Scientific Name(s): Apis mellifera
Common Name(s): Bee venom, Honeybee venom
Medically reviewed by Drugs.com. Last updated on Jun 8, 2020.
Bee venom is used to hyposensitize individuals highly sensitive to bee stings. There is some evidence that it might also help inhibit or suppress arthritis and multiple sclerosis.
There is no recent clinical evidence to guide dosage of bee venom.
Contraindications have not been identified.
Documented adverse reactions. Avoid use.
None well documented.
Various adverse reactions may occur to bee venom, the severity of which depends on the number of stings sustained.
A single bee sting can produce anaphylaxis in sensitive individuals. Regardless of history, monitor any patient with multiple stings.
Honeybee venom is obtained from A. mellifera, the common honeybee. Other venoms are derived from related members of the hymenoptera.
Anaphylaxis to insect stings is a relatively uncommon problem, affecting approximately 0.4% of the general United States population. It is the cause of an estimated 40 deaths per year in the United States.Reisman 1992
The allergic reactions are mediated by immunoglobulin E (IgE) antibodies directed at constituents of honeybee, yellow jacket, hornet, and wasp venoms. In order to minimize allergic reactions, hyposensitization immunotherapy techniques have been developed in which small doses of the venom are administered under controlled conditions over a period of months to years. Patients allergic to honeybee venom may be particularly sensitive to hymenoptera venoms in general and have been found to be at a higher risk of developing systemic adverse reactions to venom immunotherapy than patients who are sensitive to yellow jacket venom.Muller 1992
More recently, it has been suggested that honeybee venom may alleviate the symptoms and slow the progression of immune-modulated diseases such as arthritis and multiple sclerosis.
Bee venoms are complex mixtures of enzymes and polysaccharides. They are collected from the insects and diluted to standardized concentrations. Melittin, a phospholipase activating protein in bee venom, has been shown to induce neutrophil degranulationBomalaski 1989 and to increaseBomalaski 1989 or inhibitSomerfield 1986 the formation of superoxide. This variation in activity appears to depend upon the test method employed. Melittin induces neutrophil degranulation with subsequent superoxide formation in vitroBomalaski 1989; however, melittin binds to calmodulin, an effect associated with inhibition of superoxide production.Somerfield 1986
The polypeptide adolapin isolated from bee venom inhibits inflammation (carrageenan, prostaglandin, and adjuvant rat paw edema models) and appears to inhibit the prostaglandin synthase systems.Shkenderov 1982
Uses and Pharmacology
A Cochrane review of complementary therapies for acne identified 1 randomized trial (n=12) of low quality that showed a statistically significant benefit of purified bee venom for reducing the numbers of skin lesions in acne vulgaris compared to control (P=0.01). Cosmetics were applied with or without the intervention (0.06 mg/mL purified bee venom) for 2 weeks.Cao 2015
In a study using the mouse air pouch model, dilute bee venom (dBV) treatment produced a potent anti-inflammatory effect, as indicated by a marked reduction in leukocyte migration compared with that of saline pre-treatment.
Dilute bee venom's anti-inflammatory effect (dBVAI) is reversed by intrathecal pretreatment with atropine but not with hexamtehonium, indicating that dBV stimulated an increase in spinal acetylcholine, specifically activating spinal muscarinic receptors.
Intrathecal administration of a muscarinic type 2 (M2) receptor antagonist (methoctramine), but not M1or M3 receptor antagonists, abolished dBVAI, indicating that spinal M2 receptors are specifically involved in dBVAI.Yoon 2005
Systemic pretreatment with the beta-adrenergic receptor antagonist propranolol, but not the corticosteroid antagonist RU-486, inhibited dBVAI. This suggests that dBVAI is meditated by adrenal medullary catecholamines acting through beta-adrenoreceptors expressed by immune cells and that it is not dependent on corticosteroid release from the adrenal cortex.Kwon 2003 A study in mice demonstrated that bee venom-induced anti-inflammatory effect is dependent on activation of capsaicin-insensitive primary afferent fibers and the central noradrenergic system, including the locus coeruleus.
These findings demonstrate the complex nature of the neuroimmune interactions that underlie the anti-inflammatory effect produced by subcutaneous bee venom administration.
Transection of the sciatic nerve completely eliminated BVAI on zymosan-induced inflammation, indicating that BVAI is dependent on peripheral nerve integrity and is not a locally mediated anti-inflammatory effect.Kwon 2006
A study in Sprague-Dawley rats showed that sciatic nerve transaction, L4-L6 dorsal rhizotomy, and local treatment of the sciatic nerve with capsaicin produced a depression of subcutaneous injection of bee venom-induced inflammation, indicating that neurogenic components are involved in the bee venom-induced inflammatory response. Dorsal root reflex together with axon reflex conducted by capsaicin-sensitive primary afferents are the potential mechanisms underlying the generation of neurogenic inflammation.
It is further suggested that capsaicin-sensitive primary afferents may play differential roles in the development of dynamic and static mechanical allodynia in the bee venom test.Chen 2006
It has been speculated that honeybee venom may prevent the development of or improve the status of patients with rheumatoid arthritis. This conclusion is based largely on anecdotal observations of a general lack of arthritis among beekeepers stung routinely during their lifetimes. In one survey of a random sampling of the general population, 83% of respondents believed that bee venom could be an effective treatment for arthritis based on information they had read in the lay press.Price 1983
Honeybee venom administered to rats with adjuvant arthritis resulted in a suppression of the disease.Yiangou 1993 Melittin has blocked the production of superoxide and hydrogen peroxide in human neutrophils. Melittin and other agents that bind calmodulin have decreased superoxide production. An elevated superoxide level has been suggested as a possible cause of oxidative damage to synovial fluid and other joint membranes. Therefore, agents that decrease the production of the superoxide may prevent or halt the progression of inflammatory diseases such as arthritis. Also, honeybee venom has decreased the production of the inflammatory mediator interleukin-1 in rat splenocytes. Honeybee venom treatment of rats with adjuvant arthritis inhibits certain macrophage activities and, thus, indirectly inhibits the activation of T and B cells.Hadjipetrou-Kourounakis 1988
Treatment with bee venom resulted in a reduction of tissue swelling and osteophyte formation in a model of chronic arthritis, as well as reduction of edema formation in a model of acute arthritis.Reisman 1992
Bee venom inhibited lipopolysaccharide-induced prostaglandin E 2 and nitric oxide production in Raw 264.7 cells. The inhibitory actions of bee venom on the generation of inflammation mediators were also effective in synoviocytes from rheumatoid arthritis patients. The inhibitory effect of bee venom was consistent with that of indomethacin.Park 2004
The Eczema Area and Severity Index (EASI) score was significantly improved in patients with atopic dermatitis who were randomized to receive bee venom emollient in a 4-week, double-blind, controlled trial (n=114). The improvement in EASI scores was also significantly larger than those in the control group at both 2 and 4 weeks (P=0.023 and P=0.022, respectively). At week 3, the visual analog score of itching was also significantly reduced in the experimental group (P=0.03). Adverse drug reactions (ie, irritation, pruritus, erythema, urticaria, disease exacerbation) were experienced by 35.2% of participants in the bee venom group compared to 23.1% of controls.You 2016
Hypersensitivity to honeybee venom is mediated by a number of antibodies and immunomodulators, the most important of which appears to be IgE. Venom immunotherapy (VIT) reduces the likelihood of systemic response in patients with systemic allergic reactions to insect venom. Criteria to precisely identify the point in time when protection becomes persistent are unknown. In addition, despite the remote possibility of severe reaction, the supervised sting challenge test is the only current method for evaluating the efficacy of VIT. The identification of markers that can be used to predict protection is needed.Konno 2005
The infusion of beekeepers' plasma has been shown to protect patients against systemic reactions that can occur during active immunotherapy.Boutin 1994 Following infusion of this plasma, a decrease in the sensitivity to honeybee venom has been noted; in one study, this was accompanied by increases in the levels of anti-idiotypic antibodies and decreases in specific antibodies to honeybee venom (immunoglobulin G and E). The study was conducted over a 76-week period of immunotherapy with the venom. These findings suggest that several mechanisms play an interrelated role in the development of immunity to honeybee venom. An upregulation of osteopontin expression associated with successful VIT has been reported, suggesting a potential role of osteopontin as a biomarker in VIT. In addition to its known regulatory role in bone metabolism, osteopontin has been postulated to be a TH1 cytokine and is involved in TH1-associated immune responses.Konno 2005
Multiple sclerosis (MS)
Uses for bee venom, although poorly substantiated, include the treatment of diseases of the locomotor systemMund-Hoym 1982 particularly MS. Despite widespread anecdotal reports, there is no scientific consensus as to the safety and effectiveness of bee venom in the management of this disorder.Wesselius 2005
In a study of 26 patients with relapsing-remitting or relapsing secondary progressive MS, bee sting therapy had no effect on disease activity as measured using gadolinium-enhanced magnetic resonance imaging of the brain.Wesselius 2005
There is no recent clinical evidence to guide dosage of bee venom.
Pregnancy / Lactation
Documented adverse reactions. Avoid use.
None well documented.
Immediate effects after multiple stings include localized pain, swelling, and erythema at individual sting sites. Stings to the eyes can result in corneal edema and ulceration. When bees are swallowed, life-threatening pharyngeal edema and respiratory obstruction may occur. Early systemic symptoms after large-volume envenomation include fatigue, dizziness, nausea, vomiting, and diarrhea. Within 24 hours, hemolysis, hemoglobinuria, rhabdomyolysis, and hepatic transaminase enzyme elevations may develop. Subendocardial damage and cardiac enzyme elevations seen in human case reports and animal studies may result from direct venom effects in the absence of anaphylaxis and hypotension. Renal insufficiency and electrolyte abnormalities such as hyperkalemia may occur secondary to rhabdomyolysis, hemolysis, and acute tubular necrosis. Nonanaphylactic responses to multiple stings often will be apparent within the first several hours; however, severe systemic signs and symptoms have been delayed for up to 24 hours or more.Betten 2006
Bee stings cause human reactions in 2 distinct patterns. One or a few stings may induce allergic responses that are sometimes severe or fatal. On the other hand, massive attacks with hundreds to thousands of stings can cause severe systemic injury affecting many different organs, resulting in high mortality. Melittin has been shown to be the main lethal component in bee venom.
Signs and symptoms of multiple stings include urticaria (hives), nausea, vomiting, diarrhea, hypotension, confusion, seizures, and renal failure. Treatment is supportive, with attention to blood pressure, renal function, and maintenance of an open airway. Stingers should be removed with gentle scraping to prevent further venom injection.Tunget 1993 Mass inoculation of bee venom may induce acute renal failure (ARF), adult respiratory distress syndrome, liver injury, cardiac damage, pancreatitis, skin necrosis, shock hypertension, bleeding, thrombocytopenia, hemolysis, and rhabdomyolysis. Bee venom-induced ARF after multiple stinging has been sporadically reported in Europe, Africa, and Asia.Grisotto 2006
Animal studies have shown a decrease in glomerular filtration rate and urinary volume after bee venom infusion. In the same way, venom caused a sharp and immediate decrease in renal blood flow. Experimental injection of bee venom caused a reaction similar to that observed in patients with bee venom-induced ARF.Grisotto 2006
Because cardiac levels of noradrenaline have increased dramatically in animals following bee venom injection, it is suggested that all patients, regardless of sensitivity history, have cardiac monitoring if they are victims of multiple bee stings.Ferreira 1994 Rare cases of anuria and rhabdomyolysis/rhabdomyonecrosis have been reported.Azevedo-Marques 1992, Beccari 1992
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