Supplements: A scorecard

Harvard Men's Health Watch

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.

Supplements for prevention?

It's a disappointing scorecard. Most men stand to benefit from vitamin D, many from fiber, some from fish oil, and a few from calcium. And sorry to say, popular supplements used to treat medical problems fare no better.

For further information

National Center for Complementary and Alternative Medicine

Office of Dietary Supplements

Food and Drug Administration

Supplements for therapy?

Glucosamine and chondroitin. Supplements prepared from one or both of these natural components of cartilage rocketed to fame in 1997 with the publication of The Arthritis Cure; the book became a bestseller, as did the supplements, which racked up worldwide sales of nearly $2 billion in 2008 alone. Many doctors were skeptical, doubting that these large molecules could be absorbed from the gastrointestinal tract in meaningful amounts. But early trials, particularly those from Europe, were positive. Unfortunately, negative results followed, and a 2010 meta-analysis of 10 research studies covering 3,803 patients concluded that these supplements have no benefit. Aside from expense and disappointment, side effects have been minimal; some patients with arthritis may still decide to try these supplements for a month or two to see if they provide any pain relief.

Niacin (vitamin B3). It's a supplement that really does work, lowering LDL ("bad") cholesterol and triglycerides and raising HDL ("good") cholesterol. In fact, niacin was the first cholesterol-lowering substance shown to reduce the risk of heart disease. Trouble is, to achieve these gains you need extremely high doses of niacin, generally more than 25 (and sometimes over 150) times the RDA of 18 mg. In these doses, niacin has side effects that range from flushing, headaches, and itching to liver inflammation, erectile dysfunction, and gout. And since most men who need help with cholesterol take a statin drug, they should know that the important AIM-HIGH trial was discontinued in 2011 because niacin failed to add benefit to statin therapy. If you take niacin, use it under a doctor's supervision as a medication, not on your own as a supplement; although niacin is available over the counter, a prescription preparation is your best bet.

Red yeast rice. It's another supplement that really does improve cholesterol levels. That's no surprise, since it contains lovastatin, the statin drug that has been available by prescription as Mevacor since 1987. An independent 2010 analysis of 12 red yeast rice products found that although all claimed to have 600 mg of the active ingredient in each capsule, the actual content varied between 0.10 and 10.9 mg. In addition, one-third of the products were contaminated with a potentially toxic compound. It's a cautionary tale that illustrates the potential pitfalls of all supplements. Bottom line for red yeast rice: if you need a statin for your cholesterol, use one of the six well-regulated prescription statins under medical supervision.

St. John's wort. This herb may reduce your symptoms of depression. But depression can be a serious illness, and care should involve health care professionals. The supplement can interact with prescription antidepressants and other medications. If you think you may be depressed, get professional help instead of dabbling with St. John's wort or, for that matter, SAMe (S-Adenosylmethionine), another supplement that may help with mild depression.

Melatonin. Small doses of the "dark hormone" may help with symptoms of jet lag or insomnia, but much more research is needed.

Saw palmetto. By now you know the drill. Initial reports, mostly from Europe, suggested this supplement might reduce symptoms of benign prostatic hyperplasia (BPH) — but later research largely dashed those hopes. Many other supplements are touted for the prostate, but evidence of benefit is lacking. Fortunately, excellent prescription drugs are available for BPH.

Not recommended. It's a long list; here are some of the supplements that have failed careful trials: zinc (for the common cold), echinacea (for respiratory infections), yohimbine (for erectile dysfunction), DHEA (for aging, memory loss, sexual potency, and everything else), ginseng and ginkgo biloba (for any purpose), and chromium (or any other supplement) for weight loss.

Caveat emptor — buyer beware

We are proposing a conservative, evidence-based approach to evaluating supplements. It's sound advice, but it's often hard to balance sober scientific judgments against simple, forceful claims for health in a pill. In the final analysis, the decision is yours, so we'd like to offer a few additional cautions:

  • Beware of extravagant claims; if it sounds too good to be true, it is usually not true.

  • Beware of testimonials and endorsements, especially from celebrities. Even the most sincere, well-meaning success stories offered by friends and relatives without financial incentives can't establish a product's safety or efficacy.

  • Beware of the idea that if a little is good, more is better. Although vitamin A is essential for health, for example, doses that exceed the RDA (3,000 IU a day for men, 2,330 IU for women) increase the risk of fractures. And as noted above, a high intake of folic acid may increase the risk of certain tumors.

  • Beware of meaningless terms. The list includes all-natural, antioxidant-rich, clinically proven, anti-aging, and other vague but seductive claims that a product will promote heart health, prostate health, sexual prowess, energy, weight loss, fat loss, muscle power, and the like.

  • Beware of interactions between supplements and medications. A survey of over 3,000 people ages 57 through 85 found that 49% used at least one supplement, 81% used at least one prescription medication, and 37% of men over 74 used five or more prescription drugs. Always tell your doctors and pharmacists about any supplements you take and ask specifically about potential interactions with your prescription and over-the-counter medications.

  • Beware of adulterated products. The FDA has withdrawn over 140 products that were laced with undisclosed pharmaceutical ingredients. Perhaps the most shameful example was PC-SPES, a supplement that was heavily promoted to treat prostate cancer. The stuff actually did lower prostate-specific antigen (PSA) levels — not because of its eight mysterious Chinese herbs but because it also contained a potent estrogen (diethylstilbestrol) along with an anticoagulant (warfarin) and a nonsteroidal anti-inflammatory drug (indomethacin). PC-SPES is long gone, but other advertised supplements are still at large. Products touted for sexual performance, weight loss, and athletic performance are the most likely to be contaminated with medications.

  • Beware of products that contain less — or more — than they claim. Since you won't have the protection of FDA oversight, it's hard for you to know what you're actually getting. In general, products that are voluntarily submitted for approval by private organizations like the United States Pharmacopeia (USP) or NSF International are your best bet.

Supplements, not substitutes

Until (or unless) better oversight is available, supplements are likely to remain the Wild West of American health. At present, only a few are likely to help, some may do more harm than good, and most will be little more than expensive disappointments. But false hopes can be toxic in their own right if they keep you from taking good care of yourself or getting the medical care you need. So even if you take supplements, be sure to eat well, exercise regularly, and work with your doctor to keep your cholesterol, blood pressure, and blood sugar in good control. And while you're seeing your doctor for check-ups, screening tests, and treatments, be sure to tell him about all your supplements. Many men are reluctant to tell physicians that they use alternative or complementary therapies, but full disclosure is important for health, particularly since supplements can have adverse interactions with medications.