REVERSALS
Let’s start with the clear reversals. Glucosamine and chondroitin are a part of normal, healthy cartilage and are marketed to promote healthy joints. In using one of these, Joanne is in good company. As of 2004, more than $700 million was spent on glucosamine, chondroitin sulfate, or combination pills. In 2006 a trial randomized more than 1,500 people to one of five treatments. The treatments were glucosamine, chondroitin, a combination of the glucosamine and chondroitin, an anti-inflammatory drug, and a placebo. At the end of the study, there was no difference in improvement in pain among the people who took glucosamine, chondroitin, the combination, or the placebo. In 2010, researchers looking at data from 10 different trials concluded that neither glucosamine, chondroitin, nor their combination improve joint pain.
How about echinacea? When it comes to treating the common cold, there are no proven therapies. This reality is the foundation for many dubious claims. Nearly 20 percent of Americans report having used echinacea in the past 30 days. Like Joanne, many use the medication to reduce the duration of cold symptoms. In 2005 researchers randomly assigned volunteers to echinacea or placebo and then exposed them to the cold virus. (We assume the volunteers were well compensated.) They found that echinacea did not reduce the duration of symptoms among patients who contracted a cold. These results were later supported by an analysis of seven randomized trials, only one of which found that echinacea reduced the duration of cold symptoms when compared to a placebo. (In the same analysis, the authors examined 12 studies that looked at using echinacea to prevent colds; none of these studies showed an effect.)
Acupuncture dates back more than 3,000 years. It is a popular treatment for pain and has been advocated for ailments as diverse as Bell’s palsy and nicotine addiction. Recently, acupuncture has been studied relentlessly. These studies have included some beautifully designed trials in which acupuncture was compared to sham acupuncture (either using toothpicks, instead of real needles, or retracting acupuncture needles). A recent, and impressive, effort to bring together all this research analyzed any review of the acupuncture literature that was published between 2000 and 2009. The authors searched for reviews indexed in databases of the Western, Chinese, and Korean scientific literature. In the end, the authors concluded that there is “little truly convincing evidence that acupuncture is effective in reducing pain.” They also enumerated a few examples of acupuncture causing real harm.
Because of the ubiquity of multivitamin use, no topic is more controversial than this one. The reasons people take vitamins are varied. Like Joanne, they may take them because they feel their diet is inadequate, or they may hope the supplement will decrease their chances of having heart disease or cancer, or improve their longevity. In 2009 an observational study of postmenopausal women was done. This trial studied 161,808 women, who were enrolled in observational or randomized trials. Over 40 percent of these women had chosen to take multivitamins. The use of multivitamins was not associated with declines in cancer, heart disease, stroke, or mortality. However, this was an observational study, which, as we have seen, can mislead us (see chapter 10 for more on observational studies). In this case, however, randomized trials confirm the lack of benefit. In 2013, the latest and most extensive review of the randomized trials that have studied multivitamin use found no clear benefit on overall survival, heart disease, or cancer. The Annals of Internal Medicine, the journal that published this study, published an article in the same issue entitled, “Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements.”
Finally, we come to calcium and vitamin D, which Joanne takes to strengthen her bones. If multivitamins are the most controversial, calcium supplementation is probably the most confusing. Our bones are made of calcium, and vitamin D helps our body absorb calcium. In youth, adequate calcium intake is crucial as we build our skeletons. As adults, many people do not achieve the recommended intake of calcium and vitamin D—1,000 mg. of calcium and 600 international units of vitamin D daily, the equivalent of about 4 servings of dairy products. For years, the common practice among American women (a practice endorsed by countless physicians and several professional groups) was to supplement inadequate dietary intake. If you only have two servings of dairy, take a calcium and vitamin D tablet to make up the deficit. This recommendation made sense for a couple of reasons. Unlike most vitamins, if you do not consume enough calcium, doctors cannot easily detect a deficit with a blood test. Your body works hard to maintain a normal calcium level—if calcium intake is low, your blood calcium level is maintained at the expense of your bones. Also, fracture among elderly women is often a devastating injury; why not do something to try to prevent it?
Unfortunately, supplementing calcium and vitamin D seems to not help. Similar to the stories above, recent analyses of randomized trials find that calcium and vitamin D supplementation does not reduce the risk of fractures among healthy women. For this reason, the U.S. Preventive Services Task Force (USPSTF) now recommends against the supplements.*
For years we have known that calcium and vitamin D supplementation has an important adverse effect: an increase in kidney stones. In 2010 a group of researchers identified another potential side effect: heart attacks. Initially, they found that calcium supplementation (without vitamin D) actually increased a woman’s chance of having a heart attack. At that time, many argued that the increased risk was seen because calcium was being given without vitamin D. In 2011 the same group examined studies of vitamin D plus calcium, and again they found the risk of heart attack was elevated in women who took the supplements. In short, all the recent evidence argues that calcium and vitamin D supplementation probably does not improve the outcome for which it is intended but probably does increase the risk of an even more serious health outcome. Healthy women should not take this supplement.
Before we attempt to explain why we seem to be so attracted to complementary therapies, it is worth clarifying our use of the word reversal. By now, you see that not all reversals are created equal. The common thread among all medical reversals is that a large, well-done study—typically a randomized controlled trial—finds no benefit (or finds that harms outweigh any benefits that do exist) for a common practice. The reason a practice was adopted in the first place varies widely. For some practices, we had laboratory experiments, observational trials, or surrogate end points that supported their use. In this chapter, we have discussed therapies that gained traction based on little more than anecdotal testimonies. It is tempting to conclude that some reversals are worse than others, and that the mis-steps doctors make are somehow more understandable because they are based on science, albeit flawed science. By the end of this book, we believe that, like us, you will reject this conclusion. Having studied hundreds of reversals, we do not think that, on average, doctors have higher standards than other people. Many medical practices are adopted based on studies as flawed as those for herbal supplements. Ultimately, it really does not matter how many pieces of evidence support a practice—all that matters is the quality of the evidence. With that clarification, let’s turn to our psychology.
WHY WE TAKE WHAT WE TAKE
So if that is the evidence, why do Joanne and so many of us use these complementary treatments? The adoption of these therapies seems to follow a well-worn route, one that is not dissimilar to that taken by more traditional medical therapies. Most therapies begin with an engaging story or history. Complementary therapies satisfy some need that traditional medical therapies do not. These therapies do not rise to prominence unassisted. There are usually influential supporters and people positioned to profit from their adoption helping them along. In the United States, complementary treatments get a passive assist from the federal government in that, unlike the highly regulated traditional therapies, there is no requirement of proof that they are effective. Lastly, and in this way they are not dissimilar from traditional therapies, when the effectiveness of these complementary treatments is rigorously tested and they are proven ineffective, the
se treatments are not readily abandoned.
So let us follow the twists and turns along the road to acceptance for a few common complementary therapies. The road begins with a story that makes the treatment appealing. The story usually involves a long history of use, some “natural origin,” and a reason that the treatment should work. Glucosamine is a natural component of cartilage, so its ingestion should certainly benefit our joints, whose function is so dependent on cartilage. Vitamins and minerals are, by definition, substances that our body can neither synthesize nor live without. In addition, there are frightening medical syndromes caused by their absence. The fact that in today’s industrialized world we never see rickets, scurvy, pellagra, or other vitamin-deficiency syndromes in healthy people with anything remotely resembling a reasonable diet does not dissuade people from assuming the necessity of supplements. If you want a sense of how rare these syndromes are now, ask your doctor to describe the symptoms of pellagra or beriberi—and prepare for an uncomfortable silence.
Some accepted alternative therapies lack modern physiological explanations of their utility and rely on historical precedent. Few accept the explanation that acupuncture corrects imbalances in the flow of qi through our meridians. Instead, its history of use over thousands of years is convincing. Echinacea’s use for diverse medicinal purposes by Plains Indians accounts for some of the faith in its power over the common cold.
Every complementary therapy makes up for some shortcoming created by the culture and practice of 21st-century medicine. The great successes of modern medicine and public health have been to control the diseases that suddenly and tragically strike down people in their youth. Infant mortality has seen unimaginable declines, and few of us spend time worrying about dying of polio, tuberculosis, or influenza, let alone appendicitis or gallstones. These successes leave us to worry about the diseases of aging— those diseases that set in motion the unavoidable and inexorable decline to death. Since the best medicine can do is “decrease your risk” or perhaps “delay” the development of cancers and heart disease, we are left to fend for ourselves with alternative therapies. Add to this the progressively depersonalized nature of medicine. When a visit to your doctor means spending 15 minutes with an overworked physician, one who tries to keep to an impossibly busy schedule by documenting your visit in her computer while you talk, it is not surprising that people look to an acupuncture provider who might spend an hour talking to you while actually touching your body.
Complementary therapies do not reach the shelves of GNC by a magical, organic process. Some of these therapies are backed by famous thinkers. Vitamins famously got their boost from Linus Pauling, a brilliant scientist and winner of two Nobel prizes, who spent his later years promoting megadoses of vitamins, based on theory alone. If other therapies are not backed by a prize-winning scientist, there are celebrities, celebrity doctors, and companies anxious to be a part of this $27 billion industry. Every day you can turn on the television or radio and find a celebrity physician or a guest on a talk show discussing a new complementary remedy. Dr. Mehmet Oz was called before Congress to explain his exuberant endorsement of unproven supplements. Many magazines fill their pages with “healthful tips” to keep you feeling or looking healthier or younger. These are the complementary therapies we are discussing. These topics draw viewers and help television and radio shows, magazines, and websites sell advertising.
An interesting fact about vitamins and supplements in the United States is that they can be marketed without any of the rigorous testing that is necessary for prescription and over-the-counter drugs.* While makers of traditional medications and devices must demonstrate their products’ safety and efficacy to the FDA before they go on the market, supplements, defined as substances intended to provide nutrients that might otherwise not be consumed in sufficient quantities, need only to be safe. This difference makes supplements, when they are used to treat or prevent disease, terrifically prone to reversal—there is usually little or no evidence that they work. One of the few places to find information about the effectiveness of supplements is the National Institutes of Health’s National Center for Complementary and Alternative Medicine (NCCAM). NCCAM’s website is one of our favorite places to while away a few hours. Because the federal government does not regulate supplements, the frequently negative findings described on this site are only informational and do not affect labeling or marketing of these products.
We are at the final stop on the road toward acceptance for complementary therapies. This is where these therapies, as sometimes happens, are reversed. In general, as we will learn in chapter 8, medicine is slow to abandon therapies that are proved ineffective. Available evidence suggests that the lay population is even slower to abandon ineffective therapies than the medical field—in fact, we seem to be totally unaffected by negative data. We have already seen that vitamin use has increased recently, this in the setting of mounting evidence that it has no beneficial effect. As for acupuncture, in 1997 there were 27 visits to an acupuncturist for every 1,000 adults in the United States; in 2007 the number was 79. Why is this the case? Part of the increase may be explained by cognitive dissonance.
Cognitive dissonance is the psychological theory that proposes that we have difficulty making sense of information that contradicts our worldview. Imagine a person who understands that a treatment—a vitamin, say, or a procedure that he chooses and pays for—has risks and benefits. He decides to give it a try and begins to feel better, or at least not worse. He tends to believe that this treatment, in which he has invested money and time, is beneficial. Later, if he is told that the procedure never worked, this creates dissonance. People often respond to such dissonance by more fervently believing that the treatment does work, and that the critics of it are wrong. If you buy a car that you love and the axle breaks after two weeks, you are more likely to blame those darn potholes than the lemon you bought.
WHAT TO EAT
Let’s get back to Joanne, whom we have probably picked on enough. Joanne was actually pretty comfortable with her choices of vitamins and supplements, but she felt hopelessly confused about her attempts to eat a healthful diet. We think she is right to feel confused. Each week we read stories about the healthfulness of the food we eat that are hard to believe, or we hear stories that explicitly contradict stories we heard last week. Where can we find some certainty about dietary recommendations?
The PREDIMED trial (Prevención con Dieta Mediterránea) was a study published in the New England Journal of Medicine in 2013. A multicenter trial conducted in Spain, PREDIMED randomly assigned more than 7,000 patients at high risk for a cardiovascular event to either a Mediterranean diet supplemented with extra virgin olive oil or nuts, or a control diet.* The Mediterranean diet even sounded palatable: 4 tablespoons of extra virgin olive oil a day, at least seven glasses of wine each week for those so inclined, and no calorie counting. The diet did discourage soft drinks, commercial bakery goods, sweets, pastries, spreadable fats, and red or processed meats. After about five years the trial was stopped, because there were fewer strokes in the Mediterranean diet groups. This is one of the few times a randomized trial of a dietary intervention showed a benefit for this kind of end point. Most diets are never tested in a randomized trial, and when they are, the main outcome of the study is usually short-term weight loss. Still, in PREDIMED, if you looked at mortality, there was no difference between the diets. Even the reduction in strokes was small. You had to treat about 90 people with the diet for five years to prevent one stroke.
Given the flow of this book, you probably think that we are telling you about PREDIMED because it was later contradicted. It was not. We are writing about it because it shows just how difficult it is to do a study of a diet that proves anything. Even when you take thousands of people— people who, because of their age and medical conditions are at risk for bad outcomes—and randomize them to a diet, and get them to stick with it, and follow them for years, and find a statistically significant difference, the end
result is still very, very small. And even if you think this one dietary intervention is worth it, what about adding sushi to your diet, just one meal a week? What about cooking Indian lentils and rice? How about eating a little kimchi?
When you start to think about the breadth of dietary options—even just diets typically associated with healthy living—homemade Italian or Indian or Greek or Japanese or Chinese food—you start to realize that there will never be enough trials to answer all the questions. Furthermore, when you think about how to test diets for people in their thirties and forties, you realize you would have to follow even greater numbers of people for even longer periods of time to see if any diet has a survival benefit. We would need such large studies, of so many combinations, over so many years, that we would run out of people to randomize. For this reason, it is unlikely we will ever have the set of randomized trials we need to guide the dietary choices of those who are well.
So how about observational studies? Diet may be one place where all we have to go on are observational trials. As Joanne noted at the beginning of the chapter, however, observational studies often contradict other observational trials. Plus, as we will see in chapter 9, researchers can conduct so many analyses in an observational study that, when it comes to dietary habits, studies are less like science and more like an opinion poll. To illustrate the absurdity of observational research on nutrition, two researchers randomly selected 50 ingredients from a cookbook. They found articles reporting cancer risk associated with 40 of the ingredients. Their conclusion was well stated in the study’s title, “Is Everything We Eat Associated with Cancer?” The message is clear—when it comes to nutrition, you can get observational studies to say anything.
Ending Medical Reversal Page 9
