Are Supplements Killing You? The Problem With Vitamins, Minerals

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In two recently published studies, researchers suggest that supplements can do more harm than good if taken in addition to a healthy diet

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Most people understand that taking nutritional supplements that have unproven health effects is taking a gamble. Yet few realize that this may also be true for vitamin and mineral supplements.

Two recently published studies suggest that vitamin and mineral supplements can do more harm than good. One study uncovered a definite link between taking Vitamin E and an increased risk of prostate cancer. The other suggests the possibility that elderly women taking vitamin and mineral supplements were at a higher risk of early death, though the study's results are open to interpretation.

Taken together, both studies call into question the wisdom of taking vitamin and mineral supplements on top of a normal diet. It just might be too much of a good thing.

THE BACKGROUND

Vitamins, minerals, and other micronutrients are needed in small amounts for good health. Without them, diseases such as scurvy will develop (Vitamin C). Some of the effects of vitamin and mineral deficiency have been known for hundreds of years and the amounts needed to prevent deficiency are given as the recommended daily allowance (RDA), formerly the minimum daily requirement.

The current consensus is that a proper diet provides all the micronutrients that most people need.

In recent times, supplementing the diet with vitamins and minerals has shifted from trying to prevent deficiencies to taking higher amounts of them in an effort to enhance health. Studies indicate that about half of all people in the U.S. in the year 2000 were taking at least one supplement. And while the effects of too little of a vitamin or mineral are well known, there's been little opportunity to study the effects of higher levels of these substances on health.

Overdoses of vitamin A and D can occur and lead to health problems. Both are fat-soluble vitamins (as is vitamin E) and can build up in the body over time. But such overdoses are rare. And since excess water-soluble vitamins are excreted and don't build up in the body, overdoses of them are even rarer. But as with everything else, it's almost certain that the effects of vitamins and minerals on health follow an upside down U curve: too little is bad for health and so is too much. The two recent studies are fairly preliminary investigations into what constitutes too much.

VITAMIN E RAISES PROSTATE CANCER RISK: THE SELECT TRIAL

The SELECT trial (the Selenium and Vitamin E Cancer Prevention Trial) was designed to determine the long range effect of selenium and vitamin E supplements on prostate cancer. Previous studies had hinted that both of these substances might offer protection against prostate cancer. But the trial found a 17 percent increase in the risk of developing prostate cancer in men who took 400 units of vitamin E daily, and no protection against developing prostate cancer from selenium.

Over 35,000 men from the U.S., Canada, and Puerto Rico were split into four groups in a randomized controlled study. One group took 400 International Units of Vitamin E per day, the second took 200 micrograms of selenium a day, the third took both vitamin E and selenium, and the fourth took only inactive placebo.

All men were 50 years or older and showed no initial signs of prostate cancer, as judged by a digital rectal examination and PSA level. Enrollment began in August 2001 and ended in June 2004.

Preliminary results from the study in 2008 showed an increased rate of prostate cancer among both the group taking vitamin E and the group taking selenium. While these increases were not statistically significant, the increase in the vitamin E group was nearly so. The trial had been designed to seek a protective effect from either vitamin E or selenium. It wasn't finding one and instead was finding evidence of possible harm. Because of this, subjects stopped taking the supplements in October 2008. They continued to be tracked for new cases of prostate cancer.

The recently published article included results as of July 2011. It found an increase in new prostate cancers among all three groups taking supplements, with the increase only significant in the vitamin E group. That group showed a 17 percent increase in the rate of prostate cancer compared to the placebo group.

The selenium group showed a nine percent increase and the group taking both selenium and vitamin E showed a five percent increase, increases that were not statistically significant and could have been caused by chance alone. The results of the group taking both vitamin E and selenium suggest that selenium somehow blunts the ability of vitamin E to increase prostate cancers.

The researchers don't offer a biological explanation for why vitamin E appears to increase the risk of prostate cancer. They do express concern that the rate of prostate cancer continued to rise even after subjects stopped taking vitamin E supplements, suggesting that harm continues for years afterwards. They also note a 2005 study that found that 50 percent of U.S. individuals over the age of 60 take vitamin E containing supplements and 23 percent of them are taking at least 400 IU of vitamin E per day. The SELECT study may give them a reason to reconsider this. The adult RDA for vitamin E is 22.5 IU a day.

WOMEN AND SUPPLEMENTS: A CONFUSING PICTURE

The Iowa Women's Health Study looked at the effect of taking vitamin and mineral supplements on mortality on nearly 39,000 U.S. women aged 55 to 69 and used information collected from 1986 through 2008.

At the start of the study, 66 percent of the study subjects reported using at least one supplement. This increased to 85 percent in 2004, with 27 percent reporting use of four or more supplements.

The study examined the effect of taking 14 individual supplements and also a multivitamin. The researchers concluded that women who took any of six supplements or a multivitamin had a slightly higher risk of death over the study period:

  • Multivitamins were associated with a 2.4 percent higher risk of earlier death
  • Vitamin B6 gave a 4.1 percent higher risk
  • Folic acid gave a 5.9 percent higher risk
  • Iron gave a 3.9 percent higher risk
  • Magnesium gave a 3.6 percent higher risk
  • Zinc gave a 3 percent higher risk
  • Copper gave an 18 percent higher risk
  • Calcium gave a 3.8 percent lower risk of death

However, different types of statistical analyses markedly changed these results.

This was an observational study, which allowed the researchers to look at the possible effects of taking supplements in a large group of people over a long period of time. The researchers simply observed the subjects; they did not alter or affect the type or amount of supplements the subjects were taking. This type of study can only suggest a possible link between taking supplements and a change in risk of death; it cannot show that they caused death.

All supplement use was self-reported by the subjects.

The women in the study completed a 16-page questionnaire on their dietary and lifestyle habits in 1986, including supplement use. They were also asked about other factors such as their age, height, education, physical activity, diet, and certain medical conditions, such as high blood pressure. Follow-up questionnaires were completed in 1997 and 2004.

During the course of the study, 15,994 of the women died. Those who died from injury, accident, or suicide were not included in the study results, since it's unlikely that supplement use could have played a part in those deaths.

The researchers analyzed the data for any association between supplement use and mortality, using validated statistical methods and adjusting the results for other possible factors known to affect mortality including age, lifestyle, smoking, alcohol, and certain medical factors. And different statistical treatments gave different results.

Different Statistical Methods, Different Meanings

The statistical model used by the researchers adjusted the results for participants' age and energy intake, nutritional factors (alcohol use; fruit and vegetable consumption; saturated fatty acid consumption; and consumption of fruits, vegetables, and whole grain products) and non-nutritional factors (educational level, place of residence, diabetes, high blood pressure, body mass index, waist to hip ratio, hormone replacement therapy, physical activity, and smoking status). But the different adjustments gave different results:

  • When the results were only adjusted for age and energy intake, taking vitamin B complex, vitamins C, D, E, and calcium all gave a significantly lower risk of mortality, while only copper gave significantly higher mortality.
  • Adding in adjustments for the non-nutritional factors listed above, only calcium gave a significantly lower risk of death. Copper, multivitamins, vitamin B6, and iron gave a significantly higher risk.
  • Adding adjustments for both nutritional and non-nutritional factors gave the results the researchers' conclusions were drawn from, with six supplements raising the death risk and calcium lowering it.

These different results are why some people have drawn different conclusions from the study than the authors did.

In general, when an effect is present in some statistical models and absent in others, it means that if the effect actually exists, it's a small one.

THE TAKEAWAY

The results suggest the possibility that vitamin and mineral supplements may be doing people who eat a standard diet more harm than good, an idea that simply doesn't enter into the minds of most people. They also suggest that taking additional calcium is beneficial, though calcium's effect on the heart is controversial. It will take studies that are more controlled to confirm or disprove both of these ideas.

The researchers are particularly concerned about the effect of iron because they observed a dose-response relationship between the amount taken and the death rate: the higher the dose taken, the greater the risk of mortality.

The results should not be interpreted to mean that vitamin and mineral supplements can cause early death. One possible scenario is that women were taking supplements in response to illness, which may have been the reason for their earlier deaths. But since most people can get all the nutrients they require from eating a balanced diet, the study does raise the question of whether routinely taking a vitamin or mineral supplement is a good idea.

The study results have already proved controversial. Commentary has ranged from lauding the study as groundbreaking to criticizing it as an example of poor science. Perhaps the best way to look at the results is to acknowledge that they raise the question of whether vitamin and mineral supplements may generally do more harm than good, but unfortunately, they don't give a clear answer to the question.

Robert M. Russell, M.D., special expert to the Office of Dietary Supplements (ODS) at NIH and former senior scientist and director of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University told TheDoctor that, "Trying to make sense of observational epidemiology study results can at times be difficult. Different populations, study designs, lengths of follow up often can account for confusing and seemingly contradictory results."

"In general, what we have learned from an accumulating database from both observational epidemiology and interventional studies is that the vitamin and minerals are safe to take in RDA amounts (as are contained in most over the counter multivitamin-multimineral preparations). Further, we have learned that taking large amounts of single nutrients or nutrient combinations often lead to chronic undesirable toxic effects with implications for chronic disease such as cancer. We have seen this with beta-carotene with a stimulation of lung cancer at high doses, and now we are seeing a similar picture with high dose vitamin E vis-a-vis prostate cancer."

"So what is the best advice for the public? Stick to a varied diet, if you want to take supplements, take a multivitamin-multimineral that has RDA amounts. Don't jump on the silver bullet of the day single nutrient band-wagon until there is enough evidence for both efficacy as well as long term safety. That said, in order to get RDA amounts of calcium and vitamin D, a single nutrient supplement may be necessary for some people. Following the nutrient guidance of our National Academies of Science is my best advice."

Image: tazik13/Shutterstock.


This article originally appeared on TheDoctorWillSeeYouNow.com, an Atlantic partner site.

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