Science advances one funeral at a time.
—ANONYMOUS
Most of us know “alternative health”-minded people who are suspicious of the medical/pharmaceutical industries, and instead bet their lives on nutritional supplements: not only specific, identifiable vitamins and minerals, but also other “natural” ingredients like nutraceuticals, prebiotics, probiotics, omega-3 fats, and various whole food concentrates. The supplement industry has grown dramatically over the past thirty years or so; as of 2008, worldwide sales of dietary supplements were estimated at $187 billion.1 Sixty-eight percent of American adults take dietary supplements, while 52 percent consider themselves “regular” users.2 Forget apple pie—now nothing is as American as a multivitamin.
By now, I hope you recognize this as one more example of the reductionist paradigm at work, even when it’s couched in natural and alternative terms. As we saw in chapter ten, one of the major problems with modern medicine is its reliance on isolated, unnatural chemical pharmaceuticals as the primary tool in the war against disease. But the medical profession isn’t the only player in the health-care system that has embraced this element of reductionism. The natural health community has also fallen prey to the ideology that chemicals ripped from their natural context are as good as or better than whole foods. Instead of synthesizing the presumed “active ingredients” from medicinal herbs, as done for prescription drugs, supplement manufacturers seek to extract and bottle the active ingredients from foods known or believed to promote good health and healing. And just like prescription drugs, the active agents function imperfectly, incompletely, and unpredictably when divorced from the whole plant food from which they’re derived or synthesized.
The reductionist sleight of hand goes something like this: Oranges are good for us. Oranges are full of vitamin C. Therefore, vitamin C is good for us—even when extracted from the orange, or synthesized in a lab and stuck in a pill, or “fortified” into a breakfast cookie. But there’s no evidence that this is the case. As we’ll see, not only do most supplements not improve our health, some that have been studied most intensely actually appear to harm us.
RUI HAI LIU AND THE REDUCTIONIST APPLE
Consider the humble apple. We all know the folk wisdom that “an apple a day keeps the doctor away.” This insight is supported by all the evidence science has amassed that shows the apple is a food that contributes to health. But what is it about the apple that promotes health? Food composition tables tell us that the average apple contains a significant amount of the following nutrients: vitamin C, vitamin K, vitamin B6, potassium, dietary fiber, and riboflavin. Also, it’s got smaller amounts of vitamin A, vitamin E, niacin, magnesium, phosphorus, copper, manganese, and a whole host of other nutrients.3 From this long list, can we figure out what really matters about an apple?
A friend and colleague of mine, Dr. Rui Hai Liu, got curious about this question, and he and his research team set about looking for the answer.
Professor Liu was among that early wave of Chinese students who came to the United States when our two countries began to open their doors (and their hearts and minds) in the early 1980s for scholarly exchange. Because of my early work in China and the rapidly growing reputation of our joint project—the first research project jointly funded by the United States and China (and England)—Liu had sought me out to help him come to Cornell. He tells me that mine was the first American family and home that he visited. He did his PhD research program in Cornell’s food science department, and I was a member of his graduate research advisory committee. Upon completion of his studies, an opportunity then arose for him to apply for an assistant professorship in the same department (he clearly demonstrated great potential). Again, he asked me to write a reference letter to support his application. Not long thereafter, he applied for and succeeded in getting some very competitive research funding from the NIH to enable him to develop a substantial research program. Since then, Liu’s successes have been impressive. Now a tenured professor, he has amassed a very productive research career, establishing himself as an internationally prominent researcher and lecturer in his field.
The course of that career included his early findings about the health effects of the apple, an area of study that flowed naturally from his personal background. Professor Liu’s father was a well-known herbalist in China, and, as a young boy, Liu helped his father make herbal preparations. He grew up in a family concerned with human health, within a culture that viewed health care wholistically. When Chinese doctors counsel patients, they traditionally consider the whole person: physically, mentally, socially, and environmentally. Their practice of “medicine” also considers the wholistic effects of whole plants, usually multiple plants, in their preparation of herbal remedies (plants comprise about 95 percent of remedies in traditional Chinese medicine). So Professor Liu was accustomed to looking at things not only in a reductionist way, as he was trained to in his Western biomedical schooling, but also in a more wholistic way, based on his familiarity with Chinese medical philosophy.
In studying the apple, Professor Liu and his research team began by choosing to focus on vitamin C and its antioxidant effect. They found that 100 grams of fresh apples (about four ounces, or half a cup) had an antioxidant, vitamin C–like activity equivalent to 1,500 milligrams of vitamin C (about three times the amount of a typical vitamin C supplement). When they chemically analyzed that 100 grams of whole apple, however, they found only 5.7 milligrams of vitamin C, far below the 1,500 milligrams that the level of antioxidant activity associated with vitamin C indicated. The vitamin C–like activity from 100 grams of whole apple was an astounding 263 times as potent as the same amount of the isolated chemical! Said another way, the specific chemical we refer to as vitamin C accounts for much less than 1 percent of the vitamin C–like activity in the apple—a minuscule amount. The other 99-plus percent of this activity is due to other vitamin C–like chemicals in the apple, the possible ability of vitamin C to be much more effective in context of the whole apple than it is when consumed in an isolated form, or both.
Based on what I shared in chapter six, this just makes sense. The process of nutrition is profoundly wholistic, in that the way the body uses a particular nutrient depends on what other nutrients are ingested along with it. If we just take an isolated vitamin C pill, we miss out on the cast of “supporting characters” that may give vitamin C its potency. Even if we add many of those characters into the pill too, which some manufacturers have done with bioflavonoids, we are still assuming that whatever is in the apple and not in the pill is somehow unimportant.
The results of Professor Liu’s study were published in the prestigious science journal Nature4 and attracted considerable media attention. In that article, Liu’s group concluded “that natural antioxidants from fresh fruit could be more effective than a dietary supplement [of vitamin C].” What a profound finding! The outcome of a fully reductionist study design (measuring the amount of vitamin C in an apple) demonstrated the utter fallacy of the reductionist toolkit.
Dr. Liu’s subsequent research provided an even clearer picture of the mind-blowing complexity of a simple food like an apple. Once he discovered that an apple was far more powerful a vitamin C delivery system than it “should” have been, he wondered about the mechanisms that might explain that huge difference. His lab focused on searching for the kinds of chemicals that might account for the rest of the vitamin C–like activity in apples. Liu and his graduate student (now Dr.) Jeanelle Boyer eventually summarized their work—along with the findings of others—to show that there is a treasure trove of such vitamin C–like compounds in apples.5 These include other antioxidants with names like quercetin, catechin, phlorizin, and chlorogenic acid found only in plants, each of which may exist in many forms within the apple. The list of these chemicals in apples and other fruits is long, and likely reflects just the tip of the iceberg. It’s as if the inside of the apple is bigger than it looks from the outside.
Something else to keep in mind: This growing list of vitamin C–like compounds may have many important biological effects that may or may not depend on their antioxidant activities. Liu and his research group have used at least four laboratory tests to determine these various effects, including the ability of these compounds to inhibit the proliferation of cells (potentially stopping or even reversing cancer), decrease serum cholesterol (affecting cardiovascular disease and stroke), and generally block unwanted oxidation (implicated in cancer, aging, cardiovascular disease, and many other degenerative processes). Of course, there also are many other health functions that he could have tested as well.
It is now clear that there are hundreds if not thousands of chemicals in apples, each of which, in turn, may affect thousands of reactions and metabolic systems.6 This enormous number and concentration of vitamin C–like chemicals in apples poses a serious challenge to the notion that a single chemical—vitamin C or anything else—is responsible for the major health-giving properties of apples. Even if we measure the amount of vitamin C two apples contain, we can’t assume that one apple has twice the health value of a second just because it has twice the amount of vitamin C; the amount of vitamin C in a given apple may not tell us very much about that apple’s antioxidant power. Add to this what we discussed in chapter six about the complexity of nutrition—that sometimes a combination of nutrients is more (or less) than the sum of its parts, and that the body plays a role in determining how many nutrients from the foods we consume are actually used—and it’s hard to avoid the conclusion that knowing how much vitamin C (or even all vitamin C–like nutrients) there is in a given apple doesn’t tell us anything of value.
This dilemma is not unique to vitamin C–like antioxidants, or any other fruit or vegetable for that matter. The same is true for any nutrient isolated from any whole food. Many chemically similar groups of health-giving chemicals present in food and circulating in the body are composed of dozens, if not hundreds or even thousands, of analogs that have the same kind of activities but very different potencies.
The problem here is not that we can’t provide an accurate answer to how much of a nutrient there is in a given food, or even that we can’t figure out how much we need for optimal functioning (though this is still currently beyond our grasp). The problem is that we are asking the wrong questions—questions based on a fundamental misunderstanding of the wholistic nature of nutrition. We’re asking, “How much vitamin C are we getting?” when we should be asking, “What foods should we be eating to support our bodies’ ability to maintain health?”
The reductionist mind cannot see the apple as promoting health and leave it at that. If apples are good for us, it can’t be the whole apple. There must be some tiny part of the apple, some chemical inside the apple, that is responsible for its beneficial effects. And our job is to extract that thing from the apple and figure out exactly how much of it people need on a daily basis.
Under the reductionist mindset, healthy eating becomes a crapshoot of nutrient micromanagement—a list of individual nutrients that must be consumed in specific, regimented quantities. But in nature, you don’t find beta-carotene on its own. You can’t cut a slice of beta-carotene out of a carrot.
Unfortunately, that doesn’t stop the supplement industry from trying.
THE SUPPLEMENT INDUSTRY
The two-part assumption inherent to this reductionist thinking about nutrition—that there is a single active ingredient in healthy foods, and that we can take it out of context while still maintaining its effect—is the foundation of the supplements industry. Founded on the techno-fantasy that we can get all our nutritional needs met by powders, pills, or cubes, this industry has been relentless in analyzing foods known to promote health so it can extract and synthesize their active agents. We’ve already seen how the medical community treats disease with individual chemicals synthesized or isolated from their natural origins. As should now be clear, so does the “natural medicine” community. And it’s no more effective there than it is in mainstream medicine. More than that, supplements, as with their formally tested medical counterparts, can actually cause harm.
You may find it hard to swallow the truth of the ineffectiveness and potential harm of supplements. Arguably, the supplement industry has been even more effective in spreading their propaganda than the pharmaceutical industry. After all, supplements are “natural”; they are the same nutrients you find in food. And you can see ads for natural supplements in yoga magazines, at natural-living expos, and in your local health shop. Your chiropractor may recommend or even sell some pills in his or her office. You may find yourself aligned socially, politically, and even spiritually with the supplement industry. But there’s nothing natural about consuming these nutrients in isolation. And the main issue is not whether you like the marketing of natural pills, but what effects these vitamins and related supplements have on your long-term health.
There are many examples demonstrating the failure of individual nutrient supplements to do what they are expected to do. In fact, sometimes these supplements do exactly the opposite. While some individual studies may occasionally show a statistically significant health benefit for vitamin supplements in the short term (and a presumed benefit for the long term), when the findings of a large number of studies are collectively evaluated, there is little or no evidence that routine vitamin supplementation improves health. Researchers have looked long and hard, in vain and using lots of money, for verifiable reductions in cardiovascular disease,7 cancer,8 and total mortality9 as a result of supplementation. Some of the best studies show that not only is reductionist supplementation not beneficial, it can actually be harmful. Let’s take a look at three of the most studied supplements—vitamin E, beta-carotene, and omega-3 fats—to show what I mean.
Vitamin E
Vitamin E was first discovered in green leafy vegetables in 1922.10 Since then, studies have shown that vitamin E is integral to a large number of biochemical functions, suggesting a wide range of health benefits. Indeed, the higher the levels of vitamin E in the blood, the lower the risk for a large number of diseases. Vitamin E is fat soluble (rather than water soluble), so it can work in fatty environments such as cell membranes, where it protects the membranes and their enzymes from oxidation damage.11
In recent years vitamin E has become a popular and routine supplement for the prevention of cardiovascular and other diseases,12 on the theory that if vitamin E in food is so important to good health, then isolated vitamin E supplementation must be good as well. In the natural health community, vitamin E pills are widely thought of as the “wonder nutrient.”
Even theoretically this doesn’t add up. For one thing, vitamin E, like the other nutrients we’ve looked at in this book, seldom if ever acts independently; it can be substantially influenced by many other nutrients, including selenium, sulfur-containing amino acids, and polyunsaturated fatty acids. So removing vitamin E from its context within plant foods is like sending a general into battle without any troops. What’s more, what we usually call vitamin E is actually not one vitamin, but a family of eight similar but slightly different varieties (called analogs).13 While sharing many of the same functions, they vary significantly in potency14 and the tissues they target.15
The market for vitamin E supplementation surged after a 1993 study found an association between higher vitamin E levels in the blood and lower incidence of major coronary disease.16 What the study measured, however, was vitamin E that came from foods, not supplements. The authors made a small leap of faith when they concluded that high blood levels of vitamin E are what cause heart health (since the study was designed to detect an association, not a causal relationship), and a bigger one when they suggested that “vitamin E supplements may reduce the risk of coronary heart disease” (Emphasis mine). To their credit, the authors cautioned that more trials were needed before recommending widespread use of vitamin E supplements. But too many people have ignored the caution and interpreted this study to mean that vitamin E supplementation prevents heart disease.
The media hype about this study has fueled the huge market for vitamin E supplements over the past two decades. But all this interest has also brought about additional studies, which tell a very different story. Based on randomized controlled trials, vitamin E supplements do not decrease risk of cardiovascular diseases,17 cancer,18 diabetes,19 cataracts,20 or chronic obstructive lung disease.21 These findings are broad based and quite convincing. Their size, their breadth (they look at multiple diseases), the number of studies, and the contrary researcher expectations support a compelling case: that vitamin E supplements do not work the way reductionists expect them to, based on the demonstrated benefits of vitamin E–containing foods. Although there may be a few special groups of people for whom vitamin E supplementation might offer marginal benefits, the vast majority of people receive no advantage from it.
And that’s actually way too kind an assessment, according to recent research. One recent review of over six-dozen randomized trials involving nearly 300,000 subjects found that taking supplemental vitamin E (as well as vitamin A and beta-carotene, which we’ll discuss below) was associated with greater overall mortality.22 That’s right; not only does supplemental vitamin E not make you healthier, it actually can contribute to your premature death.
Advocates of vitamin E supplementation have responded to these findings in a few rather expected ways. Some have blamed these studies’ experimental design or the interpretation of their findings23—a fair, even desirable response among scientists, whose job it is to seek valid conclusions from imperfect data. But a responsible scientist can hardly ignore the growing consistency of findings among many studies questioning the supplemental use of this nutrient.
Other researchers have pointed out that the first four analogs of vitamin E (the tocopherols) were the ones used in these last trials. They’ve suggested that perhaps focusing on their brethren (the tocotrienols) might be a good idea because, in some systems, they are more active, supposedly to do good.24 But this fails to mention that these analogs also may have more potential of doing bad.
Last, still other advocates of vitamin E supplementation have responded by searching for special groups for whom the benefits might outweigh the risks, including people with various genetic susceptibilities.25 But this strategy still ignores the real possibility that a WFPB diet could do the same thing at lower cost and with fewer side effects like heart failure26 and death.27
It’s hard to argue with the mounting evidence: the beneficial effects of vitamin E are clearly lost when vitamin E is removed from its original plant-based environment and sold to us in bottles. But you wouldn’t know it from the hype masquerading as legitimate research.
Omega-3
Like vitamin E, omega-3 fatty acids are essential to our bodies’ functioning. As with all “essential” nutrients, we cannot manufacture these fatty acids, so we have to get them from our diet. There are three types of essential omega-3s: ALA, DHA, and EPA (although DHA is not usually considered essential under the right dietary conditions, as when one’s diet includes adequate omega-3 in relationship to omega-6 and total fat). They are found in certain plants and also in some types of fish and edible algae.
Omega-3s appear to protect our bodies from inflammation; that is, they are anti-inflammatory, and thus being helpful in reducing rheumatoid arthritis and cardiovascular disease. Several small studies found that omega-3 fats improved clinical biomarkers of diabetes like glucose tolerance,28 blood triglycerides,29 and levels of high-density lipoprotein (HDLs, or the “good” part of one’s total blood cholesterol),30 which suggests that omega-3 fats may protect against diabetes.
Omega-3 fatty acids are one of the current darlings of the mainstream nutritional health world. To ensure we get enough of them, the media urges us to eat lots of fish, specifically fatty species like anchovies, herring, salmon, sardines, and tuna. (They don’t often mention that one form of omega-3, ALA, which is found in certain nuts and seeds, can be converted in the body into the other forms, making fish consumption unnecessary.) And of course, we are also urged to take omega-3 supplements.
Supplement makers sell omega-3 to us mostly in the form of fish oil capsules. They focus on claims of “purity” for their products, contrasting them against the fatty fish we eat that contain dangerously high levels of mercury, PCBs, and other contaminants. The WebMD website goes so far as to warn pregnant women and children away from many species of wild and all species of farm-raised fish. So omega-3 supplementation would appear to be the smarter way to get what we need of this essential nutrient. In reality, however, this has proven not to be the case.
When the findings for a huge group of eighty-nine studies (this is a lot of studies!) were summarized, it was concluded that “omega-3 fats do not have a clear effect on total mortality, combined cardiovascular events or cancer”31 (Emphasis mine). In a very large study of nearly 200,000 individuals over fifteen years,32 increasing consumption of omega-3 fats (combined intakes mostly from fish but some from supplements) was actually associated with increased risk of Type 2 diabetes: the higher the omega-3 intake, the more likely the subject was to develop diabetes. In total, the study included almost 10,000 Type 2 diabetes cases, and as the omega-3 intake increased, the number of diabetes cases trended upward, so it’s highly unlikely that this association is due to random chance.
Do higher intakes of omega-3 fats really increase Type 2 diabetes? What about those earlier, smaller studies that suggested omega-3s might prevent diabetes? How can we explain this discrepancy? When you look at these studies carefully, there is no discrepancy. The earlier, smaller studies were short term and looked only at biomarkers associated with diabetes. That’s not the same as findings on the final occurrence of disease. Short-term findings are only isolated blips in a very complex sea of events. Yet supplement makers rely on these reductionist rushes to judgment, rather than waiting for meaningful long-term study results, to convince us that their products are effective.
Beta-carotene
A now-classic example showing this shortsighted rush to judgment based on short-term effects is the story of beta-carotene, the vitamin A precursor found in plants that our bodies convert into “real” vitamin A. Beta-carotene occurs naturally in green leafy plants and brightly colored red, orange, and yellow vegetables such as chili peppers, carrots, and pumpkins. In the 1970s, beta-carotene was discovered to be a powerful antioxidant33 that could block the activities of free radicals thought to promote cancer growth. Also, beta-carotene-rich foods (i.e., vegetables and fruits) were associated with decreased lung cancer.34 Together, these observations provided suggestive evidence that beta-carotene might protect against lung cancer, and perhaps other cancers as well.
About ten years later, however, a human study among smokers in Finland showed that beta-carotene supplements given for 6.5 years increased lung cancer deaths by 46 percent,35 a very large and statistically significant effect. In addition, cardiovascular deaths were increased 26 percent for those taking the supplements.36 This adverse effect was so prominent that the study had to be terminated early. That’s right: beta-carotene supplementation increased death rates so dramatically that the trial was ended early to prevent further deaths.
Interestingly, in this same study, baseline beta-carotene consumption from food was associated with lower lung cancer risk. This difference was stark. Food beta-carotene was associated with less lung cancer, but supplement beta-carotene was associated with more lung cancer. This finding was confirmed in other big studies as well.37
Since that time, a consensus has emerged showing that beta-carotene supplementation does not decrease cancer or cardiovascular disease.38
We now have a ton of studies showing all manner of mechanisms by which beta-carotene, vitamin E, and other antioxidant vitamins ought to prevent diseases like heart disease and cancer, but, when tested alone (e.g., in pills), they don’t. Even though researchers are beginning to accept these specific findings, and are no longer recommending supplemental beta-carotene, vitamin E, or omega-3, they still tenaciously cling to the same old beliefs, claiming that, despite disappointments, we should continue to put our faith in preventing disease through isolated chemicals. What incredible stubbornness!
In the face of increasingly robust and consistent findings showing that isolated nutritional supplements are bad news, the supplement industry and its hired researchers are responding by digging their reductionist hole ever deeper. Some want to escalate the search for new antioxidant chemicals in plants, in the hopes that they have more pluses and fewer minuses than the current bunch.39 Others suggest that a more customized selection of clinical biomarkers might help unearth new health benefits for the same antioxidants we’re studying currently. That is, since the antioxidant effects that we’re looking at now seem disconnected from meaningful health outcomes, we should instead look for different intermediate effects that do predict things we care about, like less disease and longer life. But the reason we use biomarkers as proxies for actual health—because it’s cheaper and quicker to measure biochemistry than to follow study participants for years to see what happens to them—is exactly why biomarker studies are not appropriate for determining the true effects of a supplement on human health.
The reaction of researchers to the news about the failure of vitamin E, beta-carotene, and other isolated antioxidants to create health disheartens me. Many researchers are now aware of these failed studies.40 They acknowledge the complex nature of antioxidant activity and the legitimacy of several reports showing that vitamin supplements may in some circumstances cause toxicity. But rather than consider giving up on this dead-end approach to health, in some cases these researchers present still more technical details they hope will justify additional and more complex supplement research. After all these years and all these studies, they still fail to see the futility of continuing to go down this same very expensive and virtually useless path of searching for some new antioxidant analog that has the special ability to create health. Someday, perhaps, they’ll find that needle in the haystack—the reductionist supplement that outperforms its natural counterpart. But I wouldn’t count on it.
During the mid-1980s, when the nutrient supplement industry was initially emerging, I spent about three years giving substantial testimony, at the request of the National Academy of Sciences, to the U.S. Federal Trade Commission as to whether health claims favoring vitamin supplementation were justified by the then-existing evidence. I testified against the industry’s proposed health claims both because reliable evidence did not exist and because, from the biological perspective I held then, it did not make sense. The perspective I held then is the same one I’ve presented here in this book a quarter-century later: nutrients rarely if ever act alone, or at least not properly so. After a few hundred billion (mostly) taxpayer dollars spent doing the research, we are now finally getting evidence that may prove helpful in moving this mountain.
Please understand: I’m not saying that there is no benefit for some people for some supplement preparations, especially when the chemical composition of the supplement begins to approximate the composition of whole plants, as in some dried herbal compounds. These products may be helpful under some conditions for certain people. But for me, the burden of proof is on those who make such assertions, and by “burden of proof,” I mean objective research findings that pass the test of peer review. It is not appropriate to propose or even infer that these “natural supplements” are the best health option without also making clear that the routine consumption of whole, plant-based foods—from whence these products came—will produce far better health at a far cheaper price.
The danger of our increasing consumption of supplements is more than just the documented negative effects on our health. It’s that our love affair with the magic bullet of supplementation lets us believe we’re “off the hook” when it comes to eating right. Why eat your veggies when you can binge on hot dogs and ice cream and, if you get into trouble, make it all better with a pill?
Nutritional supplementation is proving to be the canary in the coal mine for the reductionist approach to health. While the pharmaceutical approach continues unabated, the supplement initiative, at least, appears to have reached a research dead end. Only by applying reductionist research methods—attributing too much significance to biomarkers and individual chemicals and refusing to look at real health outcomes—can the supplement industry defend its project of factory-formed fragments of former food as the road to good health.