Another one bites the dust; Clinical trial for prostate cancer prevention by selenium and vitamin E halted

I’ve written here before about nutritional supplements. Specifically, I’ve expressed my dismay at the double standard, codified into law in 1994 in the form of the DSHEA. This particular bit of truly awful law in essence took away the power of the FDA and FTC to regulate dietary supplements, except under certain rather narrow conditions. In essence, if a supplement manufacturer is careful to keep the claims for a supplement from being too specific, the FDA is virtually powerless to regulate the supplement because the law defines dietary supplements as “food.” So, in other words, vague, meaningless claims, such as that a supplement will “boost the immune system” are hunky dory, and supplement manufacturers only get into trouble when they say things like, “This supplement can cure cancer.” Worse, the FDA is overburdened and apparently doesn’t consider policing these supplements, which are a multibillion dollar a year business even when their manufacturers do cross the line. Indeed, only recently, after a long period of doing little, the FDA actually cracked down hard on some notorious quacks. I roundly applauded the action, but I couldn’t help but ask what too the FDA so long.

One of the reasons I rail against the current law is that it places supplements in an exalted place, almost immune from regulation, despite the fact that snake-oil peddlers make the most outrageous claims for what they can do for your health. But there’s an even more insidious effect of the current law. Supplements could potentially have health effects, both beneficial or detrimental. They are substances that our bodies need, but in the optimal amounts. At a conference in New York today, I was listening to a discussion about vitamin D and breast cancer (something I’ll have to write more about soon), and that point was made again and again: Just because some of something is good does not mean more of it is better. In any case, we can’t know what health effects various vitamins and supplements might have and at what doses if we don’t do the research. Unfortunately, thanks to the lax regulation of these supplements and the dubious practitioners making all sorts of dubious claims for what they can do, vitamins and supplements as potential health modulators have undeservedly taken on the taint of quackery. They’ve been, in essence, “ghettoized.” Instead of being studied with funding from Institutes at the NIH that do rigorous peer review, studies of the health effects of supplements have fallen under the purview of the woo-friendly National Center for Complementary and Alternative Medicine (NCCAM).

Fortunately, some good science is being done studying supplements. Unfortunately, one such trial, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), has had to be halted because the supplement showed no benefit and showed a hint of risk:

WASHINGTON – The government is stopping part of a major study of whether vitamin E and selenium prevent prostate cancer — because the supplements aren’t working and there’s a hint of risk.

More than 35,000 men age 50 and older have been taking one or both supplements or dummy pills as part of a study called the SELECT trial.

But the National Cancer Institute announced Monday that they will be getting letters in the next few days telling them to quit the pills. An early review of the data shows neither supplement, taken alone or together, is preventing prostate cancer.

Of more concern, slightly more users of vitamin E alone were getting prostate cancer — and slightly more selenium-only users were getting diabetes, the NCI said.

The increase in prostate cancer among vitamin E users and the increase in diabetes among the selenium-only users was not statistically significant.

According to the National Cancer Institute website:

“SELECT was always designed as a study that would answer more than a single question about prostate cancer,” said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. “As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so.”

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer was not the primary outcome: a 1998 study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer surprisingly showed 32 percent fewer prostate cancers in men who took the supplement, and a 1996 study of 1,312 men and women with skin cancer who took selenium for prevention of the disease showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other earlier findings, in 2001, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.

This is normally how clinical science works. Based on scientific plausibility plus preclinical scientific studies in vitro and in animal models, smaller, preliminary clinical trials are performed and generate evidence suggestive that a given therapeutic or preventative intervention is efficacious. However, the weaknesses and drawbacks in such study make it impossible to conclude with sufficient confidence to change clinical practice, and the question is considered important enough that it needs to be answered. Hence, a randomized, double-blind clinical trial is carried out. Often, more than one are carried out asking essentially the same question. Data from these trials then drive practice. All too often in complementary and alternative medicine” (CAM), preliminary trials done over and over and over are the “evidence” that is used to justify woo. Such was not the case for the SELECT trial.

Indeed, the SELECT trial was designed to go the right way: testing in a large randomized trial whether the results of preliminary trials held up. SELECT accrued 35,000 subjects and is costing $114 million to carry out. If a CAM booster ever tells you that “there’s no money” to study supplements, point him to the SELECT trial, which was incredibly expensive–serious bucks. Indeed, I’m not entirely sure whether the question of whether vitamin E and/or selenium can prevent prostate cancer is important enough to warrant spending that much money on it, although if it hadn’t been done then we might still be recommending that men take these supplements and providing for them no benefit.

But why did the government stop the trial? Ethics demanded it. One rule of clinical trial design and monitoring is that trials in which the therapeutic agent may be causing harm must be stopped early. In this case, there was no evidence of benefit from the vitamin E or selenium supplements in terms of reducing the risk of prostate cancer. Couple that with the trend, albeit a not statistically significant trend, towards harm in the groups of men taking the supplements. Ethically, it was a no-brainer to stop the trial. Unfortunately, the result was yet another negative trial regarding supplements and health benefits claimed for them. It’s a shame; as a man who can no longer avoid the label “middle aged,” I would have been quite happy if the results did show that vitamin E and/or selenium prevent prostate cancer. Who wouldn’t be happy if a cancer could be prevented just with a pill?

Sadly, it was not to be, but at least we know with a high degree of certainty that vitamin E and selenium appear not to prevent prostate cancer.