Nov 18 2008

Vitamin E and C Do Not Prevent Cancer

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A new long term study of vitamin E and C supplementation in a group of physicians showed no protective effect for either prostate cancer specifically or cancer in general. This is a disappointing result – it would be nice if a low risk intervention like vitamin supplementation would significantly reduce cancer risk, but it does not appear to be the case.

The results of the study were presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research, and the press release states:

The Physicians’ Health Study II is a large-scale, long-term, randomized clinical trial that included 14,641 physicians who were at least 50 years old at enrollment. These physicians were given 400 IU of vitamin E every other day or its placebo, or 500 mg of vitamin C daily or its placebo.

Researchers followed these patients for up to 10 years for the development of cancer with high rates of completion of annual questionnaires, and the confirmation of reported cancer endpoints.

Analyses indicate that randomization to vitamin E did not have a significant effect on prostate cancer. This lack of effect for vitamin E also extended to total cancer. Vitamin C had a similar lack of effect on total cancer.

Vitamins and Disease Prevention

The idea is very appealing, and has gained recent popularity due in part to the larger trend toward “natural” remedies and nutritional therapies. This is turn has been boosted by a deregulated supplement industry that now rakes in billions selling the idea that “supplements” can cure or prevent anything.

But the appeal is more basic – it would be undeniably great if we could live longer and reduce our risk of a dreaded class of diseases simply by tweaking our nutrition.  I have no a priori bias against vitamins as preventives. And, contrary to the ravings of the conspiracy-mongering cranks who want to dismiss any science-based opinion they disagree with – I am not in league with any AMA conspiracy, I am not on the payroll of Big Pharma, and I don’t even treat cancer. In fact I am a salaried academic and do not make money from treating patients.

I simply want to understand the research – what is the evidence really telling us, as opposed to what we would like to be true.

Recently there have been a number of large clinical trials looking at vitamin supplementation to prevent cancer, heart disease, and other common diseases that have all shown no significant benefit. The Physicians Health study is just the latest. Wallace Sampson has summarized and referenced this research recently at Science-Based Medicine.  These include studies that show no benefit from C and E for heart disease (this is the same data set that showed no benefit for cancer), no benefit from the B vitamins for heart disease, and no benefit from E and selenium for prostate cancer. Disturbingly, there are also studies that show an increased risk of some kinds of cancers from specific vitamins.

There seems to be a clear trend in this research. While a number of retrospective or population-based studies have shown a possible correlation between supplementation, certain diets, and a reduced risk of cancer, this correlation does not appear to be holding up with large, placebo-controlled prospective trials. Generally speaking, these large prospective trials are considered a more direct test of the effect of vitamin supplementation, a stronger form of data, and they largely trump the earlier studies.

In this latest study of vitamin C and E, for example, over 14 thousand subjects were followed for 10 years.  That is pretty robust data.

Of course, like all such research, it can’t prove a negative – that there are no specific benefits from vitamins. A lack of statistic correlation shows a specific probability that any effect is smaller than the power of the study to detect. So if there is any effect, it was probably too small to measure by this large study.

Vitamins C and E in particular have garnered a great deal of interest because they are antioxidants – which means they decrease the level of oxygen free radicals which is an important mechanism of cell damage. However, the story of antioxidants has turned out to be much more complex than simply – oxygen bad, antioxidants good. The supplement industry marketing has not caught up to this reality (and probably never will – why should they). Free radicals, for example seem to trigger downstream metabolic effects that are beneficial, therefore while suppressing free radicals you may be reducing cell damage but you are also reducing these beneficial effects.

This is precisely why large clinical trials are needed in order to make reliable clinical conclusions – you cannot simply extrapolate from the basic science. It’s too complex.

Looking at the big picture it seems as if the primary role of vitamins is to treat vitamin deficiencies. There does not appear to be much of a role for supplementation beyond that, except in very specific cases for which there is evidence. For example, women who may become pregnant should take folate supplements to reduce the risk of spinal cord defects. There is reasonable evidence that vitamin B2 may reduce the severity or frequency of migraines. There is mild evidence that B6 may help nerves recovery from injury. It is standard practice to give vitamin C to patients recovering from surgery or trauma. The theme here is that during periods or conditions of particular stress, the metabolic demand for specific vitamins may be needed and supplementation can improve outcome.

There is no compelling evidence for routine supplementation in healthy individuals.

But the story of vitamins and health is far from over. Interest is simply too high – and this is not unreasonable. Again – vitamins are relatively low risk (but should not be considered risk free). They generally have no side effects, except with megadosing, which can be dangerous and should be avoided. Vitmamins by definition are those substances that we are metabolically dependent on but which our bodies cannot make for themselves, so they have to be consumed. It is therefore plausible that they can have a beneficial effect.

Recently there has been great interest in vitamin D. A recent review of studies shows that vitamin D supplementation is associated with lower overall mortality.  Low vitamin D may have a role in MS and other auto-immune diseases (although supplementation does not seem to be a benefit for breast cancer). Recently the RDA for vitamin D was doubled for children. It seems we may still have a lot to learn about specific vitamins and diseases. But to put this in perspective, it may be that there is a relative level of vitamin D deficiency, perhaps brought about by reduced exposure to the sun and UV rays which are necessary for the body to make vitamin D. We may therefore be treating a deficiency, not supplementing above and beyond basic needs.

Also, while this data is compelling we are not yet at the large, controlled, prospective trial level. We will likely not have the final word on vitamin D for many conditions for 10 years – there is no way around that fact that it takes at least10 years to gather 10 year survival data.

Another point to consider is that much of the preliminary retrospective data showing a positive correlation between vitamin intake and health may really be due to other healthful lifestyle factors that correlate with diet or supplementation. One interpretation of this recent negative vitamin data is that supplements are no substitute for a healthful diet. I don’t think this is because of any magical difference between vitamins in food and the same chemicals in pills. But it is plausible that nutritious diets are also healthy in other ways. For example they may contain less bad cholesterol or overall calories. A good diet is also probably a marker for other healthy habits.

Conclusion

The story of vitamins is complex. What we can say now based upon the evidence is that even minor deficiencies of vitamins should be avoided, and physicians needs to test for them and treat them when encountered. A well-rounded and nutritious diet is a no-brainer good idea for everyone. Specific supplementation in specific conditions may be indicated, where supported by the evidence. Megadosing is worthless and may even be harmful.

But the evidence does not support routine supplementation for healthy individuals with a good diet. Vitamins are not a panacea or an elixir of longevity (despite what the supplement industry would like you to believe). And specifically, they do not seem to have a detectable benefit for preventing heart disease or cancer.

Research on vitamins will continue, however, and evidence-based recommendations will change over time. Much of this research is reasonable, even necessary, but some is based upon hype.  We need to clear away the mystique of vitamins and keep our eyes on the science.

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16 responses so far

16 Responses to “Vitamin E and C Do Not Prevent Cancer”

  1. Oracon 18 Nov 2008 at 9:56 am

    We will likely not have the final word on vitamin D for many conditions for 10 years – there is no way around that fact that it takes at least10 years to gather 10 year survival data.

    True but not the whole story. Kaplan-Meier survival curves can give a pretty good estimates before that time if the curves are separating. True, if the survival curves are very close, it might indeed take ten years, but in a lot of oncology studies, we use estimated five and ten year survivals based on less data.

  2. Steven Novellaon 18 Nov 2008 at 11:34 am

    Orac – you are technically correct. For things like cancer where the death rate is high, you can extrapolate out survival curves.

    However, when following a general population where the death rate is very low, extrapolation becomes much less reliable statistically. There really is no substitute for actually following patients for 10 years, like this current study did.

    So it comes down to power. When measuring a small effect you either need a huge number of subjects, a long period of time, or some combination of both. With these types of studies it is unlikely you will get enough subjects that you can get by with shorter time periods. Also, the time it would take to enroll such huge numbers of patients would be considerable. No matter how you slice it, it’s going to take a long time.

  3. superdaveon 18 Nov 2008 at 1:11 pm

    I think this result hearkens back to your earlier post about the potential limited efficacy of preventative medicine. Preventative medicine looks like a concept that is much more difficult to practice than people thought. I suspect that much like vitamin therapy, the bigger picture for many potential preventative measures is more complex than originally proposed.

  4. Fizziziston 18 Nov 2008 at 3:36 pm

    That’s OK I am not much for taking pills anyways.

  5. jwittneron 18 Nov 2008 at 5:58 pm

    Steve,

    I was wondering if you could briefly explain to me how vitamins are tested for? Is it as simple as checking your blood and being able to determine what vitamins you have too little/too much/just enough of or is more complicated?

    Long time reader, infrequent commenter,
    Josh

  6. halincohon 18 Nov 2008 at 11:59 pm

    Recently , I’ve been discussing the Jupiter study ( Crestor decreasing cardiovascular events in patients who are low risk Framingham and who have a very favorable ldl – I believe the mean was 108 – with the significant marker for response being elevated HS CRP ) with my patients. It’s actually nice discussing something cutting edge and positive. I discuss the historic context ( such as the Heart Protection Study done 6-8 years prior ), the pathophysiology involved ( endothelial dysfunction ) and the fact that though this is very interesting, there is no consensus yet as how to translate this new study into clinical application.

    Some are intrigued and this leads to meaningful conversations about lipids in general, endothelial dysfunction and inflammation, other markers and risk factors, statins and other modalities such as aspirin, and concepts involved in both primary prevention and secondary prevention of cardiovascular disease.

    Some are cynical and simply feel the study is motivated by pharma wanting to treat healthy patients.

    Again, the jury is still out in how and if to apply this study to clinical practice, but I ask these cynical patients if they take vitamins. Many, of course, do. And I ask them, “so you spend your money on megadoses of vitamins to prevent disease and promote well being when you have no vitamin deficiencies ( by the way, I highly endorse using folate, B12, Vit D etc when even borderline deficiencies are discovered ), when there is no evidence that your use of vitamins in these circumstances will help you meet your goals, yet you criticize this large, random, blinded, well done, study that essentially produces evidence for the same thing you are seeking.”

    Ok … so I don’t say that in exactly those words, but MAN I WISH I HAD THE GUTS TO SAY SO. :)

  7. Steven Novellaon 19 Nov 2008 at 10:36 am

    You can check vitamin levels with a simple blood test. I do this every day, and I too treat even borderline deficiencies. B12 in older patients is probably the most common, and has wide ranging neurological implications – so I never miss an opportunity to treat even relative B12 deficiency.

  8. HHCon 19 Nov 2008 at 11:45 am

    Recently, I was bombarded with drastic medical documentation of
    heart disease and lack of proper vitamin consumption at the local
    hospital fitness center. Juiceplus was the company which was handing out dvds, using nursing staff to promote their vitamins.
    This company claims that if you swallow their pillls after meals you will prevent clogging and closure of the arteries from the bad cholesterol immediately. The nursing staff stated that women who expect to have a healthy pregnancy would be advised to take this product too. Juiceplus has a nationally known southern physician who declares his vitamin beliefs stridently on the dvd. I was offered an appointment with the nurse to further discuss my needs and purchase my monthly supply for around $70.00. I am glad I resisted this easy-fix temptation for my cholesterol levels. I guess I will have to have my Happy meals without a pill.

  9. halincohon 19 Nov 2008 at 10:06 pm

    Sorry Steve, I never meant to imply that you wouldn’t. I merely added that parenthetical clause to emphasize that though there are indeed clinical scenarios when physicians do treat with vitamins, vitamins ( especially megadoses ) for the sake of taking them without a clinical indication is not one of those scenarios.

  10. howihealedon 20 Nov 2008 at 2:33 am

    I normally would agree that simple vitamins wouldn’t prevent cancer or other diseases except for my own personal experience.

    I tested deficient for Vitamin D and I took high dose D3 Supplements and ended up euphoric for like 30 minutes on three separate occasions. I was definitely in need and Vitamin D3 still helps me. I generally don’t think large scale studies are the most reliable way to measure truths.. I usually prefer anecdotal evidence to be honest.

    I also have calmed down a ton thanks to high dose B Vitamins. I’m very grateful. Although I am not sure whether they prevent cancer but they probably prevent many stress related disease .

    Steve

  11. jonny_ehon 24 Nov 2008 at 10:56 am

    I just brought this study to the intention of a family member who takes large amounts of vitamins and herbal drugs, and he just shrugged it off and said “Of course it didn’t show anything, 500mg isn’t nearly enough!”

    Arrggh, how do I respond to that?

  12. Fifion 24 Nov 2008 at 3:07 pm

    HHC – JuicePlus are a quite well documented scam and source of pseudoscience – particularly regarding cancer. They finance http://www.beatcancer.org and attack science-based medicine under the guise of being an impartial, non-profit when they’re directly linked to and lobbying for Juice Plus. They’re also a key source of lies regarding nutrition, promoting the idea that healthy food just isn’t nutritious enough. I wouldn’t be the least bit surprised to find out they are involved in promoting these ideas within the autism and antivax communities as well.

  13. Fifion 24 Nov 2008 at 3:16 pm

    HHC – I’d make a formal complaint to the hospital ethics committee regarding Juice Plus being promoted (if you feel so inclined, of course). It doesn’t have to be a big deal, even writing a letter asking why the hospital is promoting Juice Plus with no follow up at least lets someone know that not everyone is okay with it and that it’s been noticed that the hospital fitness centre has been engaging in unethical practices and promoting pseudoscience.

    Juice Plus targets nurses as distributors, their agenda is very much to get into hospitals and associate themselves with the medical establishment (while also decrying it) in any way possible.

  14. daedalus2uon 24 Nov 2008 at 5:30 pm

    howIhealed, be careful, lots of things can make you euphoric, just before they kill you. Solvent huffing and near asphyxiation make people euphoric too, but they also cause instant and irreversible damage.

  15. weingon 25 Nov 2008 at 10:07 am

    Steve,
    Do you give injections or have them take B12 po? I usually give injections for deficiencies but have them take po for borderline and inject only if levels not rising.

  16. oderbon 03 Dec 2008 at 1:56 am

    Jonny,

    Arrgggggh……to you….

    Your family member is absolutely correct. 500 mg is not anywhere near a therapeutic dose. Once again conventional medicine discredits vitamin C by generalizing from an inadequate and non therapeutic dose and no one on this site questions whether much higher dosages – as high as 200 grams a day, such as used by Kenner and Cathcart among others produces dramatic therapeutic benefits.

    See
    http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0020307

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