on cell lines and animal models show some promise for resveratrol, there is a distinct lack of evidence for its anti-cancer and anti-ageing properties in the human population. More large-scale randomised controlled trials are needed.

The case of resveratrol highlights one of the challenges of drug development – substances that are effective in animals do not necessarily work in humans. On this point, a recurrent issue in the literature seems to be that resveratrol is readily metabolised in the human liver and then excreted by the kidneys. This means that after taking an oral supplement, only a small fraction of the dose will remain intact to exert its effects in the body. To adopt the scientific lingo, resveratrol has a low bioavailability. The same is true of topical treatments and creams, especially when these contain microparticles, which prevent resveratrol from penetrating the skin. Further research ought to address this issue.

Despite the lack of unequivocal evidence for its effectiveness, most clinical trials have shown resveratrol to be well-tolerated and safe to use. It probably won’t do you any harm but just how beneficial it is remains to be seen.

Resveratrol Box: Resveratrol and clinical studies

To date, there have been several clinical trials of resveratrol. It has been tested in groups of people with various conditions, including: colorectal cancer, Type II diabetes, heart disease, obesity, women taking the oral contraceptive pill and healthy individuals. Researchers have also assessed different treatment outcomes, such as the effect of resveratrol on: inflammatory markers in the blood, cancer markers in cells, blood pressure and patient ratings of pain.

While some of these studies have reported positive results, the issue is that existing trials have generally involved small numbers of subjects. When numbers are small, it becomes difficult to draw robust conclusions about the effectiveness of a drug. Furthermore, these trials have mainly been short-term studies, shedding little light on the effects of long-term resveratrol use.

Consider a clinical trial by Ghanim et al (2010), which found that people taking 40mg of resveratrol showed decreased markers of inflammation in the blood. Unfortunately, the study was limited to only 20 people who took the drug for only six weeks; a far cry from consumers who may take dietary resveratrol supplements over a lifetime. In addition, there were no other similar clinical trials to corroborate this finding. Contrast this with the evidence base for the retinoid drug tretinoin. According to NICE (National Institute of Clinical Excellence), four randomised controlled trials, conducted on a total of 1000 people, demonstrate that tretinoin can significantly reduce the amount of spots in people with acne. The numbers speak for themselves.

When it comes to resveratrol then, there is clearly a need for more, larger and longer-term clinical trials.