Excessive free radicals in the body are known to pose health risks, and it has long been established that the antioxidants in food can counter this oxidative stress. However, studies have suggested that antioxidant supplements can be ineffective or even dangerous, and in the absence of a robust evidence base, manufacturers are barred from making many label claims. In this special report we talk to Dr Jin Ji, executive vice president and chief technology officer at Brunswick Laboratories Inc, about what the latest thinking in the field entails.
Since the 1990s, antioxidants have played a role in popular conceptions of healthy eating. As researchers came to understand the links between oxidative stress and chronic disease, they also began to ponder how antioxidants – a class of molecules naturally present in many foods – might counteract these issues. A multimillion dollar industry was born, with thousands of people taking antioxidant supplements in a bid to improve their nutrition.
In recent years, however, antioxidant pills have been dealt a serious blow. A growing number of studies have suggested that certain classes of supplement, long marketed as healthy, might be actively harmful. With the evidence base far from clear cut, the importance of dietary antioxidants – particularly supplements – cannot be taken as a given.
“There is a persistent debate on whether antioxidants are truly effective,” admits Dr Jin Ji, executive vice president and chief technology officer at Brunswick Laboratories. “This debate is ongoing, and it will continue to be for some time. Scientists are undertaking more and more clinical studies to provide insight into whether antioxidants are beneficial to human bodies, and if so how.”
On one hand, the basic science is not in contention. When the body breaks down food into energy, it generates a byproduct known as free radicals. Also present in food itself, and the air we breathe, free radicals are a broad class of chemicals with the potential to exert significant damage. Through stealing electrons from nearby molecules, free radicals in the body may tamper with DNA and impede normal cell function.
These free radicals are not all bad, and in fact play an essential role in cellular signalling. As a result, the body has inbuilt mechanisms for maintaining appropriate levels of oxidation. However, under suboptimal conditions – where the production of free radicals exceeds the body’s ability to absorb them – the result is oxidative stress. This in turn has been linked with ageing, inflammation, and a host of chronic conditions alongside cardiovascular diseases and cancer.
For this reason, dietary antioxidants have been touted as a second line of attack. Comprising hundreds of substances, including vitamin C, vitamin E, beta-carotene, lycopene and the minerals selenium and manganese, antioxidants donate electrons to the marauding free radicals, keeping nearby cells safe in the process.
“It is generally thought that the benefit of antioxidants is that they can quench the excessive reactive oxygen radicals in the body,” explains Ji. “Scientific studies have shown that antioxidants are able to absorb these excessive radicals to absorb the oxidative stress.”
From the mouth to the ORAC-le
Unfortunately, this is as far as the current consensus will take us. While an antioxidant rich diet – typically involving a lot of fruit, vegetables and whole grains – has been linked with lower risk of various diseases, there are other variables at play here. High doses of single antioxidants are unlikely to have the same effect.
In fact, given the complexities of food chemistry, it seems that isolating nutrients will not do much to simulate their natural function in the diet. Perhaps not coincidentally, most clinical studies performed on single antioxidants have shown negative results.
Sometimes these trials show no link between supplements and mortality risk, and sometimes, concerningly, the correlation runs the other way. One often-cited study found a link between beta-carotene supplements and a higher risk of lung cancer deaths in smokers; another found a link between antioxidant supplements and bladder cancer. Overall, the picture remains inconclusive.
Lacking a solid evidence base, regulators have recently clamped down on claims made by food manufacturers, many of whom previously used antioxidants to position their product as healthy. Between 2010 and 2012, it was common to cite a food’s oxygen radical absorbance capacity (ORAC), which quantified its antioxidant strength of a food when tested in a lab. In 2012, however, this list of values was withdrawn.
“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,” said a release on the United States Department of Agriculture website, which had previously hosted the data.
Jin Ji’s laboratory, Brunswick Labs, was involved in the creation of the ORAC values. She says the criticisms levelled at the database were inconsistent with scientific evidence.
“I think the main criticism was that the values indicating antioxidant capacity have no relevance to health, but in 2010, a study using the ORAC values found decreased cancer risks for the highest total antioxidant intake compared to the lowest,” she points out. “There are other publications reporting that adhering to a certain diet rich in antioxidants can have health benefits to people who are participating in these kinds of studies.”
Although the USDA ORAC database is no longer hosted on the agency’s website, it is still exists and can serve as an informational source for food product developers. Ji says there is a clear need for a point of reference on the antioxidant value of foods, irrespective of the analytical limitations.
“If people want to compare, they can visit the online database hosted on Brunswick Labs’ website,” she says. “We found this database very helpful because essentially we are a scientific body that provides information and we help our laboratory with antioxidant quantification. ORAC values are still being used in industry and we have been seeing an enormous amount of demand for ORAC determination.’
“We have already created another database and we will continue to broaden that. Part of the new database, which includes data of antioxidant activity in a biological system like human cells, is currently available on our website.”
She feels the antioxidant metrics of the future are likely to rely less upon test tubes, and more on biological investigations. ORAC values lost their credibility in part because of the limits of in vitro testing. To gain a more accurate sense of how dietary antioxidants work in the human body, it will be necessary to conduct clinical studies, alongside cellular and enzymatic analyses.
One rule for one
For the time being, manufacturers are in a difficult position. While many of their foods do contain natural antioxidants – which do seem to have implications for human health – they can only make very specific claims in their labelling and advertising.
For instance, in the US, antioxidants are treated as nutrients, and need to have an established Reference Daily Intake (RDI) in order to merit a mention. In effect, this means you can list the amount of vitamin C but not the amount of cyanidin. Meanwhile, in Europe, the European Food Safety Authority will allow manufacturers to claim their products are rich in antioxidants, but not to cite any purported health benefits.
While the rules are complicated, evidently is it best to err on the side of caution – confectionary manufacturer Hersheys faced a lawsuit in 2012 for making ‘misleading’ antioxidant claims, and the UK Tea Council was reprimanded in 2007 for ‘exaggerating’ the health benefits of the flavonoids in tea.
William Gorman, the UK Tea Council executive chairman at the time, told the BBC: “We provided the Advertising Standards Agency with almost 100 independent scientific research papers and yet they still turned us down despite acknowledging that the antioxidants in tea are absorbed into the body. Many of the papers we presented used the same methodology to show that fruit and veg are good for you, but the ASA effectively told us we’d have had to run clinical trials, normally reserved for medical drugs.”
Faced with regulation of this kind, Ji counsels a measure of prudence.
“I am not the expert on label claims, but what I have heard talking to our clients is that people can say their food contains antioxidants but they cannot say they have high or low content,” she says. “The health benefits they’re allowed to claim are another game. I believe you can say that antioxidants reduce oxidative stress, or ease inflammation induced by sports for instance. These are the major claims people in industry are going after, through clinical trials or through extensive scientific research.”
She believes there are various reasons why a manufacturer might want to know the antioxidant potential of their food. On one hand, they might simply be looking to to develop parameters for quality control, but equally they might wish to build a foundation for research. Antioxidants, after all, are a burgeoning field of study and there are strong possibilities for future breakthroughs.
“For the first 20 years of antioxidant research, we were busy developing methods to quantify antioxidants in natural botanicals themselves,” she says. “What we have done now is to test human cells as a model and see how antioxidants impact various chronic conditions or biological processes, such as inflammation formation, ageing, cancer formation and glucose uptake. These are preclinical studies. The last stage would be clinical trials, but that does require funding and very involved study and research.”
More haste, less speed
For the time being, the jury is out on what antioxidants can achieve. It seems probable that neither the early hype not the recent scaremongering will prove to be quite accurate. So, while antioxidants may not be the magic bullet promised in the 1990s, there are strong indications they can bring benefits within the context of a healthy diet.
As Dutch scientists, Aalt Bast and Guido RMM Haenan, explained in 2013 in the journal Trends in Pharmacological Sciences: “For several decades, we have noticed that the antioxidant pendulum appears to swing vigorously from ‘only healthy’ to ‘extremely toxic’, and from ‘natural antioxidants are best’ to ‘antioxidants cannot act’… This inevitably hampers research in the field and confused both scientists and consumers. As a consequence, we might fail to spot opportunities for which antioxidants may aid in optimising health.”
Ji agrees that it is best not to jump to any conclusions. At present, we simply do not have the scientific evidence to say what patterns of antioxidant consumption have the greatest benefit to the human body. Over the years ahead, however, ever more clinical trials in the area will be conducted, and as the results are published she is optimistic this will yield some clearer answers.
“It remains to be seen how relevant antioxidant intake is to human health, and we need to find this out,” she says. “This will be ongoing, but I think maybe at some point within the next 10-15 years we will have some clear correlation of the health benefits through clinical trials.”
This article appears in the Spring 2015 edition of Ingredients Insight
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