Are Antioxidant Health Claims Misleading?

An antioxidant is a synthetic or natural compound capable of slowing or preventing the oxidation of other molecules. Most commercial food antioxidants work by scavenging free radicals or chelating metals. It is well-known that oxidation damages various biological substances and subsequently causes many diseases such as cancer, liver disease, Alzheimer’s disease, arthritis, inflammation, diabetes, Parkinson’s disease, atherosclerosis and AIDS. As a result, many diseases have been treated with antioxidants to prevent oxidative damage.

As reactive oxidative species (ROS) are involved in the pathogenesis of many diseases, finding efficient antioxidants as therapeutic agents has been a hot field in biomedicine. Excess ROS can perturb the redox balance and produce pathological changes through lipid peroxidation and protein and nucleic acid damage. Those changes could eventually be responsible for chronic diseases.

However, only relatively trivial success has been attained in antioxidant-based conventional drug discovery (e.g., idebenone and edaravone). Thus, it seems urgent to improve the translational efficiency of antioxidant research.

The use of antioxidant supplements by patients during conventional cancer treatment is another controversial area in oncology. Many studies have suggested that consumption of certain natural antioxidants leads to a reduction in oxidative stress and the development of major diseases.

In many countries, some herbal medicines have been traditionally consumed as medical foods to adjust metabolic disturbances. In recent years, data from various studies indicate many oriental herbal medicines contain a wide variety of natural antioxidants, such as phenolic acid, flavonoids and tannins.

The antioxidant hypothesis implies that all changes associated with reactive species activity are undesirable and the action of antioxidants is beneficial. It is particularly significant that some dietary compounds have beneficial activities, which are not direct antioxidant effects (e.g., glucosinolates) while others (e.g., vitamins C and E, and carotenoids), previously recognized only for their classical antioxidant characteristics, are also being shown to induce other biological responses. Unfortunately the majority of data available to support this theory have been obtained from cell culture and animal experiments and the relevance of these data, obtained under non-physiological conditions, needs to be reassessed.

The traditional “trio” of antioxidants—such as ascorbate, beta-carotene and alpha-tocopherol—have had bad press recently. Several human intervention trials have yielded mostly-negative results, and some meta-analyses and other studies suggested these agents not only fail to protect against disease, but also that some of them accelerate development of cancer or cardiovascular diseases. This obviously raised the concern about health benefits in human.

In recent years, several experiments demonstrated all reactive species act as signaling molecules in cell function, proliferation and differentiation and cell death, and that has altered this simplistic “antioxidant theory.” Overall, experts predicted it could take more than a decade before human clinical trials confirm antioxidants as physiological stimulants with specific effects on organ tissue, which will substantiate health claims.

Ultimately, antioxidants can’t be pinned to one mechanism of action (i.e., scavenging of radicals), but will be based on inflammation, immunity and oxidative stress. Future health claims could focus more on this “trio,” which better reflects biological activity and is more relevant to human disease prevention.