Antioxidant evidence is very weak, concludes review

The review, published in the British Journal of Pharmacology​, looked at the evidence behind the oxidative stress (OS) theory of disease, and some of the issues with the model. They found it to be significantly lacking for the nutrients present in a range of fruits and vegetables.

“Viewing the OS theory of disease from different theoretical perspectives developed in epistemological research, the theory comes out significantly weaker than many other pathogenic theories​,” wrote the authors.

“This might explain why the translational shortcut of this theory, antioxidant therapy, has failed so often and has never shown enough evidence to be incorporated in guidelines, approved by regulatory agencies and recommended and reimbursed by health insurance systems basing their decisions on [evidence-based medicine] criteria​,” they added.

A stressed narrative?​

The authors describe how the OS theory has become a powerful narrative: “The fight between good and evil, antioxidants preventing ageing like the Holy Grail or acting like shields against ROS, an imagery and wording often used even by scientists in their review articles or presentations​.”

But despite the strength of the narrative, the mechanisms behind reactive oxygen species (ROS) are usually contained within a “black box​” which is applied to a list of diseases “so long to include practically all of them​” – making it very hard to describe the actions of ROS.

“We have seen that this is in part due to the technical difficulties of measuring ROS, an essential step to make a claim of a ROS-mediated disease, which is complicated by the large number of analytical techniques and analytes that have been used to make such claims​,” the authors wrote.

“Trying to aggregate a plurality of diseases where different ROS are generated in different tissues by different sources may have aggravated the problem​,” they added.

They also noted potential issues with side-effects: “When taking the theory of OS from the bench to the bedside using antioxidants as drugs we are adding the problem that most of them, more than most drugs, will have off-target effects, or that ROS may have physiological functions beyond their toxic effects​.”

Open data and causal relationships​

To improve the standard of evidence around oxidative stress and antioxidants, the authors have several concrete suggestions.

First they advocate the development of international collaborations, including open data and a Cochrane-style collaboration for preclinical studies.

Second, they suggest a priority should be to “address the key question of how to demonstrate that OS is a causal component in disease X​”.

Finally, they call for researchers to “sum up the level of evidence available rather than test another new antioxidant extracted from a different fruit, where a plethora of antioxidants from other sources have already been studied​”.

“Funding agencies need to encourage scientists to take the hardest route rather than go for the easy publication and the conventional wisdom of the dominant group​,” wrote the authors.

“Only critical, honest and out-of-the-box analysis of redox research will lead to the identification of redox pathways involved in pathologies and only then will innovative therapeutics be emerging​,” they concluded.

Source: British Journal of Pharmacology​

Published online ahead of print, doi: 10.1111/bph.13544​

“The oxidative stress theory of disease: levels of evidence and epistemological aspects​”

Authors: Ghezzi, P.; Jaquet, V.; Marcucci, F.; Schmidt, H.H.H.W.