Botanical odyssey

Twenty years of drug discovery work at Bayer have paved the way for the best kept secret in botanicals, says John Dunn

A recent report from market analyst Frost & Sullivan suggests that the top five plant-derived functional food ingredients are carotenoids, isoflavones, phytosterols, polyphenols and vitamin E. And its top 10 hot list of botanicals for delivering them includes blueberries (for protection against liver cancer); cranberries (tooth decay); ginger (cancer); green leafy vegetables (obesity); rhatany root extract (skin care); and tomatoes (for blood pressure).

In Developments in the Global Phytonutrients Market, Frost & Sullivan says demand for plant-derived ingredients is on the increase in the US, Asia-Pacific and Europe. And in the US in particular, companies are intensifying their research efforts and clinical studies in a bid to demonstrate the efficacy of their phytonutrients and to identify new bioactives.

But the whole world of plant extract discovery looks set to be turned on its head. From the mundane such as olive oil (full of polyphenols that protect against cardiovascular disease) to the exotic such as African baobab fruit pulp (10 times more vitamin C than eating an orange - pictured right), the task of finding exciting new sources of bioactive food ingredients may never be the same again.

Ingredient companies no longer need to send teams of researchers flying around the globe on the lookout for some exotic new native plant, berry or root that the locals have been eating for years to cure this disease or prevent that ailment. Instead you could sit at home and talk to InterMed Discovery in Dortmund, Germany, and let its small team of scientists do the discovery work for you.

InterMed Discovery is a recent management buyout from Bayer Healthcare, the drugs arm of chemical giant Bayer. What the InterMed team did early last year was buy out the rights to the results of their 20 years of drug discovery work at Bayer, looking for bioactive compounds in thousands of plants, berries, roots and fungi from all over the world. But instead of making drugs, they are now using that knowledge to create new food ingredients.

the best kept secret

You tell InterMed what sort of bioactivity you are looking for, what you want the ingredients to do, and the team will hit its computer buttons to come up with a list of the most likely target botanicals.

It is the best kept secret in botanicals, says Dr Jörg Grünwald, founder and director of Analyse & Realize, the Berlin-based consulting firm for producers and distributors of botanical ingredients. His company is working very closely with InterMed to help prioritise its work. "We have said that obesity is the problem of the time, so let's look at the database to find natural food products that have anti-obese activities."

Bernard Becker is md of InterMed Discovery. He says: "What we have taken over is the complete technology platform, the know-how, the database and the key people." That means InterMed has access to several millions of data points which were generated by Bayer in over 100 high-throughput screening programmes to find and identify new drugs. Essentially it is a database of potentially active compounds that have been identified in a huge range of biological sources from plants to fungi, says Becker.

"What we are doing now is looking at this data to generate ideas for potential active food ingredients. We start by looking at those biological sources that are part of the food chain somewhere, in order to make it feasible for their use as a food ingredient, supplement or nutriceutical."

Unlike the traditional search for new food ingredients, it is not a random process, says Becker. "We use our database to select potential compounds and mixtures of interest. Then we take them through additional testing progammes - in vitro and in vivo - and derive from these an ingredients project which we then offer to a food company.

"We are not regulatory experts and we work closely with Analyse & Realize if there are regulatory issues to be tackled."

From his discussions with food companies, the hot topic at the moment is obesity, says Becker. "Everyone is talking about obesity. The second big thing is mental state activity - anything that can enhance mental performance and lift the mood."

The third area of interest to food companies, he says, is cardiovascular prophylaxis: the prevention and control of cardiovascular disease. There is also some interest in anti-inflammatory compounds and pain control, he adds.

What companies are looking for, says Becker, is new ideas, new biological activities from a known source. Or they are looking for a known compound, or very similar compounds, but from a completely different source so that they can differentiate themselves from the competition.

"The main aim is to find ingredients that fulfil the criteria the customer is looking for. That's our primary interest. The second stage is to identify the geographic regions they come from.

"We're not saying we can always provide a solution, but with our technology platform, with our know-how, we can certainly give it a very serious try."

InterMed is currently working on three fairly advanced projects on obesity and has some "very nice" in vitro and in vivo data, says Becker, all derived from well-known food plants. "We are also working on a number of mental-state related projects and running a number of test programmes."

InterMed's services are more suitable to large ingredients companies with deep research and development (R&D) pockets to enable them to take the large number of potential starting compounds through to a successful product launch. Smaller companies are still reliant on serendipity - coming across food botanicals that turn out to have new functional activities or which provide new, more exotic or more concentrated replacements for existing ingredients.

At Analyse & Realize, Grünwald says the newer botanicals tend to come mostly from smaller companies. "It's usually not the big companies that start these things. The big companies are open to discussion, but they all want to see some clear functional activity advantages and a clear regulatory way forward first."

Basically, says Grünwald, most of these botanicals don't have concrete health claims, which is what the big companies really want. Instead, their selling point is more about the general image of them supporting your immune system, preventing diseases and strengthening mental capacity.

"They don't have strong individual health claims. Some companies are trying to add some science to their products but these are mainly not very big companies and are not very science focused. But we are running clinical trials for a number of smaller companies - placebo-controlled double-blind trials - on a couple of botanical food ingredients and foodstuffs for the new European Nutrition and Health Claims Regulation."

And the research does not have to be expensive, says Grünwald. "We do placebo-controlled double-blind trials for ?100,000, which, if everything works out fine, gives you an individual claim for your product. That is, generally speaking, reasonably affordable for your average medium-sized company."

the novel food issue

One of the big issues for botanical producers using exotic sources is the cost of applying for approval under Europe's Novel Food Regulation, says Dr John Wilkinson, director of the UK's Herbal Sciences International, which specialises in regulatory approval of botanical-based nutriceuticals and foods.

"A novel food is a natural food product that has not had a significant history of use in the EU prior to 1997," he says. "And the regulations can be pretty hard going."

According to a new survey just completed by Herbal Sciences, just 15 non-GM full novel food applications have been made since the Regulation came into force in 1997. "This is very few considering this is over 10 years," observes Wilkinson.

"Part of the reason is the perceived high costs for getting approval. But in fact, if a company already has good safety data to support the product and can demonstrate a safe history of use in the country of origin, then in principle the costs can often be tens of thousands rather than hundreds of thousands of pounds."