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Resveratrol - found in red grape skins - might reduce bowel cancer risk (at least, in mice). Via Wikimedia Commons/CC-BY-SA 3.0

Our researchers in Leicester have published the results of a new study showing that relatively small doses of purified resveratrol, a chemical found in red grapes and wine, might have an impact in reducing the risk of bowel cancer – at least, in mice prone to developing the disease.

Judging by the kind of headlines we’ve seen in response to previous resveratrol studies, we can expect at least a few “Red wine prevents cancer” stories. But, as we’ve explained before, this is a long way from the truth: in fact, alcohol increases the risk of cancer and would outweigh any potential benefits.

To avoid any misunderstandings, we wanted to explain a bit more about the research – published today in the journal Science Translational Medicine – and why it isn’t an excuse to hit the bottle.

The grapes of wrath

Resveratrol is a chemical produced in grape skins and other plant sources such as peanuts, cocoa and berries, where it acts as a natural pesticide against fungal infections.

Over the past few decades literally thousands of papers have been published about resveratrol, and its potential benefits are touted for a wide range of ailments including diabetes, neurodegenerative diseases and – of course – cancer.

The chemical itself has a range of effects on cells, mainly by influencing energy production (metabolism), although exactly how it works isn’t entirely clear. Tests on cells grown in the lab and some animal studies have suggested that resveratrol may have anti-cancer properties. However, translating these intriguing lab results into benefits for patients is fraught with difficulties and results from human trials of resveratrol for many diseases have been inconsistent – an issue that seems to crop up repeatedly with other food-derived chemicals.

One of the biggest problems is that little is known about the best dose of resveratrol to use, or how it’s taken up and used by cells in the body. Professor Karen Brown and her team at our Leicester Experimental Cancer Medicine Centre have been finding out. And they’ve discovered that – as is so often the case in life – less is more.

Of mice and men

As well as promising tests on cells grown in the lab, researchers have known for some time that feeding large doses of pure resveratrol to genetically engineered, bowel-cancer-prone mice reduces the number and size of the cancers that they develop.

So it follows that large doses in humans should have the same effect, right?

Back in 2007, the Leicester team published the results of a small early-phase clinical trial of resveratrol supplements in healthy volunteers, measuring the levels of the chemical in the body resulting from a range of different doses. Based on previous lab experiments, the researchers had an idea of the level of resveratrol needed to see a cancer-preventive effect – but even giving the participants very high doses couldn’t hit the required level in the blood, putting a downer on its potential.

But Professor Brown figured that the logic that ‘more is better’ might not hold up with chemicals found in low levels in the diet. And that’s exactly what she and her team set out to test in their new study.

They started by looking at how well people absorbed different doses of resveratrol into their bodies – a low dose ( 5 milligrams) equivalent to the amount in a large (250ml) glass of some red wines or roughly a kilogram of red grapes, or a high dose two hundred times bigger (1 gram). First, they measured levels in the blood of healthy volunteers after they were given the chemical. The next step was giving the same doses to bowel cancer patients awaiting surgery, and then examining samples of bowel tissue removed during their operation to see how much resveratrol ended up in there.

As might be expected, when people were given a high dose of resveratrol the chemical found its way into healthy and cancerous bowel tissue, as well as other parts of the body (such as muscle and fat). But, surprisingly, the researchers also found significant levels of reveratrol in tumours and healthy tissues in people given the much smaller dose. So if low doses of resveratrol were managing to get into the body in detectable amounts, were they having an effect?

This research has been done on purified resveratrol, not red wine, and it shouldn’t serve as an excuse for a cheeky glass or two.

To find out, the scientists then tested the effects of comparable low or high doses on bowel cancer-prone mice. Paradoxically, they found that low-dose resveratrol reduced tumour growth by half, whereas the high dose only reduced tumour growth by a quarter. [Updated 10/08/2015 for clarity and correction. KA]

But – importantly – they only saw the more potent effect of low doses in animals fed a high-fat diet, which tended to develop more tumours anyway.

A closer look revealed that resveratrol was slowing down the speed at which the abnormal cells in the tumours were dividing, apparently by boosting the activity of a molecule called AMPK, which is involved in cell metabolism.

Towards Eden?

Taken together, these findings challenge the dogma that when it comes to using drugs to reduce cancer risk – an approach known as chemoprevention – more is better.

Although the team’s 2007 trial results, show that high doses of resveratrol are safe, this new study suggests that it might be more effective at preventing bowel cancer at much lower doses. But it also tells us that this approach may only be beneficial for certain people, depending on their genetic make-up, diet and lifestyle.  And we don’t know if it has any effect on other cancer types.

From a wider perspective, this discovery may help to explain why the results of clinical trials of high-dose vitamins and other food-derived supplements have been inconsistent, often failing to produce the expected results or even appearing to be harmful (for example, see our series on antioxidants, and this post on vitamin pills). More research is needed to find out whether ‘more is better’ really holds true when it comes to the health benefits of chemicals normally found at low levels in the diet.

Following on from this, this study doesn’t tell us whether resveratrol supplements could help to prevent cancer in the general population or in specific groups of people. There’s much more work to be done to figure out how best to use it and who might benefit. So unless you’re a genetically engineered bowel cancer-prone mouse, we wouldn’t recommend popping resveratrol pills.

And finally, to reiterate our earlier point – all this research has been done on purified resveratrol, not red wine, and it shouldn’t serve as an excuse for a cheeky glass or two.

Our research has shown that alcohol causes around 12,800 cancers a year in the UK – that’s four per cent of all cases. And a 2013 report from the Alcohol Health Alliance linked alcohol to around 3,200 cancer deaths a year. So any benefits from the resveratrol in red wine are likely to be outweighed by the alcohol.

If you want to reduce your risk of bowel cancer, the best thing to do is to be a non-smoker, keep a healthy weight, be physically active, eat a balanced diet low in red and processed meat with lots of fibre such as fruit and veg, and cut down on booze.

Screening can also detect bowel cancer at an early stage when it’s more easily treated – we’ve got more information about this on our website – and people with a strong family history of the disease can talk to their GP about the possibility of genetic testing and monitoring.

Emma Smith and Kat Arney

Reference

Cai, H, et al. (2015) Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci. Transl. Med. 7, 298ra117. DOI: 10.1126/scitranslmed.aaa7619.

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Comments

Kat Arney August 10, 2015

Hi Kevin,
Thanks for your comment. Well spotted, and we’ve now corrected and clarified the post above.
Best wishes,
Kat

Kevin August 10, 2015

Hi,
I believe there is a misprint above. You write that those receiving lower doses had higher levels in their blood and bowel. The data in the paper doesn’t show that. For example, in figure 1A, the 5mg dose has a scale of 0-.8 uMol whereas the 1g dose has a scale of 0-200uM.