The USDA has removed its USDA Oxygen Radical Absorbance Capacity (ORAC) Database from its NDL website, citing “mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds,” and the claim ORAC values are “routinely misused” by food and dietary supplement manufacturing companies to promote their products and by consumers to guide their food and dietary supplement choices.
 
“There are a number of bioactive compounds which are theorized to have a role in preventing or ameliorating various chronic diseases such as cancer, coronary vascular disease, Alzheimer’s, and diabetes,” the USDA said in its statement. “However, the associated metabolic pathways are not completely understood and non-antioxidant mechanisms, still undefined, may be responsible.”
 
The USDA said the ORAC test was just one of a number of chemical techniques developed to measure the antioxidant capacity of foods. “The ORAC assay measures the degree of inhibition of peroxy-radical-induced oxidation by the compounds of interest in a chemical milieu,” the USDA said. “Some newer versions of the ORAC assay use other substrates and results among the various ORAC assays are not comparable.”
 
In addition to the ORAC assay, other measures of antioxidant capacity include ferric ion reducing antioxidant power (FRAP) and trolox equivalence antioxidant capacity (TEAC) assays. “These assays are based on discrete underlying mechanisms that use different radical or oxidant sources and therefore generate distinct values and cannot be compared directly,” the USDA said, and added that “ORAC values are routinely misused by food and dietary supplement manufacturing companies to promote their products and by consumers to guide their food and dietary supplement choices.”
 
That statement was of particular concern to Ronald Proir, Ph.D., who led research related to phytochemicals and health for 32 years as a senior researcher at the USDA’s Agricultural Research Service (ARS). “It is unfortunate but true that numbers obtained from ORAC analysis have sometimes been misused, but that does not necessarily mean that the information is not useful if used appropriately,” he said in a statement of his own. “In too many cases, the goal has been to obtain the highest antioxidant value. It is not always the case that ‘more is better’ and in some cases using individual antioxidant compounds, more may be detrimental. A lot of misunderstanding results from lack of knowledge of free radical chemistry.”
 
Dr. Prior also took issue with the USDA’s statement, “There is no evidence that the beneficial effects of polyphenol-rich foods can be attributed to the antioxidant properties of these foods. The data for antioxidant capacity of foods generated by in vitro (test-tube) methods cannot be extrapolated to in vivo (human) effects and the clinical trials to test benefits of dietary antioxidants have produced mixed results. We know now that antioxidant molecules in food have a wide range of functions, many of which are unrelated to the ability to absorb free radicals.”
 
In response, Dr. Prior argued statements to that effect “are not consistent with the scientific evidence.” He noted that “in the last 3 years there have been more than 25 publications dealing with dietary antioxidants (polyphenolics) and in vivoantioxidant status or disease.” He also pointed to “a considerable amount of scientific literature on the positive health benefits of the polyphenolic flavonoid-type compounds in foods,” but added that it wasn’t “to say that all of these effects are the result of only an antioxidant mechanism.”
 
An Ongoing Debate
 
Southborough, MA-based Brunswick Laboratories issued its own critical response to the USDA ORAC statement. “First, we would like to establish some important foundational facts: no in vitro assay that quantifies a characteristic of a nutritional product describes in vivo outcomes and should not be used to suggest such a connection,” the company said. “Vital information about metabolism, bioavailability, mechanisms of action, and efficacy are not measured by any such in vitro assay.”
 
Brunswick Laboratories also took issue with the USDA’s characterization of polyphenols. “There is evidence that polyphenols are connected to beneficial human health outcomes,” the company said. “There is [also] evidence that these beneficial outcomes have antioxidant as well as diverse other mechanisms of action.”
 
And finally, Brunswick Laboratories contended that “ORAC has been and remains a valuable analytical tool in connection with other investigative methods.”
 
But not all of the response to the removal of the ORAC database has been critical. In an interview with Nutraceuticals World and speaking on behalf of the Council for Responsible Nutrition (CRN), Taylor Wallace, Ph.D., CRN’s senior director of scientific and regulatory affairs, said he felt this decision was evidence that the USDA was taking a positive step forward in promoting good science. “Back in the late 1990-2000s, researchers started the job of looking at antioxidants and compounds like flavonoids and they hypothesized that these compounds make scavenge free radicals in the body,” he said. “Since then, research has changed, as it often does, and found that these compounds, while still affecting different types of chronic disease, do so through multiple methods.”
 
The antioxidant ability, he continued, might be only one of a multitude of mechanisms. “It’s not one mechanism it’s a multi-mechanistic process for chronic diseases,” he said. “The bottom line is that supplements and foods aren’t drugs. They don’t have one pathway that they influence the body, they influence it in many different ways.
 
“CRN feels that removing the ORAC recognizes that this is a multi-mechanistic process and that nutrients and compounds in foods and dietary supplements (such as polyphenols) affect the body in many different ways. That’s a real step forward for USDA.”
 
But does ORAC have a place in the future of nutrition? Dr. Prior said there is potential, as long as it is used appropriately. “Comparisons of data must be made using a standardized method using the same standard, units of expressing the data need to be clearly defined and comparisons between dried, partially dried, fresh foods, or juices or other processed food done with full recognition that the values cannot be directly compared,” he said. “Monitoring changes in antioxidant capacity and using other analytical methods to follow individual compound changes during processing of foods is critical to assess and understand what the effects of processing are on the final product. Most important, ORAC should be used as a complementary analytical tool in the investigative process.”
 
Dr. Prior concluded his comments by encouraging the industry and the scientific community to continue developing more specific biomarkers of health. He also hoped a better understanding of what happens to bioactive flavonoid compounds during the digestion and absorption process would also surface. “The expectation has never been that any one in vitro assay, regardless of its nature, would truly reflect everything that happens during this process,” he said. “Without the ORAC database, we would not have had the opportunity to gather important epidemiology data that we now have relating antioxidant intake and various disease endpoints. Those involved in marketing are encouraged to use the data available in a reasonable way backed up with the best science that is available.”