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Bold moves from the New York State attorney general’s (AG) office are shaking up the supplement industry. In February, the AG accused four retailers (GNC, Target, Walmart, and Walgreens) of selling supplements that failed to contain their labelled ingredients. Using a testing method called “DNA barcoding“, the AG’s office concluded that few of the products it tested actually contained the labelled ingredient, and some contained undisclosed ingredients. It demanded that they stop the sale of those products. All four retailers complied.

When the recall occurred, I noted that the AG may not have had an airtight case: manufacturers and other critics challenged the AG’s methodology, claiming that DNA barcoding was unvalidated, inappropriate, and insufficient. They also stated that the DNA may not survive processing, so the absence of DNA didn’t imply a lack of the original product. Some claimed that the “contaminants” that AG found could have been acceptable fillers. The Attorney General refused to release further information about the testing methods it used, raising further questions about its validity.

Before describing what happened next, it’s important to understand how we got here. While the US Food and Drug Administration (FDA) is respected worldwide for ensuring the quality of the pharmaceuticals it regulates, the same cannot be said for its regulation of supplements. Today, the overall quality of supplements sold in the United States is unclear. Audits and recalls suggest that there is a small but persistent trend of poor manufacturing standards. Adulteration, virtually unheard of with drug products, seems to be a regular complaint with supplements. This shouldn’t surprise, as it’s likely a consequence of legislation deliberately designed to weaken the FDA from regulating and providing oversight of supplements. The Dietary Supplement Health and Education Act of 1994 (DSHEA) was an amendment to the U.S. Federal Food, Drug and Cosmetic Act that established the American regulatory framework for dietary supplements. It effectively excludes manufacturers of these products from many of the requirements that are in place for prescription and over-the-counter drugs. Amazingly, it puts the requirement to demonstrate harm on the FDA, rather than the onus on the manufacturer to show a product is safe and effective. A weak regulatory framework, which doesn’t require pre-sale testing of product quality and finished product specifications, might be expected to result in a weaker commitment to quality. And that might result in more erratic product quality. And that’s exactly what we find when you look at supplement sales today.

There’s an additional twist with herbal remedies, which gets to the criticism of the AG’s analysis and claims. This problem isn’t exclusive to the FDA, but is a challenge to manufacturers and regulators alike. With a herb, what should we be testing for? With a pharmaceutical product, there’s an active ingredient that is manufactured into a tablet or capsule to be predictably and consistently absorbed. We can easily measure the tablet’s contents by assay, or measure how completely it is absorbed by drawing blood levels after ingestion. The same cannot be said for herbal remedies, which are essentially unpurified, unstandardized, drugs. A single plant species may have dozens, or even hundreds of biologically-active compounds. The relative proportions of all of these ingredients may vary based on growth, harvesting, and storage conditions. Now add in the fact that there’s little evidence to demonstrate that herbal products have any meaningful, beneficial effects. If there was a positive effect, we could try to determine what ingredient (or ingredients) were the cause. With that in mind, we could test for it in supplements for sale. But because there’s a lack of evidence to establish that herbal remedies have any useful effects, we don’t even know what we should test for. Without knowing if there is an “active” chemical component, we can’t test for it. So the AG’s test of DNA barcoding represented a minimum testing standard of sorts. It was simply a test to see if the labelled herb was in the tablet or capsule. And the testing showed that even that basic assumption about herbal quality may have been premature.

Supplement vendors, industry backers, and even some industry critics were quick to point out that DNA barcoding wouldn’t detect any herb present if the herb had been processed so extensively that DNA traces had been destroyed or removed. This could be expected with herbal extracts, which are not raw herbs but rather the result of combining a herb with a solvent, in a process where some components of the herb are removed or “extracted”. The process of extraction brings with it a huge number of variables that can affect the finished product’s chemical composition.

Rather than responding to criticisms about the herbal testing the AG conducted, the AG decided to double down. In mid-February, it issued subpoenas to GNC, Walgreens, Target and Walmart, demanding that they substantiate their “structure/function claims” for their supplements. Manufacturers of supplements cannot claim that their product can prevent or treat a disease. But they are allowed to make claims that describe how their product can benefit the structure of the body, or some aspect of how it functions. A structure/function claim might be “calcium builds strong bones,” or “antioxidants maintain cell integrity” which tell you nothing about the effectiveness of the product in question. Structure-function claims don’t give consumers adequate information to determine if supplements are useful or effective, but they do allow manufacturer to imply efficacy without the requirement to provide any proof. The FDA notes:

These three types of claims are not pre-approved by FDA, but the manufacturer must have substantiation that the claim is truthful and not misleading and must submit a notification with the text of the claim to FDA no later than 30 days after marketing the dietary supplement with the claim. If a dietary supplement label includes such a claim, it must state in a “disclaimer” that FDA has not evaluated the claim. The disclaimer must also state that the dietary supplement product is not intended to “diagnose, treat, cure or prevent any disease,” because only a drug can legally make such a claim.

The disclaimer is the infamous Quack Miranda warning that in a few sentences tells you that what you’re holding is a product that hasn’t been tested or evaluated for effectiveness by the FDA.

The AG didn’t stop there, either. It subsequently demanded that four supplement manufacturers, Nature’s Way, NBTY (Sundown Naturals, Nature’s Bounty, Met-Rx, Solgar, Vitamin World and other brands), Nutraceutical Corp (Herbs for Kids brand), and Pharmavite (Nature Made brand), provide detailed information on their manufacturing and quality control practices. The AG noted:

The scientific community, public health officials, and others have raised serious doubt about the steps taken to ensure the safety and efficacy of the herbal dietary supplements taken daily by millions of Americans. As part of a broader investigation, NYAG is reviewing the sufficiency of the measures manufacturers and retailers are taking to independently assess the validity of their representations and advertising in connection with the sale of herbal supplements. We seek your company’s cooperation as an herbal dietary supplement manufacturer to address these issues and, ultimately, to resolve any deficiencies.

As you may know, NYAG recently commissioned an analysis that used DNA barcoding technology to test several popular herbal dietary supplements sold at four retailers in New York State. The results were shocking to many consumers and raise troubling legal questions. In addition to the frequent absence of genetic material associated with the plant depicted on the label from the tested supplements, more than one in three samples tested positive for the DNA of an unlisted plant species, potentially constituting a contaminated or substituted product. The contamination, substitution, or false labeling of herbal products would constitute a deceptive business practice and, even more troublingly, could expose consumers to unacceptable health risks. Of particular concern, companies selling herbal products may have inadequate proof that the substances come from the plant species they claim, not be able to easily identify the source of the ingredients, or have failed to put proper controls in place or conduct proper testing or measurement to prevent contamination.

The decision by the AG to go directly after manufacturers has brought considerable criticism from the supplement industry, with most of the criticism being centred on the fact that regulation of supplements was felt to be a matter for the FDA, and not for local (state) action. In other words, they prefer the FDA’s light touch. The president of the United Natural Products Alliance complained:

This is a massive fishing expedition and highly disruptive to these companies’ daily operations that are all part of the clearly defined federal regulatory structure for dietary supplements. We continue to be mystified as to why the NY AG has chosen to do FDA’s job. We regret to see this misplaced use of the AG’s time, taxpayer money and red tape for reputable supplement companies that are simply trying to do the right thing.

Perhaps not unexpectedly, one of the supplement’s industry’s biggest supporters has weighed in as well. Senator Orin Hatch and Senator Martin Heinrich have written a letter [PDF] to the FDA Commissioner, asking the FDA to comment on the AG’s methodology and the appropriateness of the AG’s demands. They note:

Attorney General Schneiderman has refused to make the test results and the details of the study methodology public, and questions about the appropriateness of DNA testing for herbal extracts have been raised that merit consideration. The question at the heart of this matter is whether DNA barcoding methodology is fit for the purpose of identifying DNA in botanical extracts found in dietary supplements. It is our understanding that the process of extracting an herb’s phytochemicals for use in finished products can either damage, destroy or simply leave behind the DNA this testing protocol is designed to find, which has left many scientists – both inside and outside the industry – to question whether DNA barcoding technology is an appropriate or validated method for determining the presence of herbal ingredients in finished botanical products.

Hatch and Heinrich’s letter raises questions in four areas:

  1. Does the FDA require testing of incoming material as well as tests of finished product quality?
  2. Does the FDA recognize DNA barcoding for the identification of botanical materials in finished extract dietary supplements? Without additional testing, is this satisfactory?
  3. Does the FDA recommend DNA barcoding for herbal extracts? Is the current technology adequate to permit use?
  4. Do federal laws and regulations require food labeling (including dietary supplements) to identify all ingredients? Are trace amounts of materials allowed without labelling? Can plant materials be used as excipients if they are labelled?

The AG’s prosecution has already had an effect that’s disrupting and angering the industry. GNC and the AG have already reached an agreement to put GNC’s products back on the shelves in New York stores. While noting that the products that were pulled do in fact meet FDA requirement for sale, GNC has agreed to implement additional testing of their products that go beyond FDA requirements and will be implemented nation-wide. As per the AG:

Under today’s agreement, GNC will perform DNA barcoding on the “active” plant ingredients used in its products; implement testing for contamination with allergens, both before and after production; and post prominent signage advising consumers of the processed, chemical nature of extracts. GNC will be required to implement these new procedures in all of its more than 6,000 stores nationwide, making this agreement the first in the nation to require testing standards for herbal supplements that exceed current FDA requirements.

The supplement industry seems to have mixed feelings. While this deal may have been necessary for GNC to allow its sales to resume, it raises the expectations of quality for all manufacturers, a move that is being likened to California’s move to tighten crash standards and emissions standards for vehicles. Moreover, it seems to reinforce what the AG’s message has been all along – that supplement product quality is dubious, and the AG is getting results. One industry magazine noted:

The agreement also serves to make the case in the mainstream media and the world of social media that Schneiderman was right: The marketers of dietary supplements and the companies that make the products don’t have their customers’ best interests at heart and can’t be trusted to mind their own store.

“The extensive media coverage of the NY AG’s actions has caused a profound shift in consumer attitudes, far beyond anything I’ve observed before. I’ve closely monitored reader comments to negative media coverage for years, and what I am seeing now indicates an overwhelming loss of confidence in all dietary supplements, not just herbs. Comments in the past could be summed up as ‘I don’t believe this article: I’m healthier and feel better when I take my supplements.’ Now I’m seeing, ‘Those people should be in jail, those products are useless / dangerous so I will never buy them again.’ ” Shelton said.

The story doesn’t stop there. Now the AG has teamed up with 13 other state AGs asking Congress to launch an inquiry into the herbal supplements industry. The letter notes:

The current investigation in New York and subsequent interest by other states, and the outstanding request to FDA, represent only the most recent indication of serious problems in the herbal supplements industry. The scientific community and the media have issued a series of troubling reports that suggest broader problems. Researchers, for example, measured high levels of heavy metals like lead, mercury, and arsenic in certain supplements. Products falsely identified as black cohosh—an herb commonly taken to reduce menopause symptoms—may have caused severe liver damage in certain women. And media reports have uncovered over-the-counter supplements, including those purporting to build muscle, aid weight loss, and reduce anxiety, that were secretly laced with dangerous prescription medications.

Additionally, if the producers of herbal supplements fail to identify all the ingredients on a product’s label, a consumer with food allergies, or who is taking medication for an unrelated illness, is taking a potentially serious health risk every time a contaminated herbal supplement is ingested.

The FDA has long been aware of problems in the dietary and herbal supplement supply chain, from dubious ingredient sourcing to a failure to carry out proper testing on finished products. In FY 2013, FDA inspectors cited two out of every three supplement manufacturers for allegedly violating current good manufacturing practices or “cGMPs.” More than one in five of those citations—called Form 483s—observed that the manufacturer failed to verify that a finished supplements batch met product specifications as to identity, purity, strength, or composition. A similar proportion was cited for failing to employ an appropriate test or examination to verify the identity of a dietary ingredient before incorporating it in the final product.

Specifically they want Congress, with the FDA, to address the following:

  • The adequacy and effectiveness of existing quality assurance measures for verifying the source, identity, purity, potency, and quality of ingredients and fillers;
  • The adequacy and effectiveness of existing regimes for verifying the identity, composition, purity, potency, and quality of the finished products sold by domestic manufacturers and retailers;
  • The degree to which product labels and marketing, including the use of the terms ‘natural,’ ‘herbal,’ and ‘extract,’ mislead consumers about the contents of herbal and dietary supplements, and whether the FDA should develop standards and restrictions governing their use;
  • The extent to which Congress should mandate, or direct the FDA to develop enhanced, uniform, industry-wide quality assurance and verification regimes to guarantee the source, identity, purity, and potency of materials incorporated into herbal and dietary supplements; and,
  • The extent to which Congress should mandate, or direct the FDA to develop, enhanced manufacturing and supply chain management requirements for the industry to guarantee the safety and efficacy of the finished herbal and dietary supplements.

Conclusion

It’s good to see the New York AG recognizing the serious concerns that have been identified with the supplement industry in the United States. However, for its actions to be truly effective, it needs to build a careful case. In the interests of transparency, the AG should be releasing the results of its own testing – just as it is asking manufacturers to do. And it needs to address the criticisms of its testing methods. On balance, however, these moves should be seen as beneficial to consumers, particularly if the FDA’s role is re-evaluated. Until consumers and health professionals alike have confidence that supplements are of uniform and consistent quality, it’s not possible to use them safely, or to expect that they will deliver any predictable effects. The marketplace has been overly friendly to manufacturers for years. Now it seems the tide has a chance of turning, with the focus on consumer protection. If we want to avoid playing health roulette when we shop the supplement aisle, we should strongly support efforts to strengthen the quality and safety of herbal supplements.


Photo via flickr user Noodles and Beef used under a CC license.

 

 

Posted by Scott Gavura