August 2009 Issue

Sorting Out the Science on Multivitamins and Minerals 
By Sharon Palmer, RD
Today’s Dietitian
Vol. 11 No. 8 P. 38

New findings portray multivitamin pill popping as unnecessary and perhaps even dangerous. Today’s Dietitian investigates the evidence on American’s daily supplement habit.

For millions of Americans, popping a vitamin and mineral supplement every morning has become as routine as drinking a glass of orange juice. The public widely views the daily “multi” habit as a safeguard against nutrient deficiencies and health problems. Many health professionals have embraced the multivitamin spirit, too. Try to count the times you’ve recommended a multivitamin and mineral supplement to a client as “insurance” for a less-than-perfect diet, and you’ll realize how mainstream supplementation has become.

A 2008 Council for Responsible Nutrition survey found that 64% of American adults take dietary supplements, including multivitamin and mineral formulas. But new research is rolling in and testing the theory that multi formulas keep disease at bay.

Are Multis Disease Busters?
Ask healthy adults why they pop a multi formula every day, and they may say that doing so protects them from disease. Unfortunately, scientific evidence hasn’t exactly supported this assumption. Basic research and observational studies had suggested that antioxidant vitamins such as C and E might protect against cancer and cardiovascular disease, but randomized trials were needed to establish a link between vitamins and disease protection.

Thus, researchers studied the effects of vitamins C and E in a large-scale, randomized, controlled trial published this year in The Journal of the American Medical Association. The Physicians’ Health Study-II followed 14,641 male physicians initially aged 50 and older for an average of eight years and found that individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily did not reduce their risk of prostate or total cancer. The effects of vitamins C and E on cardiovascular disease in this group were also evaluated and published in 2008 in The Journal of the American Medical Association. Neither vitamin C nor vitamin E supplementation reduced the risk of major cardiovascular events.

Other large studies have yielded similar results. The Women’s Health Study, which evaluated 39,876 female health professionals over 10 years, showed no benefit of vitamin E supplementation in the primary prevention of cardiovascular disease or cancer, as was reported in 2006 in the Cleveland Clinic Journal of Medicine. The Women’s Antioxidant Cardiovascular Study, a double-blind, placebo-controlled trial, studied the effects of vitamin C, vitamin E, and beta-carotene supplementation in 8,171 women for an average of 9.4 years. Researchers found that the supplements had no effect on total cancer incidence or cancer death or cardiovascular events among women at high risk for cardiovascular disease. These results were published in the Journal of the National Cancer Institute in 2009 and the Archives of Internal Medicine in 2007.

In the Women’s Antioxidant and Folic Acid Cardiovascular Study, 5,442 U.S. female health professionals aged 42 and older with preexisting cardiovascular disease or three or more coronary risk factors were randomly assigned either a daily combination of folic acid, vitamin B6, and vitamin B12 or a matching placebo for 7.3 years. The results, published in 2008 in The Journal of the American Medical Association, indicated that combined folic acid, vitamin B6, and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer.

Mark A. Kantor, PhD, an associate professor and extension specialist at the University of Maryland and an Institute of Food Technologists spokesperson, finds this research to be very meaningful, explaining: “It is difficult to perform large-scale clinical trials like these. They take several years and involve tens of thousands of people sometimes. Most of these large-scale trials, if conducted properly, give meaningful results. Epidemiological studies around the world had shown that people [who] eat a healthy diet with a low intake of meat and high intakes of fruits, vegetables, and whole grains had lower risk for chronic diseases like cancer, heart disease, hypertension, and so forth. So the next step was to see what gave this protection. People in the nutritional arena thought it must be the antioxidants and vitamins found in fruits and vegetables, since they are so rich in them. That led to the hypothesis that maybe vitamins protect from disease. In these clinical trials, they expected to find benefits. It was a huge, huge commitment to create these trials. They cost millions of dollars.”

Marian L. Neuhouser, PhD, RD, an associate member of the Cancer Prevention Program at Fred Hutchinson Cancer Research Center in Seattle, agrees, adding, “Clinical trials are the gold standard for research, so this information is a pretty powerful tool showing us that supplements are not associated with health outcomes. The fact is that some of these single-nutrient supplements provided adverse effects or no effect at all. This is valuable information to pass on to our patients.”

Nutrition science has its roots in the role of vitamins and minerals in nutritional deficiencies; nutrition scientists naturally might expect to find disease-prevention abilities in vitamins and minerals. “What I tell people is that it’s a different paradigm between nutritional deficiencies and chronic disease. There are deficiency problems around the world, but it is still in pockets. There is a reason we iodize salt and put riboflavin in milk. There was a lot of thinking that single nutrients might also help in chronic disease prevention. But the paradigm for chronic diseases such as obesity, heart disease, and cancer is different,” says Neuhouser.

Kantor reports that a couple of years ago, a National Institutes of Health (NIH) conference on the state of the science on multivitamin and mineral supplements exhaustively reviewed every study ever done on this subject. The NIH experts gleaned only a relatively small number of rigorous, well-controlled studies that they could draw information from and concluded that there is not enough evidence to prove that multivitamin and mineral supplements are beneficial or not beneficial in chronic disease prevention.

Too Much of a Good Thing?
It’s disheartening to think that a daily multi may not be doing much good for preventing disease, but it’s far more disturbing to consider that it may pose a threat. Some studies are indicating that too much of a good thing might not be such a good idea.

The NIH-AARP Diet and Health Study examined 295,344 men who were cancer free at enrollment during five years of follow-up. The findings were published in the Journal of the National Cancer Institute in 2007. Though the study did not find an association between multivitamin use and the risk of localized prostate cancer, those who took a multivitamin more than seven times per week had a higher risk of advanced and fatal prostate cancer than those who did not.

Scientific findings have sifted out a few nutrients of concern.

Folic Acid
The story on folic acid, a B vitamin that plays an important role in forming DNA, is not a simple one. Data have suggested that folic acid may protect against colon cancer. But a Dartmouth Medical School randomized trial published in The Journal of the American Medical Association in 2007 that included 1,021 men and women with a recent history of colorectal adenomas found that high doses of folic acid were associated with higher risks of having three or more adenomas and of noncolorectal cancers. Some scientists believe that adequate folic acid may protect against developing cancerous tumors by repairing errors in DNA, but too much folic acid may nurture the growth of tumors already present.

Many experts are concerned about the levels of folic acid people are now consuming since folic acid fortification began and highly fortified foods became popular. Naturally occurring folate found in leafy greens, beans, orange juice, and other plants doesn’t appear to be a concern because it is not absorbed as well.

Antioxidants: Vitamins A and E and Beta-Carotene
We know that vitamins A and E and beta-carotene are antioxidants that may prevent carcinogens from damaging DNA. Yet, the now-famous Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (published in The New England Journal of Medicine in 1994), which enrolled more than 29,000 male smokers taking daily supplements of beta-carotene, vitamin E, both, or a placebo, found that after an average of six years, the incidence of lung cancer was 16% higher among supplement users than among the placebo group. The rate of death from all causes was 8% higher in those taking beta-carotene supplements.

The Beta-Carotene and Retinol Efficacy Trial published in 2004 in the Journal of the National Cancer Institute included more than 18,000 men and women who were smokers, former smokers, or workers exposed to asbestos. Participants took daily supplements of beta-carotene and vitamin A or a placebo. After an average of four years, lung cancer incidence was 28% higher and the rate of death from any cause was 17% higher among beta-carotene supplement users.

More recently, the results from the VITAL Vitamins and Lifestyle study, published this year in the American Journal of Epidemiology, found that among those aged 50 to 76, longer duration use of individual beta-carotene, retinol, and lutein supplements was associated with a statistically significant elevated risk of total lung cancer and histologic cell types. The researchers concluded that long-term use of individual beta-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.

Some research links selenium to decreased prostate cancer risk, but results from the Nutritional Prevention of Cancer trial, published in a 2003 issue of the Journal of the National Cancer Institute, demonstrated that 200 mcg of selenium supplementation increased the risk of squamous cell carcinoma and total nonmelanoma skin cancer. A study from the State University of New York discovered that among the 1,202 study participants, long-term supplementation with 200 mcg selenium/day was linked with an increased rate of type 2 diabetes. These findings were published in 2007 in the Annals of Internal Medicine.

Not Enough Evidence
“Most studies on vitamin and mineral supplements have found no benefits and no harm. We do know that beta-carotene supplements might be harmful for smokers because of two very large studies. With folic acid, we need more research. It’s complicated for the public, but it will be a big topic in the coming years. The folic acid fortification program provides only a small amount of the folic acid people get. They are mostly getting it through fortified foods like vitamin waters and granola bars,” says Neuhouser.

Kantor adds, “The most famous example of a nutrient causing harm was in the trial that found beta-carotene seemed to increase the risk of lung cancer. Virtually every study that I’m aware of shows that antioxidant supplements show no benefits with regard to preventing chronic diseases. There is not yet enough evidence on the risks of folic acid supplementation to draw any conclusions. I think at this point, the benefits of folic acid supplementation still outweigh the potential risks.”

Complex Vitamin Science
Do these results mean it’s time to recommend tossing out the vitamin bottle? Keep a steady hand—we have much more to learn.

It’s important to note that the science on vitamin supplementation and health risk has been mired in inconsistencies. Some studies have shown health-protective effects while others have demonstrated risks. These negative findings don’t mean that vitamins are not good for the body. We know that the human body requires an array of micronutrients—from vitamin A to zinc—to maintain normal function. And we don’t yet fully understand how supplemental forms of micronutrients work in the body, according to the American Cancer Society. Compared with whole food sources, supplements can be in a different form, dosage, and combination with other nutrients. Individuals may react to supplements differently, based on genetic characteristics and health conditions.

“The public wants information on what they’re supposed to do in this whole area, but the policy makers and the scientists can’t give them information yet. So it’s difficult to know what to tell people to do,” says Kantor. “This field of research is very complicated. These studies look at people taking vitamins and their risk of getting disease, but other things can influence these results, like heavily fortified foods, drugs and medications they are on, and individual genetics. In human nutrition studies, it’s hard to account for these variables, and it is very difficult to get really good results.”

Don’t forget that many groups and individuals can benefit from vitamin/mineral supplementation. Pregnant women, young children, frail elders, and individuals with compromised nutritional intake are populations that typically benefit from supplementation. And many Americans don’t make the right food choices to meet their micronutrient needs; surveys consistently show that people fall short on calcium, fruit, vegetable, and whole grain intake.

“There is good evidence with some nutrients. For instance, calcium and vitamin D can prevent osteoporosis, and folic acid can prevent birth defects. Although there is controversy associated with folic acid—too much may increase the risk for cancer—there are certain times that people may need to take a multivitamin. I don’t want people to think that multivitamin supplements are totally worthless. But if you look at the total body of evidence and well-designed studies, I’m not aware of anything that indicates they can prevent chronic disease,” says Kantor.

He believes that there is probably little harm for people, in most cases, to take multivitamins as insurance when they are not eating well, but he stresses, “I do not recommend taking high levels of antioxidants to give health benefits, and for the normal, healthy person eating a well-balanced diet, a multivitamin is probably not going to be helpful. Of course, it can make them feel good psychologically, and this is important, too. The placebo effect is important. But based on the studies, if people think they can reduce cancer and heart disease with their multivitamin, I don’t see any evidence to support this.”

The Center for Science in the Public Interest recommends that men or postmenopausal women who consume a multivitamin with 400 mcg of folic acid should take it every other day to ensure they not getting too much folic acid, and that premenopausal women should take a multivitamin with 400 mcg of folic acid every day to lower the risk of neural tube defects. In a world that finds vitamins and minerals stirred into everything from water to candy, it’s important for people to consider the supplemental intake of micronutrients they are consuming, particularly for folic acid. It’s not difficult to exceed a day’s worth of folic acid in fortified foods.

Foods First, Pills Second 
Perhaps the important lesson to remember is that a diet should focus on whole food sources of micronutrients. We don’t know enough about how supplements can protect from or trigger disease, but there is no controversy over the benefits of eating a diet rich in nutrients from whole foods. Fruits, vegetables, whole grains, legumes, nuts, and seeds contain a symphony of vitamins, minerals, phytochemicals, and fiber that appear to work together to protect against chronic disease.

The American Institute for Cancer Research urges people not to rely on supplements to protect against cancer because the disease-fighting properties from a diet with antioxidant-rich plant foods cannot be packaged into a pill. “Whole foods have much more than vitamins and minerals. They are complex. It’s naïve to think it’s a certain vitamin that may provide health protection. There’s a new way of looking at it that is a more holistic approach: the total diet, healthy foods in the diet, and lifestyle. This is going to really determine health opposed to reductionist thinking that there is a magic bullet,” says Kantor.

“Study after study has shown that eating higher amounts of fruits and vegetables protects you against a whole host of diseases. It is thought that if you don’t eat enough fruits and vegetables, you take supplements and it might do the same thing, but this is faulty thinking,” stresses Neuhouser. “The fact is it’s reductionist thinking to consider that a few things in fruits and vegetables protect against disease. There are hundreds of compounds in plants that might work together to protect against chronic disease. It may not be appropriate to pull out 10 to 20 ingredients and put it in a multivitamin or even to provide single ingredients to get the same effect of whole foods.

“There is a lot of shifting now to emphasize whole foods,” Neuhouser continues. “Pills are not a substitute for a balanced diet with a lot of variety. Companies are advertising supplements and telling consumers that they need these to be healthy, but there’s pretty good evidence that the supplements are not living up to what they say they do. I think it does go back to our first line of defense is nutrients from foods. This is the simple message we should keep telling the public.”

You can’t go wrong with this sage advice.

— Sharon Palmer, RD, is a contributing editor at Today’s Dietitian and a freelance food and nutrition writer in southern California.


Peering Inside the Vitamin Bottle
Some multivitamin formulas are on overdrive. It may benefit people to flip the bottle over and read the facts, making sure that it doesn’t exceed 100% of the Daily Value (DV) for any nutrient. The DV listed on the Nutrition or Supplement Facts panel can help people understand how foods and supplements contribute to the total diet. The DVs are set high to cover the needs of 97% to 98% of the U.S. population with a margin for safety.

Nutrient                                              Daily Value
Vitamin A                                             5,000 IU
Vitamin C                                             60 mg
Vitamin D                                             400 IU
Vitamin E                                             30 IU
Vitamin K                                             80 mcg
Thiamin (Vitamin B1)                             1.5 mg
Riboflavin (Vitamin B2)                 1.7 mg
Niacin (Vitamin B3)                               20 mg
Vitamin B6                                            2 mg
Folic Acid                                            400 mcg
Vitamin B12                                           6 mcg
Biotin                                                   300 mcg
Pantothenic Acid                             10 mg
Calcium                                                1,000 mg
Iron                                                      18 mg
Phosphorus                                          1,000 mg
Magnesium                                           400 mg
Zinc                                                      15 mg
Copper                                                            2 mg
Selenium                                               70 mcg
Chromium                                            120 mcg
Iodine                                                   150 mcg
Manganese                                           2 mg
Molybdenum                                        75 mcg
Chloride                                               3,400 mg
Potassium                                             3,500 mg

— Adapted from Daily Values established by the FDA