*For medical professionals only
Maybe every field has its own "indecision, xxxx", which can be quantum mechanics, intestinal flora, or reactive oxygen species (ROS).
Reactive oxygen species appear to have a kick in every biological process and have a variety of complex effects on pathophysiology. Perhaps the most well-known is the killing power of reactive oxygen species, which can cause fatal blows to cells and surrounding tissues. Oxidative stress has been implicated in the pathogenesis of a myriad of diseases, including neurodegenerative and cardiovascular diseases, diabetes, and cancer.
Antioxidants can directly resist the oxidation process. Strictly speaking, an antioxidant is defined as "a substance that reacts with an oxidant to delay, prevent, or eliminate oxidative damage to a specific target molecule." From this definition, we can read some positive tendencies, and the products that we come into contact with in real life that contain antioxidant effects are mostly from the perspective of promoting health benefits.
In tumor tissues, due to metabolic alterations, inflammation, a hypoxic environment, and upregulation of oncogene-driven reactive oxygen species, there will be more reactive oxygen species, which will need antioxidants to "hedge" in any case. But what are the facts?
Recently, the journal Molecular Cell published a review paper systematically discussing the various roles of antioxidant regulation in cancer, during which the view may surprise viewers who have a filter for "antioxidants".
Antioxidants do not prevent cancer, but rather promote cancer
This statement that uncontrolled oxidative stress can lead to DNA damage, mutations, and tumors may seem at first glance to lead to a simple conclusion: reactive oxygen species are inherently harmful, while antioxidants are beneficial in almost all aspects of human health. Guided by this common misconception, it's no surprise that antioxidant dietary supplements such as vitamins/minerals are selling well.
Don't say you haven't eaten it, I don't believe it.
Although the results of different epidemiological surveys vary slightly, the reported prevalence of antioxidant supplement use is generally above 50%, and older and more educated people are more likely to try it.
However, the preventive effect of antioxidants on cancer has not been proven. In large randomized controlled trials conducted from the 90s to the early 21st century, no clinical benefit was observed, and some antioxidants even increased all-cause mortality.
Perhaps, taking health supplements is still not the same as eating well?
There is an assumption that the antioxidants tested in clinical trials are not the same as if they were ingested as separate chemicals because of the complex combination of antioxidants, vitamins, and minerals in food.
If such a mysterious combination exists, we still haven't decoded it.
Whether antioxidants actually help fight cancer is also debatable. It is important to know that oxidative damage is the main mechanism of cancer treatments such as radiotherapy, and antioxidants may protect tumors by reducing the effectiveness of treatment. Laboratory findings also provide conclusive evidence that antioxidants accelerate cancer progression through a variety of mechanisms.
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Scientists have found that vitamin C and other factors will promote the growth of blood vessels in tumors
Scientists have found that taking supplements such as iron and antioxidants before or during chemotherapy has a clinical finding that the risk of recurrence increases by 79% and 41%, respectively
Scientists have discovered that antioxidants can enhance the ability of cancer cells to use glucose and promote cancer metastasis
The data of 50,000 people in 20 years shows that vitamin E supplementation with specific gene mutations can reduce the risk of cancer Clinical findings
Antioxidants drive cancer to occur, develop, and metastasize
Leaving aside foreign antioxidants, we have our own endogenous antioxidants in the human body that are deeply involved in the biology of cancer cells.
Glutathione (GSH) is a substrate for a variety of antioxidant enzymes and also spontaneously removes reactive oxygen species at low levels. Interestingly, a modified subunit of glutathione-cysteine ligase (GCLC), which is essential for glutathione synthesis, allows intracellular accumulation of glutathione, while the absence of GCLM significantly prevents tumor initiation and progression.
Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcriptional regulator of a variety of antioxidant enzymes and also supports tumorigenesis. Somatic mutations that prevent NRF2 degradation have been found in up to 25% of lung squamous cell carcinomas, 15% of lung adenocarcinomas, and 23% of esophageal/gastric squamous cell carcinomas, and high levels of NRF2 are associated with poor cancer prognosis.
There is also the involvement of antioxidants in the transfer process. Metastatic cancer cells are subject to a stronger threat of oxidative stress, and the folic acid pathway can promote NADPH production and help cancer cells cope with oxidative stress.
Without going into too much detail about the complex molecular mechanisms, in summary, antioxidants actually play the role of cancer agents and may lead to resistance to anticancer therapies.
Antioxidant regulation in cancer
In fact, cancer cells themselves are also very active in antioxidation. Analysis of substances in the tumor microenvironment (TME) reveals rapid uptake of antioxidant precursors by tumors, and cancer cells also receive corresponding nutrients from surrounding stromal cells.
Tumors take in resources from the microenvironment to maintain antioxidants
Do antioxidants fight cancer?
After reading the above content, everyone's impression of antioxidation may be completely reversed. Is it true that in cancer, antioxidants are all bad things?
If I could say no to the question, it would be much easier. Unfortunately, it is difficult to briefly describe the complexity of the reality, and some studies have found that the effect of NRF2 activation on tumorigenesis can be reversed to slow down the progression and metastasis of cancer in different environments.
For carcinogen-driven tumors, NRF2 can exert an inhibitory effect in the initial stage but support progression, and for genetically driven tumors, NRF2 can be referred to as the initiating driver but prevent progression to high grade.
You see, it's a real mess.
Cells at different stages of carcinogenesis require different characteristics to thrive, so the role of antioxidants in the carcinogenesis process is also very smooth.
Give up and leave the complex problems to the experts.
For us ordinary people, the useful information may be that if you are still taking antioxidant supplements to prevent cancer, it is really unnecessary.
Resources:
[1]https://www.cell.com/molecular-cell/fulltext/S1097-2765(23)00917-6
The author of this article丨 Dai Siyu