Monday, February 9, 2015

Herbal Supplements Questioned: Fighting Bad Practices with Bad Science?

This past week, the NY Attorney General accused major retailers (Walmart, Target, Walgreens and GNC) of selling herbal supplements that do not contain the herbs claimed on the label and issued a cease-and-desist letter demanding they stop selling those products.

Testing of the supplements was conducted using DNA barcoding, a technique that uses specific DNA sequences  to look for markers that indicate a specific plant species.  This technique has had much success in determining  animal and plant material authenticity and inclusion of potential adulterants.

However, these techniques work best on material where the DNA is likely to be there intact.  As pointed out by the critics of this investigation, many of the herbal supplements sold are highly processed, and this processing may degrade the DNA to a point where it will not be detected.

In DNA barcoding of medicinal plant material for identification (Techen, etal 2014 Current Opinion in Biotechnology Volume 25, Pages 103–110):
The isolation of pure, high molecular weight DNA is critical for the successful application of molecular methods. This can be quite a challenge since in processed medicinal plant material the DNA is often highly degraded or the plant material contains high amounts of polysaccharides, polyphenols and other secondary metabolites, such as, alkaloids and flavonoids. Various commercial kits and modified traditional methods are available to yield in good quality DNA from raw and powdered medicinal plant material, herbarium specimens, capsules, tablets, or tinctures for downstream applications 
In  DNA barcoding as a new tool for food traceability (Galimberti et al. 2013, Food Research International Volume 50, Issue 1,  Pages 55–63):
DNA is normally more resistant to industrial processes than other molecules, such as proteins (Martinez et al., 2003), and DNA fingerprinting methods can be successfully used in identifying animal or plant materials, even when in small traces (Bottero and Dalmasso, 2011, Costa et al., 2010, Kesmen et al., 2007, Mane et al., 2009, Martin et al., 2009 and Soares et al., 2010). Nonetheless, food processing causes chemical and physical alterations, degradation and fragmentation being the most common effects (Bauer, Weller, Hammes, & Hertel, 2003). DNA integrity largely influences the effectiveness of molecular methodologies (Hellberg and Morrisey, 2011, Meusnier et al., 2008 and Pafundo et al., 2007). DNA barcoding can have two advantages if compared to DNA fingerprinting approaches: i) it requires the amplification of a short DNA fragment (hence there is a lower risk of fragmentation), and ii) it is based on mitochondrial or plastidial genome (more preserved during processing).
The supplement industry is not regulated as a food or drug, but has its own regulations.  These rules are lax compared to those for drugs in that these products do not need to have FDA approval before selling on the market, and those claims do not necessarily need to stand to the same standard as a drug.  FDA requires that the herbal supplements are safe and that the ingredients listed on the label be in the product.  There is however, still the question whether these products actually have  any significant impact on health.

From the National Institutes of Health website:
Dietary supplements are not required to be standardized in the United States. In fact, no legal or regulatory definition exists for standardization in the United States as it applies to botanical dietary supplements. Because of this, the term "standardization" may mean many different things. Some manufacturers use the term standardization incorrectly to refer to uniform manufacturing practices; following a recipe is not sufficient for a product to be called standardized. Therefore, the presence of the word "standardized" on a supplement label does not necessarily indicate product quality.

In 2007, the FDA issued Good Manufacturing Practices (GMPs) for dietary supplements, a set of requirements and expectations by which dietary supplements must be manufactured, prepared, and stored to ensure quality. Manufacturers are now expected to guarantee the identity, purity, strength, and composition of their dietary supplements. For example, the GMPs aim to prevent the inclusion of the wrong ingredients, the addition of too much or too little of a dietary ingredient, the possibility of contamination (by pesticides, heavy metals such as lead, bacteria, etc.), and the improper packaging and labeling of a product.

Like other dietary supplements, botanicals are not required by federal law to be tested for safety and effectiveness before they are marketed, so the amount of scientific evidence available for various botanical ingredients varies widely. Some botanicals have been evaluated in scientific studies. For example, research shows that St. John's wort may be useful for short-term treatment of mild to moderate depression. Other botanical dietary supplements need more study to determine their value.

The dietary supplement industry has estimated sales of $6 billion, part of a $13 billion dietary supplements industry.  This investigation, while questionable in terms of methodology, may trigger further investigation into whether or not the dietary supplement industry is following questionable practices.

CBS/APFebruary 8, 2015, 3:59 PM
Herbal supplements industry lashes out at fraud claims

ALBANY, N.Y. - DNA barcoding has exposed some infamous cases of food fraud, like cheap catfish sold as pricey grouper and expensive "sheep's milk" cheese that was really made from cow's milk.

But can it tell if a pill touted as an energy-booster contains ginseng or is just a mix of rice powder and pine?

Some scientists say yes, while industry groups and some independent experts say DNA testing alone is inadequate for analyzing botanical products that have gone through a lot of processing from leaf to tablet.

About 65,000 dietary supplements are on the market, consumed by more than 150 million Americans, according to a 2013 Canadian government study. The American Botanical Council estimates U.S. sales of herbal supplements came to $6 billion that year.

The U.S. Food and Drug Administration requires companies to verify their products are safe and properly labeled, but supplements are exempt from the FDA's strict approval process for prescription drugs.

New York Attorney General Eric Schneiderman says lax oversight of supplements can have serious public health consequences, noting a 2013 hepatitis outbreak traced to a tainted diet supplement and the death of a baby at a Connecticut hospital after doctors gave the child a probiotic supplement later found to be contaminated with yeast.

Last week, Schneiderman ordered Wal-Mart, Walgreen's, Target and GNC to stop selling store-brand herbal supplements that DNA tests found questionable.

Schneiderman's action followed a Clarkson University study he commissioned and he also referenced a 2013 study published by University of Guelph researchers.

The Clarkson study tested hundreds of bottles of store-brand herbal supplements sold as treatments for everything from memory loss to prostate trouble, and found 4 out of 5 contained none of the herbs listed on the labels.

The investigation looked into numerous supplements, including echinacea, ginseng, St. John's wort, garlic, ginkgo biloba and saw palmetto, were contaminated with substances including rice, beans, pine, citrus, asparagus, primrose, wheat, houseplant and wild carrot. In many cases, unlisted contaminants were the only plant material found in the product samples.

The retailer with the poorest showing was Walmart, where only 4 percent of the products tested showed DNA from the plants listed on the labels.

At the University of Guelph, researchers used DNA fingerprinting to find that a third of 44 supplements tested contained no trace of the plant on the label.

But the dietary supplement industry takes issue with DNA testing and some consumer advocacy groups say the method by itself is inadequate because it cannot detect the most serious problems with supplements - contamination with heavy metals or chemical adulterants.

"There's no problem with DNA barcoding as a science; however, it should be used appropriately. It has limitations," said Nandakumara Sarma, director of dietary supplements for US Pharmacopeia, which sets quality standards and testing protocols for drugs, vitamins and supplements.

The United Natural Products Alliance, a trade group, says it is sending people out around the country to buy large quantities of the supplements cited by Schneiderman and submit the bottles, unopened, to five or six certified botanical testing labs for analysis.

"They will perform universally accepted methods and procedures to test the products and will independently report their findings, which will be made public," said Loren Israelsen, the group's president. "We feel the most appropriate response to bad science is good science."

The American Botanical Council, a nonprofit research and education organization based in Austin, Texas, was particularly critical of the Guelph study.

"We raised the question if any of these products are extracts, and if so, what other analytical technologies were used to help ensure the validity of the results obtained by DNA testing," said Mark Blumenthal, the council's founder and director.

"DNA testing seldom is able to properly identify chemically complex herbal extracts, because often DNA doesn't get through the extraction process," Blumenthal said.

He said at least some of the products cited by Schneiderman are likely made from extracts, which can be validated by other common lab tests.

Tod Cooperman, president of the consumer-funded, also dismissed the Guelph and attorney general's DNA studies as inappropriate for validating herbal supplements.

"There are definitely problems with herbal supplements but this is not the right method to test those products," Cooperman said.

His lab performs a range of tests on vitamins, herbal products and other dietary supplements to determine quality and purity, and provides the results to consumers who subscribe to his service.

Blumenthal also is working to expose bad products. He launched the Botanical Adulterants Program four years ago to ferret out suppliers who sell adulterated or mislabeled ingredients to manufacturers of herbal supplements. One goal of the program is to identify what laboratory tests are most effective.

Pieter Cohen, a Harvard Medical School researcher whose area of expertise is tracking down dangerous supplements, said the new versions of methamphetamine he has found in diet and sports supplements would never be spotted by DNA testing.

"There is so much wrong with the quality of supplements today that it's a shame the New York attorney general is not using sound science to focus on the most important problems," Cohen said. "The FDA has done hundreds of spot inspections of supplement companies, and they have found that 7 in 10 are not compliant with basic manufacturing practices."

Schneiderman's office stands by the validity of its DNA testing.

"Rather than attacking testing methods that have been validated by more than 70 published papers, the time has come for the herbal supplements industry to put concerns about what is and is not included in its products to rest," Matt Mittenthal, spokesman for the attorney general, said in an email.

The attorney general's office did not respond to a follow-up email asking why conventional, widely accepted testing wasn't used to verify the DNA test results, which would have made the findings more indisputable.

US Pharmacopeia provides independent third-party certification to drug and supplement manufacturers, who can then use the certification to assure consumers their products are genuine.

But John Atwater, director of verification programs for the organization, said less than 1 percent of herbal supplements carry the USP mark.

He noted the program is voluntary. "It's up to manufacturers and consumers to demand it," he said.

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