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Special edition: Polyphenols

The big challenges in polyphenols: Providing credible evidence and a quality supply chain

By Nathan Gray+

28-Jan-2014
Last updated on 28-Jan-2014 at 13:49 GMT

Professor Chang Lee:
Professor Chang Lee: "In short, many investigators have ultimately been testing the wrong compounds in their search for the biologically plausible mechanism by which dietary polyphenols impact human health."

With surging interest in the potential health benefits of polyphenols around the globe, experts suggest that there are still some major sticking points in the polyphenol success story.

Industry and consumer interest in polyphenolic compounds, and their much mooted beneficial health effects is booming. Yet many still lack credible evidence of such benefits, and even if they did have such benefits, the supply of quality materials for use in consumer products is a massive challenge.

From fruits and vegetables to cereals, coffee, chocolate, and wine, the last 20 years has witnessed growing evidence of the potential health benefits for polyphenols - including anti-oxidant effects, anti-aging, anti-cancer, anti-inflammation. They have also been suggested to have the ability to enhance cardiovascular health, endothelial function, cell growth, and even benefit cognitive functions.

"In spite of the extensive research and health claims emerging over the past two decades, not one dietary phenolic compound has been accepted by government regulatory agencies as an agent that may mitigate disease or that has health benefits," noted professor Chang Lee of Cornell University in a recent commentary published in the Journal of Functional Foods .

The claim above may seem strong, especially given a 2011 positive opinion from the European Food Safety Agency (EFSA) relating to olive oil polyphenols and the protection of blood lipids from oxidative stress  and the existence of phenolic structure-function claims in the US, but these are rare examples.

Fact remains despite the body of work, little of it is taken seriously by regulators and health professionals.

Building credible evidence

According to Lee, many studies and claims to not take enough note of issues relating to bioavailability, noting that the study of bioavailability must include absorption, distribution, metabolism, and excretion, and should also investigate metabolites of compounds using both in vitro and in vivo studies.

"According to Lipinski’s rule for drug development... the compound should have a molecular weight less than 500 Da, no more than 5 hydrogen bond donors, and no more than 10 hydrogen bond acceptors in order for a chemical compound (as dietary polyphenol) to be absorbed into the human body," he noted.

"However, chemical properties of most native dietary polyphenols do not meet the rule. For example, EGCG in tea has more H-bond acceptors and H-bond donors than the rule specifies; likewise, catechin, catechin-gallate and epigallocatechin have more H-bond donors than the rule, and thus these compounds are not well-absorbed."

Lee suggested that only by studying the breakdown metabolites of these compounds can bioavailability and biological plausibility to be truly investigated: "In short, many investigators have ultimately been testing the wrong compounds in their search for the biologically plausible mechanism by which dietary polyphenols impact human health. All in vitro studies using aglycones or polyphenol-rich extracts derived from plant foods have to be revisited and revised in light of our new understanding about bioavailability of dietary polyphenols."

Digestion issues

The complexity of digestion in both the small and large intestine add to this challenge, he explained - noting that the bioavailability of a nutrient "is affected not only by its ability to cross a membrane, but also by maintenance of structural integrity."

"Dietary polyphenols are metabolised in the lumen of the small intestine, and again by the liver and other organs, where they undergo further modification. Moreover, some flavonoids and related compounds are not absorbed by the small intestine, but by the large intestine, where there is also substantial structural modification by colonic microflora."

By identifying the which members of the intestinal microbiota are responsible for the metabolism of bioactives dietary polyphenols, will ultimately contribute to our making sense of the variable results of epidemiological studies in different populations, and allow us to make qualified statements about the impact of food on health, Lee suggested.

Challenges in supply and quality

While there are huge challenges ahead in building evidence for dietary polyphenols, the industry faces several other - and potentially bigger - challenges when it comes to sourcing and supply chain quality, according to Professor Monique Simmonds from the Royal Botanical Gardens at Kew, UK.

"I think the challenges are increasing," said Simmonds. "And they will increase further because of what is happening to land use."

Indeed, with increased pressure on land for agriculture and development, the Kew expert believes that investment in sustainable supply chains and research to identify the exact class of plant required for production are key to the future of the industry.

"The companies that are really focused on quality are investing in this area," she commented. "You see a shift from relying on plants with a third party that maybe wasn't connected with the company. But they are now taking much more care and control over their supply chain."

"You see more companies and retailers really having greater concern that they do know exactly what is happening on their supply chain, and therefore linking closer with the source. And that's not just about ethical issues, it's also that they want to make sure what they are getting is what it says."

Simmonds believes that a lot more research must be done in developing cultivation methods, and that this research must also take great care in the selection of material for cultivation, "and making sure that is actually a good quality material which contains the profiles of chemicals that are associated with the potential use."

"It might be the right species, but it could be the wrong variety. And then you end up with the wrong material being grown and ending up in the trade, when has a knock on negative effect."

Don't forget the pollinators

Another key issue that many people do not consider is the rapidly dwindling number of bees and other pollinators, and the potential impact this may have on supply volume and quality.

"It's quite clear that something is going on with pollinators," said Simmonds. "And the majority of plants - and especially our fruits - require pollination to get what we want to eat."

"So if we have a loss of our pollinators then that will have an impact. You will be able to grow the plant - that will be OK - but the product you want, the fruit, that won't be."

"It's not just a decrease in honey, it's a decrease in other commodities that is going to be affected," she said.

Online issues

"Another challenge we face, of course, is the internet," said Simmonds. "That is more and more people buying things on the internet, and how we - so to speak - police that."

Indeed, the sale of polyphenol based dietary supplements and plant extracts online is big business and offers many the opportunity to set up wider distribution networks at lower costs than can be achieved with a shop based in one location.

However, the current way in which goods are sold online leaves it ripe for exploitation by people supplying goods that do not meet quality standards.  

"If you do find something dodgy, then right away they've evaporated in to thin air and sprung up again with a different website," noted Simmonds. "It's very difficult."

Quality assurance

While greater investment and focus on quality and getting the right course material may be great in principle, Simmonds does concede that good quality materials and proper supply chain management require investment - and questions remain over whether people will pay for that quality material or whether they will go for something cheaper.

"It must be difficult for somebody who does go that extra distance to provide a good quality material, and then is up against somebody who doesn't bother but gets away with it," she commented.

"The question remains on how somebody walking in to a shop and looking at these products on the shelf can make any decision on which is the best quality."

"When you bring them to a laboratory like here, we see big differences, but how do you get that across on a label. What's the sign that says 'this is quality'."

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