Dietary Supplements: We Can Do Better?>

Dietary Supplements: We Can Do Better

by Wellness Letter

Three out of four American adults now take dietary supplements regularly, including four out of five older people, according to the FDA. Many people take four or more supplements every day. It’s hard to remember, but a generation or two ago, before drugstores and even supermarkets had entire sections devoted to them, dietary supplements meant one-a-day multi­­vitamins to most Americans.

The rise of the modern dietary supplement industry and marketplace was made possible by federal legislation in 1994—the Dietary Supplement Health and Education Act (DSHEA). Passed after intensive lobbying by the fledgling supplements industry, DSHEA removed supplements from most federal regulation. Since then, the U.S. supplement market has grown from 4,000 products and $4 billion in annual sales to anywhere from 50,000 to 80,000 unique products and $40 billion in annual sales, the FDA estimates.

The 25th anniversary of DSHEA seems a good time to step back and look at the world of supplements. This is especially true now, since the FDA announced in February 2019 that it is planning to “modernize” its regulation of the marketplace in coming years. The promises remain vague, but the need for stronger oversight is real.

What are dietary supplements?

By definition, they are substances taken by mouth in any form (gel, capsule, tablet, powder, and so on). Sold without a prescription, they can contain vitamins, minerals, botanicals (such as herbs and other plant extracts), amino acids, enzymes, or other ingredients—natural or synthetic or something in between—in any combination. They are called supplements because they are supposed to provide something the diet doesn’t supply or may not supply in sufficient quantity.

Dietary supplements fall under the purview of the FDA, with their ads overseen by the FTC (Federal Trade Commission). There are legal limits to the claims that can be made on labels of dietary supplements (see below), but in their advertising and especially on the internet, many products go beyond these regulatory limits and claim or strongly imply (without credible evidence) medicinal and therapeutic effects.

How supplements are different from drugs

Surveys show that many consumers have misconceptions about dietary supplements. They wrongly believe that supplements have been approved by the FDA and are regulated somewhat like drugs—and thus must be safe, must deliver on their advertised claims, and must contain what’s stated on the labels.

Medications are strictly regulated by the FDA. They must be tested for safety and efficacy in clinical trials before they are marketed; they must contain what the label says they contain; and potential adverse effects must be stated on package inserts and in ads.

Supplements are completely different. Under DSHEA, they are regulated as a class of foods, not drugs, and their manufacturers do not have to prove safety and efficacy or warn about possible adverse effects. Thus, companies don’t have to do any pre-market testing, let alone publish their results in peer-reviewed journals, which is what makes it so hard to evaluate supplements.

There is little or no incentive for supplements companies to fund well-designed, placebo-controlled studies, which are expensive to carry out. For one thing, any positive research findings would also benefit the sponsoring company’s competitors, since most supplements are substances found in nature and thus can’t be patented. In addition, studies—particularly those conducted by independent researchers—may produce disappointing or even worrisome results.

It is the FDA’s responsibility to demonstrate harm and remove dangerous supplements from the market. The task is formidable because of the vast, ever-changing array of products, and the FDA’s supplements division is underfunded and understaffed. Building a case against a supplement can take years.

Ephedra was a case in point. This stimulant herb was the active ingredient in many weight-loss and exercise-performance supplements. It took a decade for the FDA to gather sufficient evidence to ban its use in 2004—after years of industry resistance and the leading manufacturer’s withholding of reports of adverse effects. Eventually, the FDA received reports of thousands of adverse events, including heart attacks, strokes, and deaths (notably of 23-year-old Baltimore Orioles pitcher Steve Bechler), leading finally to the ban on ephedra.

Un­­fortunately, similar concerns remain about some of the stimulant compounds that took ephedra’s place in weight-loss or performance-enhancing supplements. It’s like whack-a-mole—regulators hit one product, and three more pop up.

Since 2007, in the aftermath of the ephedra debacle, supplements manufacturers have been required to inform the FDA about serious adverse events. It’s not clear how well this system is working, and the problems reported are undoubtedly only the tip of the iceberg.

Another problematic aspect of supplements regulation: Federal law requires manufacturers to notify the FDA at least 75 days before marketing a supplement that contains a “new dietary ingredient” (one that was not marketed in the U.S. before 1994). Supplements containing a new ingredient that has not been submitted to the FDA are considered adulterated and thus illegal. However, despite the fact that several thousand new supplements are marketed each year, the FDA received only about 750 notifications about new ingredients in total between 1994 and 2015. The FDA and the industry have been debating in recent years about how best to update the review process for new ingredients. This is just one of many holes in the system that the FDA is attempting to plug.

Deciphering supplement claims: good luck

DSHEA limits the claims made on supplements’ labels and on the internet (even in testimonials and website links)—or at least attempts to do so. With only a few exceptions, the claims cannot assert that supplements treat or cure disease, which would make them drugs. Only “structure/function” or “health maintenance” claims are allowed. Here are some examples:

  • A label can say “helps improve mood” but not “reduces depression.”
  • It can say “maintains a healthy circulatory system” but not “prevents cardiovascular disease.”
  • It can say “maintains cholesterol in a healthy range” but not “lowers cholesterol.”
  • It can say “supports the immune system” but not “prevents colds and flu.”

Confused? For years, the FDA has at­­tempted to make a distinction between disease claims (also called medical claims), which it strictly limits, and structure/function claims (health maintenance claims), which are only loosely regulated. It is nearly impossible for consumers to tell the difference between reasonable, permitted claims and the overblown ones, or to spot deceptive advertising. The fine line between a disease claim and a structure/function claim is often hard to define.

Disease claims. In order for a supplement to make any claims about preventing, treating, curing, or diagnosing a disease or its signs or symptoms, the FDA must re­­view the proposed claims for efficacy and find “significant scientific agreement.” Some examples of such claims would be “prevents osteoporosis,” “protective against cancer,” “lowers cholesterol,” “reduces the pain and stiffness of arthritis,” “alleviates constipation,” and “improves urine flow in men.” Among the few explicit health claims that have met the FDA’s high standards of proof are the claims that calcium helps prevent osteoporosis and that folic acid (a B vitamin) helps prevent birth defects.

Even “implied” disease claims require FDA approval, though this is where things get really murky. Such claims would include “prevents bone frailty,” “promotes urinary tract health,” and “improves joint mobility.”Companies, denying that these are disease claims, often push to see how far they can go with such implied claims.

Health maintenance or structure/function claims. These include claims such as “maintains a healthy circulatory system” as well as claims about common conditions associated with “life stages,” such as aging, menopause, or pregnancy. Other nondisease claims include “arouses sexual desire,” “boosts stamina,” and “enhances muscle tone.” None of these vague claims need FDA approval, but their presence requires a disclaimer on the label saying that the product and the claims have not been evaluated by the FDA and that the product is not intended to diagnose, treat, cure, or prevent disease.

Of course, this disclaimer is usually in tiny type. And many consumers either do not notice the disclaimer or disregard it, according to a research review in Health Affairs.

Qualified health claims. In 2004, bowing to pressure from industry via freedom-of-speech court cases, the FDA started allowing more questionable, “qualified” health claims, which are hedged with qualifiers and based on “very limited,” “preliminary,” and possibly even poor-quality evidence. Because the qualifiers must be on the labels, supplement makers rarely use such claims. Though the industry pushed for the right to use qualified health claims, some supplement makers have challenged the restrictive wording demanded by the FDA by taking the agency to court and arguing that their freedom of speech is being limited.

In recent years, the FDA has issued a record number of warning letters to marketers about illegal disease claims made on supplement labels, in ads, and on the internet. A few years ago, an investigation by the Inspector General of the Department of Health and Human Services concluded that many companies do not comply with federal law about structure/function claims on their supplements’ labels or make unsubstantiated health claims. The report recommended that the FDA be given greater authority in order to crack down on such illegal claims.

What about the risks?

Though they are almost never listed on labels or mentioned on websites, the risks posed by supplements include the following:

  • Supplements can have serious and even fatal side effects. They lead to an average of 23,000 visits to U.S. emergency rooms and more than 2,100 hospitalizations each year, according to a decade-long federal study in the New England Journal of Medicine in 2015. Nearly 30 percent of the visits involve people ages 20 to 34, and 20 percent unsupervised children. Supplements marketed for weight loss and energy boosting were found to be the most common culprits, often causing cardiac symptoms such as palpitations, chest pain, and fast heart rate. Allergic reactions, headaches, dizziness, vomiting, and abdominal pain were also commonly reported.
  • In particular, many supplements can be toxic to the liver, especially when taken long term or in high doses, according to the American College of Gastroenterology. Herbal products that can harm the liver include green tea extract, chaparral, comfrey, kava, and skullcap. Body-building and weight-loss formulas account for many cases of liver damage. Impurities or toxins introduced during processing of supplements increase the risk.
  • Some supplements have the same adverse effects as prescription drugs. For example, red yeast rice extracts that claim to lower cholesterol actually contain an unpurified statin ingredient in doses that can vary as much as 120-fold, as a 2017 study found. Other supplements illegally contain hidden pharmaceutical ingredients. Thus, supplements that claim to “cure” impotence may actually contain the drug sildenafil (brand name Viagra), along with other potentially dangerous adulterants. But while the drugs require a doctor’s supervision (and precautionary labeling), people generally take supplements on their own, so there’s no one to check for side effects.
  • People who self-medicate with supplements may be missing out on treatments or dietary measures that could really help them. Or they may unwisely stop taking an effective drug in favor of a “natural” product.
  • Dietary supplements can interact with prescription and nonprescription medications, making the drugs less or more potent.

    Supplement Crackdowns and Recalls

    The FDA has cracked down on a variety of dangerous supplements in recent years, including many products marketed for sexual enhancement, weight loss, body-building, and improved cognition.

The ABCs of good manufacturing practices (GMPs)

Critics of the industry have long warned that you don’t really know what you’re getting when you buy supplements. Over the years, there have been numerous reports of products containing much less, or much more, than what’s listed on the labels. Worse yet, supplements have been found to contain undisclosed prescription drugs, as mentioned above, as well as contaminants such as lead and other heavy metals.

To address these concerns, the FDA issued rules (in 2010 and subsequently updated) that require supplement makers to follow more extensive “good manufacturing practices” (GMPs) to ensure the identity, purity, strength, and composition of their products. This is a good step, but how much of a difference can GMPs really make?

Since DSHEA went into effect, supplements have been regulated under the category of food—and as such, they’ve been covered by GMPs that basically check for sanitary conditions and consistency in production. The newer GMPs, however, are specific for dietary supplements and add higher standards for the manufacture of these products than food GMPs do. For example, companies are supposed to test all raw materials, set expiration dates based on documented science, ensure that workers are appropriately trained and follow proper procedures, and keep more extensive records.

But the final rules were watered down from the original proposals. Not surprisingly, manufacturers fought against measures that would increase costs. In particular, the provision to test finished products was weakened by various loopholes. Notably, products for which there are no validated testing methods, such as herbs, are exempt from testing. In effect, manufacturers can still cut corners and make poor-quality products and get away with it, even if they meet GMPs.

What’s more, the FDA, despite a pledge to substantially increase inspections, lacks the resources to fully monitor compliance, which is often done through inspection of paperwork, not facilities. Thus, more than half of 656 FDA inspections of manufacturing facilities conducted in 2017 resulted in letters indicating GMP violations.

What to keep in mind about GMPs:

  • GMPs don’t guarantee safety. Ingredients can still have side effects and unknown long-term effects and interact with drugs.
  • GMPs have nothing to do with whether a product “works.” Manufacturers are still not required to submit evidence of efficacy to the FDA. Even if, say, the glucosamine or ginkgo pills contain what the label states, that does not mean they will relieve arthritis or improve memory, as claimed.
  • GMPs do not change how supplements are labeled. Unlike labels on drugs, those on dietary supplements still need not list any precautions, contraindications, or possible drug interactions.
  • Many supplements still fail to meet quality standards when put through random testing by independent organizations. GMPs should improve matters somewhat, but so far it isn’t clear by how much.

We can do better

Clearly, stronger regulation of supplements is needed. Proposals to put more regulatory teeth in DSHEA come up periodically but never get far in Congress. Some members of Congress, especially from states where most supplements are made, such as Utah (where supplements are the No.1 industry), have resisted proposals to increase the regulation of supplements. Lobbying by the industry has been very effective.

In February 2019, FDA commissioner Scott Gottlieb, MD (who subsequently resigned) announced new efforts to strengthen the regulation of supplements. He called for improved and faster ways to inform the public about potentially harmful or mislabeled products, and to ensure that supplements contain the ingredients listed on labels (and nothing else) and are manufactured according to quality standards. What’s more, he said, “we want to foster an environment where consumers and health care professionals are able to make informed decisions before recommending, purchasing, or using dietary supplements.”

Dr. Gottlieb also announced the creation of a consortium of experts from academia, government, and industry to evaluate the safety of botanical ingredients used in supplements.

It won’t be easy to balance industry concerns about allowing the flexibility and innovation needed to market new and existing products (while not incurring increased regulatory burdens) with the public’s concerns about safety and efficacy—especially in light of the agency’s limited resources. And it’s not known if Dr. Gottlieb’s successor at the FDA will continue these efforts

It is unreasonable that medications are subject to the rules of science and strict laws, while dietary supplements conform to few rules except those of the marketplace. This leaves not only the public but also medical practitioners in the dark about how and whether supplements work. More well-designed studies of supplements are urgently needed. The public needs and deserves enforceable standards to ensure quality and purity as well as established criteria for both safety and efficacy. Herbal remedies, in particular, need to be standardized so that purity and potency do not vary from batch to batch. Finally, the FDA needs adequate resources to enforce the laws and standards.

Private Supplement Watchdog Groups

Some supplements carry “seals of approval” from independent certification programs, which claim to keep tabs on the industry. But these programs have limitations.

A checklist for supplement users

  • Beware of anecdotal evidence and celebrity endorsements in ads or on the internet. You can never be sure whether testimonials were paid for or made up by a copywriter. And for every person who felt the supplement helped, many may have seen no benefit or even gotten worse, and such negative results never turn up on websites or in ads. Even if they are real comments from actual customers, testimonials are not proof or even reliable evidence of efficacy. Medical claims in marketing are strictly regulated and must be supported by adequate clinical data.
  • Be particularly wary of anti-aging claims. So far there is no supplement or any known substance that will help keep you young, unfortunately.
  • Be skeptical of ads or websites claiming that doctors don’t want you to know about the cure-all supplements the marketers are promoting because these products will hurt the doctors’ business.
  • Talk to your doctor, pharmacist, or other health care provider about any supplements you are taking. Many supplements, notably herbal products, can have adverse effects, especially when taken with other supplements or with drugs. And don’t rely on supplements to self-treat a serious health problem—see your doctor for a proper diagnosis and recommendations on treatment.

This article first appeared in the UC Berkeley Wellness Letter.

Also see Some Supplements You May Need.