When hormone replacement therapy was found to put some menopausal women at increased risk of cancer and cardiovascular disease, many went in search of safer treatments to decrease their symptoms. In the ensuing decade black cohosh has won out as an overwhelming consumer favorite, now reaping millions of dollars in sales each year.

But controlled trials of this supplement have seen mixed results, sometimes showing it to be effective in relieving hot flashes, sleep disruptions, mood swings and other symptoms whereas other times revealing it to be ineffective. And some case reports even suggest that it can be toxic, damaging the liver.

This messy track record gave Damon Little, a bioinformaticist at The New York Botanical Garden (NYBG), and his colleagues an idea: What if patients—in these trials and out in the community—were not always taking pure, actual black cohosh (Actaea racemosa), but one or more related species? Fortunately, they had just the tool on hand to figure that out: DNA barcoding.

Using this technology, which locates and sequences specific areas of a plant's genome (specifically, two matK gene nucleotides), they were able to determine that one quarter of commercially available "black cohosh" pills were not the herb at all. Their findings were published this July in the Journal of AOAC International.

"Misidentification and adulteration in black cohosh supplements [has been] known for many years as a matter of concern," notes Rolf Teschke, an internist at the Teaching Hospital of the Johann Wolfgang Goethe University in Frankfurt and who was not involved in the new research. "The present study confirms—but extends—previous findings."

Unlike drugs, however, supplements are not required to be tested for safety or efficacy by the U.S. Food and Drug Administration before they hit the market. And testing to make sure the contents match the label are much more lax than it is for pharmaceuticals, opening the opportunity for mislabeling, whether it is accidental or intentional.

Wild roots
Black cohosh has been used traditionally by Native Americans as a natural remedy for a variety of ailments. It is often harvested in the wild, where it grows in similar environments to many of its close cousins that look very similar. And some species of Actaea are suspected to be toxic to humans. "Unless you're looking very carefully, you can't assume that any black cohoshlike thing is actually black cohosh," Little says. In eastern North America, where black cohosh grows, it is not uncommon to also find yellow cohosh (A. pachypoda and A. podocarpa) and baneberry (A. spicata and A. rubra). During harvesting, the rhizomes (buried stems) are often collected and then ground up to make the supplements, leaving telling botanical clues, such as leaf shape, forever lost.

In recent years, with the vast increase in the herb's sales, commercial growing operations have also sprung up in North America as well as Europe and Asia.

David Baker, a gynecologist at Stony Brook University Medical Center, had many patients who took black cohosh, but he was intrigued by the ambiguity of the medical literature on the supplement. So he, Little and their colleague at the NYBG, Dennis Stevenson, wanted to see if all of these pills labeled as black cohosh were, indeed the correct species.

Sampling supplements
To test just how reliable the supplement's label was, the researchers sequenced plant material from 36 supplements purchased in the New York City area and online.

One quarter of those contained another species entirely—not just in addition to black cohosh, but instead of black cohosh. "The samples, as far as we found, were purely the wrong sample," Little says. The version of the sequencing they ran would not have picked up low levels of contamination (below about 10 percent), but Little notes that they could ramp it up and look more closely if they suspected some samples held minuscule portions of other herbs.

None of the mislabeled supplements were from other North American species of the Actaea genus. Instead, they were Asian species: A. cimicifuga, A. dahurica and A. simplex. That means "they're not growing in the wild next to real black cohosh" in North America, Little says. So it is unlikely these adulterated supplements were the result of mistakes made by wild harvesters. Rather, these plants' presence in the supplements were from mislabeling of seeds or the rhizomes themselves that were then sold to supplement manufacturers.

Some other species of Actaea are sometimes marketed for relief of similar symptoms that black cohosh helps to diminish. But these species do not have the same cachet, and thus are not likely to bring in as much money. "So there's a huge financial incentive for them to be mislabeled," Little says. And their safety has yet to be tested.

Link for uncertainty?
Not everyone is convinced that black cohosh supplements explain the mixed results from trials of the herb. Teschke and his colleagues have authored numerous papers that took aim at the link between black cohosh and reports of toxicity. Dozens of case reports and reviews of clinical trials fail to make a convincing case for black cohosh specifically being to blame. Teschke notes that this might be due to the fact that black cohosh as it is used in clinical trials is more carefully regulated (often as a drug, rather than as a supplement), especially in Europe, where many of the studies have been done. "In the U.S. regulatory surveillance is not stringent enough for black cohosh and other herbal supplements," he notes, suggesting that this market might be more vulnerable to adulterated supplements.

Nevertheless, Little thinks that this contamination "is probably a pretty strong explanation" for the herb's erratic track record, he says. But we lack crucial evidence to prove that, including samples of what was used in clinical trials. Currently, those executing these sorts of clinical trails are not required to archive samples of the products they used, so there is no way to perform DNA bar coding of the actual supplements study subjects were receiving.

And for consumers, there is still no way to know with certainty that pills labeled as black cohosh actually are—without access to the bar-coding technology the researchers used. Little and his colleagues found mislabeling even among the most expensive brands they sampled. But they declined to release the names of the companies (for fear of legal action) and because content could vary from batch to batch, as they are often sourced from different suppliers.

He and others who have been following the challenge of monitoring herbal supplements in the U.S. have recommended more frequent and more thorough testing of contents by manufacturers. But instituting this is always a question of paying for the equipment or lab time and allocating more FDA resources to monitoring.

Tracking supplements based on genetic material, however, could become commonplace. Any preparation using plant parts that are ground up or compressed to be put into a tablet or capsule offer promising fodder for DNA testing. Even some extracts, whether oil or alcohol-based, can often yield some bits of the original plant that can be used for genetic sequencing. Little and his co-authors originally purchased 40 randomly selected brands of dried black cohosh supplements, but four did not offer any genetic material for testing. This is likely because they had been heated during processing to an extent that destroyed the DNA—a key challenge for this testing method.

The NYBG researchers are already setting their sights on other popular plant-based supplements. Supplements currently under study include saw palmetto (from Serenoa repens, often used for prostate troubles); ginseng (in the Panax genus, marketed for improved mental function); devil's claw (Harpagophytum procumbens, sometimes indicated for arthritis or other ailments); and even garlic (Allium sativum, often taken for cardiovascular health, which they suspect might sometimes be adulterated with elephant garlic—A. ampeloprasum—a similar species, but one that has not been subject to the same testing as common garlic itself).

Many of these other supplements are not likely to carry the possibility of toxicity the same way that black cohosh does. But, as Little maintains, "you should know what you're buying."