Multivitamins and mortality: ‘Seeing-what-you-want’ science

By Stephen Daniells

- Last updated on GMT

Related tags: Supplements, Dietary supplement

Multivitamins and mortality: ‘Seeing-what-you-want’ science
During a week when the industry gathered under clear blue skies in Las Vegas to celebrate 15 years of SupplySide West, black clouds rolled in and unleashed a short sharp downpour: I am of course referring to the articles published on multivitamins and vitamin E.

First of all, research published in the Archives of Internal Medicine​ (a journal from the American Medical Association) concluded that older women who take multivitamins and copper supplements are at greater risk of dying from heart disease, cancer and other causes than women who don’t take them.

And then the headlines followed: Your Multi-Vitamin May Be Killing You​ (Shape Magazine) and Study: Vitamins may increase death risk in older women​ (USA Today).

We’ve seen similar studies before (more often than not published in journals from the American Medical Association) but what was different this time was the industry was ready, it had advanced warning and reacted immediately to their publications – this is progress.

Comments came in from the Natural Products Association (NPA), the Council for Responsible Nutrition (CRN), and the United Natural Products Alliance (UNPA)​ to put the studies in context, to highlight their limitations (which just isn’t done in the main stream media), and for this I would commend the associations.

I would also suggest that the industry gather a team of academic champions to support their comments, much like it has champions in the Senate and elsewhere: A reaction from a trade association, no matter how measured and insightful, will always be seen by some as ‘damage control’ (as someone remarked on Twitter​ in relation to my coverage of the studies​).


Which leads me on to the studies themselves. The multivitamin study was observational, and relied on questionnaires – so it was always going to show correlation and not causation.

The researchers did tweak their results to account for a number of potential confounding factors, such as BMI, use of hormone replacement therapy, smoking status, alcohol intake, exercise levels, intakes of saturated fatty acids, and so on, but you can never fully remove the suspicion of confounding.

My one big question is over compliance – just because the women said they were supplement users, does not necessarily mean they were actually taking supplements​. Compliance is notoriously low even in clinical trials where participants have signed up and agreed to swallow a capsule every day.

Just because these ladies ticked the box on a questionnaire that came in every 10 years does not mean that they were taking supplements – and the same supplements – everyday for all that time.

In addition, the researchers provide no information whatsoever about actual nutrient levels. No blood samples were taken and so we have no idea – none whatsoever – if the women had high levels of vitamin B6, for example, flowing through their veins. For all their posturing on the questionnaires, they may have been vitamin B6 deficient for all we know.

What did Twain say about statistics?

Also, if you look at the statistics, only copper and the multivitamins actually had a statistically significant association, and even then the one for multivitamins was relatively small.

The copper one was large, and you’d be hard pressed to find people to argue against excessive intakes of copper. Or iron, for that matter. There is too much of a good thing, as I shall come on to in a moment.

On the other hand, the apparent benefits for calcium supplements remained statistically significant, a result that may raise eyebrows for some in the medical fraternity following a high-profile meta-analysis in the British Medical Journal ​that concluded that calcium supplements may be dangerous.

Observational studies show correlation and not causation and headline writers running with Your Multi-Vitamin May Be Killing You​ (Shape Magazine) is irresponsible and naïve.

But the study should not be dismissed. It adds to the debate and perhaps does raise questions over when supplements should be used: And so on to the vitamin E-prostate SELECT study: A well-designed study, by all accounts, that shows the benefits of longer term analysis of study cohorts. However, an interesting comment by Bill Sardi, a well known personality in the industry, posted​ on NutraIngredients-USA today adds some nice context:

“The problem with these studies is that they don't show cause-and-effect. The researchers could not surmise any mechanism for the increased deaths related to vitamin E use. The problem is that men with prostate cancer take more supplements and in higher doses. They may have also been wearing tennis shoes. But obviously these are only associated factors, not causal factors.”

Take home

So what to make of all this? It’s a high profile journal with a reputation of only publishing damning studies about supplements – look to the likes of the American Journal of Clinical Nutrition​ or the Journal of Nutrition​ and you will see tens, even hundreds of studies reporting benefits of good nutrition, of which supplements play a role. JAMA​ has a better PR department, it would seem, and the medical community looks to it with reverence – don’t get me wrong, it is a great journal… for medical research.

The comments from the supplement trade associations have a lot of wisdom about them. Their comments cannot be simply dismissed as spin or damage control (as someone on Twitter suggested), but they provide some balance to the JAMA articles. Supplements, as the name suggests, supplement the diet, and people with poor diets may benefit greatly.

A wider problem may be that the public view supplements as a fix-it for poor lifestyle. Perhaps industry and academia should work even harder on explaining that supplements should not be expected to undo a lifetime of poor habits or diet: Black clouds will always appear in the sky, but it doesn’t hurt to have an umbrella ready.

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The folly of "controlled studies" on supplement and pharma drugs

Posted by Herman Rutner,

As a lifelong chemist and observer of the drug and supplement scene, I have developed a low opinion of the value of gold standard drug screening via "controlled studies" focusing on testing a single substance in far more complex or "uncontrolled" living bodies than a petrie dish.
Witness the high incidence of adverse effects, morbidity and lethality of nosocomial events (the major cause of health damage in the USA) of FDA approved drugs proving the failure of current protocols. Don't take my word: just listen to the litany of side effects, often far worse than the treated often illusory maladies "cured" in TV commercials. I applaud the trend to systems biology as practiced in personalized medicine that is based on metabolic profiling.
Ironically, a similar approach aka anecdotal testing has been practiced by witch doctors for eons and is one reason for our survival. Toxicity studies in animals can still be done to eliminate overt toxicity. But the effectiveness of new pharmas, as is commonly done with alt medicines and supplements, would be more effective evaluated by starting with microdosing in diverse users. Such personalized test protocols would have eliminated many of currently approved Rx drugs that cause far more harm than the widely used alt medicines and supplements.
The FDA, pharmas and dispensers are excused from malpractice, while peddlers of and prescribers of alt medicines are hounded by the FDA or hauled into courts for far lesser health damage.
H Rutner, biotech consultant

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Other causal factors

Posted by Brian N. Sabowitz, MD, FACP,

It is also important to note that there are other plausible explanations to the results. Perhaps people who eat a nutritious, healthy diet and whom exercise more don't feel compelled to take vitamins. So, vitamin takers may be less healthy to begin with and thus have a greater mortality rate.

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Extremely Misleading

Posted by Mike,

No thought was given to the possibility those reported taking supplements were actually ill from some other cause. Supplementation is a natural event during an illness.

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