Fifty-Four Thousand Supplements:
Which Ones Work?
There cannot be two kinds of medicine. There is only medicine that has been adequately tested and medicine that has not.
—Marcia Angell, former editor-in-chief of the New England Journal of Medicine
Health food stores are a wonderland of promise. If people want to burn fat, detoxify livers, shrink prostates, avoid colds, stimulate brains, boost energy, reduce stress, enhance immunity, prevent cancer, extend lives, enliven sex, or eliminate pain, all they have to do is walk in. The question, however, is which products work? And how do we know they work?
Fortunately, thanks to James Lind, we can figure it out. When Lind climbed aboard the HMS Salisbury—intent on finding a cure for scurvy—he moved medicine from a faith-based system to an evidence-based system. No longer do we have to believe in treatments. Now we can test them to see whether they work. For example, alternative healers recommend ginkgo or rose and orange oils for memory; graviola, astragalus, and cat’s claw for immunity; guarana and Cordyceps for energy; chicory root for constipation; lemon balm oil, ashwagandha, eleuthero, Siberian ginseng, and holy basil for stress; sage and black cohosh for menstrual pain; coconut oil and curry powder for Alzheimer’s disease; saw palmetto for prostate health; sandalwood bark to prevent aging; garlic for high cholesterol; peppermint oil for allergies; artichoke extract and green papaya for digestion; echinacea for colds; chondroitin sulfate and glucosamine for joint pain; milk thistle for hepatitis; St. John’s wort for depression; and tongkat ali for sexual potency. Although the size and cost of clinical studies have increased dramatically since the days of James Lind, the claims made by alternative healers are testable—eminently testable.
When pharmaceutical companies make drugs and biologicals, the rules are clear. Company scientists first test the product in animals. If the results are promising, they take the next step, testing it in progressively larger numbers of people. If the results are still promising, they perform a definitive (so-called Phase III) study proving that the product is safe and that it works. For example, two rotavirus vaccines are distributed in the United States (I’m the co-inventor of one of them). These vaccines prevent a common cause of diarrhea and dehydration in infants. Before the existence of a rotavirus vaccine, about 70,000 children in the United States were hospitalized with dehydration caused by rotavirus every year; in the developing world, rotavirus killed 2,000 children every day.
Making a rotavirus vaccine wasn’t easy. The Phase III trial for one rotavirus vaccine, RotaTeq, included more than 70,000 children from eleven countries, tested for four years at a cost of about $350 million. If stacked one on top of another, patients’ records from that trial would have exceeded the height of the Sears Tower in Chicago. The FDA allowed the manufacturer of RotaTeq to make claims about safety and effectiveness only after those claims had been supported by rigorous scientific studies; otherwise, it wouldn’t have licensed the product.
The situation for plants, herbs, and dietary supplements is different. Because of the Supplement Act, the FDA doesn’t regulate them, so they don’t have to be tested before they’re sold. Sometimes supplements are tested by the National Center for Complementary and Alternative Medicine (NCCAM), a branch of the National Institutes of Health. One difference between the FDA and NCCAM is that the FDA requires products to be tested before they’re sold, whereas NCCAM might test some products after they’ve been put on the market. If researchers funded by NCCAM find that dietary supplements don’t work or have harmful side effects, they publish their results in scientific journals. No product recall. No change in the label. No FDA warnings. If people don’t read scientific journals, they won’t know that claims on the label are false and misleading.
The driving force behind the creation of NCCAM was Tom Harkin, a popular senator from Iowa who believed his allergies had been cured by eating bee pollen. Harkin figured that the only reason alternative remedies hadn’t been brought into the mainstream was that they hadn’t been properly tested. Once they were tested and everyone could see that they really worked, alternative medicine would be embraced by modern science and paid for by insurance companies. Since its birth, in 1999, NCCAM officials have spent about $1.6 billion studying alternative therapies. They’ve spent $374,000 of taxpayer money to find out that inhaling lemon and lavender scents doesn’t promote wound healing; $390,000 to find out that ancient Indian remedies don’t control Type 2 diabetes; $446,000 to find that magnetic mattresses don’t treat arthritis; $283,000 to discover that magnets don’t treat migraine headaches; $406,000 to determine that coffee enemas don’t cure pancreatic cancer; and $1.8 million to find out that prayer doesn’t cure AIDS or brain tumors or improve healing after breast reconstruction surgery. Fortunately, NCCAM has recently abandoned these kinds of studies, choosing instead to focus on studies of dietary supplements and pain relief.
Let’s assume for a moment that everyone wants what’s best for the patient. Alternative healers believe that ancient medicine is of value. And mainstream doctors and pharmaceutical companies believe that modern science has the most to offer. Peter Medawar, a Nobel Prize–winning immunologist, calls the battle for recognition by those who promote various remedies a “kindly conspiracy.” “Exaggerated claims for the efficacy of a [therapy] are very seldom the consequence of any intention to deceive,” he writes. “They are usually the outcome of a kindly conspiracy in which everybody has the best intentions. The patient wants to get well, his physician wants to have made him better, and the pharmaceutical company would like to put it into the physician’s power to have made him so. The controlled clinical trial is an attempt to avoid being taken in by this conspiracy of goodwill.”
Using Medawar’s logic, terms like conventional and alternative medicine are misleading. If a clinical trial shows that a therapy works, it’s not an alternative. And if it doesn’t work, it’s also not an alternative. In a sense, there’s no such thing as alternative medicine. For example, Hippocrates used the leaves of the willow plant to treat headaches and muscle pains. By the early 1800s, scientists had isolated the active ingredient: aspirin. In the 1600s, a Spanish physician found that the bark of the cinchona tree treated malaria. Later, cinchona bark was shown to contain quinine, a medicine now proven to kill the parasite that causes malaria. In the late 1700s, William Withering used the foxglove plant to treat people with heart failure. Later, foxglove was found to contain digitalis, a drug that increases heart contractility. More recently, artemisia, an herb used by Chinese healers for more than a thousand years, was found to contain another anti-malaria drug, which was later called artemisinin. “Herbal remedies are not really alternative,” writes Steven Novella, a Yale neurologist. “They have been part of scientific medicine for decades, if not centuries. Herbs are drugs and they can be studied as drugs. My problem is with the regulation and marketing of specific herbal products, because they often make claims that are not backed by evidence.” Unfortunately, when natural products promoted by alternative healers have been put to the test, they’ve often fallen far short of their claims.
Although mainstream medicine hasn’t found a way to treat dementia or enhance memory, practitioners of alternative medicine claim that they have: ginkgo biloba. As a consequence, ginkgo is one of the ten most commonly used natural products, netting hundreds of millions of dollars a year for its manufacturers. Unfortunately, sales exceed claims. Between 2000 and 2008, the National Institutes of Health funded a collaborative study by the University of Washington, the University of Pittsburgh, Wake Forest University, Johns Hopkins University, and the University of California at Davis to determine whether ginkgo worked. More than 3,000 elderly adults were randomly assigned to receive ginkgo or a placebo (a sugar pill). Decline in memory and onset of dementia were the same in both groups. In 2012, a study of more than 2,800 adults found that ginkgo didn’t ward off Alzheimer’s disease.
Another example is St. John’s wort. Every year, ten million people suffer major depression in the United States, and every year 35,000 people kill themselves. For each successful suicide, eleven more have tried. Depression is a serious illness; to treat it, scientists have developed medicines that alter brain chemicals such as serotonin. Called selective serotonin reuptake inhibitors (SSRIs), these drugs are licensed by the FDA. Because they’ve been shown to help with severe depression, doctors recommend them. Practitioners of alternative medicine, however, have a better idea—a more natural, safer way to treat depression: St. John’s wort. Because so many people use St. John’s wort, and because severe depression, if not properly treated, can lead to suicide, NCCAM studied it. Between November 1998 and January 2000, eleven academic medical centers randomly assigned 200 outpatients to receive St. John’s wort or a placebo, finding no difference in any measure of depression.
Another favorite home remedy is garlic to lower cholesterol. Because high cholesterol is associated with heart disease, because heart disease is a leading cause of death, because lipid-lowering agents lower cholesterol, and because many people are choosing garlic instead of lipid-lowering agents, researchers studied it. In 2007, Christopher Gardner and coworkers at Stanford University School of Medicine evaluated the effects of garlic on 192 adults with high levels of low-density lipoprotein cholesterol (bad cholesterol). Six days a week for six months, participants received either raw garlic, powdered garlic, aged garlic extract, or a placebo. After checking cholesterol levels monthly, investigators concluded, “None of the forms of garlic used in this study . . . had statistically or clinically significant effects on low-density lipoprotein cholesterol or other plasma lipid concentrations in adults with moderate hypercholesterolemia.” In other words, patients who choose garlic to treat their bad cholesterol are choosing to do nothing for a problem that could lead to severe and even fatal heart disease.
Saw palmetto is also popular. As a man ages, his prostate enlarges, which blocks the flow of urine. If untreated, prostate enlargement can cause urinary tract infections, bladder stones, and kidney failure. Fortunately, medicines that relax muscles within the prostate or reduce its size have been available for years. But practitioners of alternative medicine prefer saw palmetto; more than 2 million men use it.
In 2006, NCCAM supported a study at the University of California at San Francisco, the San Francisco Veterans Affairs Medical Center, and Northern California Kaiser Permanente. Investigators assigned 225 men with moderate to severe symptoms of prostate enlargement to receive either saw palmetto or a placebo twice daily for a year, finding no difference between the two groups in urinary flow rate, prostate size, or quality of life.
Five years later, the study was repeated, this time with higher doses. Researchers from Washington University School of Medicine, in St. Louis, studied 369 men who received increasing doses of saw palmetto or a placebo. Again, no change in urinary symptoms. “Now we know that even very high doses of saw palmetto make absolutely no difference,” said study author Gerald Andriole, chief of urologic surgery at the school. “Men should not spend their money on this herbal supplement as a way to reduce symptoms of an enlarged prostate because it clearly does not work any better than a sugar pill.”
A choice to believe the hype about saw palmetto was a choice to risk the occasionally severe complications of prostate enlargement. Again, natural wasn’t better. It was worse.
Another popular remedy is milk thistle. “A most interesting tonic herb from the tradition of European folk medicine is milk thistle, Silybum marianum,” wrote Andrew Weil in 1995. “The seeds from this plant yield an extract, silymarin, that enhances metabolism of liver cells and protects them from toxic injury. I recommend this herb to all patients with chronic hepatitis and abnormal liver function.” Unfortunately, Weil’s recommendation didn’t stand up to scientific study. In 2011, Dr. Michael Fried, of the University of North Carolina at Chapel Hill, led a group of investigators in determining whether milk thistle helped patients with chronic hepatitis C. More than 150 people infected with hepatitis C virus were given either milk thistle or a placebo. Then investigators determined the amount of liver damage, as well as the quantities of hepatitis C virus in blood. They found no difference between the two groups.
Alternative healers also recommend chondroitin sulfate and glucosamine for joint pain. In 2006, Daniel Clegg, of the University of Utah, led a group of investigators to see whether it worked. They studied more than 1,500 people who were given either chondroitin sulfate alone, glucosamine alone, both, a placebo, or Celebrex (an FDA-licensed anti-inflammatory drug). Only Celebrex worked.
Perhaps the most popular herbal remedy in the United States is echinacea. Used to treat colds, it’s a $130-million-a-year business. In 2003, James Taylor and coworkers at the University of Washington, in Seattle, studied more than 400 children with colds who had received either echinacea or a placebo for ten days. The only difference: children taking echinacea were more likely to develop a rash.
Not all the news is grim. Some dietary supplements actually might be of value. Of the 54,000 supplements on the market, four might be of benefit for otherwise healthy people: omega-3 fatty acids to prevent heart disease, calcium and vitamin D in postmenopausal women to prevent bone thinning, and folic acid during pregnancy to prevent birth defects.
Like vitamins, omega-3 fatty acids aren’t made in the body, so they have to come from other sources. Some studies have shown that omega-3s protect against high blood pressure and heart disease; others haven’t. The best place to get them is in the diet, specifically in fatty fish such as salmon, in vegetable oils such as soybean, rapeseed (canola), and flaxseed, and in walnuts. To get enough omega-3 fatty acids, the American Heart Association recommends that people eat at least one serving of fatty fish at least twice a week. Most Americans consume about 1.6 grams of omega-3s every day, well above what is needed to maintain heart health.
Unfortunately, not everyone gets what they need. People who choose not to eat any of the rich sources of omega-3 fatty acids are often advised to take a supplement containing 500 milligrams a day. But not more than that: too many omega-3s (such as one finds in Eskimo diets) might actually increase the risk of bleeding and stroke.
Calcium is the most abundant mineral in the body, required for vascular tone, muscle function, nerve transmission, and hormone secretion. Of interest, less than 1 percent of the total body calcium is necessary for performing these functions. The remaining 99 percent is stored in bones, where it supports bone structure and function. The problem with calcium occurs when people get older.
In children and teenagers, bone formation exceeds bone breakdown. In early and middle adulthood, these two processes occur at equal rates. Past the age of fifty, however, especially in postmenopausal women, bone destruction exceeds bone formation. This problem isn’t trivial. When bones get thinner (a condition called osteoporosis), they break more easily. About one in three postmenopausal women will fracture their spines, and one in five will fracture their hips. Indeed, every year more than 1.5 million fractures occur in the United States because of bone thinning. The best way to avoid this problem is to eat calcium-containing dairy products such as milk, yogurt, and cheese. Calcium can also be found in calcium-fortified fruit juices, beverages, tofu, and cereals.
To lessen the risk of bone thinning, postmenopausal women are advised to eat diets rich in calcium. Because most women get enough calcium in their diet, and because supplementary calcium has not been shown to reduce fractures in otherwise healthy postmenopausal women, the United States Preventive Services Task Force does not recommend supplemental calcium.
Vitamin D and calcium are linked. People who take in adequate amounts of calcium might still have a problem with bone strength if they do not also get sufficient amounts of vitamin D. That is because vitamin D helps the body absorb calcium from the gut. The good news is that vitamin D is readily made in the skin when exposed to sunlight. To get an adequate amount of vitamin D, people need only expose their face, arms, hands, or back to sunlight (without sunblock) for ten to fifteen minutes a day at least twice a week. This will provide the 600 IU of vitamin D recommended by the Institute of Medicine.
Some people, however, either don’t get out into the sun much or live in climates where there isn’t much sunlight. For this reason, many foods are supplemented with vitamin D, such as milk, bread, pastries, oil spreads, breakfast cereals, and some brands of orange juice, yogurt, margarine, and soy beverages. Because most people get enough vitamin D in their foods or from exposure to sunlight, the United States Preventive Services Task Force does not recommend supplemental vitamin D. There are, however, two exceptions: babies who are exclusively or partially breast-fed should receive 400 IU a day of supplemental vitamin D, because it isn’t contained in human milk and because they don’t get out into the sun much; and elderly adults over sixty-five years old should receive 800 IU daily because it’s been shown to reduce the high risk of bone fractures.
Finally, folic acid is a B-complex vitamin necessary for the production of red blood cells. Without folic acid, people develop anemia. But that’s not the biggest problem. Researchers have shown that folic acid deficiency can cause something far worse: severe birth defects. Pregnant women deficient in folic acid have delivered babies with malformations of the spine, skull, and brain. To avoid folic acid deficiency, people need about 400 micrograms a day.
Foods rich in folic acid include vegetables such as spinach, broccoli, lettuce, turnip greens, okra, and asparagus; fruits such as bananas, melons, and lemons; and beans, yeast, mushrooms, beef liver and kidney, orange juice, and tomato juice. Although there are plenty of sources of this nutrient, many pregnant women weren’t getting enough folic acid in their diets. So on January 1, 1998, the FDA required manufacturers to add folic acid to breads, breakfast cereals, flours, cornmeals, pastas, white rice, bakery items, cookies, crackers, and some grains. Now it’s almost impossible to become folic-acid deficient. Nonetheless, women are advised to take 400 micrograms of folic acid every day, obtained either from foods or supplements or both. Because about half of pregnancies are unplanned and because birth defects occur very early in pregnancy, all women of childbearing age should make sure they’re getting enough folic acid.
In the end, if a medicine works (like folic acid to prevent birth defects), it’s valuable, and if it doesn’t work (like saw palmetto to shrink prostates), it’s not. “There’s a name for alternative medicines that work,” says Joe Schwarcz, professor of chemistry and the director of the Office for Science and Society at McGill University. “It’s called medicine.”