Calgon in your joint health supplements? Experts identify recently discovered adulterant of chondroitin sulfate
The experts were convened by leading supplier Synutra International after earlier internal work by the company identified an adulterant in chondroitin sulfate, which the company called Zero One.
Weiguo Zhang, President, Synutra Ingredients, told NutraIngredients-USA that the study was geared to detect and identify sodium hexametaphosphate and other adulterants in ingredients, and not finished products. “Efforts are being made to do the same with market samples of supplement products,” he said, “but this takes time.
“We have known it was being sold to ingredient suppliers for about a year, so assume it has found its way into finished products. We are encouraging manufacturers to adopt our recommended testing protocol so they can keep it from getting into their products to begin with.”
Chondroitin-containing supplement products are in the top five best-selling dietary supplements, with annual sales of about $1 billion, and all chondroitin sold in the US is from overseas. The US is estimated to have imported about 3,500 metric tons of chondroitin in 2012, and about 3,000 in 2011.
Chondroitin sulfate is extracted from animal cartilage. In dietary supplements the compound is often formulated in combination with glucosamine.
Zero One was first reported by Aishan Li, director of R&D and Quality Control of Meitek Technology, a Synutra subsidiary, in 2013. The identification was achieved using electrophoresis as an effective screening tool. Synutra subsequently assembled a research group that included Synutra’s Weiguo Zhang, James Neal-Kababick, Director of Flora Research Laboratories, Jana Hildreth, Director of Technology and Scientific Affairs of Synutra Pure, Gabriel Giancaspro, Vice President of the United States Pharmacopeia (USP), Kristie Adams, a nuclear magnetic resonance spectroscopy scientist at USP, and the late Dr Mark Roman, Director of Tampa Bay Analytical Research Laboratories. The resulting research paper is dedicated to Dr Roman.
The team elucidated that Zero One was a form of polyphosphate salt, namely sodium hexametaphosphate.
“It is an industrial chemical that is inexpensive and easily available,” said Neal-Kababick, who performed polarized light microscopy, elemental and infrared analyses of the suspect substance. “It is commonly used in detergent or as a water treatment agent, and is sold under the commercial name Calgon.”
‘Just because it is monographed as a food additive does not mean it is safe’
Neal-Kababick told us that, while Calgon is sodium hexametaphosphate, not all sodium hexametaphosphate is Calgon. It is an industrial chemical used in many industries from water treatment, ceramics, and tanning, he said. At extremely low levels it also used as an emulsifier, texturizer, and sequesterant in limited food ingredients that are not consumed in high levels such as syrup and jam.
“I want to stress that the food use of this compound is limited to very specific applications and the material would be required to meet the specifications for food grade not reagent or industrial grade polyphosphate. The Food Chemicals Codex contains a monograph on this compound under ‘Sodium Polyphosphates, Glassy’ along with various tests and metrics that must be met. The EU only allows use in specific foods and the approval is on an ingredient basis.
“I don’t want anyone getting the idea that just because it is monographed as a food additive that it equates to safe. There are a lot of chemicals used in processed foods with very restricted values based on exposure. Unlike the high purity food grade sodium hexametaphosphate, Zero One, the material we characterized has significant still unidentified impurities and is probably an industrial grade chemical wholly unsuited for food use.”
Synutra Pure’s Hildreth added that if the level of sodium hexametaphosphate adulteration reaches 10% of the supplement serving size then it will deplete calcium from the body. “Its use in joint health supplements may pose serious safety and health risks to consumers,” she said.
The commonly used chondroitin assay procedure is called cetylpyridinium chloride (CPC) titrimetry, but this can be fooled by adulterants, which titrate with CPC to produce assay readings as chondroitin at levels equal to or much higher than chondroitin itself.
Indeed, Zero One is such a potent adulterant that it appears in CPC as chondroitin at 235% assay value, Synutra previously stated.
As a result of the research group’s work, Synutra is now advocating the use of CPC after cellulose acetate membrane electrophoresis (CAME). Electrophoresis is a method that uses an electric field to separate substances – the substances move by different amounts when in a colloidal suspension.
CAME is a complementary methodology to CPC that has been in the USP monograph for years to address the selectivity issues of the CPC titration monograph method used for assay, explained Neal-Kababick.
“Like almost all titration methods, CPC is not selective and will respond to many other compounds. The functional group(s) that are reacting with the titrant could be from the compound of interest or come from an adulterant and the titration technique has no way of differentiating that. This is why CAME is so critical. CAME is used to ensure that the CS being analyzed by CPC titration is actually pure and does not contain one of the many adulterants that will spoof the titration test.
“Since most of the industry stakeholders that have historically had us test CS were only willing to pay for an assay and not the CAME analysis, our lab has not used the CPC method for years because it was never meant to be used alone,” he said. “While we favor the enzymatic HPLC method for quantitative analysis, even this method’s standard deviation is large enough to miss the detection of adulterants that CAME can detect.
“When you consider the health issues of adulterants like polyphosphates in chronic dosages, one has to realize that CAME is no longer an optional analysis for CS raw material."
Neal-Kababick also addressed the issue of widespread use of FTIR for ID, saying that while sodium hexametaphosphate and CS look different by FTIR in the pure state, when blended, it can be almost impossible to detect adulteration even up to 10% using the standard COMPARE algorithm which is what most companies are using now. “The match quality will be about 0.99 which would cause companies to pass the product as authentic by FTIR,” he said. “FTIR has its utility in the analysis of CS but one must embrace the limitations of using simple method that do not rely on chemometric modelling and principle component analysis.”
‘It is imperative that all responsible companies be proactive in ensuring the purity and identity of ingredients’
Synutra’s Zhang called for widespread adoption of CAME as a qualitative, raw material screening tool before running quantitative methods such as CPC for assay, or other specific methods such as enzymatic HPLC. “CAME is an inexpensive, simple, and effective procedure that can serve us well in effectively deterring the practice of adulterating chondroitin ingredients with known adulterants.”
“Because of the size and scope of the supply chain, it is imperative that all responsible companies be proactive in ensuring the purity and identity of ingredients,” he added.
Zhang told us that most of the chondroitin sulfate materials are made overseas in places like India, China, Spain, and South America. “However, it is our belief that adulteration takes place more in the trading process of the material as a commodity. In other words, it’s not WHERE it is made, it is WHO is making it and handling it. Before materials reach market, much of it change hands through traders, aggregators, and exporters, and this way it is susceptible to intentional and unintentional adulteration.
“When price is the primary criteria, there is ample incentive and opportunity for adulteration. Introduction of effective and meaningful testing methods will help disrupt such likely chain of adulteration by giving manufactures reason to reject adulterated ingredients before they get into the production process.”
Zhang confirmed that the company has kept the regulators informed of the studies' progress on an ongoing basis, and that the FDA has had access to the same conclusions as a those presented in a press release released publically.
“We’ve made a point to keep major industry stakeholders in the loop about all of our efforts to stamp out chondroitin adulteration in the dietary supplements industry,” he said.
The research team intends to publish its findings in a peer-reviewed journal, with details of the collaborative studies currently being finalized.