Thursday, April 8, 2010

Vitamin B6 in the Regulatory Arena

By Dr. Arianna Staruch, ACHS Academic Dean

On April 6, 2010, there was an alert released by the Alliance for Natural Health that stated “A natural form of the vitamin, Pyridoxamine, was recently yanked off the market by the FDA. Why?”

The “why” seems to be about who gets to control the money gained from selling a product, which puts the supplement industry at odds with the drug industry. This fight over pyridoxamine is an example of this struggle that has the U.S. Food and Drug Administration (FDA) in the middle.

Let’s clarify this issue. According to the Linus Pauling Institute: “There are three traditionally considered forms of vitamin B6: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM). The phosphate ester derivative pyridoxal 5'-phosphate (PLP) is the principal coenzyme form and has the most importance in human metabolism.”[1]

Pyridoxine is the natural form of the B6 vitamin and PLP is the active form. The FDA has been reviewing the status of the pyridoxamine form of the vitamin since 2005. A petition, submitted on behalf of BioStratum, Inc., requesting the removal of dietary supplements containing the drug pyridoxamine was first submitted to the FDA on July 29, 2005.

BioStratum is the manufacturer of Pyridorin, a form of pyridoxamine dihydrochloride that was submitted as the subject of an Investigational New Drug (IND) Application filed with the FDA in 1999 as a potential therapeutic agent to slow or prevent the progression of diabetic neuropathy. It was granted fast-track status in 2002. A phase II trial was started that was expected to lead to the approval of this drug by 2005 or 2006. This current action by the FDA may reflect the completion of these studies and the impending approval of the drug.

BioStratum claims that after they released the data from their phase II trials, supplement manufactures began marketing pyridoxamine as a dietary supplement, and that pryridoxamine was never marketed as a dietary supplement before the compound was part of the Pyridorin IND filing. They further state that existing dietary ingredients must be chemically altered by sophisticated multi-step synthetic processes to produce pyridoxamine. This is why they petitioned the FDA to list pyridoxamine as a drug and not as a dietary supplement.

One of the supplement companies selling 100mg pyridoxamine directed consumers to a website that made specific health claims that “pyridoxamine may be useful in treating diabetic retinopathy.” This is clearly in violation of FDA regulations that say that dietary supplements can only make structure function claims, not health claims.

Another problem is that pyridoxamine can have potential side effects, and as part of an investigational drug study, its use should be monitored by a physician. When BioStratum analyzed the 100mg product from the supplement company, it found that some of the capsules contained up to 140mg of pyridoxamine, and also contained up to 8.3% impurities. (Drugs and supplements manufactured according to Good Manufacturing Practices (GMPs) would never be allowed to have this level of contamination.) This could further exacerbate side effects.

In September 2005 the Council for Responsible Nutrition, a leading trade association representing dietary supplement manufacturers and ingredient suppliers, contested BioStratum’s petition stating that pyridoxamine is one of the two natural forms of B6 found in animal products used as human food. They also stated that pyridoxamine is on a list of dietary supplements marketed prior to 1995 and the passage of the DSHEA. This Natural Products Association (formerly the National Nutritional Foods Association or NNFA) list included Pyridoxine ketoglutarate. BioStratum countered in September of 2005, saying that pyridoxamine was not marketed as a dietary supplement until after July 1999, and the NNFA list was never verified by any agency. In addition, they say that pyridoxaime can be metabolized in vivo to the active form of PLP, but that it is not the natural form of the vitamin, which is pyridoxine. However, a dietary supplement fact sheet on B6 produced by the Office of Dietary Supplements of the National Institutes of Health (NIH) listed pyridoxamine as one of the three major chemical forms of B6 in 2002.

Further, Jarrow Formulas began marketing “Pyridoxall with pyridoxamine”. The label lists pyridoxamine 50mg 2500% DV, pyridoxine 5mg 250% DV, and pyridoxal-5-phosphate 250% DV. The abbreviation “DV” refers to the Daily Value found on the NIH vitamin Fact Sheet for B6 from 2002. The RDA for B6 is 1.3-1.7mg and the Upper Tolerable Limit (UL) is 100mg. Above 100mg can cause reversible nerve damage.

The public should be involved in the decisions being made by the FDA. If you want to continue to have access to specific products sold by supplement manufactures, then add your voice to the FDA debate. Understand the issue and the players involved and know that both sides do have a financial interest in the debate.

If you would like to review the FDA document for yourself, click here for the link.


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