Do vitamins and other supplements live up to their promise? from the Harvard Men

StephenW

Supplements: A scorecard                                                                                               
                                                                                                                                Dietary supplements are wildly popular. About 114 million Americans — roughly half the adult population — take at least one supplement, running up a collective tab of over $28 billion in 2010 alone. It's easy to see why supplements are such big sellers. The public has a legitimate desire for good health, and the supplement industry has a strong desire for good sales.
Medications are regulated by the FDA. Before a prescription or over-the-counter drug can be sold in the United States, the manufacturer must submit data supporting its safety and efficacy, and after the medication is approved, the FDA continues to monitor adverse reactions. Even with all these safeguards, problems still occur, prompting the FDA to withdraw many medications and to require strong warning labels on others.
In 1994, the Dietary Supplement Health and Education Act sharply restricted the FDA's ability to regulate products marketed as "dietary supplements," even though most people buy them for health, not nutrition. Manufacturers can sell these products without submitting evidence of their purity, potency, safety, or efficacy.
For most claims made on product labels, the law does not require evidence that the claim is accurate or truthful. In fact, the FDA's first opportunity to weigh in comes only after a product is marketed, when it can take action against products that are adulterated, misbranded, or likely to produce injury or illness. Since nearly all supplements are used without medical supervision or monitoring, most of the estimated 50,000 adverse reactions that occur in the United States each year go unreported. It's a situation that Harvard's Dr. Peter Cohen has called "American roulette."
How do we really know?If a supplement's label or ads won't give you reliable information, how can you find out if a supplement can help — or, for that matter, hurt? Although it's a slow process, careful, objective medical studies provide the guidance that counts.
In most cases, scientific investigations of supplements start with simple observational studies, in which researchers compare the health status of folks who take a particular supplement with the health of people who don't take the supplement. It's an important effort, but the results don't always hold up. So the next step is to conduct randomized clinical trials, in which volunteers are assigned by lot to take either the supplement or an identical-looking placebo ("dummy pill") while researchers track their health. In the best studies, neither the volunteers nor the researchers know who is getting the real thing until the code is broken at the end of the trial.
What do we know?Everyone wants to know if supplements can help. It's a good question. Here's where we stand today — but you should keep an eye out for new results, since recommendations will change as scientific studies trickle in. Unfortunately, in most cases, the studies have failed to confirm our hopes, though there are exceptions.
Many people take supplements in the belief that they will preserve health or ward off illness; many others use supplements in an attempt to treat specific conditions that have already developed. We'll have a look at popular supplements in both categories, starting with preventive supplements used principally by healthy people.
Supplements for prevention Vitamin D. To get vitamin D the old-fashioned way, by producing it in the skin, we need lots of sunshine. But as work has shifted from the farm to the office and as we've learned to use sunscreens to reduce the risk of skin cancer and wrinkles, about 70% of Americans lack sufficient amounts of the "sunshine vitamin." Older adults, patients with chronic illnesses, and people of color are at particular risk.
Vitamin D is needed to absorb calcium from the intestines; that's why vitamin D is so important for healthy bones. But vitamin D also appears to reduce the risk of various neuromuscular problems, particularly falling, and some preliminary evidence holds out hope that good levels of vitamin D may help reduce the risk of prostate cancer and certain other malignancies and perhaps of autoimmune diseases. Current guidelines call for 600 IU (international units) a day below age 71 and 800 IU a day thereafter. But many experts recommend 800 to 1,000 IU a day for most adults; daily doses up to 4,000 IU are considered safe, but more can be toxic.
It's very hard to get the vitamin D you need from your diet; oily fish and fortified dairy products are the only important sources. So supplements do make good sense for most adults. The form known as vitamin D3 is usually recommended, but D2 is also effective; for best results, take your vitamin D along with a meal that has some fat. If you want to be sure you need this supplement, ask for a blood test; levels of at least 30 nanograms per milliliter are considered best.
Calcium. All the vitamin D in the world won't protect your bones unless you get enough calcium. In theory, diet can fill the bill, but many of us don't consume enough dairy products and other calcium-rich foods. The Recommended Dietary Allowance (RDA) of calcium for men is 1,000 milligrams (mg) before age 71 and 1,200 mg thereafter. If your diet falls short, supplements make sense; calcium carbonate and calcium citrate are best. Although many doctors routinely recommend calcium supplements for women, who have a high risk of osteoporosis, men should limit themselves to the RDA since some evidence suggests very high levels may increase the risk of prostate cancer. And a 2011 report linked calcium supplements, with or without vitamin D, to an increased risk of heart disease. It's not a proven risk, but it underlines the need for careful study of the risks and benefits of supplements, including the popular items that "everybody knows are good for you."
Antioxidants. Vitamin E, vitamin A, beta carotene, and vitamin C were the favorites of the 1980s and early '90s. But many careful randomized clinical trials have not shown any benefit against heart disease, cancer, or other illnesses. And that's not the worst of it. In fact, even moderately high doses of vitamin A increase the risk of hip fractures, and high levels of vitamin A have been linked to an increased risk of prostate cancer; beta carotene increases lung cancer risk in smokers; and vitamin E increases the risk of prostate cancer and has been linked to an increase in respiratory infections, heart failure, and the overall death rate.
Do not take antioxidant supplements. One exception: people with moderate or advanced age-related macular degeneration (AMD) benefit from special antioxidant supplements that also contain zinc. Unfortunately, though, this preparation does nothing to prevent AMD in people who have healthy eyes.
The "Three B's"Just as the antioxidants were going from boom to bust, three more white knights burst onto the scene. The putative "heroes" were three B vitamins: B6 (pyridoxine), folate (also known as folic acid in its synthetic form), and B12 (cobalamin). The "villain" was homocysteine, an amino acid that's present in everyone's blood. Study after study linked high levels of homocysteine to a high risk of heart disease, and study after study showed that folic acid, alone or with B6 and B12, could reduce homocysteine levels.
Based on solid research, there was reason to hope that B vitamins, even in the amounts found in ordinary multivitamins, might reduce the risk of heart disease and stroke. But in the past few years, a series of randomized clinical trials has dashed these hopes. Except in people who have inherited a metabolic glitch that sends homocysteine levels sky-high, B vitamin supplements do not protect the heart or brain. It's another major disappointment for supplements. Still, two of these B vitamins deserve an additional look.
Vitamin B12 is found only in animal-based foods, so strict vegetarians may need supplements. In addition, many older people don't make enough of the stomach acid that's needed to liberate B12 from animal products so it can be absorbed. But B12 is also added to fortified grain products and other foods, and this synthetic B12 is easy to absorb even without stomach acid. That means a single bowl of cereal can provide your RDA of 2.4 micrograms (mcg) a day. Still, if your fortified grain consumption is erratic, a B12 supplement is reasonable.
Folate is more complex. The vitamin is essential for the production of red blood cells, and it has an important role in DNA production and in repairing defects in the genetic code. Although folate is present in a variety of leafy green vegetables, fruits, legumes, and meats, until the late 1990s, many Americans didn't get their RDA of 400 mcg from foods — and folate deficiencies during pregnancy sharply increase the risk of devastating birth defects. That's why the U.S. and Canadian governments issued regulations mandating folic acid fortification of all grain products (including cereal, bread, flour, pasta, and rice) from 1998 onward.
Folate fortification has eased the birth defect problem, but obstetricians still recommend supplements for pregnant women. It's a rare success story for supplementary vitamins, but it may have an unintended negative consequence. Although normal amounts of folic acid appear to protect cells from malignant transformation, high amounts may fuel the growth of rapidly dividing tumor cells. And some recent studies suggest that even modest doses of supplementary folic acid, when added to the folic acid in fortified food and the natural folate in food, may increase the risk of colon cancer, prostate cancer, and breast cancer. Other studies find neither risk nor benefit; in any case, it's not a worry for women who just take supplements that contain folic acid during pregnancy, and it's no reason to shun healthful foods containing folate. But it does provide a cautionary note about the most popular of all supplements, the multivitamin.
Multivitamins. Despite their iconic status, there is no evidence that multivitamins enhance health and well-being or prevent illness. In fact, both the authoritative U.S. Preventive Services Task Force and a 2006 National Institutes of Health State-of-the-Science Conference concluded that multivitamins do not offer protection against heart disease or cancer.
Without disputing these conclusions, many doctors have continued recommending (and taking) multivitamins. One rationale is that they are a convenient and inexpensive way to get vitamin D — but most preparations provide just 400 IU, much less than the 800 to 1,000 IU currently in favor. In addition, multivitamins appeal to many scientists the way prayer appeals to many agnostics: "just in case." But for multivitamins to have merit as a nutritional insurance policy, they must at least be safe. Are they?
We don't know for sure. A 2007 study raised the possibility that men who take more than seven multivitamins a week face an increased risk of prostate cancer, particularly if they take other supplements as well. In addition, a 2011 study linked various supplements with an increased mortality rate in women. And the research about large amounts of folate adds to the concern.
A typical multivitamin provides just 400 mcg of folic acid, only 40% of the dose that has been shown to promote the growth of precancerous adenomas in the colon. But now that folic acid is added to so many fortified grains, it's easy to see how a healthy diet high in whole grains and folate-rich vegetables and legumes could easily combine with a multivitamin to boost a person's daily folate intake to 1,000 mcg (1 milligram) or even more.
Despite these worries, there is still no proof that a daily multivitamin is harmful. At the same time, though, there is no evidence that it is helpful. If it won't help, even a slight chance of harm argues against taking a multivitamin. After all, one of the first principles of medicine is primum non nocere: first, do no harm.
Other supplements Fish oil. For years, doctors have known that people who eat fish regularly enjoy substantial protection against heart disease and stroke. A major European randomized clinical trial showed that fish oil also works. As a result of this research, the American Heart Association now recommends 1,000 mg a day of the marine fatty acids DHA and EPA for people with coronary artery disease. It's also reasonable advice for people with major cardiac risk factors such as high blood pressure, abnormal cholesterol levels, and diabetes. People who eat fish at least twice a week are not likely to benefit from extra fish oil.
While fish oil does appear to protect the heart, its other advertised benefits — ranging from treating depression and bowel inflammation to helping with arthritis — have not been validated. In high doses, fish oil can reduce triglyceride levels; a prescription formulation is now available. If you decide to take fish oil, don't choose fish liver oil, which has too much vitamin A.
Fiber. Most people think of fiber supplements as a treatment for constipation. But a high intake of fiber has many potential benefits for several health conditions, ranging from heart disease and obesity to hernias, varicose veins, and diverticulitis. The Institute of Medicine recommends 38 grams of fiber a day for men younger than 50, 30 grams a day for older men, 25 grams a day for women younger than 50, and 21 grams a day for women over 50. Whole grains, fruits, vegetables, nuts, and seeds are the best sources of fiber, but many people need supplements to meet these goals. If you need supplementary fiber, consider psyllium, which has the added benefit of lowering cholesterol levels.
Selenium. Few men had heard of this mineral until 1996, when American researchers reported that it appeared to reduce the risk of prostate cancer. Subsequent reports were mixed, raising doubts. Then in 2009, a 35,553-man multinational trial of selenium and vitamin E, alone or in combination, reported that neither selenium nor vitamin E had any benefit against prostate cancer. Selenium also appears to increase the risk of diabetes, and earlier studies dashed preliminary hopes that the supplement might protect against heart attacks. Selenium is not for you.