The herbal supplement market is lightly regulated in many countries. A consequence is often quality assurance: With no mandatory testing for quality and consistency, consumers and health professionals alike are largely at the mercy of a manufacturer’s claims. Unlike prescription pharmaceuticals and over-the-counter drugs, which are more tightly regulated, there could be (depending on the country) no requirement for supplement manufacturers to make products that are uniform, standardized, and of consistent quality. While third-party testing can provide consumers with some degree of assurance, it is limited and not routine. Strengthening the quality and safety standards for supplements should be a win for consumers and arguably beneficial for the industry itself.

Earlier this week I was listening to a podcast about a Canadian scientist who had published papers that utilized a technology called “DNA barcoding” and whose work was now being called into question. The research sounded familiar. I checked the SBM archives and sure enough, I blogged about DNA barcoding and the work of this scientist way back in 2013. Give the current investigations I thought it would be worthwhile to summarize the current controversy.

A “DNA barcode” is short DNA sequence that can uniquely identify a specific species of any living thing. About 700 nucleotides in length, the “barcode” is a portion of DNA that varies significantly between different species. Beyond the obvious biology benefits of helping to identify new species, DNA barcodes have commercial applications, such as being used to detect fraud in foods (e.g., sushi) and other products. What DNA barcoding cannot do is quantify the content (in terms of milligrams of active ingredient) or confirm the presence (or absence) of any active ingredients.

I will draw heavily on the writing from the journal Science, who have written several articles on this controversy:

In 2013, a team led by Steven Newmaster, a botanist at the University of Guelph (UG), took a hard look at popular herbal products such as echinacea, ginkgo biloba, and St. John’s wort. The team published a study that used DNA barcoding—a system to identify species using small, unique snippets of genetic material—to test whether the bottles really contained what was printed on the label.

The results were troubling. Most of the tested products contained different plants, were larded with inert fillers, or were tainted with contaminants that could cause liver and colon damage, skin tumors, and other serious health problems. The paper, published in BMC Medicine, received prominent attention from The New York Times, CBC, and many other media outlets. The findings “pissed me off,” Newmaster told PBS’s Frontline. “I go in to buy a product that I believe in, that I care about and I pay a lot of money for, and it’s not even in the bottle? Are you kidding me?”

His work inspired then–New York Attorney General Eric Schneiderman to sponsor a similar study conducted by James Schulte, then at Clarkson University, who confirmed that consumers were often misled. At Schneiderman’s request, major retailers such as GNC, Walgreens, and Walmart pledged to pull suspect products from the shelves or take other measures.

In that 2013 paper, the authors describe authenticity testing of 44 herbal products. They found that only 48% of the tested products were authentic, with 59% of the products containing species not listed on the label, and one-third contained a substitute product with none of the labelled ingredient. These results were surprising, but not inconsistent with concerns about the quality of dietary supplements that had been identified (and blogged about) before. Importantly, other DNA barcoding analyses (by other, unaffiliated authors) had found similar concerns with herbal tea ingredients, or with the actual components of black cohosh supplements.

Science continues:

Almost overnight, Newmaster became an authority on the verification of food and supplement ingredients. He quickly went from industry adversary to ally, as major supplementmakers hired companies he created to certify their products as authentic. In 2017, Newmaster also founded the Natural Health Products Research Alliance (NHPRA), a venture within UG that aims to improve certification technologies for supplements. It raised millions of dollars from herbal suppliers, boosting UG’s finances and prestige.

But in an ironic twist, eight experts in DNA barcoding and related fields now charge that the 2013 paper that indicted an entire industry and launched a new phase in Newmaster’s career is itself a fraud. In a 43-page allegation letter, sent to UG in June 2021 and obtained by Science, the researchers—from UG, the University of Toronto, the University of British Columbia, and Stanford University—cited major problems in the study and two others by Newmaster and collaborators. “The data which underpin [the papers] are missing, fraudulent, or plagiarized,” the letter flatly stated. The group also charged that Newmaster “recurrently failed to disclose competing financial interests” in his papers.

There was subsequently considerable criticism of the 2013 paper.

In the 2013 supplement paper, Newmaster, Ragupathy, and collaborators describe how they derived DNA barcodes for 44 popular herbal products and compared them with barcodes from validated sources. The explosive results—most of the products had DNA from herbs not on the label, and many contained plants with “known toxicity”—alarmed experts. “This suggests that the problems are widespread and that quality control for many companies, whether through ignorance, incompetence or dishonesty, is unacceptable,” nutritionist David Schardt, then with the Center for Science in the Public Interest, told The New York Times.

The paper drew criticism as well. A stinging 2013 analysis in HerbalEGram—a journal of the American Botanical Council, a nonprofit research group—claimed many egregious errors and called for a retraction. The analysis accused Newmaster of not understanding that supplements use benign inactive substances such as rice powder as “carriers,” and that DNA can be destroyed during processing without altering a supplement’s effects.

When I blogged about the paper in 2013, I noted the authors stated that they had no conflicts of interest. However, there was activity, that if not a conflict of interest, is certainly surprising:

Although the paper claimed “no competing interests,” Newmaster and UG geneticist Robert Hanner in 2012 had created Biological ID Technologies Inc., which conducted DNA barcoding for foods and herbal products and offered purity certifications for product labels. On 11 July 2013, about 1 week after the paper was submitted, Newmaster and Hanner incorporated a second company, named Tru-ID, which apparently assumed the business initiated by Biological ID Technologies. (Tru-ID folded in 2020, under “financial hardship during the pandemic,” Newmaster said in his response to the misconduct complaint. Hanner would not provide any comment for this article.)

When the New York attorney general’s probe triggered by Newmaster’s paper pressured companies to validate their ingredients, Tru-ID was ready to help, says Stefan Gafner, chief science officer at the American Botanical Council and co-author of the HerbalEGram critique. At least three major supplementmakers [sic], Nature’s Way, Herbalife Nutrition, and Jamieson, hired Tru-ID and adopted its certifications.

The Science paper goes on to document some astonishing activity from Newmaster, including plagiarism, presenting research from other authors as his own, and unbelievably, presenting “magnetic resonance profiles” for three cannabis strains using a graphic that identical to one showing arrest data for 50 U.S. states. He is also on record of describing working on COVID-19 tests in the summer and fall of 2019 (i.e., pre-pandemic) at the behest of the CDC. Science notes, “A CDC spokesperson could not locate information about working with Newmaster”.

Newmaster has denied all charges of misconduct, Science reports. It should also be noted that a University of Guelph investigation committee has recently reviewed complaints against Newmaster and concluded that he did not engage in scientific misconduct:

Newmaster “displayed a pattern of poor judgement and failed to apply the standards reasonably expected in research activity in his discipline,” panel chairman John Walsh wrote today in a letter to the eight scientists who lodged a complaint against Newmaster last year. Yet despite “many shortcomings” in his work, the panel said there was “insufficient evidence” to find Newmaster guilty of misconduct in three studies that his accusers had singled out.

The university has yet to reach a final conclusion. In the meantime, there are cautions on the 2013 herbal supplement paper, another paper has been retracted, and another is now appended with an “expression of concern“.

What does this say about supplement quality?

Without reliable, consistent products, consumers can’t use commercially packaged herbal remedies safely. Health professionals are in a similar bind, where product quality concerns may limit their confidence in making treatment recommendations. When regulators do not enforce quality assurance processes or standardized products, testing and quality assurance is often left in the hands of third parties. In the case of DNA barcoding, serious questions have been raised about work coming from the lab of one researcher. Allegations were made about product quality, that manufacturers struggled to respond to. In a world where supplements were subject to routine quality assurance and were standardized, the findings should have been easily refuted. Despite the allegations made against a particular researcher, there may yet be utility in DNA barcoding in the quality assurance of supplement manufacturing. But the larger issues of quality assurance and product quality remain.

Author

  • Scott Gavura, BScPhm, MBA, RPh is committed to improving the way medications are used, and examining the profession of pharmacy through the lens of science-based medicine. He has a professional interest is improving the cost-effective use of drugs at the population level. Scott holds a Bachelor of Science in Pharmacy degree, and a Master of Business Administration degree from the University of Toronto, and has completed a Accredited Canadian Hospital Pharmacy Residency Program. His professional background includes pharmacy work in both community and hospital settings. He is a registered pharmacist in Ontario, Canada. Scott has no conflicts of interest to disclose. Disclaimer: All views expressed by Scott are his personal views alone, and do not represent the opinions of any current or former employers, or any organizations that he may be affiliated with. All information is provided for discussion purposes only, and should not be used as a replacement for consultation with a licensed and accredited health professional.

Posted by Scott Gavura

Scott Gavura, BScPhm, MBA, RPh is committed to improving the way medications are used, and examining the profession of pharmacy through the lens of science-based medicine. He has a professional interest is improving the cost-effective use of drugs at the population level. Scott holds a Bachelor of Science in Pharmacy degree, and a Master of Business Administration degree from the University of Toronto, and has completed a Accredited Canadian Hospital Pharmacy Residency Program. His professional background includes pharmacy work in both community and hospital settings. He is a registered pharmacist in Ontario, Canada. Scott has no conflicts of interest to disclose. Disclaimer: All views expressed by Scott are his personal views alone, and do not represent the opinions of any current or former employers, or any organizations that he may be affiliated with. All information is provided for discussion purposes only, and should not be used as a replacement for consultation with a licensed and accredited health professional.