Professor Lam Ching-wan (left) and two of his team members working with an advanced mass analyser for researches in clinical metabonomics.
THE SCIENCE AND FICTION OF ANTIOXIDANTS
A whole industry of health supplements and food marketing has sprung up around the idea that antioxidants can prevent cancer. Unfortunately, the promise has not held up in clinical trials. New research explains why and shows how antioxidants may in fact promote cancer.
Visit some of the major health websites, search ‘antioxidants’ and you will find sweeping statements about their benefits. “Add antioxidants to your diet,” says the Mayo Clinic, “[They] may protect your cells against the effects of free radicals… [which] may play a role in heart disease, cancer and other diseases.” “Do your immune system a favour and pack more fruit and vegetables on your plate. They’re loaded with nutrients, called antioxidants, that are good for you,” says WebMD. “Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage,” says the website of the National Library of Medicine of the US National Institutes of Health.
Marketers have picked up the cue and slapped the ‘antioxidant’ label on a whole range of products such as cereals, dried fruit, herbal tea and dark chocolate and supplements such as Vitamin C, Vitamin E and beta carotene.
The science behind this enthusiasm makes sense in theory. Cells can be damaged by too much oxygen, called reactive oxygen species (ROS), which can lead to cancer and other diseases and contribute to the ageing process. Antioxidants help to reduce ROS, so the logical conclusion should be that they reduce the risk of disease.
However, the theory has not stood up in the field. Recent large-scale randomised control trials – the gold standard of clinical testing– have turned up alarming results. In some trials, antioxidant supplementation actually increased the cancer rate. For example, healthy men taking Vitamin E supplements had a higher rate of prostate cancer and smokers given beta carotene experienced more lung cancer than those not taking the supplements.
People think antioxidant supplements are safe. Now we have evidence that they are not good for health.
Professor Lam Ching-wan
Fuel for tumour cells
Research by an international team of scientists from North America, Europe, Japan and Hong Kong, including three scholars from HKU’s Department of Pathology, has now explained what is going on and pointed to new approaches to antioxidants and new directions for cancer treatment.
Professor Lam Ching-wan was part of the HKU contingent and contributed findings from the burgeoning field of cancer metabolomics. He and his colleagues showed how cancer cells generated and used antioxidants to stay alive.
“Cancer cells, like normal cells, have a lot of ROS. They require ROS to develop into a cancer cell but if the ROS level remains high, the cell will kill itself because ROS eventually turns on the mechanism of apoptosis, or cell death. So for a cancer cell to develop and grow, on the one side it has to increase ROS, but on the other it has to increase antioxidant levels to prevent the accumulation of too much ROS in the cell,” he said.
Professor Lam helped to identify how the cancer cell performed this balancing act by using two pathways for antioxidants to contain ROS levels. The glutathione pathway is turned on in the cell in the early stages, then as the cell becomes established the thioredoxin pathway takes over. He likened their role to that of a car with two brakes.
“The ROS is like the accelerator in the tumour cell and glutathione and thioredoxin are the brakes to suppress cell oxidative stress in case there is too much. This finding explains the clinical paradox that giving antioxidants to healthy patients can lead them to develop more cancers than expected.”
Glutathione and thioredoxin antioxidant pathways synergise to drive cancer initiation and progression.
Like a car crash
It also points to potential treatment. Professor Lam said they had applied inhibitors to both pathways in the laboratory and these resulted in cell death. “By removing the brakes, there will be a car crash and the cancer cells will die,” he said.
“People think antioxidant supplements are safe. Now we have evidence that they are not good for health. For someone who does not yet have cancer, they may help the cancer to be initiated. For those with cancer or receiving treatment, it’s possible that antioxidants may cause a recurrence. Anti-antioxidants may help to improve the prognosis but we do not have the data on that yet.”
Professor Lam’s findings were published in the journal Cancer Cell.
That is not to say that antioxidants should be eliminated from the diet. They are naturally occurring and they do serve multiple functions. The challenge will be in determining how much is safe.
Professor Lam anticipated that their findings, which were published in Cancer Cell last year with an accompanying editorial highlighting the results and which also earned him a Best Research Output Prize 2015 under HKU’s Strategic Research Themes – Development and Reproduction, would trigger widespread study and debate about the use of antioxidants in food and supplements and their potential
Professor Lam (right) was presented with the Best Research Output Prize 2015 at the Symposium on Stem Cells, Reproduction, Development and Disease 2015.