The ongoing story of athletes and dietary supplements continued to gain attention with last week's announcement. Two triathletes had tested positive for ostarine, a banned substance under the WADA code. One of the athletes confirmed the presence of that substance in a nutritional supplement in her possession through further product testing of the same lot. The other athlete has not been able to provide any valid scientific support for a possible contaminated supplement, and the athlete was given a ban from competition consistent with no mitigating circumstances.
Dietary supplements are useful, especially for endurance athletes competing at the highest level. As well, certain medical conditions such as low iron, low vitamin D, low electrolytes (including calcium) can be addressed with supplements that can have a profoundly positive benefit.
An individual needs determine which supplements are appropriate; and then where to get them.
Not all supplements are made the same way. Both ingredients and manufacturing quality and safety must be scrutinized. The Food and Drug Administration (FDA) regulates supplements in the United States. Per the FDA website: “Manufacturers and distributors of dietary supplements and dietary ingredients are prohibited from marketing products that are adulterated or misbranded,” and “FDA is responsible for taking action against any adulterated or misbranded dietary supplement product after it reaches the market.”
Consumers often take for granted that the contents inside a bottle of supplement X matches exactly the label on the outside. Fortunately and for the most part this is true. However there are multiple opportunities during production where the contents of the bottle may no longer be represented correctly by the label. Somewhat analogous to bicycle frame builders, most brands of nutritional supplements are manufactured in a limited number of facilities, or contract labs. It’s generally not economically feasible for a small company with a product line of nutritional supplements to have its own production facility.
Contract labs specialize in the production of supplements, analytical testing, and packaging, though often these steps can take place at difference companies or locations. Since 2010, these labs must follow cGMP standards (current Good Manufacturing Practices). The actual contract lab used by any given supplement company is usually a guarded secret as part of one’s competitive advantage. Still, rather than looking to the name on the bottle, one must look at the actual contract lab as the source of the product, ingredients, and the inherent production risks.
Is cGMP enough?
cGMPs are intended to establish a comprehensive system of process controls including documentation of each stage of the manufacturing process that can minimize the likelihood of, or detect, problems and variances in manufacturing as they occur and before the product is in its finished form. These process controls that are a part of cGMPs are essential to ensure that the dietary supplement is manufactured, packaged, held, and labeled in a consistent and reproducible manner. Manufacturing according to cGMP means that the process incorporates a set of controls to assure a quality finished product.
Ensuring quality in dietary supplement cGMP, in part, means that you produce what you intend to produce.
Basically, cGMPs tell manufacturers what is needed, but not how to do it. This leaves individual companies to comply with the regulations in their own ways, which can lead to potential differences between production output.
From start to finish at a contract lab
Starting Materials: Most contract labs source their raw materials from a wide range of outside suppliers, many of whom specialize in certain classes of materials, such as amino acids, protein powders, minerals, etc. Each supplier provides to the contract lab a certificate of analysis (COA) that is issued for each and every lot (batch) of raw material. Suppliers can be located overseas or domestically with the actual starting material produced anywhere around the world.
When raw materials are received by a contract lab, they should be positively identified. This is usually done easily and quickly by near infrared (NIR) spectroscopy. Purity is not usually assayed at this time. This is the first intersection where impurities that originated in the starting material factory or packaging would enter the contract lab undetected. Note that the NIR identity confirmation is not sensitive to pick up foreign matter in the raw material and is a bulk test only.
A different set of concerns arises with herbal/botanical ingredients. Many materials such as St. John’s wort, royal jelly, ginkgo biloba, yucca root, grape seed extract, and many others originate from plant extracts. Currently, there are few standards in place to qualify these raw materials for potency or purity. This means that a bottle containing 100 percent St. John’s wort may actually have 5 percent active while another labeled the same way may have double or triple that amount. The FDA final rule guidance on these materials is still 100 percent identification testing, which is problematic due to current analytical testing limitations of some of these materials.
Not only are herbal/botanical ingredients of often unreliable content, but their toxicity and benefits have generally not been tested in clinical settings, which further prompts the warning: buyer beware.
Minerals, often sold commercially in ton quantities, are significantly more likely to be in purified form. Specialty ingredients, sold in small quantities from unusual suppliers are more likely to face contamination issues.
Processing of ingredients: Once the raw materials are identified upon receipt, the contract lab prepares the formulation according to specifications required by the supplement company. This can include dry mixing, wet mixing, granulation, and other physical handling steps. Containers used for these processes are part of machines that can be manually or automatically operated. Often made of stainless steel parts, these complex mixing bowls are used for a given batch and then cleaned and readied for the next product, one that may be totally distinct from the batch before and after it.
cGMP contract labs will follow a set of Standard Operating Procedures (SOPs) that dictate how the machine is to be cleaned, rinsed, and dried. Some facilities conduct a “cleaning verification” whereby some of the rinse wash is tested for the active ingredient from the previous batch. Possible source of contamination #2 arises if a machine is incompletely or incorrectly cleaned leading to carryover from one product to another.
In this way, for example, a steroid material from one product batch could be carried over to a protein supplement in the next batch of processed product. However, this can only occur if banned substances are processed and used on site for other products. Some facilities, as we will discuss later, are certified not to process or utilize banned substances, making cross-contamination impossible.
Encapsulation/bottling/packaging of the product: The final step within the contract lab takes the mixed product into its final form for the consumer. This can include bulk powder in plastic tubs, pressing powder into pills, or filling capsules with powder. Once again, industry-specific machines are used for this step. Careful cleaning between batches of different product is critical to ensuring no cross-contamination between products. Once the product is in its final packaging, a quality control (QC) unit serves to qualify and inspect the final product. Once again following SOPs, the QC analyst inspects the product against specifications that can include fill weight, color, particle size and other physical characteristics.
Testing of the final product for quantitative content of active material has been required since 2010. What this means is that upon QC approval and issuance of a batch-specific certificate of analysis (COA), the product is ready to be released to consumers.
Testing products for banned substances
Part of the FDA guidance for dietary supplements indicates that the contents of the label must match the contents within the product. However, small amounts of impurities can be considered acceptable, and these do not need to be disclosed on the product label. Therefore, it is entirely possible that a substance, otherwise legal but for sports, can contaminate a finished product and still be compliant with FDA regulations.
In regards to the recent news about ostarine contamination, it is worth noting that ostarine is actually not a permitted dietary supplement ingredient, but actually an experimental (unapproved) drug, that has been the subject of> investigation and enforcement by the FDA.
FDA’s Office of Criminal Investigations (OCI) has also been >reportedly looking into complaints that marketers of sports supplements have sold Ostarine in their products.
Testing products for banned substances can be carried out in analytical laboratories following established protocols. Some labs are accredited by WADA. As with any analysis, there can be variability, false positives and mishandled samples. Fortunately, the scientific process requires replicate samples and preparations, multiple assays per sample, and careful system suitability checks to ensure the assay in question provides reliable data. As assays are able to detect minute traces of material, it becomes an important consideration for labs to have rock-solid evidence-based science when they are responsible for providing quality data to manufacturers, athletes and regulatory agencies. There are no "alternative facts" in science.
Suggestions for Athletes
- Choose supplements based on your need to resolve a particular nutritional deficiency. If a products sounds "too good to be true", it probably is.
- Supplements containing herbal/botanical (plant) ingredients are more variable in their composition and are likely not to have been evaluated as thoroughly or have as much safety history as simpler minerals and vitamins.
- Encourage your national governing body (USAT, USCF, etc…) to support supplement testing programs that encourage manufacturers to test products, and provide athletes with a means to understand contamination of supplements.
- Patronize products and manufacturers that undergo testing or partake in certification programs. Membership/certification is an expensive and voluntary effort, and in order to continue their efforts, manufacturers need encouragement to continue.
- Be aware of the differences between programs and certifications and their limitations. Just like the supplements they test, not all programs are created equal. Some manufacturers may opt to use a certified facility and test their own products, exceeding the level of testing within some programs.
- Consume supplements that have been produced in a cGMP facility. This is your assurance that controls are in place to ensure the product you consume is exactly what is listed on the label, minimizing contamination and other handling and production issues. Manufacturers are typically proud of cGMP production and provide this information willingly on their website. Lack of this information tends to suggest a lack of cGMP compliance.
- WADA’s efforts are always evolving, with their prohibited list revised every year, and differences between prohibited lists of other drug-free sporting bodies that may differ from the list against which a supplement is tested. Be sure to read the small print and understand which list your sport follows.
Jonathan Toker is a Canadian elite-level runner and triathlete. He received a Ph.D. in organic chemistry from The Scripps Research Institute in 2001, and raced in the professional ranks as a triathlete for 5 years and now mostly runs on trails. Dr. Toker worked as a scientist in the biotech industry for 5 years prior to launching his unique SaltStick Electrolytes and Dispensers lineup.