10

LOOKING BEHIND THE HEADLINES AND THROUGH THE BIAS

“Whoever controls the media—
the images—controls the culture.”

—Allen Ginsberg

MANY AMERICANS ARE UNAWARE that prior to 1997 it was illegal for drug companies to advertise directly to consumers. Drug companies last year spent more than $6 billion advertising to consumers, and these ads resulted in an increase of more than 30 million prescriptions. Because of the continued success of direct-to-consumer advertising (despite the fact that most ads disclose side effects), you can expect even more such ads this year.

Over the years many of us in the natural health field have seen the media continue to disseminate questionable results from research studies in major medical journals and to hold these up as “proof” that the public is being duped into spending money on worthless natural products. (Interestingly, positive studies on natural products do not seem to receive nearly as much attention from the media. I hope this is not because drug companies are among their leading advertisers.) Of course, those of us who are knowledgeable about the merits of natural products try to mobilize our resources to counteract the negative statements, but this is often difficult when we are up against a research article published in a respected journal like the New England Journal of Medicine, Lancet, British Medical Journal, or Journal of the American Medical Association (JAMA). Such journals are seemingly more credible than even the most reputable organizations, companies, and experts in the natural product industry.

THE SAW PALMETTO STORY

To illustrate my point, let’s take a quick look at a recent double-blind study, which the media presented as evidence that saw palmetto extract does not relieve the symptoms of benign prostatic hyperplasia (BPH). This study was published in the New England Journal of Medicine.1 The news releases that ensued included a report by the Associated Press that the “popular herbal pill used by millions of men doesn’t reduce the frequent urge to go to the bathroom or other annoying symptoms of an enlarged prostate.” That is not true at all. I have been writing about the benefits of saw palmetto extract in the treatment of BPH for more than 20 years. In my major publications on the subject I have pointed out that the success of saw palmetto extract is most obvious in the early stages of BPH, i.e., in mild to moderate cases. Most natural products are simply not powerful enough to overcome a disease in its advanced stages: e.g., this is true of ginkgo biloba extract for severe Alzheimer’s disease, CoQ10 for severe heart failure, and Saint-John’s-wort for severe depression. Nonetheless, by studying cases of severely advanced disease researchers seem to want to set the stage for a situation in which no observable effect can be seen with natural products. That is exactly how this study of BPH was designed: it was conducted with men who had severe cases.

This study of saw palmetto extract tells us only that it is important to use the extract early in the disease process. The study tells us nothing new, because detailed double-blind studies have clearly shown that roughly 90 percent of men with mild to moderate BPH experience improvement in symptoms during the first four to six weeks after starting saw palmetto extract: 320 milligrams (mg) per day of the liposterolic extract.2, 3 The key is to start saw palmetto as soon as symptoms of BPH appear. (The symptoms include progressive urinary frequency and urgency; increased nighttime urination; hesitancy and intermittency; and reduced force and caliber of urine.) If a man waits until his prostate has enlarged so much that it results in significant obstruction of the bladder, saw palmetto is not likely to work. But if he starts saw palmetto early enough, it actually works at least as effectively as popular prescription drugs, without the side effects. Perhaps that is what makes the drug companies nervous. Presumably, the drug companies are upset because more than 2 million men in the United States use saw palmetto extract instead of drugs to control the symptoms of BPH.

SOME “FISHY” MISINFORMATION

In early April 2006, there was another blatant misinformation campaign when headlines in the media claimed “Fish Oil Supplements Have No Effect on Heart Disease or Cancer.” The source of this false statement was a review article published in the British Medical Journal (BMJ).4 What the study concluded and what the media grabbed hold of was this: “Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.” That is far different from what the study actually found. According to the lead author of the study, Dr. Lee Hooper:5

We did not report that “long chain omega-3 does not offer any protection from heart disease,” that “omega-3 fats have no effect on total mortality, combined cardiovascular events, or cancer” or that omega 3 fats are of “no benefit”—this is not what we found, or what we reported (despite our being misquoted in much of the press).

So, what was the truth behind the headline? Read on. But before you do, I want to stress that a high-quality fish oil supplement is one of the most important tools in the prevention and treatment of many diseases. That fact is irrefutable and is based on a large body of clinical evidence from double-blind, placebo-controlled trials. What Dr. Hooper and her group actually found by looking at the data was that taking omega-3 fatty acid was associated with a 13 percent reduction in mortality in study participants.

I do have some issues with this study, however. First, it was not a new study, but rather a detailed review and meta-analysis. The authors of a meta-analysis review the medical literature and then apply certain criteria to select published studies to include in their analysis. As a result, a meta-analysis is only as good as the studies it includes. If all the studies are of high quality and well designed, a meta-analysis can be quite helpful, because the total number of subjects is often greatly increased and that increase leads to greater statistical significance. However, if the meta-analysis includes a very large poorly designed study, it can tip the scales toward a wrong conclusion. That appears to be exactly what happened in this particular meta-analysis. Dr. Hooper’s group included a study (the DART-2 study) that has been judged by the U.S. Department of Health and Human Services and various experts as having an extremely poor design.6 One of the most serious problems was that the dietary instructions were given only at the start of the nine-year study and again after six months. People were simply told to eat more fish, but there was never any real verification that the subjects actually complied. If this single study is excluded (as it should have been), the results would have shown dramatically that fish oils are quite protective against cancer, heart disease, and strokes.

Another huge problem with the meta-analysis is that many of the studies utilized based the intake of omega-3 fatty acids on dietary, or “food frequency,” questionnaires—which have been sharply criticized because they are often inaccurate. Researchers who have relied instead on blood measurements of the long-chain omega-3 fatty acids EPA and DHA have found that these are very clearly associated with a reduction in heart attacks and strokes. For example, the group with the highest intake of EPA and DHA had an 80 percent reduced risk of a fatal heart attack relative to the group with the lowest intake.7 Obviously, that is a major reduction.

Another issue arises when the effects of fish are linked to the effects of long-chain omega-3 fatty acids. Fish is the best natural source of the long-chain omega-3 fatty acids, but our fish supply is also tainted with mercury, lead, pesticide residues, and other harmful compounds. Mercury has been known to increase the risk of cardiovascular disease. Although fish oils may protect against heart disease, is the benefit of eating fish worth a higher intake of mercury? Apparently not, as it has been shown that even though higher body levels of EPA and DHA were associated with a decreased risk of heart attacks, the higher the body mercury level the greater the risk of a heart attack.8 Researchers have concluded that the high mercury content of fish may diminish the protective effect of fish against heart disease. So, it is entirely inappropriate to lump consumption of fish into an analysis of the health benefits of long-chain omega-3 fatty acids.

A pharmaceutical-grade fish oil supplement is part of the foundation for good health. In fact, the development of high-quality fish oil products is one of the major achievements of nutritional medicine. According to the totality of research, in order to significantly promote health and reduce the risk of cardiovascular disease the daily dosage of EPA and DHA combined should be at least 1,000 mg.

A MATTER OF PERSPECTIVE…

The next issue I want to address is the perception many people have that drugs are safe but dietary supplements are dangerous. It amazes me that adverse reactions to prescription drugs are estimated to kill more than 100,000 Americans every year, yet the media seem to be interested only in inaccurately portraying the dietary supplement industry as dangerous and “unregulated.” I think a better perspective is in order. I agree that some natural products pose health risks and are potentially harmful, but on the whole there is significantly greater risk with many over-the-counter and prescription drugs. Even a drug as casually used as aspirin can produce serious side effects; it is a well-established fact that each year aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs) account for an estimated 16,500 deaths and 100,000 hospitalizations in the United States. The NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, ketoprofen, and tiaprofenic acid as well as the new, much maligned COX-2 inhibitors such as Vioxx and Celebrex.

Even though less than 10 percent of all adverse drug reactions (ADRs) are ever reported to the FDA with regard to prescription and over-the-counter drugs, the data that do exist on the scope of the problem are sobering. For example, on the basis of detailed analysis and projections presented in the most respected medical journals, including the Journal of the American Medical Association, it is estimated that 6.7 percent of hospitalized patients have a serious ADR, with a fatality rate of 0.32 percent. This translates to more than 2.2 million serious ADRs in hospitalized patients, causing more than 106,000 deaths annually. These statistics do not include ADRs that occur outside hospitals, or the estimated 350,000 ADRs that occur in U.S. nursing homes each year. Moreover, as noted above ADRs are substantially underreported.9, 10, 11

If we use these statistics to calculate monetary figures, the cost of drug-related illness and mortality is probably now more than $200 billion annually. To put this dollar amount into perspective, it is more than the total cost of treating diabetes or heart disease in the United States. The obvious question is, “Why are there so many ADRs?” There are many reasons. Here are just a few.

MISGUIDED CONCERN

Recently, Consumer Reports came up with what it referred to as the “dirty dozen” among natural products. When you take a look at the list as a whole, it is laughable that these were presented as a public health concern, both because of what is listed and because the risk is insignificant compared with ADRs.

Consumer Reports’ Dirty Dozen

     Androstenedione (andro, for short)

     Aristolochic acid

     Bitter orange

     Chaparral

     Comfrey

     Germander

     Kava (or kava kava)

     Lobelia

     Organ and glandular extracts

     Pennyroyal oil

     Skullcap

     Yohimbe

I agree that androstenedione (andro) is certainly not a dietary supplement and that aristolochic acid and pennyroyal oil are definitely hazardous, but most of the health food stores that I have been in do not carry these products or others on the list. For example, the natural product industry has been aware of the dangers of comfrey root’s pyrrolizidine alkaloids for more than 20 years. In fact, I haven’t seen a comfrey root product designed for oral use containing these compounds in a health food store in the last twenty years or so. I could be wrong—there could be some comfrey out there being sold as a tea. But my point is that comfrey is really not a public health hazard. If you take a good look at some of the other members of the “dirty dozen,” you will see that they pose little risk simply because they are not widely available. How many people in the last decade have had an adverse reaction to comfrey or the others?

The media keep harping on the dangers of ephedra, a source of the stimulant ephedrine that was used in combination with caffeine to aid weight loss. But was ephedra really all that bad? My feeling is that the abuse of ephedra was the primary issue. If ephedra is used responsibly at appropriate dosages, there is no question that it is a safe and effective natural product. Granted, there was a tendency toward abuse, because Americans typically believe that if a little is good, a lot is even better. But again, let’s try to keep things in perspective. In the worst case scenario, over the last 20 years ephedra was linked to approximately 150 deaths (virtually all of which were related to excessive dosage or abuse). In contrast, there were approximately 2 million deaths in the United States from ADRs, including more than 140,000 deaths caused by aspirin and other NSAIDs.

Taking anything by mouth—whether it is a food, a drug, or a supplement—requires some personal responsibility. But the relative risk of danger from taking a nutritional supplement or herbal product is substantially less than that seen with prescription and over-the-counter drugs. This fact is very clear.

A DIETARY SUPPLEMENT PRIMER

What distinguishes a dietary supplement such as a vitamin, mineral, or herbal product from a drug is that a dietary supplement must not claim to treat, cure, or prevent disease even if it obviously does have such effects. A product sold as a dietary supplement and touted on its labeling as a new treatment or cure for a specific disease or condition would be considered an unapproved—and thus illegal—drug. The FDA allows manufacturers of supplements to refer to a supplement’s effect on bodily structure or function, including its overall effect on a person’s well-being. Such references are known as structure-function claims. Examples of structure-function claims are:

  • image Calcium builds strong bones.
  • image Antioxidants maintain cell integrity.
  • image Fiber maintains bowel regularity.

As with any food product, federal law requires manufacturers of dietary supplements to ensure that the products they put on the market are safe. It is the FDA’s responsibility to police the safety of nutritional supplements. The FDA must show that a dietary supplement is unsafe before it can take action to restrict the product’s use or take the product off the market. The Dietary Supplement and Nonprescription Drug Consumer Protection Act of 1994 was designed to increase reporting of serious side effects from dietary supplements. Labels will have to feature a U.S. address or phone number to which reports of serious adverse events can be directed. I am confident that even with this new regulation, dietary supplements will continue to have a tremendous reputation for safety.

WHY IS THERE SUCH A BIAS?

In 1998, an article in Archives of Internal Medicine by James Goodwin M.D. and Michael Tangum M.D. highlighted what most physicians who prescribe nutritional supplements as medicines have been saying for years: there is a clear bias in conventional medical circles against nutritional supplementation.12 Medical bias, regardless of type, represents an abandonment of scientific impartiality and of the search for truth. The bias results largely because doctors, researchers, medical colleges, drug companies, and other vested interests want to maintain the status quo. Professional self-interest and profit are regarded as being more important than integrity and the best interests of patients.

As Dr. Goodwin and Dr. Tangum pointed out, the bias against and resistance to nutritional interventions are evidenced in at least three ways: (1) uncritical acceptance of any news pertaining to toxicity, (2) use of an angry and scornful tone in discussions of nutritional supplementation in the leading textbooks of medicine, and (3) ignoring of evidence supporting the benefits or therapeutic efficacy of nutritional supplements.

Tips for Buying Supplements

Obviously, the current situation regarding the regulation, label claims, and intended use of natural products is less than ideal. As a person who has dedicated his life to understanding how these products work, and who is closely involved in the natural product industry, I know firsthand the relative merits of particular natural products. There is a tremendous gap between the purposes for which these products can be used safely and effectively and what the manufacturer is allowed to tell consumers. In addition, it is unfortunate that many products on the market provide little benefit, despite overstated claims.

I am a strong advocate of responsible self-care with natural products because I know that they can make a huge difference in the quality of life. However, I am also aware that many products on the market do not fulfill label claims and are of extremely poor quality. Though in most situations I cannot tell you exactly what product or brand to buy, I can offer you some general guidance. My most important recommendation is to buy from respected manufacturers within the health food industry that follow good manufacturing practice (GMP). A manufacturer that follows the FDA’s guidelines for GMP is the most likely to have a high-quality product. Here is a practical tip: if the price of one product is substantially less than that of a seemingly identical product, buy the more expensive one. With nutritional and herbal products (like many other things), you get what you pay for. A company that follows appropriate GMP and has its own quality-control laboratory will have a higher overhead then a manufacturer who does not follow GMP and as a result will have to charge more for its product.

The example used in the article to support the first point is the uncritical acceptance of the notion that vitamin C (ascorbic acid) can cause oxalate kidney stones. This unsubstantiated, long-standing opinion is written as law in most medical textbooks. But there are no data to support it. Administration of up to 10 grams (g) per day of vitamin C has not shown any effect on urinary oxalate. In the large-scale Harvard Prospective Health Professional Follow-Up Study, those groups in the highest quintile of vitamin C intake (> 1500 mg/day) had a lower risk of kidney stones than the groups in the lowest quintiles. Despite this evidence, the myth that vitamin C causes kidney stones continues to be uncritically accepted and promulgated in major textbooks and review articles.

The examples provided for the second point—the angry and scornful tone adopted in discussions of nutritional supplementation in the leading textbooks of medicine—are numerous direct quotations from several editions of two major American textbooks: Harrison’s Principles of Internal Medicine and Cecil’s A Textbook of Medicine. The words used include “false,” “indefensible,” “wasteful,” “unnecessary,” “deplored,” and “poor medical practice.”

The third point—ignoring evidence of benefit or therapeutic efficacy—is the most serious problem because it has the effect of withholding potentially life-changing and even lifesaving therapies. The example used in the article is that despite numerous controlled clinical trials demonstrating that in the treatment of intermittent claudication vitamin E is at least as effective as vasodilators (but without side effects), no mention is made of this fact in any of the thirteen editions of Cecil’s A Textbook of Medicine or the twelve editions of Harrison’s Principles of Internal Medicine. Although there are even better examples, it is surely a sign of bias that vitamin E has shown such good effects in improving intermittent claudication as well as decreasing the rate of leg amputation and overall mortality but is not even mentioned in any of these editions.

Why the resistance? For some reason, resistance to nutritional science has been deeply ingrained for more than 200 years. Keep in mind that the medical community and the British navy did not give a ration of lime juice to naval crews until 1804, 62 years after the discovery and proof offered by the British physician James Lind in 1742 that lime juice prevents scurvy. The process seems to run a little faster now, but it is still too slow for the adoption of scientific information on the importance of nutrition into mainstream medical thought.

THE UNNECESSARY TIME LAG

In our current medical system there appears to be an unnecessary lag between the time when a vitamin or mineral is proved to be effective for preventing or treating a certain health condition and the time it becomes widely accepted and is recommended by physicians. A case in point is the time lag between the demonstration and the acceptance of the role folic acid plays in the prevention of neural-tube defects such as spina bifida, a defect in which the vertebrae do not form a complete ring to protect the spinal cord.

The discovery that folic acid supplementation (400 mg per day) in early pregnancy can reduce the incidence of neural-tube defects by as much as 80 percent is regarded as one of the greatest findings of the last part of the twentieth century.13 The evidence became so overwhelming that the FDA finally had to reverse its previous position and acknowledge the association, allowing folic acid supplements and foods high in folic acid to claim that “daily consumption of folic acid by women of childbearing age may reduce the risk of neural-tube defects.”

The interesting thing concerning the discovery of the link between folic acid deficiency and neural-tube defects is how long it took for obstetricians and other medical doctors to begin making the recommendation of folic acid supplementation to pregnant women. In addition, given the safety of folic acid, why was the FDA so dead set against the possibility that it might help prevent such a serious birth defect? My feeling is that its attitude, again, was related to an inherent bias. That bias is getting in the way of the advancement of medicine and the health of Americans.

Once it became “accepted medical practice” to recommend folic acid to women of childbearing age, obstetricians felt they had to do everything possible to make sure their patients were taking folic acid, presumably to prevent a malpractice suit if a child was born with a neural-tube defect.

Although obstetricians and other medical doctors claim that the protective effects of folic acid were not known until 1992, when the U.S. Public Health Service issued a recommendation that all women of childbearing age capable of becoming pregnant should consume 400 mg of folic acid per day, folic acid deficiency was linked to neural-tube defects since the early 1960s. How long will it take the medical profession to accept other links related to nutritional supplementation in the treatment and prevention of disease?

There are countless examples of how supplementing one’s diet with an inexpensive vitamin or mineral can have significant preventive or therapeutic effects, yet many physicians place an unnecessary burden of proof on the vitamin or mineral before they feel inclined to make such a recommendation. My message to these physicians is to rethink their position. Instead of waiting for absolute proof, they should ask whether there is reasonable certainty that a particular recommendation may be beneficial. What do I mean by “reasonable certainty”? Basically, does the recommendation make sense? Is there a good chance that the recommendation may be of value? Does it provide a favorable cost-to-benefit ratio? Is the recommendation safe?

MAGNESIUM SUPPLEMENTATION IN DIABETES

One of the best examples of a situation when the medical community has hesitated to recommend a nutritional supplement that would significantly reduce suffering and death is the use of magnesium supplements for diabetes. I am offering it here as a model nutritional recommendation that should be mainstream, as there is considerable evidence that diabetics should take supplemental magnesium.14, 15, 16 The reasons: over half of all people with diabetes show evidence of magnesium deficiency; magnesium improves blood sugar control; and magnesium may prevent some of the complications of diabetes, such as retinopathy (eye disease) and heart disease. Magnesium is a mineral that resides primarily within the cells of the body, not the blood. When the blood level of magnesium is low, it means that the level in the cells is very low. Even when blood (serum) magnesium is used to assess status, levels are usually low in diabetics and lowest in those with diabetic complications such as retinopathy and neuropathy. Clinical studies have shown that magnesium supplementation (usually 400 to 500 mg per day) improves insulin response and action, blood sugar control, and the fluidity of red blood cells, enabling these cells to deliver oxygen better.

To deal with the growing evidence that magnesium supplementation is beneficial in the treatment of diabetes, the American Diabetes Association sponsored a consensus panel to examine the data and make a recommendation to physicians. This presumably expert panel clearly acknowledged the weight of the scientific literature supporting magnesium supplementation in diabetics and noted that serum (blood) magnesium does not reflect body magnesium stores, yet it cannot seem to realize that magnesium supplementation is appropriate for diabetics. In fact, “the panel recommends that patients with diabetes at increased risk of magnesium deficiency, but in whom such deficiencies cannot be demonstrated by clinically available tests, not receive magnesium supplementation.” They believe that “adequate” dietary magnesium intake can generally be achieved by a nutritionally balanced meal plan as recommended by the American Diabetes Association.

This position strikes me as illogical. What the panel appears to be saying is something like, “Yes, we know that magnesium is critical to the regulation of blood glucose and blood pressure, as well as for the possible prevention of complications of diabetes. We also know that magnesium supplementation has been shown to be beneficial in the treatment of diabetes and may enhance insulin sensitivity. We understand that current tests of magnesium status are not reflective of magnesium tissue stores. Yet despite all this information we cannot recommend magnesium supplementation unless a person has magnesium deficiency documented by a test (serum magnesium or urine magnesium) that reflects only 0.3 percent of the total body magnesium pool and is reduced only when the level of magnesium within cells is severely depleted.”

The reason for the apparent contradiction is that this was a “consensus” panel. Even after Columbus returned from America, there were still those who argued that the world was flat. If a group of geographical experts in 1492 had been asked to make a consensus statement on the shape of the world, their conclusion would probably have sounded similar.

FINAL COMMENTS

One of the myths about nutritional supplementation has been that there is no firm scientific evidence to support it. However, this argument is quickly becoming outdated. There is more than enough reasonable certainty to use nutritional supplementation for virtually every common health condition. Yet nutritional supplementation is still an undervalued and underused therapy because of selective bias in conventional medical circles. To borrow from closing comments by James Goodwin, and Michael Tangum, in their editorial on bias against nutritional supplementation, the merits of nutritional supplementation should be based on its benefits versus its risks, safety, and cost. They write: “Issues such as the theory underlying the treatment or the guild to which the proponents of the treatment belong should be irrelevant.” Eventually this enlightened thinking will prevail and conventional medicine will embrace nutritional supplementation as a preventive and therapeutic measure.