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 assumed 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 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 food down into energy, it generates a by-product 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. By ‘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 aging, 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 and, therefore, 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. 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 failed to find positive results.

Sometimes, these trials show no link between supplements and mortality risk, and sometimes, worryingly, the correlation runs the other way. One oft-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, then, the picture remains inconclusive.

"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." 

Lacking solid evidence, regulators have recently clamped down on food manufacturers’ claims, many of which 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 the 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 US Department of Agriculture website, which had previously hosted the data. Brunswick Labs was involved in the creation of the ORAC values, but Ji 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, but in 2010, a study using the ORAC values found decreased cancer risks for the highest total antioxidant intake compared with the lowest," she points out. "There are other publications reporting that adhering to a certain diet rich in antioxidants can have health benefits for people who are participating in these kinds of studies."

Although the database is no longer officially recognised, it still exists and is maintained through Brunswick Labs’ own internal research. Ji says there is still 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 come here to compare," 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.

"Are there efforts underway to create another database? Yes, we have already done so and we will continue to broaden that."

Ji feels the antioxidant databases of the future are likely to rely more upon biological investigations than test tubes. ORAC values lost credibility in part due to the limits of in-vitro testing. To gain a more accurate sense of how dietary antioxidants work, 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 cyanadin. 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 it is best to err on the side of caution – US confectionery manufacturer The Hershey Company 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 flavonoids in tea.

William Gorman, the UK Tea Council executive chairman at the time, told the BBC: "We provided the Advertising Standards Agency [ASA] 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 from talking to our clients is that people can say their food contains antioxidants but they cannot say they have high or low content.

"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."

"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.” 

She believes there are various reasons why a manufacturer might want to know the antioxidant potential of its food: on one hand, they might simply want to develop parameters for quality control but, equally, they might want 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," says Ji. "What we have done now is to test human cells as a model, and see how antioxidants affect how the human cells grow and develop, and look at the cancer formation process. That’s a preclinical study. 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 antioxidants. It seems probable that neither the early hype nor the recent scaremongering will prove to be entirely accurate. So, while they may not be the magic bullet promised in the 1990s, there are strong indications that antioxidants can bring benefits within the context of a healthy diet.

Dutch scientists Aalt Bast and Guido RMM Haenan explained in 2013 in 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 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, more clinical trials in the area will be conducted, and as the results are published, Ji 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 ten to 15 years, we will have some clear correlation of the health benefits through clinical trials."