Trial and Error

Originally Published NO May 2010

The European Food Safety Authority (EFSA), on February 25, released some rather unfavorable opinions of antioxidants in a large-scale evaluation of 416 general health claims. Dating back to 2008, many of the submitted claims were for foods and substances in relation to antioxidants-all of which were denied approval.

Leatherhead Food Research reported in its 2009 Antioxidants Report that the global antioxidant market had grown 3% annually since 2004, with expectations for a $470 million market for antioxidant functional foods and drinks alone in 2010. "There is no doubt that EFSA's negative evaluations of [antioxidant claims] will have a negative impact on the antioxidant market in the European Union," says Miguel Fernandes da Silva, health and nutrition policy director at European Advisory Services (Brussels), a consultant specializing in international regulation of food and nutrition products. "A negative evaluation by EFSA will most certainly lead to a legal prohibition of the claims in question. As a consequence, these claims will simply gradually disappear from the EU market."

EFSA found no cause-and-effect relationships between submitted claims and "a beneficial physiological effect related to antioxidant activity, antioxidant content, or antioxidant properties." Other claims denied included "protecting cells from premature aging" and "protecting DNA, proteins, and lipids from oxidative damage."

Why is EFSA's panel shaking its head at submitted science? For starters, the term antioxidant has largely become commoditized. Consumers are very familiar with the term and the health benefits believed to come with it, so there is good reason to ride the antioxidant train, from a marketing standpoint.

But the sheer number of substances referenced as "antioxidants" in the health claims submitted to EFSA highlights another issue.

"We call a lot of substances antioxidants, but for those studies where they've actually done research in animals and humans, some may not be acting as antioxidants," says Andrew Shao, PhD, senior vice president of scientific and regulatory affairs at the Council for Responsible Nutrition (CRN; Washington, DC). "Flavonoids, anthocyanins, and polyphenols like resveratrol, [all of which were tied to the term antioxidant in the EFSA claims submissions], may not exert their action by quenching free radicals and reactive oxygen species. What the research is showing is that these affect the expression of pro-inflammatory markers, in some cases reducing inflammation. That's really not an antioxidant effect, so even when we continue to call these compounds 'antioxidants,' they really aren't functioning that way."

Another reason for the sometimes inappropriate use of the term antioxidant is an overreliance on in vitro tools that measure antioxidant capacity, like the ORAC test (Oxygen Radical Absorbance Capacity) and the FRAP test (Ferric Reducing Ability of Plasma). Shao says these tests can be easily manipulated to show maximum antioxidant capacities of just about any substance claiming to be an antioxidant. Such high capacities don't always translate to a health benefit to humans, and EFSA is likely aware of that.

The industry's overreliance on in vitro testing must be replaced by what EFSA calls its hierarchy of evidence, with the gold standard being the randomized, controlled human trial. EFSA received many submissions lacking in human clinical trials, and, in some cases, lacking in science entirely (several claims were supported by zero to few studies).

Now, interested parties are entering a new stage of the claims process. Cognis Nutrition & Health (Cincinnati), supplier of Xangold brand natural lutein esters, is one of those parties.

After receiving unfavorable results on lutein claims submitted three years ago, Cognis is now submitting an Article 13.5 dossier to EFSA, which can be submitted by any manufacturer or interested party in this second stage.

"We have new clinical studies now, and a lot of them are trying to summarize and present the data in the best possible light so EFSA's panel can understand the benefits of this nutrient," says Sharrann Simmons, North American marketing manager at Cognis.

Simmons says that Cognis immediately began working on new submissions after EFSA published its unexpected opinions in February.

"I think all of us and the European Union member states thought our initial dossier was quite strong and based on very well-founded science and well-designed studies," says Simmons. "I think the final ruling was perplexing and disappointing to everyone involved."

EFSA is funded by the European Union and has only been an operating body since 2002. The food and supplement industries are still working to better understand the panel's approach to claims substantiation, as its health claims opinions have differed from those of other bodies, such as the U.S. Food and Drug Administration. In an attempt to ease any confusion, EFSA will hold a technical meeting on June 1 with interested stakeholders in an attempt to create new dialogue regarding health claims evaluations.