People often think that dietary supplements are safe because they are “natural.” As we’ve discussed many times, natural doesn’t always mean safe—and, in any case, many supplements are synthesized in labs.
Vitamins and minerals, in particular, may seem safe because, after all, the body needs them. But while deficiencies in vitamins and minerals can cause diseases and other adverse effects, excessive doses from supplements are known to cause problems as well. Usually this involves very large doses, but sometimes levels not much higher than the recommended dietary intakes for vitamins and minerals can be risky.
Probably the best-known example of unexpected hazards came from studies linking beta carotene supplements to increased risk of lung cancer in long-time smokers.
Here are three popular vitamin or mineral supplements that produced surprising and unsettling results in studies this year.
Can selenium increase mortality rates?
In a Danish clinical trial published in Free Radical Biology and Medicine, researchers analyzed data on 491 people over age 60 who were randomly assigned 100, 200, or 300 micrograms of the mineral selenium a day or a placebo, which they took for five years; at that point there were no significant differences in mortality rates. But after another 10 years of follow-up, those who had taken 300 micrograms were found to have a 60 percent higher mortality rate than the placebo group.
The lower doses had no significant effect on mortality rates. The study was not large enough to tease out the effects on specific causes of death, such as cancer. The researchers concluded, “our findings suggest that the public should avoid high-dose selenium supplements, particularly in countries with an adequate background selenium intake,” which includes the U.S.
Some background: Selenium is an essential trace mineral that is plentiful in foods, though this varies from region to region, depending on the amount in soil. The Recommended Dietary Allowance (RDA) is just 55 micrograms a day (a microgram is one-thousandth of a milligram); the “tolerable upper intake” is 400 micrograms a day.
It has been proposed that selenium can help prevent cancer (notably prostate cancer) and reduce the risk of heart disease and other disorders. Despite some promising early research, clinical trials have yielded conflicting—and sometimes alarming—results.
In 2014, for instance, an important clinical trial on prostate cancer found that selenium supplements (200 micrograms a day) taken for at least four years actually increased the risk of high-grade prostate cancer in men who started with relatively high baseline levels (as measured in toenail clippings, a standard indicator of selenium status). And back in 2007, another clinical trial found that the same dose increased the risk of developing diabetes in people with higher baseline selenium levels.
Our advice: Opt for selenium-rich foods (such as nuts, seeds, whole grains, and seafood) and leave the supplements on the shelves. Most Americans already get more than the RDA. If you take a multivitamin/mineral supplement, it shouldn’t contain more than 100 micrograms (which you don’t need anyway if you have a healthy diet). For more on selenium, see Selenium Supplements.
Does folic acid increase bladder cancer recurrence?
An NIH-funded study, published in the American Journal of Clinical Nutrition (AJCN), looked at whether intake of the B vitamin folate was related to the risk of recurrence in 619 people who had bladder cancer. In particular, it compared the effect of the natural folate in plant foods and that of folic acid, the synthetic form of folate used in supplements and in fortified or enriched foods.
Multivitamins were the main source of folic acid. Over a five-year period, people with moderate to high intakes of folic acid were 70 percent more likely to have a recurrence than those with low intakes. Natural folate did not affect the risk. The researchers called for more research to confirm these findings.
Some background: Folate is essential for healthy cell growth, so it is especially important during pregnancy, when it helps prevent neural tube birth defects and possibly autism. Thus women who are pregnant or may become pregnant are advised to consume 400 to 800 micrograms a day, preferably in the form of folic acid, which is better absorbed than natural folate.
But in regard to cancer risk, this vitamin is a double-edged sword. Much observational and animal research has linked folate deficiency to increased risk of various cancers. But most clinical trials, which use folic acid supplements, have found no effect, and a few have suggested that high-dose supplements (usually 1,000 micrograms a day) increase the risk of prostate or colon cancer, particularly in people at elevated risk.
Overall, research suggests that people who are deficient in folate may get some protection against cancer by boosting their intake, while those who already have enough in their body and take high doses may actually be harmed. Complicating matters is the likelihood that healthy people who increase their folate or folic acid intake may reduce their risk of developing cancer, but in those who already have precancerous growths or cancer (as in this new study on bladder cancer), large amounts of folic acid may promote progression.
Thus, the accompanying editorial in AJCN compared folate to Dr. Jekyll and Mr. Hyde. It concluded that “folic acid supplementation should be avoided in cancer patients and survivors and in highly predisposed and susceptible individuals at risk of developing cancer,” which includes most people over age 50, who have a “high prevalence of precursor lesions.”
Our advice: Take folic acid supplements if you are pregnant or may become pregnant. Otherwise, look to food sources of folate. Few Americans are deficient in this vitamin because many foods are now fortified with folic acid.
It’s easy to inadvertently consume more than 1,000 micrograms of folic acid a day, the amount found to increase cancer risk in some studies. For instance, a multivitamin typically supplies 400 micrograms, which is the RDA; one small serving of a highly fortified cereal (such as Total or Special K) adds another 400; a B-complex pill, 400 more; enriched grain products, perhaps another 200; and vitamin-spiked bottled waters, energy drinks, and nutrition bars add more. For more on folate, see Folate: Nutritional Chameleon?
Can calcium increase the risk of colon cancer?
A clinical trial in the journal Gut involved over 2,000 people with a history of colorectal adenomatous polyps (adenomas), who were given calcium (1,200 milligrams a day), vitamin D (1,000 IU), both, or a placebo for three to five years and then were followed for another three to five years. Colonoscopies were done before and after the follow-up period. The second colonoscopies revealed that people who had taken calcium, with or without vitamin D, were two to four times more likely to have developed certain types of serrated colorectal polyps than those taking neither supplement or just vitamin D.
Women and smokers were at highest risk. There was no increase in conventional adenomas, and calcium from food and beverages had no effect. Serrated adenomas differ from conventional adenomas in their biology and appearance and are associated with even greater risk of colorectal cancer.
Some background: The researchers admitted these results were “surprising,” since they had hypothesized that the supplements would be protective or have no effect. Indeed, much evidence, mostly from observational studies, suggests that calcium from food or supplements helps lower the risk of colon cancer, notably by reducing adenomas. In fact, a 2017 report on diet, nutrition, and colon cancer from the American Institute for Cancer Research and the World Cancer Research Fund concluded that calcium supplements (as well as dairy products) probably protect against colon cancer.
The new study didn’t last long enough to be able to detect changes in incidence of cancer. But it does show that supplements can have unpredictable effects that sometimes show up even years after people stop taking them. At this point, the best we can say is that there’s uncertainty about the effect of supplemental calcium on polyp formation.
Our advice: This new study doesn’t change our general recommendation about calcium for bone health, except that people with a history of colorectal adenomas should consult their doctors before taking the supplements. It’s best to get calcium from your diet because foods naturally rich in calcium supply many nutrients important for bones and general health. In addition, high doses of calcium supplements increase the risk of the most common type of kidney stones, while foods naturally rich in calcium (notably dairy products) protect against stones.
If you can’t get 1,000 to 1,200 milligrams a day of calcium (which is the RDA) from diet alone, you may need only a small amount of supplemental calcium to fill the gap. More is not necessarily better. For more on calcium, see Calcium in the Spotlight and Calcium Pills: Heartening News.