Robert Green 04.01.04
The Laboratory Notebook
Answering important questions about quality.
By Robert Green
Not surprisingly, we generated many comments on our last column discussing chondroitin sulfate and the various methods used to analyze it. We have also seen increasing frustration from supplement companies trying to provide a quality product but stymied by the state of confusion in the industry. While we cannot resolve every problem, below we provide some guidance. Following that is a question about the difference between natural and synthetic vitamin E.
Here are some thoughts to consider while steering through the chondroitin sulfate confusion:
1. Define what you consider to be chondroitin sulfate. Remember that chondroitin sulfate is not a single entity with a single molecular weight, but rather, a polymer composed of repeating linear units with a distribution of molecular weights.
The molecular weight of chondroitin sulfate in the body is >50,000. We have seen chondroitin sulfate in the marketplace with a molecular weight of <1000. From a purely technical viewpoint once the molecular weight drops below around 5000 it may no longer be classified as a polymer, and therefore probably should not be considered as chondroitin sulfate. Much chondroitin sulfate on the market is indeed below 5000. You cannot determine what is acceptable chondroitin sulfate until you determine what molecular weight is acceptable to you.
But molecular weight is not the only variable. There are, in effect, three types of chondroitin sulfate: A, C and B. Generally speaking, type A (bovine derived) is the most desired. Most supplements on the market are a combination of A and C (also existing in bovine to about 8% by weight). In judging chondroitin sulfate you must first also determine what percentages of A and C are acceptable to you.
And finally, all chondroitin sulfate exists as a “salt” of sodium, potassium or calcium, so this must also be considered when setting a specification for your desired product.
Unfortunately, there is no supplement industry standard, or even understanding, of what constitutes acceptable chondroitin sulfate. In fact, the market is flooded with all kinds of dramatically different material, all of which is labeled “chondroitin sulfate.” This widely varying material simply cannot all be deemed the same. With this in mind, the rush by some to select a method of analysis is taking the cart before the horse. So the first step in exiting this quagmire is to determine what you consider to be acceptable chondroitin sulfate. Once defined, you can then systematically select qualifying material.
2. Once you determine your acceptable specification for chondroitin sulfate, you should then select an analytical method by which material can be judged. Higher molecular weight material can be analyzed by size exclusion chromatography, but will probably fail the USP-27 method. The desired material and the method must match.
Often forgotten, the analytical standard used in the analysis is also of critical importance. You may recall from an earlier discussion in this column that a standard is authenticated material against which a sample is judged. The standard must match the material you desire. If you want higher molecular weight material make sure you (or your lab) use a standard composed of higher molecular weight material, and visa versa. Otherwise you (or your analytical lab) will be failing the material you seek.
With this in mind, we asked the USP for the specification of the chondroitin sulfate standard they are selling. Shockingly, we received a boilerplate response stating that the USP “generally does not provide certificates of analysis for USP Reference Standards…This is done for scientific and legal reasons.” While we have the highest regard for the USP, quite honestly we believe this position is untenable. As we have said here innumerable times, anyone providing any analytical service has an obligation to make full and complete disclosure. This position only further frustrates those trying to provide quality material.
Hope this helps. (See the December column for a detailed discussion of the various analytical methods in use.)
Q. I placed an order with a contract manufacturer for a large bottle run of natural vitamin E. It is my understanding that natural vitamin E should consist of four tocopherols. A post-production analytical test listed primarily one. Is there a problem here?
A. Yes there is. A little background is in order first. Vitamin E is one of the most popular vitamins in the supplement industry. It has been associated with improving heart and circulatory health, reducing risk of infections, anti-inflammatory properties and reducing the amount of free radicals in the body. It may also be helpful in preventing prostate and other cancers, Alzheimer's disease, rheumatoid arthritis and diabetes, among other conditions.
Vitamin E is one of several fat soluble vitamins that are chemically tocopherols. The term tocopherol was used to name the initial four compounds that shared a similar structure: a complex ring and a long saturated side chain. These compounds are designated as alpha, beta, delta and gamma, with alpha being the predominate form in the body.
Natural vitamin E is derived from vegetable oils, primarily soybean oil. Synthetic vitamin E is produced from petrochemicals. Unlike most vitamins, natural and synthetic vitamin E are distinctly different. Natural vitamin E is a mixture of four stereoisomers, while synthetic E is primarily one stereoisomer, either d-tocopherol acetate or succinate.
The biological activity of vitamin E is generally determined in international units (IU). One IU is defined as 1 mg of the acetate ester of synthetic alpha-tocopherol (dl-alpha-tocopherol acetate).
A great debate exists concerning whether natural or synthetic vitamin E is better. Natural vitamin E is generally more expensive.
Now to the specific question. Your lab report lists one stereoisomer clearly indicating that your capsule contains synthetic vitamin E. Since we do not provide legal advice in this column, the next step is yours.NW