The Effects of Dietary Supplements that Overactivate the Nrf2/ARE System

Background: Inflammation is one of the most misunderstood aspects of human health. People have been encouraged to eat foods that have a high antioxidant capacity, and in vitro tests for total antioxidant capacity emerged. They were based on measuring the destruction of oxidized test compounds in direct reactions with the antioxidants in foods. Many dietary supplements arrived in the market. They contained purified antioxidants, such as resveratrol and EGCG that were and still are widely assumed by many to be quite healthy at any dose. Methods: The literature on inflammation and the Nrf2/ARE antioxidant system was searched systematically. Articles from prestigious, peer-reviewed journals were obtained and read. The information obtained from them was used to write this review article. Results: Over 150 articles and books were read. The information obtained from them showed that very few dietary antioxidants exert their effects by reacting directly with Reactive Oxygen and Nitrogen Species (RONS). Instead, most of the effective antioxidants activate the endogenous Nrf2/ARE antioxidant system. This helps prevent smoldering inflammation and the diseases that it can cause. However, when overactivated or activated constitutively, the Nrf2/ARE antioxidant system can cause some of these diseases, including many types of multidrug resistant cancer, autoimmune, neurodegenerative and cardiovascular diseases. Conclusion: Even though green tea, as well as many fruits, vegetables and spices are quite healthy, dietary supplements that deliver much higher doses of antioxidants may not be. People who are diagnosed with cancer and plan to start chemotherapy and/or radiotherapy should probably avoid such supplements. This is because multidrug resistant tumors can hijack and overactivate the Nrf2/ARE antioxidant system.