Part I of a Series on Apitherapy
By Susan T. Marcolina, MD, FACP
Honeybees, apis mellifera, have long been appreciated for more than just honey.
Bee venom, although widely accepted in this country for use in desensitization protocols for patients who have suffered life-threatening anaphylactic reactions to bee stings, has not been widely accepted for the treatment of other ailments. It has long been used in Europe and Asia for the treatment of arthritic conditions and, more recently, multiple sclerosis (MS), a chronic neurodegenerative disease that may have different disease presentations and clinical courses in given patients.1
The use of bee stings for the treatment of rheumatism and baldness was discussed in the Edwin Smith Surgical Papyrus, which dates from approximately 2000 BC and is an important archive of medical practices in the ancient Nile Valley.2 Even Hippocrates used dried pulverized bees and bee stings in his practice of medicine.3
Formal scientific inquiry into bee-related clinical applications began with Terc, an Austrian physician in 1880, who was the first to use bee stings in his practice as therapy for rheumatoid arthritis and neuritis. Although he published several favorable reports about salutary effects in his patients, widespread use of this modality in European medical practice did not occur until the early 1900s.4
Chemical Constituents of Bee Venom
Table 1 outlines the major chemical constituents of bee venom and their effects.
Depending upon the trees and flowers available to the bees in a given geographic area, the chemical make-up of the bee venom, as well as any other hive product, may vary significantly, thus affecting its potency and subsequent medicinal effects.5
Possible Mechanisms of Action of Bee Venom
Whether whole bee venom or an individual constituent is responsible for a sting’s ability to mitigate symptoms is the subject of controversy.
One mechanism by which bee venom has been postulated to suppress the induction of arthritis is via adrenocortical hormone release. Zurier et al demonstrated the ability of whole bee venom, but not its component melittin, apamin, or phospholipase A fractions, to block the onset of adjuvant arthritis in rats. Neither whole venom nor its constituents had any effect on established disease. The suppressive effects of the venom were reversed by adrenalectomy.6
Previous studies by Vick and Shipman and Vick and Mehlman showed that whole bee venom produced sustained rises of plasma cortisol in dogs and monkeys, whereas hypophysectomy prevented bee venom-induced adrenal stimulation in these animals.7,8
Chang et al, however, showed that the time course of adjuvant arthritis suppression by bee venom (0.5 mg/kg concentration) to be different than steroid use.9 These authors theorized that bee venom directly suppressed immune cells responsible for arthritis initiation. They also demonstrated that the inhibitory effect of bee venom on arthritis initiation was greatest when it was administered simultaneously with (and into the same animal paw as) the adjuvant. This suggested a role for antigen competition in blocking arthritis onset.
Finally, Somerfield et al showed in in vitro studies that whole bee venom inhibited superoxide and hydrogen peroxide production from normal human polymorphonuclear leukocytes in a dose-dependent fashion with maximal effect at 1.5 microgram/cc.10 The investigators were able to isolate melittin as the peptide constituent responsible for this action. On this basis, they postulated that whole bee venom may have an important role to play in the treatment of inflammatory tissue damage in rheumatic, cardiac, and central nervous system disease. However, the doses of venom required for anti-inflammatory effects would require patients to be exposed to a prohibitively large number of bee stings or the equivalent in venom dosage.11
Kroner et al performed an uncontrolled study of 100 patients ages 21-74 years with rheumatoid arthritis treated with intradermal injection of bee venom solution (Apicosan) into their most painful joints.4 All were given a test dose of venom prior to therapy and excluded from the study if they had a reaction. Seventy-three showed definite improvement as judged by a decrease in sedimentation index and an alleviation of clinical symptoms. Seventeen of these patients remained symptom-free six months to a year after discontinuation of the treatments.
Subsequently, however, Hollander et al reported the first controlled trial of bee venom efficacy in 24 patients with rheumatoid arthritis.12 These patients received the equivalent of 10-30 bee stings as intradermal injections per visit over an average of 18 sessions with sessions performed twice weekly. Controls were nine rheumatoid arthritis patients injected with a milk protein mixture. Improvement occurred in seven of 24 (29%) venom-injected patients and in three of nine (33%) milk protein-injected patients. The conclusion was that bee venom therapy (BVT) offered no significant improvement in patients with rheumatoid arthritis.
Hauser et al performed a study of the response of 73 patients diagnosed with either chronic progressive MS or relapsing-remitting MS to BVT.13 Patients were diagnosed with MS on the basis of MRI imaging, clinical symptoms, and/or clinical evaluation by their referring neurologists/physicians. Patients with a positive test dose to bee venom were excluded. Patients received a subdermal injection equivalent to one bee sting every other day for one week and dosages were increased each week by one shot per session until positive clinical effects plateaued. If a skin wheal developed that was larger than a silver dollar, patients were to halve the venom dose.
Tracking of improvement/disability was assessed every three months for 12 months using the Multiple Sclerosis Follow Up Questionnaire, the Related Ob-servable Symptoms Scale Survey (ROSS), and patient ratings on the Karnofsky Performance Status Scale. Twenty-two of 73 patients were dropped from the study due to lack of follow-up, inability to handle the pain from BVT injections, or inability of caregivers to give the injections. At 12 months, the remaining 51 subjects perceived improvement in balance (34%), co-ordination (32%), fatigue (44%), and bowel control (31%). Sadly, the study lacked a control and objective methods of measuring improvement in perceived parameters and had small numbers of patients with a large drop-out rate.
Table 2 summarizes the products from bees and bee hives currently used medicinally.
Administration of Bee Venom
Although many flying insects have a venomous sting, it is the honeybee that has been domesticated and easiest to raise and, therefore, its venom has been the subject of much study. Bees produce approximately 0.1 mg dried venom per venom sac.14
The use of live bees as sting therapy for various conditions presents practical problems, which include finding a source of bees, and then storing and retrieving the bees for use as stingers. It is difficult to control the amount administered when venom from live bees is used for therapy.14
Present day collecting technologies are based upon the use of a collector frame in the bottom of the hive, which contains wire grids from which electrical shocks are administered to the bee. When the bees receive the electrical shock they sting onto a glass sheet. The collected venom dries on the sheet to a gum like substance without loss of potency and is subsequently scraped and stored in a cool, dry place and used to produce solutions in an injection form.
Dilutions of 1:1,000 (3x), 1:1,000,000 (6x), and 1: 1, 000,000,000,000 (12x) are used in homeopathic products. Apitronic Services in Calgary, Canada, collects and processes whole, dried honeybee venom, which it provides to research institutes, chemical and pharmaceutical companies, physicians, and pharmacies.1,3
For 0.5-2% of the population, a bee sting can trigger anaphylaxis with hypotension, respiratory collapse, and even death unless prompt medical attention with epinephrine and supportive care is instituted. Use of BVT in these patients is contraindicated except for desensitization protocols under the supervision of qualified medical professionals.
Side effects reported during BVT include localized itching, burning, swelling, and pain at the injection site. BVT is contraindicated during pregnancy as it is an abortifacient.15
There is no conclusive evidence in clinical studies that BVT is useful for the treatment of arthritis or multiple sclerosis at this time.
Physicians should not recommend BVT to their patients suffering from arthritis or multiple sclerosis because there is no evidence from clinical studies to show benefit to balance the inconvenience of pain, swelling, and possible risk of anaphylaxis. BVT is contraindicated in pregnancy.
Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA.
1. Broadman J, MD. Bee Venom: The Natural Curative for Arthritis and Rheumatism. Silver Spring, MD: Health Resources Press, Inc; 1997.
2. The Edwin Smith Surgical Papyrus. Available at: www.crystalinks.com/egyptmedicine.html.
3. Simics M. Bee Venom: Exploring the Healing Power. Calgary, Alberta, Canada: Apitronic Press; 1994.
4. Kroner J, et al. The treatment of rheumatoid arthritis with an injectable form of bee venom. Ann Intern Med 1938;11:1077-1083.
5. Bankova V. Determining quality in propolis samples. J Am Apitherapy Soc 2000;7(2). Available at: www.apitherapy.org/determiningquality.htm.
6. Zurier RB, et al. Effect of bee venom on experimental arthritis. Ann Rheum Dis 1973;32:466-470.
7. Vick JA, Shipman WH. Effects of whole bee venom and its fractions (apamin and melittin) on plasma cortisol levels in the dog. Toxicon 1972;10:377-380.
8. Vick JA, et al. Pharmacological studies of bee venom in the unanesthetized monkey. Pharmacologist 1971; 13:240.
9. Chang YH, et al. Anti-arthritic effect of bee venom. Agents Actions 1979;9:205-211.
10. Somerfield SD. Bee venom and arthritis: Magic, myth or medicine? N Z Med J 1986;99:281-283.
11. Caldwell JR. Venoms, copper, and zinc in the treatment of arthritis. Rheumatol Clin N Am 1999;25: 919-928.
12. Hollander J. Bee venom in the treatment of chronic arthritis. Am J Med Sci 1941;201:796-801.
13. Hauser RA, et al. Bee venom therapy for treating multiple sclerosis. Altern Complement Ther 2001;7:37-45.
14. The American Apitherapy Society. Available at: www.apitherapy.org/faq16.htm.
15. Simics M. BVT and pregnancy. J Am Apitherapy Soc 2000;6(4). Available at: www.apitherapy.org/bvtpregnancy.htm.
16. The biology of the honeybee, Apis mellifera. Available at: http://koning.ecsu.ctstateu.edu/Plants_Human/bees/bees.html.