ORAC values might be passé, but antioxidant activity still demands research, experts say
It has been more than five years since the United States Department of Agriculture shuttered its database of ORAC values, which was pretty much the death knell for these claims in the marketplace. According to USDA, the agency took this action in 2012 “due to mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds, including polyphenols on human health.”
But the underlying chemical processes of reactive oxygen species within the body are still very much in the forefront of researchers’ minds. Oxygen is of course essential to life and plays a key role in almost all of the estimated 37x10^21 reactions that take place every second with the body. And some of those reactions go bad, spraying collateral damage in form of oxygen radicals, which figure into the inflammatory states that underlie many diseases. A search using the term ‘reactive oxygen species’ on the PubMed database that is maintained by the National Institute of Health turns up more than 200,000 studies, of which more than 7,000 were published in 2017 alone.
Does term still have relevance?
Has the term ‘antioxidant’ become passé? Experts in the field of botanical ingredients research agree that it was probably always a gross oversimplification of the relative quality and potential health benefits of ingredients. It was perhaps akin to trying to judge a car’s quality and suitability for a certain task based solely on the number of cylinders in its engine. But that doesn’t mean that ORAC values were frivolous measures, merely that they had perhaps been misused. And overused.
Jeffrey Blumberg, PhD, is the chief scientist at the Antioxidant Research Laboratory at Tufts University in Medford, MA. Being connected to an institution with ‘antioxidant’ in its name could of course make him somewhat protective of the continued relevance of the concept, but even Blumberg admitted that the way ORAC values came to be applied in the marketplace bore little resemblance to how researchers used the tool.
“Assays intended to assess foods and ingredients for 'total antioxidant capacity” like the ORAC, FRAP, DPPH, and TAP were useful research methods for ranking and selecting items for further study. These tools, particularly ORAC values, then morphed into marketing claims touting the antioxidant content of foods, beverages, and supplements,” Blumberg told NutraIngredients-USA.
One measure sells concept short
This use of the measure, in a ‘my dog’s better than your dog’ fashion, was always doomed to failure, Blumberg said. The biological activity of natural compounds is multifaceted and can’t be adequately captured by one measure. And the marketplace seems to have gotten the message, he said.
“The desirability of having a simple, single number to rate products is understandable but entirely unfounded when it comes to fairly reflecting a complex array of literally thousands of compounds defined as dietary antioxidants. Further, the implication that one in vitro assay can meaningfully measure aspects of in vivo health is groundless as it can never account for critical factors like bioaccessibility, bioavailability, metabolism, distribution, and elimination,” Blumberg said.
“Interestingly, this notion of having a single, universal biomarker contrasts greatly with more recent developments, particularly in personalized nutrition, of relying instead on complex algorithms of –omics approaches and other ‘big data’ sources to inform us and guide our nutrition, exercise, and other lifestyle choices,”he said.
Stefan Gafner, PhD, chief science officer of the American Botanical Council (ABC), did some work on measuring antioxidant activity during his doctoral studies and came up with a TLC spray method using a stable reagent that is still often cited. Gafner said the ability to measure this activity within natural compounds open a door into new era of health properties for these compounds. Some of those vistas glimpsed at that time remain tantalizingly beyond reach, he said.
“Antioxidant activities come in many shapes or forms, and can for example include the scavenging of free radicals, a direct antioxidant effect, or the inhibition of enzymes that catalyze oxidative reactions in the body,” Gafner said.
“There was much hope that antioxidant ingredients may have beneficial properties for many diseases where oxidative damage is linked to disease initiation or progression. This hope was fueled in part due to the fact that antioxidant rich food has shown to be beneficial in the prevention of many chronic diseases, including cancer, cardiovascular diseases and diabetes. However, it has been difficult to establish if these benefits are indeed due to the antioxidants or if these are due to the difference in lifestyles among people with different diets,”he said.
Both Blumberg and Gafner said that future research needs to focus on the specific functional benefits of the compounds in question. They might all display the ability to soak up free radicals, but that is just their ticket though the door, so to speak, of providing a potent health benefit.
“It is important to keep in mind that the term dietary antioxidant defines a mechanism of action decreasing the adverse effects of reactive oxygen and nitrogen species on physiological function—but provides no distinction between carotenoids, (poly)phenols, thiols, tocopherols, etc. The term ‘antioxidant’is certainly not dead—just widely misunderstood, perhaps because it is likely that some classes of antioxidants, while possessing free radical-quenching properties, actually act principally as anti-inflammatory nutrients. To make matters more complicated, it is also worth noting that a dynamic and vicious cycle exists between oxidative stress and inflammation and teasing them apart sometime seems like the old conundrum about whether the chicken or the egg came first,” Blumberg said.
“I don’t think that antioxidants should be put to grave, but we may have to look beyond antioxidant mechanisms for some of the ingredients of interest, provide data from clinical studies that show that these molecules are absorbed, or provide benefits via interaction with the gut microbial flora, and consider the importance of other molecules to help absorb, stabilize, or otherwise increase the efficacy of the antioxidant in question,” Gafner said.
Whether that research will continue at a sufficient pace in light of the USDA’s action is an open question. Mark Blumenthal, founder and executive director of ABC, said that he has heard that academic journals have been discouraging the submission of papers with the term ‘antioxidant’ in their titles or abstracts. A recent paper published in the journal Foods suggests that there was in fact a chilling effect on this type of research, with a very distinct slowdown in the growth of the number of ‘food and antioxidant studies’ in the years 2013 and 2014. But the author found that the number of studies jumped up again in 2016 and into 2017, showing a renewed rate of growth that roughly parallels that of the 2008-2012 time frame.