Tuesday, February 10, 2015

What's in that Supplement (part 2)?

On February 3, 2015, Eric Schneiderman, the State of New York Attorney General, pulled off his glove and slapped the supplement industry in the face. His office sent out cease and desist letters to GNC, Walmart, Target and Walgreens asking them to stop selling certain supplements in New York. His office issued a press release revealing the results of an investigation into the authenticity of common store brand supplements purchased at GNC, Target, Walgreens, and Walmart stores throughout New York. The Attorney General had hired a population and evolutionary biologist - James Schulte, PhD of Clarkson University - to analyze the samples. Dr. Schulte was hired because of his expertise using a technique called DNA barcoding.  

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DNA barcoding – what it is and what it is not

What it is

The technology of DNA barcoding emerged in 2003. Originally created to help taxonomists identify and classify new species, DNA barcoding takes a small specific region of DNA and basically makes a barcode out of the nucleotides. The developers of the technology soon realized  broader applications for its use and it is now a tool used by  a variety of disciplines, including evolutionary biology. The DNA barcode information is maintained in an open-source database and is available for other users to access. Dr. Schulte, an evolutionary biologist, uses this technology is his research and his expertise with this method is part of why the  NY Attorney General’s office hired him to analyze dietary supplements. One of the outpourings of DNA barcoding is that it is user friendly – non-experts can use the technology and information. 

What it is not

DNA barcoding is not a standard method used in phytochemical (plant chemical) research, in clinical testing related to phytochemicals, or as a lab test to detect for the use of dietary supplements as performance enhancement aids. The standard, most common, and recognized techniques used in dietary supplement research including clinical and lab testing are high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), mass spectrometry (MS) and different types of MS like  MS/MS and gas chromatography-mass spectrometry analysis (GC/MS). If you read literature about phytochemicals these are the methods  used to determine the presence and quantity of phytochemicals in products as well as in biological samples  (Hoggan, Shelby, Crouch, Borges, & Slawson, 2007; Li & Seeram, 2011; Ma et al., 2012; Prior, Wu, & Schaich, 2005; Thomas et al., 2010; Vaclavik, Krynitsky, & Rader, 2014)

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The results

Six herbal samples were identified and selected for the study. The 6 dietary supplements were selected because they are samples that can be identified by DNA barcoding technology. As I said before, this is a new technology and not everything in the world (not every plant species) is included in the database. If it does not exist in the DNA database, it cannot be detected. Of the possible herbal supplements that they could select from, they focused on more popular dietary supplements. The researchers tested 3-4 samples from each of the stores and they tested each sample multiple times. In total, the researchers had 78 samples and they performed 390 DNA tests on those 78 samples. I have not read the full report of the research (I have not come across it in my research and I do not know if it is publicly available yet). Here is a summary of what the Attorney General’s office has released.

When Dr. Schulte looked at all the data from all the stores together it showed that:
  •  21% contained DNA for the ingredients listed on the label (they contained what they advertised – at least by name, do not know about quantity);
  • 79% contain DNA evidence of plant-based ingredients not listed on the label – these are considered filler ingredients and contaminated ingredients;
  • A “large number” of samples (percent not provided by AG’s office) contained no DNA at all – whatever is in the product could not be identified by DNA barcoding analysis.

More specifically:


Store brand
Supplements tested
Overall results of DNA barcoding tests
Ingredients detected but not listed on the label
Walmart
Spring Valley
Gingko biloba
St. John’s Wort
Ginseng
Garlic
Echinacea
Saw palmetto
 4% of the contained DNA matches for the ingredients listed on the product label
  • A single bottle of garlic  contained minimal garlic
  • A single bottle of saw palmetto contained minimal saw palmetto

Allium
Pine
Wheat/grass
Rice mustard
Citrus
Houseplant
Cassava
GNC
Herbal Plus
Gingko biloba
St. John’s Wort
Ginseng
Garlic
Echinacea
Saw palmetto
22% contained DNA matches for the labeled ingredients
  • Garlic consistently contained garlic
  • One bottle of saw palmetto contained saw palmetto DNA but other bottles did not
Allium
Asparagus
Rice
Houseplant
Saw palmetto
Primrose
Alfalfa/clover
Echinacea
Spruce
Legume

Walgreens
Finest Nutrition
Gingko biloba
St. John’s Wort
Ginseng
Garlic
Echinacea
Saw palmetto
18% contained DNA matches for labeled ingredients
  • Saw palmetto supplements consistently tested positive for saw palmetto DNA
  • Other results were mixed – for example,  one sample of garlic contained garlic DNA but others did not

Allium
Rice
Wheat
Palm
Daisy
Houseplant
Target
Up & Up
Gingko biloba
St. John’s Wort
Valerian Root
Garlic
Echinacea
Saw palmetto
41% contained DNA matches for labeled ingredients
  • Echinacea, garlic and saw palmetto consistently contained DNA for the labeled ingredients
  • St. John’s Wort, gingko biloba, and valerian root did not contain DNA for the labeled ingredients
Allium
Asparagus
French bean
Wild carrot
Pea
Saw palmetto

Allium atropurpureum.
Photo: JLPC / Wikimedia Commons, via Wikimedia Commons

Walmart, GNC, Walgreens and Target received cease and desist letters from the State of New York’s Office of the Attorney General. The companies were informed that the state was unable confirm the content of some of their store brand dietary supplements, that they found evidence of product adulteration, and that some products needed to be removed from store shelves within the state of New York. Additionally, each company was asked  to provide the Attorney General’s office with information and documentation about the procedures for manufacturing, processing, testing, and quality control of their store brand dietary supplements.

Needless to say, companies were not thrilled to receive with this correspondence. 


A GNC spokesperson stated that the company stands by the herbal products and that DNA barcoding may not be the best test method to use for phytochemicals. Target has replied with a comment regarding that they aim for high quality and safe products. Walgreens is working to remove the supplements from their shelves and will review the process and procedures for their store brand herbal supplements, and Walmart states it is reaching out to its suppliers.

Final thoughts

I am not surprised that they found unexpected and potentially dangerous ingredients in supplements. Supplement manufacturers are required to list all active and inactive ingredients on the label and they failed to comply with this requirement. Every company tested showed that their supplements contained unlisted ingredients, some of which are known allergens. This is a health concern and a serious problem. It does not matter how they tested for it. These ingredients were probably cheap and made good fillers. Just like with medications and with foods, manufacturers must disclose all ingredients and supplement manufacturers need to be held accountable when they do not comply. I believe what has been shared with the public so far is a list of the most prevalent unlisted ingredients.  Also, only plant-based DNA included in the DNA barcode database are part of this study. This is probably just the tip of the list because unlisted pharmaceutical ingredients and plants not yet part of the database have not been considered.   

Supplement manufacturers often extract the active component(s) from the whole plant and include the extracted part in the supplement. It is unrealistic to use whole plants to make supplements (the volume needed would be immense, there could be spoilage issues, there would not be enough plants, and the whole point – theoretically – is to deliver a concentrated dose of a phytochemical beyond that which you get in a complex food item where it is diluted with other components). The DNA barcode is derived from a section of DNA taken from the whole plant but most herbal supplements contain extracts. I have no idea if any changes occur to DNA during extraction procedures. More importantly, I have no idea if they tested and controlled for this in any sort of way when they did they NY study. For example, did they purchase any pure and validated St. John’s Wort and then examine that with DNA barcoding to determine that it can be detected using this method?  Have they verified their results using standard methods of detection like HPLC and MS?  DNA barcoding is interesting and we will encounter more of it in the future. As with any new method, it has to be validated. To do that, results need to be compared to existing gold standard methods. I hope that as this issue moves forward, we can see that happen with DNA barcoding and currently used methods in phytochemical research.

I am passionate about the potential of phytochemicals (plant chemicals) to impact health. I am very interested in the differences between how phytochemicals work when they are part of food versus how they may function when they are extracted and taken as supplements. That is, of course, assuming the supplements contain what they should. Phytochemical research is a new discipline and much remains unknown about if and how phytochemicals function, and yet in 2009 Americans spent over $25 billion dollars on all types of supplements, according to Consumer Reports. We seem to be more interested in the possibility than the science and that fuels their fire. They are taking advantage of us, but we are letting them. It is time for this to stop and the New York Attorney General is paving the way.  

Other Posts on this Blog about Dietary Supplements:



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Literature Cited

Hoggan, A. M., Shelby, M. K., Crouch, D. J., Borges, C. R., & Slawson, M. H. (2007). Detection of bumetanide in an over-the-counter dietary supplement. J Anal Toxicol, 31(9), 601-604.
Li, L., & Seeram, N. P. (2011). Further investigation into maple syrup yields 3 new lignans, a new phenylpropanoid, and 26 other phytochemicals. J Agric Food Chem, 59(14), 7708-7716. doi: 10.1021/jf2011613
Ma, H., Yuan, T., Gonzalez-Sarrias, A., Li, L., Edmonds, M. E., & Seeram, N. P. (2012). New galloyl derivative from winged sumac (Rhus copallinum) fruit. Nat Prod Commun, 7(1), 45-46.
Prior, R. L., Wu, X., & Schaich, K. (2005). Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem, 53(10), 4290-4302. doi: 10.1021/jf0502698
Thomas, A., Kohler, M., Mester, J., Geyer, H., Schanzer, W., Petrou, M., & Thevis, M. (2010). Identification of the growth-hormone-releasing peptide-2 (GHRP-2) in a nutritional supplement. Drug Test Anal, 2(3), 144-148. doi: 10.1002/dta.120
Vaclavik, L., Krynitsky, A., & Rader, J. (2014). Mass spectrometric analysis of pharmaceutical adulterants in products labeled as botanical dietary supplements or herbal remedies: a review. Analytical and Bioanalytical Chemistry, 406(27), 6767-6790. doi: 10.1007/s00216-014-8159-z