Science and the 'c' word

Related tags Cancer

Broccoli has a name as a cancer buster. But behind all the hype for cancer-preventing 'super foods', where's the science? Bill Lavers finds out

Can we choose to eat foods that will substantially reduce our risk of developing cancer? If so, which foods, which cancers, and what's the evidence? Is it strong enough, for instance, to make a health claim under the new European Nutrition and Health Claims Regulation? Well, not yet. But one day soon, perhaps.

Of course, cancer is not just one disease but many, affecting different parts of the body, with a large number of causal effects, not to mention factors such as genetic predisposition. And moving from epidemiology - statistical associations - to convincing links is quite a challenge.

"There is no food close to this," says Professor Tim Key of Oxford University's Cancer Research UK Epidemiology Unit. "In a review for the World Health Organisation, we concluded that the only convincing links between dietary factors and cancer were for alcohol and obesity.

"No dietary factor was convincingly associated with a reduction in cancer risk, with fruit and vegetables in general judged as 'probable'. There is a lot of ongoing observational research, and this will produce substantially more evidence over the next few years."

Professor Ian Johnson at the Institute of Food Research, UK, is a little more up-beat, but he also thinks that a risk reduction claim is pretty remote given that most evidence is still epidemiological.

"I doubt that even large amounts of epidemiological evidence would be sufficient to satisfy claims regulations, although it is enough to drive or shape public health recommendations - such as 5-a-Day (in the UK)."

He expects that "super broccoli" will be marketed soon as a cancer preventer, but without a firm health claim. "What you need is an understanding of the biological mechanism involved. I've done a lot of work on Brussels sprouts, but wouldn't dream of making a health claim. And I can't think of any cases where understanding of mechanism is sufficiently advanced for a food product."

As for probiotics, the science is "not strong enough to support any one specific product for cancer prevention on a proven mechanistic basis", says Johnson. And he urges caution in claims for prevention. Because of the long gestation, there is a need to be careful that there are no adverse effects.

"If you look hard enough at fibres, there are just a few pro-cancer effects in the literature." Fibre is the first example postulated as a cancer preventative and mechanisms have been under study for 30 years, with hundreds of published papers, but knowledge of how it works is still not strong enough, says Johnson.

According to Key, the results of studies into fibres have been inconsistent and there is no agreement among epidemiologists.

The European Nutrition and Health Claim Regulation does allow, under article 14, health claims for disease risk reduction, provided they are based on sufficient scientific evidence. Antioxidant vitamins, flavonoids, prebiotics, probiotics and various extracts of fruit and vegetables have all been associated with cancer prevention or risk reduction. But amassing enough convincing evidence for a cancer risk reduction claim is a formidable task.

"Claims for reduced risk of cancer would have to be based on human intervention trials," says Professor Ian Rowland, head of Human Nutrition at Reading University. "This would be very difficult in the case of cancer because there are not many validated biomarkers for cancer."

Intervention trials, says Rowland, tend to take years - four to five years for benign tumours and 20 years or more for malignant cancers - depending on the end-point chosen. "You can do them in months or weeks for DNA damage - we recently did one for DNA damage on watercress. But DNA damage is not a validated biomarker for malignant cancer."

It has been suggested that about one third of all cancers may be caused by an inappropriate balance of food components, and back in 2004 "pass claim criteria" were published identifying 18 markers under five broad headings (Rafter et al, European Journal of Nutrition, June 2004).

It's in the genes

So, what type of claims will producers be making in future specific to cancer risk reduction? "Most likely they will do studies looking at end-points, such as DNA damage," says Rowland, "with a scientific explanation of the context, whether the end-points are validated or not. But there is a tendency to misinterpret scientific data and its context."

And then there is the role of nutri-genomics - the relationship between nutrition and genetics - in unravelling the complexities of cancer and diet. How close are we to identifying tailor-made dietary products for risk reduction in people predisposed to specific conditions?

"Nutrigenomics is a new technology that has come a long way recently," says Dr Sian Astley of the European Nutrigenomics body NuGO. "But cancer is just too complicated."

She contrasts the drug industry - where there is a single powerful product and at least one known biological pathway for that product - with the dietary approach. Here there are small variations in small amounts of a large number of inputs, and numerous pathways.

Astley argues that tailor-made products for people predisposed to certain health risks are already on the market - for high blood pressure, cardiovascular disease and gut health, for example - and that genetic studies have more to offer.

"We are understanding a lot more single gene, single food compound, single disease interactions such as fat and cardiovascular disease. But cancer is so long gestating, with numerous complaints affecting different parts of the body." Astley also points out that a lot of nutrients have to be eaten in just the right amount. Too little increases health risk and too much increases it also.

"There is always a U-shaped risk curve and we don't necessarily know where the middle is, especially with cancer, with different areas of the body responding differently to individual compounds."

So, although nutrigenomics has come a long way quickly, it still has far to go. "Don't judge it yet," says Astley. "And not on cancer."

But do consumers want to see specific cancer risk reduction health claims, and are they necessary to market a product successfully? Well, actually no.

The commercial reality

While consumers are definitely interested in wellness claims and food-related issues - and health is undoubtedly a big motivator - marketing expert Dorothy MacKenzie at consultancy Dragon Brands says consumers don't necessarily want scientific claims and discussions of a deep scientific nature.

"Communicating health benefits of foods is more about empathising with naturalness. Going further and making specific claims narrows the appeal," she says. "You get more people buying into functional messages if they are more general - buying into an ingredient or trend - but not the claim itself unless it is packaged up in an appealing way."

Dr Adrian Hughes at essential fatty acid (EFA) supplier Bioriginal points out, however, that the usage of condition-specific supplements has doubled since 1999. His company has launched a new range of EFAs in combinations for consumers concerned with specific health areas, such heart, eye and prostate. But the promotional material for Bioriginal Men's Health - containing fish oils, borage oils and lycopene - stresses reduced inflammation, reduced adhesion and reduction of cell damage, rather than making any specific reference to cancer risk reduction. Similarly, Ocean Spray's publicity on cranberry products focuses on urinary tract infections in general rather than prostate cancer in particular.

Hughes also points out that studies have shown a link between elevated oestrogen levels and increased risk of developing hormone-dependent cancer, such as breast cancer. Lignans from flaxseed (nature's most abundant source) have been shown to reduce the effects of oestrogen changes in the body. But he goes no further.

Indena is promoting glucosinolates obtained from cruciferous vegetables for their effects against colo-rectal and lung cancers. Marketing director Christian Artaria believes the first claims under the new EU Regulation will be based on short-term demonstrable results, rather than on a long-lasting prevention claim.

His colleague Dr Carla Manzotti points out that, although there is a large body of epidemiological studies supporting the anti-carcinogenic effects of glucosinolates, the relationship between intake and cancer development "is more complex than previously thought"

Orafti is researching the effects of prebiotic fibres - inulin and oligofructose - on colon cancer. Marketing manager Tim van der Schraelen says that there have been more than 300 studies, including about 100 human intervention studies, on the effect of inulin, oligofructose and combinations of the two. But the company is still not ready to substantiate an application for a health claim for reduced cancer risk under article 14 of the new Regulation.

Rather, Orafti will be submitting claims for digestive health, stimulation of healthy microflora and increased calcium absorption under the regulation's list of pre-approved claims (article 13), he says. Van der Schraelen is confident, however, that the new legislation will stimulate detailed scientific research in the food industry, which will help consumers get more accurate information.

Meanwhile, trials backed by the charity Cancer Research UK using a polysaccharide fermented from mushrooms in the prevention and treatment of cancer are poised to start, and a new report claiming to be "the most comprehensive ever written about the links between cancer and food, nutrition and physical activity" will be published by the World Cancer Research Fund (WCRF) at the end of October. Food Nutrition, Physical Activity and the Prevention of Cancer - A Global Perspective, analyses 7,000 studies selected from some 500,000 in the global literature. It will be interesting to read the conclusions.

Glucosinolates

Glucosinolates are chemically and thermally stable. But their hydrolysis products - isothiocyanates and indoles - are said to be potent inducers of detoxifying enzymes promoting the elimination of potential carcinogenic agents.

Some have been found to inhibit carcinogen activation by other enzymes. Although glucosinolates are present in all cruciferous vegetables - broccoli and rapeseed to cabbage and turnips - Indena's Dr Carla Manzotti says that cancer inhibition was observed in human volunteers fed with watercress homogenate.

High intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer, and a large number of epidemiological studies conducted in China since the 1980s and more recently in the US and Europe support the anti-carcinogenic effect of glucosinolates. But Manzotti says the majority of the studies were not controlled, and so are not considered conclusive. Larger randomised controlled trials are needed, she believes, as individual genetic factors could affect their efficacy.

Prebiotics

Up to 70% of cases of colorectal cancer could be prevented by following a healthy lifestyle, which would include consuming prebiotics, say Orafti's Tim van der Schraelen and his colleague Dr Douwina Bosscher. Several mechanisms, they say, lie at the basis of the beneficial effect of the prebiotic fibres inulin and oligofructose, of which the following are most important:

  • The bulking effect dilutes carcinogenic substances present
  • The prebiotic effect reduces the number of pathogenic bacteria, some of which are able to secrete enzymes that promote carcinogens
  • The production of short-chain fatty acids, such as butyrate, by fermentation of inulin and oligofructose, has anti-cancer effects
  • Inducting carbohydrate fermentation in the distal colon reduces the protein fermentation that would create products that increase cancer risk

Van der Schraelen and Bosscher say that, while colon cancer can affect any part of the colon, it is most likely in the distal region. Oligofructose promotes changes in the proximal colon while the longer-chain inulin is effective in the distal colo-rectum, and so a combination of the two - oligofructose-enriched inulin - provides the greatest chemo-preventative potential along the whole of the colon. Although they believe such a product - Beneo Synergy 1 - has the potential to reduce cancer risk, the potential for claims is greatest "in the area of healthy ageing, related to reduced risk"

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