Still more evidence that supplements probably don't prevent cancer after all...

After a bit of ranting earlier this week, I thought now would be a good time to cool it down a bit, if only for a moment. There's plenty more out there to rant about, but I'm intentionally ignoring it, if only for a day (or even half a day). If there's one thing I've learned about blogging in the three years I've indulged in this little habit of mine, it's that a blogger has to mix things up. Too many rants in a row, and even I start to get bored. And if I'm bored you're almost certainly bored.

We wouldn't want that, now, would we?

So it was with great interest that I came across, albeit somewhat belatedly, this story about a recent study. If there's one claim that supporters of so-called "alternative" medicine like to make, it's that supplements or vitamins can prevent cancer. Particularly favored are vitamins C, D, and E as anti-cancer talismans. In the more extreme form, this claim even sometimes goes so far as claiming that one or more of these, along with other supplements, can actually treat cancer. Of course, the situation is far more complicated, as I discussed a while back about a claim that vitamin D is an all purpose cancer preventative. Vitamin D may prevent some cancers, but it may also accelerate others. Whether vitamin D supplementation is on balance more beneficial than harmful is thus not nearly as clear-cut as certain cranks would make it sound.

Well, wouldn't you know it, but another group recently looked at the relationship between vitamins C and E and cancer. Once again, the results were disappointing. Moreover, one of the findings suggests that vitamin supplementation may slightly increase the risk of cancer.

The study was published a week ago in the American Journal of Respiratory and Critical Care Medicine by a group led by Dr. Christopher Slatore at the University of Washington collaborating with a group from the University of North Carolina Chapel Hill and entitled Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer.¹ It's title more or less describes its conclusions.

The study examined the role of supplementation in the prevention of lung cancer. At the very beginning, the authors describe well the rationale that makes supplementation as a cancer preventative measure so attractive:

Fruits and vegetables are associated with a lower incidence of lung cancer (7), but because dietary habits are difficult to change (8), there is considerable interest in supplemental vitamins for chemoprevention. Supplements are used by over half of adults in the United States (9), and a majority of them believe they are "good for health and well-being" (10). This belief that supplements are helpful, or at least safe, is controversial because there is growing evidence to the contrary and some supplements are associated with an increased risk of death (11, 12). A systematic review of randomized controlled trials found little evidence that vitamin supplementation prevents chronic disease, including cancer (13), and a National Institutes of Health (NIH) panel did not make recommendations about their use (14), noting the lack of research with "accurate and current data on the public's total intake of these nutrients."

Yes, it's much more seductively easy to take a pill rather than to make the effort to eat a healthier, more balanced diet. Indeed, that's one of the things I always wondered about when it comes to "complementary and alternative" medicine (CAM) claims. After all, if there is one aspect of "CAM" claims, it's that natural is better, coupled with an inherent distrust of pharmaceuticals and taking pills. Yet, what do many "CAM" mavens recommend to prevent or treat disease? Taking supplements in the form of pills. But I digress.

In any case, the authors examined data from a large cohort known as VITAL (VITamins And Lifestyle). This particular cohort was part of a study designed specifically to examine the association between supplement use and cancer in the general population, and in particular lung cancer. Of course, lung cancer is primarily associated with cigarette smoking, and indeed it's estimated that over 90% of lung cancers are directly attributable to tobacco use. In any case, the VITAL cohort consists of 77,719 people aged 50-76 in the Puget Sound area who filled out detailed questionnaires about their health, cancer risk factors, and supplement use between 2000-2002, of whom 70% provided DNA specimens by buccal swab. One of the biggest problems with following a cohort this large is, well, following the cohort. The useful thing about the VITAL database is that it has a passive followup system that links patients to the SEER database annually, identifying patients diagnosed with cancer. Even better, it tracks participants who move out of the Puget Sound area through the National Change of Address file annually by using a vendor who contracts with the US Postal Service. The system identifies correctly at least 65% of moves, and "possible" moves are followed up manually with letters and attempts to contact the person. It's also useful in that it has a far more detailed assessment of supplement use over at least the ten years prior to the filling out of the questionnaire than most studies, and rigorous quality control measures were implemented.

Using this database, Slatore and colleagues examined the association between the use of vitamin C and vitamin E and the later incidence of lung cancer. First, they noted that 521 subjects developed lung cancer in the years following 2002. After controlling for confounding factors, they found that prior history of cancer, COPD, a family history of lung cancer, and BMI were associated with lung cancer were all associated with an increased risk of cancer, along with, unsurprisingly, cigarette smoking. There was, however, no association between lung cancer and the use of vitamin C or folate supplementation that could be detected. Specifically, the ten year average intake of these supplements, whether continuous or intermittent, was not associated with a change in lung cancer risk. Neither was lung cancer type or morphology (small cell versus non-small cell, for instance) associated positively or negatively with these two supplements. In contrast, there was association between vitamin E use and lung cancer. Specifically, there was a small increase in the risk of lung cancer among long term users of vitamin E, on the order of a relative risk of 1.05 for every 100 mg per day increase in dose. This effect was largely confined to current smokers and greater for non-small cell lung cancer (in essence, adenocarcinomas and squamous cell carcinomas).

Of course, this study was an epidemiological study. Although it was prospective, it is prone to all the potential confounding factors and biases to which all epidemiological studies can fall prey. This study, however, had a number of strengths that help it avoid many of these problems, including a rigorous assessment of supplement dose over a long period of time that has been validated, care in accounting for confounding factors, and the automatic linkage to the SEER database. On the other hand, despite the large size of this cohort, the study's power is limited to reliably detecting only a 30% or greater increase or decrease in incidence, and the study enrollees consist of a higher proportion of nonsmokers than the general population. Smaller effects may not have been detected. Be that as it may, this study is important because it is the largest prospective study of its kind thus far. At the very least it is fairly strong evidence that supplementation with vitamin C, vitamin E, or folate does not decrease the risk of lung cancer. At the most, it suggests that current smokers should not be taking vitamin E supplementation, as, if this study is correct, it will increase the already high risk of lung cancer. Once again, this study is more evidence suggesting that at higher doses vitamin E might go from being an antioxidant to a pro-oxidant, which is what might account for this result.

We all want a "magic bullet" to make us healthy. I'm no different; indeed, like many physicians, I'm fairly weak when it comes to diet. I love fast food as much as the next guy, and if my wife doesn't prod me I tend to be too lazy to eat a healthy diet, particularly when work gets really busy (and, sad to say, when it might take time away from other activities, such as blogging). I'd love it as much as the most die-hard supplement maven if taking a few pills could counteract all my bad lifestyle choices. Unfortunately, biology and human physiology don't always cooperate with our wishful thinking, and this study is just one more bit of evidence that this is true.

REFERENCES:

1. Slatore, C.G., Littman, A.J., Au, D.H., Satia, J.A., White, E. (2007). Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer. American Journal of Respiratory and Critical Care Medicine, 177(5), 524-530. DOI: 10.1164/rccm.200709-1398OC