Too many antioxidants can damage the heart
High levels of radical oxygen species (ROS) have been linked to diseases including cancer, Parkinson’s disease and myocardial infarction. Research has shown that the other side of the spectrum, too many antioxidants, can be just as bad for the health of your heart.
Radical oxygen species (ROS) are molecules with an uneven number of electrons, meaning they are extremely reactive and can initiate a variety of ‘oxidative’ chemical reactions. Oxidation is a necessary process within the body, as it helps fight off pathogens to prevent infections.
Antioxidants are molecules which regulate the number of ROS within the body. They do so by donating an electron to a single ROS, thereby balancing the number of electrons and reducing its reactivity. If there are too many ROS in the body, they can start reacting with proteins, lipids (fats) and DNA, eventually leading to disease over time.
It is therefore important to ensure the correct balance of ROS and antioxidants. The body has a special mechanism for this known as ‘redox homeostasis’, which automatically triggers the production of endogenous antioxidants once the level of ROS is too high.
It was previously thought that the more antioxidant-rich foods in the diet, the better. Now science has shown that too many antioxidants can damage heart tissue, leading to heart failure.
Too many ROS causes oxidative stress, whilst too many antioxidants causes reductive stress – something which has been recently linked to heart failure by a team of researchers from the University of Alabama and California. Working with mice, the researchers found that reductive stress causes the heart to become dangerously enlarged, and disrupts the process of diastole – when the heart refills with blood after contraction.
The mice were genetically engineered to overexpress genes responsible for the production of antioxidants in the heart, which caused a surge in antioxidant proteins to be produced and resulted in reductive stress. Comparing these ‘transgenic’ mice to normal, ‘wild-type’ mice, they found that the mice with high reductive stress had an enlarged heart which pumped out an abnormally large volume of blood, and did not refill to the normal amount. These pathological changes appeared in the mice when they were 6 months of age, and 60% of these mice died by 18 months.
The scientists were able to confirm that it was the surge in antioxidants which caused heart damage, as administering a drug to block the production of a particularly potent antioxidant – glutathione- was able to prevent the pathological changes to the heart. Crucially, this drug had to be administered in the first weeks of life, before the changes had begun to evolve.
The researchers also engineered mice with a low level of reductive stress, which had a normal survival rate but also developed the associated heart changes later on in life, suggesting that even a slight increase in reductive stress in the body can cause permanent damage to the heart.
Although the use of mice to model human disease may not be truly indicative of what happens in the human body, this study at least offers valuable insight into the potential risks of antioxidant overconsumption. This is important, as a very large percentage of people are consuming antioxidants on a daily basis without knowing their redox state. It may be that some people are inducing redox stress within their bodies and putting themselves at risk of heart failure in an attempt to prevent other diseases.
Doctors should be aware of a patients’ redox state before prescribing or administering antioxidants. Heart failure is also linked to an excess in ROS (oxidative stress), so it may be tempting to encourage patients to take antioxidant supplements. However, this may cause more harm than good, so it is important to know exactly which type of stress is causing the heart failure.
- Gobinath Shanmugam, Ding Wang, Sellamuthu S Gounder, Jolyn Fernandes,, Silvio H Litovsky, Kevin Whitehead, Rajesh Kumar Radhakrishnan, Sarah Franklin, John Hoidal, Thomas W Kensler, Louis Dell’Italia, Victor Darley-Usmar, E. Dale Abel, Dean P Jones, Peipei Ping, Rajasekaran Namakkal Soorappan. Reductive Stress Causes Pathological Cardiac Remodeling and Diastolic Dysfunction. Antioxidants & Redox Signaling, 2020; DOI: 10.1089/ars.2019.7808