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Many modern medicines are derived from plant products, with the active chemical components having been identified and made synthetically. But there are plenty of plants that have (or are thought to have) medicinal properties that haven't been turned into pharmaceuticals. That fact, along with a misguided sense that "natural" probably means "better," has helped turn herbal remedies and supplements into a multi-billion dollar business.

Unlike the strict regulatory oversight faced by the pharmaceutical industry, however, herbal products are a bit of a Wild West. Those selling them are simply forbidden from making specific medical claims. In light of that, a group of Canadian researchers have now confirmed that the results are exactly what one might expect: mislabeled products, lots of filler, and plant material that can be allergenic or cause reactions that can threaten health.

The researchers relied on a technique called DNA barcoding, which relies on finding genes that are highly conserved through evolution so that every organism has a copy that will be nearly identical. This technique enables the design of DNA primers that will allow the sequence to be amplified from just about any species out there. Sets of primers for plants, animals, fungi, etc. have all been designed.

If a gene is completely identical, however, these primers would simply amplify the same sequence from every species. So researchers have identified genes that have highly conserved sequences that flank a region where variability is tolerated, which lets the primers work regardless of the species but ensures that they amplify something that's going to vary from species to species. This variable sequence is the barcode—when you find it, you can use it to look up the species.

The challenge with herbal products is that last step: looking up the species. For that to be successful, someone has to have previously matched the sequence to a species. For most herbs, that's not likely to have been done. Even when a barcode is available in a public database, there's no guarantee that the plant was identified by someone who can recognize the often subtle differences between a species of plant and its close relatives.

To deal with this issue, the authors worked with experts from a botanic garden, which helped them identify 100 species used in herbal products to barcode. They then went out and bought 44 different herbal products and compared them with their barcode database.

The results did not look good for the producers. Of the dozen companies that produced what the authors tested, only two managed to make something that contained the herb that was promised and lacked fillers or other plant material. In three cases, the herbal products contained species that the authors were unable to identify. Sixty percent of the products contained plants that weren't listed on the product information, while in 10 percent of the samples, the only plant matter detected came from rice or wheat, meaning that the pills were simply filler.

Filler might not seem like much of a problem, but the authors note that wheat allergies exist and could potentially cause problems for people who are trying to stay gluten-free.

Most problematic, however, is the finding that manufacturers were substituting something else for the advertised herbal contents. "We found contamination in several products with plants that have known toxicity, side effects, and/or negatively interact with other herbs, supplements, or medications," the authors note. In one case, St. John's Wort was replaced by an herb that is touted as a laxative. In another, the promised herb was replaced by one that has "negative side effects such as swelling and numbness of the mouth, oral ulcers, nausea, vomiting, abdominal pain, diarrhea, and flatulence."

The authors don't name any names—presumably, they and/or the journal don't want to mix it up with the herbal industry based on a small and preliminary survey. But the authors are expanding their barcode library to include more herbal species, so there's a reasonable chance that they will be back for more.

Even in its preliminary form, the study indicates that herbal products should be approached with extreme caution. Unfortunately, about the only legal risk these manufacturers are likely to face in the US is one based on their false advertising. Given the producers' economic clout and the general anti-regulatory mood in Washington, that situation is unlikely to change. In the absence of regulation, the best we can hope for is a public awareness campaign, and the extensive coverage received by the paper is effectively just that.

BMC Medicine, 2013. DOI: 10.1186/1741-7015-11-222  (About DOIs).

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Saturday, November 9, 2013

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