February 2002
by Steven Novella, MD

It is administered in private homes by unlicensed practitioners. It is not prescribed by a doctor, yet it is used like any other drug, given in regular doses at regular intervals. There is no scientific evidence to support its use, and yet thousands of multiple sclerosis sufferers tout its effectiveness. Apitherapy, or bee-sting therapy, is a relatively small phenomenon, but it is a classic example of grass-roots alternative medicine, and a careful examination will illuminate much about this type of phenomenon.

Multiple Sclerosis

In order to fully understand how apitherapy arose, one needs to understand the disease at which it is primarily targeted: multiple sclerosis. MS is a disease of the central nervous system, resulting in a variety of neurological symptoms. The cause of MS is still unclear, but what is known is that in patients with the disease the immune system attacks the brain and spinal cord, which are normally isolated from the immune system. The resulting inflammation causes areas of demyelination (myelin is the insulation around nerve fibers) which results in a plaque, an area where normal conduction is slowed or blocked. The location of the plaque determines the neurological deficit which results.

The important feature of MS, however, is its unpredictability. New plaques arise at random times and locations, and 90% of plaques are silent (without noticeable symptoms). Plaques can also vary in size and severity, and also in their potential to heal. Most new lesions will resolve spontaneously, either partially or even completely. Also, even in a person with stable MS, with no new lesions forming, symptoms can vary significantly and rapidly based on other factors, such as body temperature.

The end result is that nobody, not the patient nor the physician, can predict the course of MS in any individual. The MS sufferer must live with the uncertainty of what the future will bring, as they are buffeted by unpredictable exacerbations and remissions. It is for this reason that MS patients are especially susceptible to the claims of new miracle cures, and why anecdotal information regarding such therapies are all but worthless in terms of forming reliable scientific conclusions. In this way, MS is typical of diseases which are favorite targets of alternative medicine: it is unpredictable, susceptible to spontaneous remissions, and cannot be cured by mainstream medicine.

Anecdotes and Human Nature

How, then, does the existence of MS result in the American Apitherapy Society, which claims to be tracking over 6,000 patients receiving regular bee-sting therapy (for MS and arthritis). Often times such a phenomenon begins with a single observation, one patient who, for example, receives bee sting for another ailment, or even accidentally, and then experiences a remission of their symptoms. Human psychology does the rest.

It is human nature to associate two events which are temporally related and assume cause and effect. Eat a roast beef sandwich and then get sick, and most people will assume that the roast beef was bad, even though they may be sick from a virus they were exposed to a day earlier. It is important to realize that coincidences are much more common than one would naively believe, and that the assumption of cause and effect is perhaps the most common logical mistake that people make.

So, once the story that a person was cured, or even helped, by bee venom gets around, many MS patients will seek out this new therapy out of desperation and hope. This is a reasonable and, one might even argue, rational response. Out of this self-selected (not random) assortment of MS sufferers who will try apitherapy, many are destined to have spontaneous remissions. Those that do are likely to spread the praises of this new therapy at MS support group meeting and other public venues and will give stunning testimonials at apitherapy meetings. The rare patient with a dramatic remission is likely to become a crusader for their miracle savior. Those without a response are likely to abandon therapy and not be heard from. They will probably move onto the next potential cure, and will not spend their time spreading the word that apitherapy did not work for them.

This process described above is the essence of anecdotal evidence, and is the reason why it is unreliable – because it is not controlled. For example, it is possible that MS patients are more likely to seek out an alternative therapy, such as bee-sting therapy, when they are having an exacerbation and are therefore at a low point in their symptoms, therefore they are more likely to have a remission and improve in the near future. Also there is the well described placebo effect, which is the tendency for people to believe they have benefited from a treatment even when there is no objective benefit. Perhaps people receiving apitherapy will expect to improve, or just have a positive emotional outlook resulting from the hope of a new therapy and having a support group, and will therefore be more active, perhaps even eat better and in general take better care of themselves. Some experts have also hypothesized that natural steroids released from the pain of the sting itself causes a temporary improvement in symptoms.

It is also possible that apitherapy is effective in the treatment of MS. At this time no one can say either way, because research designed to definitively answer this question has not been done. Anecdotal information is useful in pointing in the direction of new research, but not as a basis of therapy.

The phenomenon of apitherapy also benefits from the fact that it has two outstanding virtues, from the perspective of current culture, it is both ancient and natural. Apitherapy literature makes frequent reference to these two “benefits.” Part of the current counter-cultural reaction against overwhelming technology – of which alternative medicine is a part – is the belief that things which are new and artificial (often equated with technological) are bad, whereas things which are old and natural are good. Indeed, the concept of “natural” has risen to mythic proportions in our culture.

It is interesting to compare these beliefs with those of the turn of the century. At that time technology was new and exciting and was seen as the ultimate answer to all man’s problems. Soon after radiation was discovered, but before its potential harmful effects were known, many popular remedies were marketed which contained radioactive elements, such as cesium. The remedies were said to cure all sorts of ailments from simple fatigue to migraine headaches. Advertisements extolled the virtues of the tonic’s newness and technological basis. These radiation remedies enjoyed remarkable popularity, even after people started dying of radiation poisoning. It took federal legislation to remove them from the market.

In recent years the Internet has played an increasing role in the spreading of claims for alternative therapies, and the marketing of those therapies, and bee venom therapy is no exception. A review of such websites reflects the nature of such phenomena. Although there are numerous sites which extol the virtue of the been venom products they sell, complete with glowing anecdotal reports, some are careful to point out in their fine text disclaimers such as, “The medical efficiency (sic) of bee hive product treatments have not been adequately approved in many countries, therefore, this WEB site, its sponsors and / or contributors makes no claims about the safety or efficiency (sic) of any honeybee products and does not endorse any form of apitherapy.”1 What they mean is that the efficacy is unproven. Although this site touts itself as the “Apitherapy Reference Data Base” it does not contain any references to published scientific studies which show that bee venom therapy actually works.

Another site calls itself the Bee Venom Therapy Journal2 although it is not a journal in the scientific sense of published scientific data, rather it is “one man’s account” of his experience with bee venom therapy. Grass roots alternative medicine movements have elevated anecdotes to the exalted position of being not only sufficient to establish that a treatment works, but to being the final word on the question.

Clinical Research

Until well designed and reliable scientific investigations are completed which demonstrate honey bee venom’s safety and effectiveness, there is no rational basis for using it to treat MS. Many will argue, however, that those patients with severe progressive MS “have nothing to lose” and therefore they should not be denied any hope of a treatment. The use of unproved therapy in otherwise untreatable illnesses is a complex ethical issue, beyond the scope of this article. There are a few points I would like to discuss, however.

First, MS patients do have something to lose. Apitherapy certainly has its risks. All drugs have side effects and toxicity, which need to be weighed against their therapeutic effect. Bee stings commonly cause allergic reactions, which may result in anaphylaxis and death. Also, patients who put their hopes in an unproved treatment may be kept from mainstream treatment. There are now four FDA approved drugs for the treatment of relapsing remitting MS: Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (copolymer I), and Rebif (interferon beta-1b). Other drugs are available for patient with more aggressive disease, such as Novantrone (mitoxantrone). These drugs do not cure MS but they do decrease the number of new lesions which occur, keeping MS patients more functional for longer. In short, they slow down the progression of the disease. There are many treatments for the symptoms of MS to help maintain the highest quality of life for the longest time possible. In addition to risk of side effects, and potentially distracting patients from mainstream therapy, there is also the more subtle psychological harm of being given false hope in a treatment that may not work.

Second, compassionate use of experimental drugs is already built into the system. Drug trials are conducted in multiple phases. Before human testing can occur, potential new drugs are tested in animals to see if they are safe, and then to see if they have any potential benefit on the disease in question (or a close animal model of the disease). A phase I human trial may then be performed simply to test for safety in humans, and learn about the pharmacology of the drug – how it affects the body and how the body metabolizes it. A phase II trial is a placebo controlled human trial conducted in a small number of patients (dozens to a few hundred), tracking side effects and dosage response, but now also therapeutic effect. These trials involve too few patients to achieve reliable results, and are used to screen drugs for safety and possible benefit before they are given to a large number of patients. A phase III trial is a large, usually multicenter placebo controlled trial involving many patients (hundreds to thousands) over a longer period of time. This trial is designed to answer definitively the question of whether or not a drug is safe and effective, two of which are required for FDA approval. A phase IV trial is uncontrolled and simply tracks the side effects of a new drug once it is in wide-spread use (post FDA approval and marketing).

This testing process for new drugs may seem long and laborious, but it has protected the American public from many potentially harmful drugs, such as the infamous thalidomide. (Many people don’t realize that thalidomide was never used in pregnant women in the US because it was still under FDA review while it was causing birth defects in Europe.) There is a recognized need, however, to get potentially useful drugs to patients with lethal and incurable diseases as soon as possible. Towards this end, after a successful phase II trial, drugs can be given to patients as part of an open label trial on a compassionate basis.

Proponents of apitherapy will often point to basic science research which indicates that honey bee venom contains several compounds with powerful anti-inflammatory properties. There is a rationale to believe that anti-inflammatory drugs, like those currently used to treat MS, may have some benefit. This sort of basic science information, however, is pre-phase I, meaning that it is useful for picking a drug to study as a possible treatment for a particular disease, but it is a long way from concluding that the drug should be used to treat that disease. A very small percentage of drugs which enter phase I trials ultimately achieve FDA approval, most because the balance of risks and side effects to potential benefit is unfavorable.

Current Research

The National Multiple Sclerosis Society (NMSS) sponsored a study and published the following reports: Preliminary Test Results Of Bee Venom In Mice With Ms-Like Disease May 8, 1998. They studied the effect of bee venom on mice with experimental allergic encephalitis (EAE), the standard animal model of MS. They conclude:
“In their initial series of small experiments, honey bee venom had no beneficial effect against the course of EAE, and some of the mice treated with bee venom experienced a worse course than those that received inactive placebo.

“Honey bee venom contains a mixture of toxins and other biologically active compounds. Additional studies are underway to determine whether any of these individual components may have potential benefit for treating symptoms of MS.
“The investigators caution that their finding that some mice experienced a worse course of disease after receiving honey bee venom raises possible safety concerns for the use of honey bee venom therapy in humans.”3

There is currently a Phase I study being conducted at Georgetown University Medical Center in Washington, DC, by Dr. Joseph A. Bellanti. This study will examine the safety and tolerance of honeybee venom extracts as a possible therapy for patients with progressive MS. As described above, however, this is a phase I study, and therefore will not answer the question of whether or not bee venom therapy works. It is a preliminary study which will look as side effects and dosing. If bee venom looks safe in this trial, Phase II or III trials may come later. This current study is being funded by the Multiple Sclerosis Association of America (MSAA), a patient advocacy group.

Conclusion

The MSAA says about bee venom therapy, “Bee venom therapy entails a real risk of dangerous allergic reaction as well as an emotional and monetary cost in chasing false hopes. MSAA does not recommend or endorse the use of honeybee venom for the treatment of MS or other disorders. We are funding this study to determine if this approach has any neurological benefit. If the results prove positive, then additional clinical studies and possible treatment practices of MS can begin. If the results prove negative, then MSAA has helped to eliminate false hope. Anyone interested in BVT should first consult his or her physician.”4 The NMSS also officially states that bee venom therapy is unproven.

It may be imperfect, like all human endeavors, but the system for drug testing and approval exists for a purpose. It has evolved over many decades, and is still evolving, guided by well-meaning clinicians, advocacy groups, ethicists, law-makers, and patients themselves. It is designed to provide new safe and effective therapies to patients, while protecting them from drugs which are harmful or useless. Bee venom therapy may or may not work, only time and science will tell, but some of its advocates and promoters have chosen to abandon the system which is designed to both protect them and discover the final truth of the drug’s utility.

References:
1) The Apitherapy Reference Database, http://www.sci.fi/%7Eapither/, Feb., 2002
2) The Bee Venom Journal, http://www.gilbertsville.com/bee/, Feb. 2002
3) http://www.nationalmssociety.org/research-1998may3.asp
4) Multiple Sclerosis Association of America, http://www.msaa.com/, Feb. 2002

Filed under: Uncategorized, bee venom