On June 16th the FDA issued a warning advising consumers not to use Zicam Nasal Gel or Nasal Swabs because of reports that it can damage the sense of smell, a condition called anosmia. This event highlights some problems with current regulations of health products.

There have been 130 cases reported to the FDA of decreased sense of smell following the use of one of these Zicam products – sometimes after a single use, sometimes after repeated use.  All of these cases were reported by patients or their doctors; none were reported by the company, Matrixx Initiatives. According to reports, the FDA has asked Matrixx to turn over 800 consumer complaints regarding to Zicam. There is a 2007 law that requires company to report such complaints to the FDA, although the FDA has not said whether Matrixx violated this law.

Anosmia is a serious medical condition. The senses of smell is one of those things we take for granted until it is gone. People who lack a sense of smell cannot tell if milk has gone sour or if their food is bad. They cannot smell smoke to warn of a fire, nor can they smell a gas leak. The FDA fears that some of the cases of anosmia associated with Zicam use may be permanent.

Correlation does not prove causation, but there is reason to think that the anosmia in some of these cases may have been caused by the zinc in these Zicam products. As the FDA reports, viral upper airway infections can also cause anosmia, but the anosmia that results from zinc is associated with burning and is much more rapid in onset. Apparently some of these cases had features suggestive of zinc-caused anosmia.

Further, it has already been described in the literature that decreased smell (hyposmia) or loss of smell (anosmia) can result from the intranasal use of zinc.

There is some evidence that zinc preparations may reduce the severity or duration of the common cold if used within 24 hours of onset.  This review of the literature concludes:

Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects.

Therefore, intranasal zinc products may have a modest effect in reducing the symptoms of a cold, but come with the risk of permanent damage to the sense of smell. Since the common cold is a self-limited illness that typically lasts about 7 days, this would not seem to be a favorable risk vs benefit ratio.

How, then, did these Zicam products make it onto the market in the first place?

The FDA regulates, among other things, drugs. They require adequate evidence for both safety and effectiveness before a drug can be placed on the market and sold to consumers. They also determine the level of regulation for each drug – can it be sold over the counter, with prescription only, and it is a controlled substance, like a narcotic.

There are two important exceptions to this general rule. The first is an exception that was carved out for homeopathic products in 1938. The FDA states:

The Federal Food, Drug, and Cosmetic Act (the Act) recognizes as official the drugs and standards in the Homeopathic Pharmacopeia of the United States and its supplements (Sections 201 (g)(1) and 501 (b), respectively). Until recently, homeopathic drugs have been marketed on a limited scale by a few manufacturers who have been in business for many years and have predominantly served the needs of a limited number of licensed practitioners. In conjunction with this, homeopathic drug products historically have borne little or no labeling for the consumer.

Homeopathy was much more popular early in the 20th century in the US, and the homeopathic lobby was sufficient to gain legitimacy under the FDA. Specifically, Senator Royal Copeland of New York, a physician trained in homeopathy and a principal author of the FDCA, pushed for the inclusion of homeopathy as approved drugs. Homeopathic remedies are classified as “drugs” by the FDA, which means they fall under FDA oversight, but at the same time they are granted automatic approval as long as they appear in the Homeopathic Pharmacopeia.

What this means is that the Homeopathic Pharmacopoeia Convention of the United State, the non-governmental agency that writes the homeopathic pharmacopoeia, only has to add an agent to their list and it is granted automatic FDA approval.

Homeopathic remedies are typically diluted beyond the point where any active ingredient remains. Therefore, in practice there is no difference between any one homeopathic preparation and any other – or just plain water. (Here is a recent overview I wrote about homeopathy.)

The biggest problem with this regulation is that it amounts to official government recognition of pseudoscience. The FDCA should be amended to remove homeopathy completely.

But there is also a problem with definition. While most homeopathic remedies are diluted to the point that they are indistinguishable from water, that is not a requirement. Lesser dilutions may contain small amounts of active ingredient. If a “homeopathic remedy” contains a biological active amount of a drug as an active ingredient, is it not a regular drug?

This is relevant to Zicam because these products are regulated as homeopathic drugs – which means they were allowed on the market without having to provide any evidence for safety or efficacy.The homeopathic exception allowed the manufacturer to simply bypass the usual requirements, even though Zicam is not really homeopathic but contains biologically active levels of zinc.

But because homeopathic remedies do fall under FDA regulation the FDA has the power to decide that a product poses a safety risk to the public and therefore can demand evidence for safety. In this case the FDA has requested that Matrixx Initiatives “submit a new drug application to demonstrate safety and efficacy.” (I confirmed this over e-mail with the FDA.)

The second exception to the FDA regulation of drugs was created by the Dietary Supplement Health and Education Act of 1994 (DSHEA). This law allows botanical drugs to be sold as supplements, with no requirement to prove safety or efficacy. While with products marketed as homeopathic “drugs” the FDA can step in if they feel there is a safety concern, with supplements under DSHEA the FDA bears a high burden of proof to show that a product is harmful before it can take action.  So far it has only done this for one ingredient – ephedra.

Here, too, we see a significant problem with definition. Why is a botanical drug or herb regulated like food rather than a drug?

A more science-based regulatory system would eliminate homeopathic agents altogether. They are a relic from the past. Further, any substance meant to be consumed or taken internally for its pharmacological activity is a drug and should be regulated like a drug.  This could still leave room for subcategories of drugs, as we have now (for example, over the counter vs prescription only). But regulating herbal drugs as food has only opened the flood-gates for dubious products with even more dubious claims.



Posted by Steven Novella