Pat Wagner (or “The Bee Lady,” as she likes to be called) treats herself for multiple sclerosis (MS) by allowing bees to sting her. She calls this bee-venom therapy (BVT) and believes it has saved her from MS.
There are now thousands of people who administer BVT to themselves or others, mostly in private homes by unlicensed practitioners. BVT 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 and others tout its effectiveness.
BVT, which is one modality within Apitherapy, or the use of various bee products as a medical treatment, is still a relatively small phenomenon. It is largely an unrecognized grassroots or folk medicine treatment – but like all such phenomena has been given a huge boost recently by the easy spread of information via the internet. It has also been adopted by many so-called alternative medicine (CAM) practitioners, and has been increasingly wrapped in the typical marketing jargon of CAM. So, in a way, this grassroots treatment has been corporatized by the CAM industry.
And yet, there if no convincing evidence that it is an effective treatment for any of the conditions for which it is used. Apitherapy.com claims it can be used to treat over 500 conditions (always a red flag for quackery), but I will focus on one – 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 folk 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.
In fact this is exactly what I see in my practice. Patients with chronic neurological diseases with often try many therapies, even unconventional ones. If these treatments did not work, they do not talk about them much, and often will only report them if I directly ask about specific prior treatments. If, however, they feel they were helped by a treatment, they will shout it from the roof tops.
This process described above is the essence of anecdotal evidence, and is the reason why it is unreliable – because it is not controlled. The waxing and waning potential of MS symptoms makes it especially difficult to draw conclusions from uncontrolled observations.
It is also possible, although unlikely, that apitherapy is effective in the treatment of MS. Bee venom contains many biologically active chemicals. One or more may have anti-inflammatory or immune modulating effects. We will never learn this from anecdotal clinical evidence alone, however.
Until well designed and reliable clinical trials 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.
In the last decade several effective drugs for the treatment of relapsing remitting MS have emerged: Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (copolymer I), and Rebif (interferon beta-1b). More recently Tysabri has come on the market. This is an extremely effective drug and reduces MS exacerbations dramatically.
These are all powerful drugs, and not without their side effects, but they are useful in the treatment of MS and there is a large and growing body of data to support their use and to inform doctors and patients about their risks and benefits.
No such information exists for BVT. It is also impossible to regulated the dose of BVT with the precision that pharmaceuticals can.
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).
After a successful phase II trial, drugs can be given to patients as part of an open label trial on a compassionate basis. Also – treatments that are considered unproved or experimental can and should be given in the context of a clinical trial. One could argue that every patient getting BVT should be part of a trial until such time that we can confidently conclude that it either works or does not work.
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. There is also interest in a wide variety of venom therapies (snake venom, and anemones, for example) as potential sources of pharmaceuticals, including as anti-inflammatories.
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.
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)
A recent randomized cross-over (unblinded) study published in Neurology in 2005 found absolutely no effect by any measure for relapsing-remitting MS (the most treatable form) from BVT. Another small Phase I study showed no effect.
At this time the animal data and the preliminary (phase I and II) clinical data for BVT in MS is negative. Of course, this is not definitive, but strongly argues against an effect, and at the very least rules out a large clinical effect.
Unfortunately, as we often see with grassroots or folk medicine in general – practice and belief are completely disconnected from scientific research. Apitherapy has evolved into another CAM belief system – one with an almost spiritual belief in the power of the honey bee to “heal”. Evidence is irrelevant.