Novel Cancer Hypothesis Suggests Antioxidants Are Harmful

It had to happen. We have been inundated by every Tom, Dick and Harry telling us all to consume as much anti-oxidants as we can. Now Dr James Watson (yes, Nobel prize holder) has suggested that they might not be the wonderful cancer-preventing substances so often claimed.

You will not have noticed, but I never make the claim that something is good because it contains anti-oxidants. Simple reason for that is that I have never been convinced I understand it sufficiently. And I have been sort-of waiting for someone to start claiming otherwise.

This does not mean that Dr Watson is right, still less that I am, but it is like night following day - whatever is shouted from the rooftops today, will be dismissed as hokum tomorrow.

Thyroid connection? Well one is that selenium is touted as a wonderful anti-oxidant! My view has always been that selenium has a very important role but not necessarily due to any anti-oxidant capacity. Again, I do not know.

Please excuse my ignorance...

Medscape Medical News > Oncology

Novel Cancer Hypothesis Suggests Antioxidants Are Harmful

Zosia Chustecka

Jan 11, 2013

A new hypothesis that focuses on reactive oxygen species (ROS) proposes that antioxidant levels within cancer cells are a problem and are responsible for resistance to treatment.

The theory destroys any reason for taking antioxidative nutritional supplements, because they "more likely cause than prevent cancer," according to Nobel laureate James Watson, PhD, from Cold Spring Harbor Laboratory, New York.

Dr. Watson, who shared the Nobel prize for unraveling the structure of DNA, regards this theory as being "among my most important work since the double helix," notes a press release from his institution, where he has been director since 1968.

The theory was published online January 8 in Open Biology.

Dr. Watson explains that the vast majority of agents used to directly kill cancer cells, including ionizing radiation, most chemotherapeutic agents, and some targeted therapies, work by generating — either directly or indirectly — ROS that block key steps in the cell cycle.

This generation of ROS creates a hypoxic environment in which cancers cells undergo a transformation from epithelial to mesenchymal cells (EMT).

These transformed cells almost inevitably posses very high amounts of antioxidants, which effectively block the effects of anticancer treatments, Dr. Watson notes. Once a cancer becomes resistant to chemotherapy, it usually is equally resistant to ionizing radiation, he points out.

In addition, these transformed EMT cancer cells generate free-floating mesenchymal cells, which have the flexibility and movement that allows them to metastasize to other body locations (brain, liver, lung). "Only when they have moved do most cancers become life-threatening," Dr. Watson notes.

Interestingly, the widely used antidiabetic drug metformin has been shown to preferentially kill mesenchymal stem cells. "In a still much unappreciated article published 3 years ago," metformin added to chemotherapy "induced prolonged remission if not real cures" in mouse models of cancer (Cancer Res. 2009;69:7507-7511), Dr. Watson writes. He notes that clinical trials are currently looking to see if adding metformin to chemotherapy provides clinical benefits, but adds that diabetics who have been using metformin regularly have a reduced incidence of many cancers.

Resistance to Therapy From Antioxidants in Cancer Cells

Dr. Watson proposes that anticancer therapies work by generating ROS, which cause apoptosis. However, as cancer cells evolve, they produce antioxidant proteins that block this effect, such as glutathione, superoxide dismutase, catalase, and thioredoxin.

The fact that cancer cells largely driven by RAS and Myc are among the most difficult of cancers to treat could be due to their high levels of ROS-destroying antioxidants, Dr. Watson argues. High antioxidative levels might also explain the effective incurability of pancreatic cancer, he adds.

If this theory is correct, then drugs that lower antioxidant levels within cancer cells would be therapeutic. In fact, the ROS-generating agent arsenic trioxide has been shown to reduce levels of glutathione and thioredoxin. Arsenic trioxide is currently being used to treat promyeloblastic leukemia, but this theory suggests that the drug could be useful in many major cancers.

Nutritional Antioxidants Could Be Harmful

One far-reaching implication of this theory is that antioxidants as nutritional supplements, including beta-carotene, vitamins A, C, and E, and selenium, could be harmful in cancer.

For years, such supplements have been widely hyped for cancer prevention and/or treatment, as has encouragement to eat colorful fruit and berries, which contain antioxidants.

However, Dr. Watson warns that recent data strongly hint that much of the untreatability of late-stage cancer might be the result of "its possession of too many antioxidants, [so] the time has come to seriously ask whether antioxidant use more likely causes than prevents cancer."

Many nutritional intervention trials have shown no obvious effectiveness in preventing gastrointestinal cancer or in lengthening mortality, he writes. "In fact, they seem to slightly shorten the lives of those who take them."

Hence, he concludes, "blueberries best be eaten because they taste good, not because their consumption will lead to less cancer."

Very Complex Process

Maurie Markman, MD, national director for medical oncology at the Cancer Treatment Centers of America, who writes the Medscape Markman on Oncology blog, was asked to comment on the theory.

"The importance of the critical relationship between oxidating activity and antioxidants in the normal functioning of cells has been recognized by many investigators, and it is not surprising that this process would be quite relevant in cancer. However, it must be emphasized that this is a very complex process and the balance between these powerful influences at the cellular level is certain to be very carefully controlled. Further, it should be noted that antioxidants are components of our normal diets. Finally, while a provocative concept, it is most unlikely that a simple approach to somehow removing antioxidants from the body will be a useful strategy in cancer management," he explained.

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19 Replies

  • "Everything in moderation" is what I was always brought up with, and my grandma used to say "A little of what you fancy does you good".

    I always think too much of anything can't be good for you. Look at the giant pandas, for example.

  • Exactly what I was going to say! I noticed that at one point he refered to 'too many antioxidants.

    My doctor always told me that 'too many antioxidants are oxidising'!


    PS are you really saying that we have too many giant pandas???

  • lol! I think Carolyn meant too much bamboo! ;-)



  • Oh, really? They ate themselves to death? I haven't heard about that.

  • I think that may be a bit extreme! ;-) I just didn't want you thinking our Admin team had something against pandas...! lol!



  • Nooooooo, I didn't think that. lol Who could possibly have anthing against pandas!

  • Cochrane review of same subject:

    Guardian article on same subject:

  • But when we look at meta analysis of supplement research what are we looking at?


    If I was a researcher and wanted to get a paper published it would be much easier to publish a paper proving supplements don't work than a paper showing they do work.

    That is because the people who advertise in the Journals are DRUG COMPANIES who make lots of money selling DRUGS not supplements.

    If you were a journal would you antagonise your main income source by publishing anti drug articles?

    It's very easy to devise studies that you know produce the results drug companies will be delighted to read.

    There are two forms of Vitamin D, Ergocalciferol and Cholecalciferol one is more potent that the other.

    Which do you think many researchers choose to use? and why do you think they make that choice?

    The human body is set to produce vitamin D daily given sun exposure so the nearest equivalent for research is daily oral supplements.

    Now go check the research and you'll see the extent researchers go to ensure vitamin D research produces results favourable to the drugs industry.

    We know naturally humans reach vitamin d equilibrium at 125nmol/l or 50ng/ml so check out the vitamin d research and see how many researchers are trying to bias the results by using too little vitamin d, for too short a time or are not measuring 25(OH)D or keeping levels at optimum for sufficient time for the results to be meaningful.

    The same applies to Vitamin A Vitamin C and Vitamin E it doesn't take much time to find which are the effective forms of each of those and then compare that with the forms generally used in research trials.

    When you've done that you'll see why I have a very jaundiced view of the integrity of most published research.

  • Trouble is, we only know what we know from published research plus, pretty much, personal experience.

    Much vitamin D research in the USA has considered milk as a source because, in the USA (but not in the UK) milk is fortified. One way in which milk is fortified with vitamin D is by exposure to ultraviolet which produces D3 / Cholecalciferol.

    Although a very simplistic approach, checking PubMed for Ergocalciferol and Cholecalciferol produces around 3251 and 21,541 results respectively. Which suggests a strong bias towards Cholecalciferol. (Those numbers obviously include papers which compare the two substances in both totals.)

  • If we want our cars to run reliably we get them regularly serviced and retuned to the manufacturers original default settings.

    Humans don't come with a service manual but we do have an example of the 25(OH)D levels early humans would have attained and maintained living near naked outdoor lives.

    You won't find any vitamin D research as yet that starts from the human perspective and looks at what happens when 25(OH)D are kept at a safe natural level for an extended period.

    Similarly we know the activation of Calcitriol is enabled by the presence of magnesium and other cofactors.

    It's a bit like getting your car retuned but returned from the garage with all the tyres under-inflated. You'll not get good performance running with under-inflated tyres and more than getting effective vitamin D response without correcting Vitamin D cofactor deficiency states.

    Early humans only had the opportunity to consume free range organic pastured meats and had no access to omega 6 rich vegetable/seed oils. We know how having an omega 3 <> omega 6 ratio affects inflammation and we know both Vitamin E and omega 3 DHA are vitamin d ligands. (they bind with the Vitamin D receptor so it activates calcitriol production)

    We have to understand that when researchers claim they are using "healthy volunteers" these trial participants are just ordinary people with the same micro-nutrient deficiencies that over the next 30 yrs or more will result in obesity, diabetes, cancer, dementia etc.

    Now go looking for Vitamin D research where they ensure all the appropriate default settings for humans are reset prior to study commencing?

  • A nutritionist I consulted advised me to stop taking a selenium supplement precisely because I'd had breast cancer.

  • But you do have to retain your common sense when reading any research or hypothesis.

    It doesn't take long to find out what controls MYC

    Vitamin D receptor as a master regulator of the c-MYC/MXD1 network

    Vitamin D is an antioxidant, so throw antioxidants out of the story and you lose control of MYC regulation.

    Watson talks about

    " The circadian rhythm regulator (PER2) by negatively regulating Myc levels functions as an important tumour suppressor"

    But we all know what controls circadian rhythm.

    The ANTIOXIDANT melatonin.

    It's absolutely true that if you work shifts or otherwise disrupt melatonin secretion you increase your cancer risk.

    From dawn to dusk your body is set to produce the ANTIOXIDANT Vitamin D3 and from dusk to dawn it's supposed to create the ANTIOXIDANT Melatonin.

    Do we think that the Evolutionary process got it absolutely wrong by setting human DNA to produce antioxidants 24/7 whenever it gets the chance?

    it's just unbelievable anyone can suggest that antioxidants such as vitamin D and melatonin are the cause of cancer.

    If you don't believe me go to pubmed and search for the antioxidant CURCUMIN and CANCER and you'll see the many different routes by which this antioxidant also helps reduce your risk or improves your prognosis.

    Seleniium is a slightly different story because selenium toxicity is a fact in some parts of the USA as is Selenium deficiency. The way our food system works now it's impossible to know exactly where your food was sourced. However one thing is certain and that is if you are in a selenium toxic region adding a selenium supplement will make it worse and if you are in a selenium deficient region adding a selenium supplement may be helpful. UK readers should be aware we are borderline and declining and adding selenium may be a good idea. But this is not a one size fits all situation because there will be International readers living in Selenium toxic environments where the recommendation to add selenium will not be sensible.

  • We are all different, but I did not read the article as saying we should dump all anti-oxidants and doing so would cure cancer.

    But I did infer that we should be circumspect of those who go on and on about anti-oxidants. You only have to listen to a tele-doctor, health correspondent or "food expert" to hear that we should be consuming lots of x, y or z because they help prevent cancer due to the anti-oxidants they contain. (And that is not meant to damn all such people - some are very careful of what they say.)

    Many substances may be classed as anti-oxidants but that is only one of the many attributes they can be considered as having - and maybe not the most important one for many substances in many circumstances.

    I have long suggested moderation in selenium - and yet have been shouted down because I said that maybe 200 mcg every day is excessive (though still well below the danger levels). When I take any, I take 100 mcg and not every day.

    Further, putting an anti-oxidant into your mouth does not guarantee that an anti-oxidant appears within the cells of your body - which is the simplistic story pushed by many.

    22. Free-radical-destroying antioxidative nutritional supplements may have caused more cancers than they have prevented

    For as long as I have been focused on the understanding and curing of cancer (I taught a course on Cancer at Harvard in the autumn of 1959), well-intentioned individuals have been consuming antioxidative nutritional supplements as cancer preventatives if not actual therapies. The past, most prominent scientific proponent of their value was the great Caltech chemist, Linus Pauling, who near the end of his illustrious career wrote a book with Ewan Cameron in 1979, Cancer and Vitamin C, about vitamin C's great potential as an anti-cancer agent [52]. At the time of his death from prostate cancer in 1994, at the age of 93, Linus was taking 12 g of vitamin C every day. In light of the recent data strongly hinting that much of late-stage cancer's untreatability may arise from its possession of too many antioxidants, the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.

    All in all, the by now vast number of nutritional intervention trials using the antioxidants ß-carotene, vitamin A, vitamin C, vitamin E and selenium have shown no obvious effectiveness in preventing gastrointestinal cancer nor in lengthening mortality [53]. In fact, they seem to slightly shorten the lives of those who take them. Future data may, in fact, show that antioxidant use, particularly that of vitamin E, leads to a small number of cancers that would not have come into existence but for antioxidant supplementation. Blueberries best be eaten because they taste good, not because their consumption will lead to less cancer.

    From Jim Watson's paper linked in original post.


  • But how do you think most people will interpret the title

    "Novel Cancer Hypothesis Suggests Antioxidants Are Harmful"

    Personally I don't think anyone dying when aged 93 should be regarded as a failure. It when apparently fit people are suffering serious strokes aged 53 that we should be reconsidering how good accurate and safe most modern medical advice really is and how much that advice it based on good HONEST research and not reflecting the best interests of big pharma.

    Nice paper here that may help you understand why cholesterol lowering may not be in your best interests.

    The “Mevalonate hypothesis”: a cholesterol-independent alternative for the etiology of atherosclerosis

  • I am on the same wavelength as CarolynB. Too much of anything is bad for you.

    I think you should not eat any foodstuff every single day, because everything has its dark side!

    Also I have always been a bit anti supplements because I think it's better to eat the natural thing, your body will usually utilise it better, because the micronutrients in food combine for the best effect. (which is probably why NDT works better than SYNTHETIC Thyroxine tablets!)

    Obviously there are exceptions such as coeliac disase where gluten is clearly a no-no. (But is this because the modern strains of wheat are different from the traditional ones? The more they mess about with our foodstuffs, the more sensitivities are likely to appear. Industrial food production is a serious issue for humankind, I think)

    This information about cancer is very interesting, I shall have to look at it a bit more to understand it fully. Years ago I used to use a selenium-based shampoo for severe dandruff, and I remember there was a warning on the package that selenium was poisonous and should not be used too often!

  • Be interesting to know how much selenium can be absorbed through the scalp!

    The traditional view of such shampoos is that they act purely as anti-fungal agents outside the body. But I have long wondered if they actually provide some selenium to at least the hair follicles. Such cells are among those that are capable of independently converting T4 to T3 (but not, so far as I know, of passing any T3 back out into the blood stream). So hair follicles do have a specific requirement for selenium to form the seleno-protein enzymes.

  • Thanks for your comment, how very interesting! I wonder if that is also why I noticed it made my hair feel so much more luxuriant!

    The shampoo in question was called 'Lenium' (very imaginative) but I have not seen it for years. There were others but they were nowhere near as effective.

    The anti-dandruff shampoos on sale nowadays seem to disagree with me, but I don't get dandruff now anyway, only an itchy scalp like eczema. It drives me insane and nothing seems to help it except Betacap which I'm not keen on as it's a steroid. I just use it once in a while to get a bit of relief.

    Let's face it though, it's not just in the modern era that poisons have been used therapeutically. It's all a question of degree and balance.

  • Many (so far as I am aware) are zinc-based or tea-tree oil or whatever, not selenium.

    There is one Head and Shoulders product, and one L'Oreal Elvive product I know about - plus various other less well-known brands such as Selsun.

  • I am on same wavelength as ted h here. bUt I do think doctors learn very little about nutrition and we don't yet know what keeps us healthy. I do know as a former journalist how much big pharm and industry biases research.

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