Many supplements are sold worldwide with antioxidants, such as vitamins C and E. These supplements are said to prevent cancer and aging. New research from UMC Utrecht questions the thinking behind the protective role of antioxidants, and that puts the use of supplements with high doses of antioxidants in a different light.
It is widely believed that antioxidants can prevent damage to DNA. This damage is said to be caused by the release of free radicals during energy production in our cells. This reasoning is often even the basis for the idea that these antioxidant supplements could prevent aging and cancer. But new research shows that the assumption that free radicals from energy production cause DNA damage is incorrect.
The suspicion that this assumption is incorrect has existed for some time, and the research group of associate professor Tobias Dansen from the UMC Utrecht now provides important evidence for this in the scientific journal Nature Communications.
“It sounds very attractive: ‘If we take a pill that scavenges radicals we might be able to prevent cancer, stay healthy and live very long.’ But unfortunately it just doesn’t work that way,” says Tobias.
What was that again?
When oxygen is used in the combustion of nutrients in the body, free oxygen radicals and substances derived from them are released, together known as Reactive Oxygen Species (ROS). Mitochondria, the energy factories of our cells, play an important role in this and ensure the production of these ROS. As the name suggests, these substances are very reactive. This means that they can easily enter into a chemical reaction, for example a reaction in which DNA is damaged. Damage to DNA can lead to mutations, and mutations can cause cancer.
Antioxidants, such as vitamins C and E, are substances that can scavenge ROS. Dansen’s research group is concerned with the molecular mechanisms surrounding ROS. What do these do in our cells? And what role do they play in diseases such as cancer and age-related diseases?
No direct evidence
It is often assumed that ROS from energy production in the mitochondria are responsible for damage and mutations to DNA and thus contribute to the development of cancer. “At first glance, this is not a strange thought: DNA can be damaged by ROS, and mitochondria are the main source of ROS in the cell. But in fact there is no evidence at all for a direct link between ROS from energy production and damage to DNA further down in the cell nucleus,” says Daan van Soest, PhD student in Tobias’ research group.
More insight thanks to a new system
With a grant from the Dutch Cancer Society, the Dansen Lab developed a new system. This allows precise amounts of ROS to be produced very accurately at specific locations in the cell. Using a protein that originally comes from yeast, the researchers came up with a clever trick. This protein produces ROS as soon as the substance (D-Ala) is added to the cells. The amount of D-Ala added determines the amount of ROS produced. They attached this protein to the mitochondria. This makes it possible to simulate the effect of ROS produced by mitochondria, without interfering with energy management.
No DNA damage due to energy management
Daan wondered whether ROS produced by the mitochondria could lead to DNA damage in the cell nucleus. To achieve this, these ROS must first travel from the mitochondria to the DNA.
“That intermediate step has actually never been properly investigated. We have now done that,” Daan explains. And guess what? ROS produced by our energy balance (in the mitochondria) do not reach the DNA in the cell nucleus at all and therefore do not cause any damage there. “About 100 times more ROS must be produced than is normally produced by the mitochondria to lead to DNA damage,” says Daan.
The multi-billion dollar industry of antioxidant supplements is based in part on a mechanism that now appears to have been debunked. “They may not like our story,” Tobias notes. “Because the idea that our energy balance would cause DNA damage forms the basis for the idea that antioxidants work against cancer and aging.”
It is one of the reasons that antioxidants are popular and taken by many people. The researchers hope to make it clear that there appears to be no direct evidence for this, and that taking high doses of antioxidants may also have negative effects.
The downside of antioxidants
Free radicals also have important functions in our body. Previous research by Tobias’ team already showed that they are indispensable for correct cell division. The researchers therefore question taking high doses of antioxidants because this may also eliminate these positive effects.
There is also still a lot of uncertainty about the effects of taking antioxidants for cancer patients. Tobias: “There are plenty of studies in which antioxidants actually show a negative effect. For example, mouse studies in which metastases return more quickly when antioxidants are administered. We also see that some tumor cells need more antioxidants to survive than healthy cells, and that these tumor cells therefore benefit from extra antioxidants. It is a very complex story in which all kinds of factors play a role.”
According to the researchers, there are still too many questions to provide concrete advice about taking extra antioxidants for cancer patients. “Continue or consult with a treating physician about taking antioxidants,” is their advice.
A question that the researchers want to answer in the future is where (oxidative) DNA damage in the cell nucleus comes from. In any case, this damage is not caused by ROS from the energy system, but other processes may play a role in it. The researchers are also curious whether the molecular mechanisms surrounding ROS can tell more about the development of cancer and the effectiveness of existing therapies. This may also provide starting points for new treatments.
“We often see that something is labeled as healthy because it contains many antioxidants. There is an excess of everything, including antioxidants. We hope that our research contributes to the idea that free radicals are not necessarily a bad thing and that their removal with antioxidants is therefore not necessarily a good thing,” Daan concludes.
Read more?
Read the article ‘Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA’ in Nature Communications.
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