Are botulinum toxin (Botox) injections riskier than commonly thought?

Botulinum toxin type A is a neurotoxin produced by the bacterium Clostridium botulinum. In very small doses it can be used to treat a number of medical conditions. However, it is best known and most commonly used as a treatment for the so-called motion wrinkles (wrinkles caused by facial movements). Botulinum toxin type A, most commonly sold under the brand Botox, helps improve wrinkles by partially paralyzing certain facial muscles and thereby reducing movements that cause wrinkles. (See our article on Botox in cosmetic rejuvenation).

Botox has been one of the big successes of cosmetic rejuvenation industry, with high levels of customer satisfaction and good risk/benefit profile. However, a number of safety concerns have recently been raised.

One Botox safety concern came from the 2008 study published in the Journal of Neuroscience by Dr. Caleo and co-workers of the Italian National Research Council. The researchers injected botulinum toxin type A in the muscle of a rat and then traced its propagation from the injection site. Until Dr. Caleo's study, it was assumed that the peripherally injected toxin stays confined to the injection site and acts only locally. However, Dr. Caleo and co-workers found that some of the toxin migrated along the nerve fibers into the rat's spinal cord and the brain. In theory, this may indicate a potential for the central nervous system side effects when Botox is injected into a muscle.

Dr. Caleo's study is clearly noteworthy and deserves further research. However, it should be viewed in perspective. First, animal physiology is similar but not identical to the human one. Therefore, the CNS migration of the toxin may not occur in humans to the same extent. Second, the dose used in the rat study was about 150 times higher than the typical human dose. Third, botulinum toxin type A is a degradable protein. In the body, it is eventually broken down by enzymes (whether it migrates or not). Therefore, even if small amounts of the toxin do migrate to the spinal cord and the brain, they are unlikely to accumulate there to dangerous levels as long as the injected doses are sufficiently low and infrequent.

Another Botox safety concern has to do with reports of serious complications or deaths possibly associated with botulinum toxin injections (see the index of Botox-related adverse event reports). Serious Botox-related adverse events are rare: probably about one per 10,000 to 100,000 treatments, although more data are needed for a better estimate. It appears that most (but not all) serious Botox-related complications occur in the individuals with neurological disorders, the elderly and young children. The site of injection also seems to impact the risk. For example, botulinum toxin injections administered to the neck area (to relieve painful muscle spasms) have been reported to cause swallowing problems -- apparently due to proximity to the nerves that regulate swallowing. On the other hand, when Botox is injected into small facial muscles to treat wrinkles in otherwise healthy adults, life-threatening complications appear to be exceedingly rare - as long as the toxin is administered correctly and in appropriate doses.

For more safety information, see the communication about the FDA's ongoing safety review of Botox.

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