Multivitamins and cancer: a mixed bag

A major new study published this week in the Journal of the American Medical Association (JAMA)  came to the surprising conclusion that

"daily multivitamin supplementation modestly but significantly reduced the risk of total cancer."

The report included some caveats, such as the fact that all 14,641 participants were healthy male physicians.

But the result is still surprising, because other recent studies, some of them even larger, have concluded that vitamin supplements do not provide any significant health benefits.  On the contrary, some studies found that supplements could actually be harmful.  As I wrote last year, a very large study of 38,772 older women, who were followed for 25 years, showed that the risk of death INCREASED with long-term use of multivitamins, vitamin B6, folic acid, iron, magnesium, zinc, and copper.  That's death, not just cancer.  The authors of that study, Jaakko Mursu and colleagues, concluded that there is

"little justification for the general and widespread use of dietary supplements."

The new study, PHS II (Physicians' Health Study II) looked at overall death rates as well as cancer, and found that men on a daily multivitamin had fewer deaths, but too few to be statistically significant.

So we have a large study in men showing that multivitamins seem to reduce overall cancer, and maybe even death, but an even larger study in women showing the opposite effect.

A second study from last year, in 35,533 men, looked at vitamin E and selenium supplements. That study, also published in JAMA, found that risk of cancer INCREASED for men taking vitamin E, selenium, or both.

The media reports aren't helping to clarify things.  The NY Times proclaimed "Multivitamin use linked to lowered cancer risk, and the Wall St. Journal reported that "Multivitamin cuts cancer risk, large study finds."  Bloomberg News went right for the business angle, announcing that "Pfizer multivitamin reduces cancer 8% in men, study finds."

Compared to Bloomberg news, Pfizer's own website was remarkably restrained, saying only

"Centrum Silver was part of the recently published landmark study evaluating the long-term benefits of multivitamins."  

No claims about reducing the risk of cancer - surprisingly, the independent media made far stronger statements than Pfizer.  Not true of supplement manufacturer GNC, which was flashing a pop-up headline that "Taking a daily multivitamin could cut cancer risk", linking to a news article at the Boston Herald.

So what do we make of this new study?  Are multivitamins good for you after all?

The new JAMA study appears to be very well done.  It's a double-blind, placebo-controlled study in which half of the physicians received a daily multivitamin, Centrum Silver, and half received a placebo.  The participants didn't know if the pill they were taking was a vitamin or a sugar pill.  The authors report some minor conflicts of interest, but none of them work for or received major funding from Pfizer (PFE, the manufacturer of Centrum).  So how to explain the seeming contradiction with two larger studies published only a year ago?

To answer this question, we must look at the details of the study itself.  This study looked at 21 different types of cancer risk.  For most cancers - colon cancer, prostate cancer, lung cancer, pancreatic cancer, lymphoma, leukemia, melanoma, and others - multivitamins did not provide a benefit.  But when all the numbers were added up, the effect was just large enough to be "significant", at a level of p=0.04.  More on that in a moment.

Here are the raw numbers: among the 7,317 men who took a daily multivitamin, there were 1,290 cases of cancer over the 11-year study.  Among the 7,324 men who took a placebo pill, there were 1,379 cases.  That's about 1.2% more - far less than the 8% reported by Bloomberg News. The statistical analysis showed that this difference had a p-value of 0.04, a result the authors considered significant. When the authors looked only at men with no history of cancer, the effect was smaller, and not statistically significant.

One explanation of the new finding is that the effects were indeed due to chance. Let's look at that p-value of 0.04. In much of the scientific literature, any p-value below 0.05 is considered "significant," but this has been widely criticized, in part because it encourages binary "true, false" thinking that is not the way scientists actually think. Also, the "0.05 threshold actually represents evidence much weaker than the number "0.05" suggests. A back-of-the-envelope Bayesian calculation shows that if the cancer-preventing power of multivitamins was a 50:50 proposition before this study, then after this study there is still a 10-26% chance that the cancer prevention claim is wrong. If we thought that prior evidence made this effect less than 50:50, (say 25:75), then the study has roughly a 25-50% chance of being wrong.* Either way, I won't be stocking up on Centrum Silver anytime soon.

Looking at this small effect, and at the contradictory results from other studies, neurologist Steven Novella writes in his blog that

"About the only thing we can say with a high degree of confidence is that there is no large risk or benefit from taking a multivitamin. There may be a small benefit, no benefit, or even a small harm."

That's a good summary.  So should men take a multivitamin?  Well, it's your money, but if you don't have a vitamin deficiency, it's probably not worth it.  Should women?  The evidence still says no.

*Thanks to Stanford biostatistician Steven Goodman (formerly of Johns Hopkins University) for crunching some numbers to produce Bayes factors.

Don't take your vitamins

We've known for a long time that vitamins are good for you. Perhaps the best example is vitamin C, which completely cures scurvy, a disease that has plagued mankind for millenia. (It was described by Hippocrates some 2400 years ago.) Scottish doctor James Lind described how to cure scurvy with citrus fruit back in 1753, but it wasn't until 1932 that scientists Albert Szent-Gyorgyi and Charles Glen King identified vitamin C as the essential nutrient behind the cure for scurvy. (Szent-Gyorgi gave vitamin C the name ascorbic acid because of its anti-scurvy properties.)

Many other vitamins and micronutrients are required for good health, such as vitamins B and D, iron, folic acid, calcium, and potassium. Deficiencies in these vitamins cause all sorts of diseases, some of them very serious.

So it seems intuitively obvious that if a little bit of these nutrients is good for you, then a lot should be even better. Right? This intuition is the basis for the a huge and powerful nutritional supplements industry, which makes billions of dollars each year selling multi-vitamins and high-dose supplements in a bewildering variety.

The problem is, our intuition is wrong. Two separate studies published this past week, involving tens of thousands of subjects, showed that high doses of vitamins and supplements, rather than being helpful, can sometimes kill you.

In the first study, Jaakko Mursu and colleagues have been following 38,772 older women since 1986. The women in the study, whose average age was 62 back in 1986, have reported their use of multivitamins and supplements for the past 25 years. The news was not good: the risk of death INCREASED with long term use of multivitamins, vitamin B6, folic acid, iron, magnesium, zinc, and copper. The risk of death only decreased with the use of calcium. They also noted that in other studies, calcium had the opposite effect.

The authors concluded that there's

"little justification for the general and widespread use of dietary supplements,"

and the story was widely reported as showing that supplements are risky (Wall St. Journal) and unnecessary (New Zealand Herald).

In the second study, Eric Klein and colleagues studied 35,533 men over the past 10 years, looking at whether vitamin E or selenium would decrease the risk of prostate cancer. Both supplements have been claimed to have benefits, so the researchers randomly divided the subjects into four groups, giving them daily doses of (1) vitamin E only, (2) selenium only, (3) vitamin E and selenium, and (4) nothing (in the form of placebo pills).

The result: the risk of cancer INCREASED for the men taking vitamin E, selenium, or both. Although the increased risk is small, it is abundantly clear that neither of these supplements is helpful against prostate cancer.

Not surprisingly, the supplements industry hasn't taken this news lying down. The Council for Responsible Nutrition is an industry lobbying group representing the supplements industry (don't be fooled by the name). They released a statement by their vice president, Duffy MacKay (a naturopath, which is a form of quackery I'll have to treat separately in the future), grasping at the fact that, in the study, the increased risk of cancer from vitamin E plus selenium wasn't quite as big as the increase from vitamin E alone.

"This reinforces the theory that vitamins work synergistically," said MacKay.

Aha! So if I take even more supplements, perhaps my risk of cancer will go up only an eensy-teensy bit?

The Council released a second statement about the study on multivitamins, saying

"CRN maintains that nutrients may be robbed of their beneficial effects when viewed as if they were pharmaceutical agents, with scientists looking to isolate those effects, good or bad."

I see... so the benefits of supplements will disappear if we treat them as drugs: wouldn't that include taking vitamins and supplements as pills?

The supplements industry (Big Supp?), which is largely unregulated, has a darker side too: countless hucksters, many operating primarily through the Internet, who are making a fortune selling overpriced supplements (and advice on how to use them) that they claim will cure cancer, diabetes, and a host of other diseases. These include internet quack Mike Adams, who posted a response to this week's studies on his Nature News website, claiming:

"Recent attack on vitamins a fabricated scare campaign."

In Adams' response, he starts by arguing that the American Medical Association"has a long and sordid history of openly attacking vitamins and nutrition," a bizarre claim that has nothing to do with the study results even if it were true (it's not). He goes on to claim that the

"study data were ALTERED!"

(the all-caps is his) and

"voodoo statistics [were] used to alter the outcome."

I looked at the numbers he extracted from the paper to support these claims, and he failed - badly - to understand the data. Apparently for Mike Adams, statistics that he doesn't understand are just "voodoo."

So I'm afraid the news boils down to this: eat lots of fruit and vegetables, and a balanced diet, and you'll get all the micronutrients and vitamins you need. Supplements are only needed if you have a demonstrable deficiency. For most people, multivitamins and other supplements are a waste of money, and they might even be harmful. But hey, apples are in season right now, and spinach can be kind of tasty if you prepare it properly.