Accepted Manuscript

To bee or not to bee: The potential efficacy and safety of bee venom acupuncture in
humans

E. Paul Cherniack, Sergey Govorushko

PII: S0041-0101(18)30393-3
DOI: 10.1016/j.toxicon.2018.09.013
Reference: TOXCON 5990

To appear in: Toxicon

Received Date: 20 June 2018

Revised Date: 4 September 2018
Accepted Date: 26 September 2018

Please cite this article as: Cherniack, E.P., Govorushko, S., To bee or not to bee: The potential
efficacy and safety of bee venom acupuncture in humans, Toxicon (2018), doi: https://doi.org/10.1016/
j.toxicon.2018.09.013.

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 ACCEPTED MANUSCRIPT

To bee or not to bee: the potential efficacy and safety of bee venom acupuncture in humans

E Paul Cherniack1,2 and Sergey Govorushko3

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1
Division of Geriatrics and Palliative Medicine, University of Miami Miller School of Medicine

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Miami VA Medical Center, Miami, USA

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2
To whom correspondence should be addressed:

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Room NH445,

Miami VA Med Ctr

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1201 NW 16 St.

Miami, FL 33125, USA

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Tel. 3055757000 ext 2273

[email protected]
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Pacific Geographic Institute, Russian Academy of Sciences, Vladivostok, Russia
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Far Eastern Federal University, Vladivostok, Russia

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Keywords: efficacy, safety, bee venom acupuncture

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Abstract

Bee venom acupuncture is a form of acupuncture in which bee venom is applied to the tips of
acupuncture needles, stingers are extracted from bees, or bees are held with an instrument
exposing the stinger, and applied to acupoints on the skin. Bee venom is a complex substance

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consisting of multiple anti-inflammatory compounds such as melittin, adolapin, apamin. Other
substances such as phospholipase A2 can be anti-inflammatory in low concentrations and pro-
inflammatory in others. However, bee venom also contains proinflammatory substances, melittin,

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mast cell degranulation peptide 401, and histamine.
Nevertheless, in small studies, bee venom acupuncture has been used in man to successfully

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treat a number of musculoskeletal diseases such as lumbar disc disease, osteoarthritis of the knee,
rheumatoid arthritis, adhesive capsulitis, and lateral epicondylitis. Bee venom acupuncture can also

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alleviate neurological conditions, including peripheral neuropathies, stroke and Parkinson’s Disease.
The treatment has even been piloted in one series to alleviate depression.
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An important concern is the safety of bee venom. Bee venom can cause anaphylaxis, and
several deaths have been reported in patients who successfully received the therapy prior to the
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adverse event. While the incidence of adverse events is unknown, the number of published reports of
toxicity is small. Refining bee venom to remove harmful substances may potentially limit its toxicity.
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New uses for bee venom acupuncture may also be considered.

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1. Introduction
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Bee venom acupuncture is form of acupuncture in which bee venom is applied to the tips of
acupuncture needles, stingers are extracted from bees, or bees are held with an instrument, such as a
forceps, squeezed to cause the stinger to emerge from the lower abdomen, and then either the
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needles or stinger is applied acupoints on the skin.1 Bee venom itself is a complex compound
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consisting of multiple components, some of which are surprisingly anti-inflammatory and anti-
nociceptive despite the well-known pain of a bee sting.1, 2 While the venom itself consists of more
than fifty components, the most common constituent, melittin, is anti-inflammatory, as are other
components, apamin, adolapin, and (low concentrations of) phospholipase A2.1-3 A recent review,
which summarized research on animal models and potential applications, outlined the beneficial
physiologic mechanisms of bee venom as suppressing inflammation, and altering cellular gene
expression, apoptosis, and fibrosis.4 However, bee venom also consists of many proinflammatory

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compounds, such as higher doses of phospholipase A2, mast cell degranulation peptide 401,
hemolytic compounds, including melittin, and allergenic substances, such as several protease
inhibitors and peptides.1 Thus while the healing potential is present, the potential for side effect and
allergic reaction certainly exists.1The risk of harm was underscored by a recent report of a Spanish
women who died of an anaphylactic response to live bee acupuncture.5

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The purpose of this manuscript is to outline the published medical literature regarding the
potential of bee venom acupuncture to treat disease in man, and the documented harms (with

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reference to animal studies when appropriate). Potential references were identified from the
PubMed reference database using search terms such as “bee venom,” “acupuncture,” and

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“apitherapy”.
Some investigations have attempted to establish the mechanism by which bee venom
acupuncture may act. In one study, researchers injected various substances into a paw acupoint

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of rats followed by a proinflammatory substance with or without bee venom.6 Preadministration of
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the acupoint with capsaicin attenuated the activity of bee venom in reduction of inflammation,
suggesting that bee venom substances act through capsaicin-responsive pain pathways.
Other studies imply the involvement of other neural pathways, such as spinal alpha pathways.
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After causing an induced injury to a rat’s paw, researchers blocked bee venom relief of thermally-
created pain with an alpha-2-adrenergic antagonist, idazoxan, suggesting a role for spinal alpha-2-
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adrenergic receptors in pain perception.7 In another rodent pain model trial, clonidine, an alpha-2-
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receptor agonist, enhanced the effect of bee venom apipuncture in reducing experimentally induced
rat paw pain.8 When rats received idazoxan, the synergistic effect of clonidine and bee venom
attenuated.
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Idazoxan suppressed bee venom acupuncture relief of peripheral neuropathy in rats induced
by a chemotherapy drug, paclitaxel, but the alpha-1-receptor antagonist prazosin had no effect.9 An
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alpha-2-receptor-antagonist, yohimbine, blocked the pain-relief induced by bee venom in neuropathic

murine paw pain induced by another chemotherapeutic agent, oxaliplatin.10 Two other adrenergic
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antagonists, phenotolamine and idazoxan, inhibited the pain alleviating effect of acupuncture in an
oxaliplatin induced rat pain model.11
Additional neural pathways may mediate the effect of bee venom. Methylsergide, which
antagonizes serotonin receptors, blocked the effect of bee venom acupuncture in a rat paw pain
model, implying serotoninergic mediation of the effect of bee venom.12 CT imaging of rodent brains
during bee venom acupuncture also revealed activation of catecholaminergic brain pathways as

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well.13 Furthermore, one study implied a role for nicotinamide receptors. In a rat pain model in which
neuropathic injury had been induced by the chemotherapy drug oxaliplatin, the serotonin-depleting
substance DL-p-chlorophenylalanine prevented pain relieve by bee venom acupuncture.14 An
additional investigation of oxaliplatin-induced rat pain, nicotinic receptor antagonists
methyllycaconitine and erythroidine hydrobromide attenuated the effect of bee venom acupuncture

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on an injured rat’s paw exposed to cold.15 In one study, mice that had experimentally induced
neuropathy caused by the chemotherapy agent oxaliplatin.16 When the pain was exacerbated by cold

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or mechanical stress to the paw, injections of 0.25-1mg/kg morphine relieved the pain, but the relief
was increased by acupuncture combined with 0.25-2.5mg kg bee venom, and the opioid antagonist

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naloxone decreased pain relief.
The neurologic mediation of analgesia by bee venom acupuncture may be specific to the type
of pain induced. In a rat model in which investigators induced osteoarthritis by administration of

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collagenase to the knee, bee venom injected into acupoints achieved greater pain relief into other
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non-acupoint sites. Opioid and adrenergic receptor agonists did not improve analgesia, but δ-opioid
antagonist and α2 adrenergic receptor antagonists attenuated analgesia.17
Another mechanism by which bee venom acupuncture relief pain is through its effect on
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cytokine concentrations. Rats subjected to experimental spinal cord injury then subjected to bee
venom acupuncture at acupoints developed a decrease in serum concentrations of the
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proinflammatory cytokines IL-6 and IL-1β, while increasing concentrations of anti-inflammatory

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cytokines IL-4, and IL-10.18 Rats also performed better on a test of locomotor function after bee
venom acupuncture.
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2. Musculoskeletal pain
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On important application for bee venom acupuncture may be to treat musculoskeletal pain. In
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a relevant animal experimental pain, models, investigators who created arthritic pain in rats through
the injection of collagen derived from cows, mitigated the rodents’ discomfort using apipuncture. The
α2 receptor antagonist yohimbine quelled the response to acupuncture. Furthermore, another animal
pain model investigation noted that bee venom inhibited pain in true acupoints better than non-
acupoints.19
A metaanalysis one decade ago of bee venom acupuncture use for musculoskeletal pain found
no more than four appropriate studies in each form of, but noted that bee venom acupuncture alone

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or in combination with traditional acupuncture was superior to traditional acupuncture alone at pain
relief, and in particular, for herniation of lumbar discs.20 In a recent human trial, fifty-four people,
blinded to group assignment mean age 50, experienced treatment with bee venom or sham
acupuncture. Participants obtained six treatments over three weeks from an acupuncturist also
blinded to substance placed on the needle tips. Those subjects receiving bee venom experienced a

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26% reduction on pain on a visual analog scale after three weeks (p<.05).21 Forty dogs, evaluated by
veterinarians to have thoracolumbar disc diseases and needled twice weekly with 20µ bee venom in

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addition to usual treatment (prednisone and the non-steroidal anti-inflammatory agent carprofen) or
usual treatment alone for 1.5 months.22 Bee venom acupuncture significantly lowered veterinarians

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ratings of animal pain on a six point scale in animals with moderate (mean score 3.43 to 0.98,
p=0.001) or severe pain (5 to 3.40, p=0.002) where as usual treatment did not significantly alleviate
pain.

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Researchers also utilized bee venom acupuncture to alleviate osteoarthritis pain in the knee.
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Sixty-nine Korean subjects received either bee venom (0.05 ml of a 1: 10,000 dilution) injections to a
joint intra-joint acupoint injection, or both biweekly for nine injections.23 Subjects in all three groups
obtained an approximately thirty percent improvement, in pain and function (68 point WOMAC
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[Western Ontario and McMaster University Osteoarthritis Index] score, p=0.0001).

Other studies, not randomized controlled trials, imply a role for bee venom acupuncture in the
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treatment of other musculoskeletal disorders. In a retrospective study of the effects of bee venom
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acupuncture on adhesive capsulitis, a telephone survey of subjects, who received either both bee
venom acupuncture and physical therapy, bee venom acupuncture, or physical therapy with a saline
injection, for adhesive capsulitis of the shoulder. Individuals receiving both treatments reported
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significantly better mean pain and function on the 130-point SPADI pain and disability index (13.57 for
both treatments vs 4.35 for physical therapy alone; p=0.043).24 One case series also suggested that
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bee venom acupuncture may alleviate lateral epicondylitis. Among twenty Korean patients who
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experienced a combination of acupuncture with heated needles (hwachim) and bee venom
acupuncture for as many treatments as patients required based on their condition, pain on a visual
analog scale decreased from a mean 10/10 to 4/10 (p=0.000).25

3. Neuropathic pain

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Several studies suggest bee venom acupuncture might be used to treat neuropathic pain. In
one animal studied, previously cited, bee venom acupuncture treated cold-induced neuropathic pain.7
In addition, rats with experimental spinal cord injury obtained significantly greater pain relief when
bee venom was injected into a paw acupoint.26 Two case series documented the effect of bee venom
acupuncture on neuropathy resulting from chemotherapy. In one, eleven participants obtained six

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acupuncture sessions in twenty-one days. Mean pain scores on a one to ten visual analogue scale
decreased from a mean of six to 2.63 (p<0.05).27 In a second case series, four people who received

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three treatments over seven days experienced a decline on the ten-point visual analogue scale from a
mean of 8.75 to 2.75. 28

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4. Neuropsychiatric disorders

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Another role for bee venom acupuncture has been to alleviate neuropsychiatric disorders. Bee
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venom acupuncture improved hematologic parameters in a rodent model of amyotrophic lateral
sclerosis. In one study, bee venom acupuncture at a tibial acupoint (0.1µg/g body weight) every
second day for fourteen days prevented reductions in neuron number in brain section slices.29 In
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another, anti-inflammatory enzyme cyclooxygenase 2 and Iba-1 concentrations increased in

hepatocytes, splenocytes and nephrons after treatment at a tibial acupoint with bee venom
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acupuncture.30 The enzyme concentrations did not increase in mice injected intraperitoneally with
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saline alone.30
An additional trial of bee venom acupuncture in mice suggested it might be useful to treat
methamphetamine dependence.31 Mice given methamphetamine received bee venom at
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concentrations from 0.01mg/ml exhibited a lower body temperature and greater locomotor activity
than those that received saline acupuncture alone.
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Human trials of bee venom acupuncture show bee venom improved human subjects’
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assessments of function in Parkinson’s disease. One study used bee venom acupuncture as an
adjunctive therapy for Parkinson’s in a double-blinded controlled trial. Seventy-three individuals
already on conventional medications for Parkinson’s obtained bee venom acupuncture sessions with
1mg bee venom in 20ml saline every other day for three months or placebo acupuncture with saline.
Those participants that experienced bee venom acupuncture received a small (1.16 points/101) but
statistically significant (p=0.001) improvement in Parkinson’s disease rating scale scores (UPDRS II +
III) for activities of daily living and gait.32 Another unblinded trial provided actively treated subjects

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with Parkinson’s disease bee venom acupuncture with 0.005% bee venom in saline every other day
for three months. Participants improved their Parkinson’s disease rating scores by a mean 27 points
(p<0.05).33
An additional trial suggested a benefit for stroke patients. Sixteen subjects obtained
acupuncture injections of 0.005% bee venom in saline or saline alone into acupoints biweekly for

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twenty-one days to relieve pain.34 The mean visual analogue pain score decreased in the bee venom
treated group from a mean of 72 out of 100 to 35.5 (p<0.007) while no significant change occurred in

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the control group.
One use of bee venom acupuncture in neuropsychiatric disorders has been to treat

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depression. In one case series, thirty-seven depressed subjects, rated by the Beck’s Depression Scale,
“twenty-one rated as moderately depressed” (19-29 points/63) and five as “severely depressed” (>30
points).35 Subjects received live beestings to multiple acupoints, twice a week. At the end of one year,
none were depressed.

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Finally, in a case report, bee venom acupuncture treated a neurofibroma. A clinician injected
sweet bee venom (venom processed by gel filtration chromatography and propionic acid/urea
polyacrylamide gel electrophoresis to separate away potential allergens) through acupuncture 20ml
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every two weeks (concentration not stated) for four years. 36During that interval, the authors claim
that the neurofibromas on her right pelvis stopped growing, and the range of motion in her right hip
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increased.
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5. Autoimmune disorders
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Bee venom acupuncture has also been used to treat autoimmune disorders. In a mouse model
of atopic dermatitis, induced by trimellitic anhydride, bee venom acupuncture created favorable
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immunological responses.37 After trimellitic anhydride had been injected into the skin, bee venom
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injections with an insulin needle of 0.3 mg/kg into an acupoint resulting in lower concentrations of the
proinflammatory cytokines IL-4 and IgE, than at a non-acupoint. In another experiment, using a rodent
model of autoimmune encephalitis, researchers injected 0.25-0.8mg/kg bee venom or saline into an
acupoint or control acupoints before exposure to the agent used to induce autoimmune toxicity.38
Brain sections of animals pretreated with bee venom exhibited reduced neuronal loss and
inflammatory cell infiltration.

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In man, investigators have used bee venom acupuncture to treat rheumatoid arthritis. A
systematic review of the effects of bee venom acupuncture produced just one study meeting search
criteria.39 In that investigation, subjects with rheumatoid arthritis obtaining twice monthly
acupuncture for eight weeks experienced a significantly mean lesser pain on a visual analog scale
(16.9/100), and fewer swollen and tender joints. 40

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6. Safety

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An important concern with bee venom acupuncture has been its safety. To date, no

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systematic analyses have been conducted on safety in clinical practice, although there have been a
number of reports of adverse reactions to bee venom acupuncture. In the most recent published case
of a death, a woman developed anaphylaxis after safely experiencing monthly bee venom

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acupuncture treatments for two years. The victim had no history of any medical disorders, reaction to
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bee stings, or allergies. Desiring relief from “muscle contractures” and “stress”, she developed acute
shock suddenly during a treatment and died.
One previous case of a fatality involved a sixty-five year-old woman, who experienced
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disseminated intravascular coagulation during a second acupuncture session following an initial

treatment without incident.41 She suddenly developed symptoms, one half-hour after the treatment,
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and died a day later of hypovolemic shock.

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Fortunately, these are the only two reported cases of deaths due to bee venom acupuncture
in the published scientific literature. Descriptions of single persons after uneventfully previously
treatment developing acute anaphylactic shock responding to treatment,42 Guillaume- Barre
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syndrome (which led to two months stay in an intensive care unit, but the patient was ultimately
released, months later without deficit),43 an irreversible ulnar nerve injury,44 thrombocytopenia with
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ecchymoses,45 an “acute lung injury,”46 and a M chelonae infection47 have been reported. Other
individual adverse events noted include arrhythmia,48 stroke,49, 50 nephrotic syndrome,51 pulmonary
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edema,52 liver failure,53 hepatitis,54 and uterine contractions.55

In addition, individual case reports cite dermatologic complications. A collective summary of

dermatological case reports of adverse events with acupuncture noted that bee venom acupuncture
was the frequent form of acupuncture in such complications (13 of 25 cases).56 These included local

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anaphylactic skin reactions, an abscess, pyoderma, lipoatrophy, and foreign body granuloma.56 Other
reports of skin reactions include a case of chronic folliculitis57 and giant dermatofibroma.58
To date, although no systematic study has evaluated the safety of bee venom acupuncture in
clinical practice, or even recorded the prevalence or incidence of adverse events, one systematic
metaanalysis recorded adverse events in published trials and case reports. In that investigation, the

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incidence of adverse events was 28.87%. or a relative risk of 3.61 (95% CI 2.10-6.20) compared to
parenteral saline administration.59 Furthermore, research has not identified the possible risk factors

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for adverse sequelae to bee venom acupuncture, such as dose, frequency, site, or form of
administration (e.g., live bee vs acupuncture needling). Thus, despite the two deaths, and the

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metaanalysis suggesting increased risk, no firm conclusions can be drawn about safety from the
published scientific literature in the absence of large-scale investigations of safety in clinical use. The
suggestion of heightened adverse effects experimentally and anecdotally should prompt such
investigations.

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7. Future directions and conclusions
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Despite a number of investigations and a couple of systematic reviews, (see Table) it is

difficult, as with safety, to ascertain with certainty the efficacy of bee venom acupuncture in treating
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health disorders. Thus far, bee venom acupuncture demonstrates greatest promise in the treatment
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of musculoskeletal disorders and Parkinson’s disease, but rigorously designed scientific trials remain
to be performed. In addition, in most cases, the optimal dose, frequency duration, and form of bee
venom still need to be determined for optimum effect and safety.
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Table Summary of cited studies

Topic/study Species Size (N) Summary

Lumbar disc disease
Seo et al21 Human 54 Single-blind, BVA=26% reduction
in pain on visual analog scale

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over 3 mos (p<0.05)
Tsai et al22 Dog 40 Reduction of pain assessment
(32% in severe pain, 72% in

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moderate pain)(p=0.001)
Knee osteoarthritis
Lee et al23 Human 69 Improvement in WOMAC

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score(p=0.0001)
Rheumatoid
arthritis
Lee et al40

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Human Improved tender & swollen joint
count (p<0.0001. p=0.05)
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Adhesive capsullitis N
Park et al24 Human 25 Reduction in pain and disability
index w/ PT (13.57) vx PT alone ewer
(4.35)(p=0.043)
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forms of
Lateral epicondylitis
Jung et al25 Human 20 Reduction in pain on visual bee
analog scale from 10 to 4
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(p=0.000) venom
Neuropathic pain
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Yoon et al27 Human 11 Reduction in pain on visual delivere

analog scale from 6 to 2.63
(p<0.05) d with
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Park et al Human 4 Reduction in pain on visual
analog scale from 8.75 to 2.75 the
Parkinson’s Disease
Cho et al32 Human 73 Improvement in UPDRS scale acupunc
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score (p=0.001)
ture
Doo et al33 Human 11 Improvement in UPDRS score by
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27 points (p<0.05)
needle
Stroke
Cho et al34 Human Pain by visual analogue score might
from 72 to 35.5 (p<0.007)
Depression improve
El Wahab et al35 Human 26 Full recovery from depression
safety.

In one instance, researchers modified bee venom by extracting out what they deemed the most likely

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allergenic substances, histamine and enzymes, creating what they termed “essential bee venom.”60

They treated 20 normal adults with either essential or natural venom by acupuncture and observed

that, while subjects generally did not experience less pain, those injected with essential bee venom

noted significantly less swelling and itching after one to two days (80% after one day).60 Essential bee

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venom induced an 83% smaller erythematous wheal at the injection site after one day. Furthermore,

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delivery of individual components of bee venom, such as melittin, may be more effective and safer

than whole bee venom.

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In addition, there may be additional uses for bee venom acupuncture. One of these might be

gouty arthritis. A preliminary study of rats indicated that intradermal administration of bee venom as

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a gel transdermally with a microneedle resulted in decreased inflammatory response as measured by
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nitric oxide release.61

Other possible uses of bee venom might be extended to bee venom acupuncture. Bee venom,
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and its components, particularly melittin,62 have been tested in vitro for antineoplastic potential in

leukemia,63-65 lung,65, 66 ovarian,65, 67 liver,65, 68 prostate,65, 69 breast,65, 70 and bladder cancer,65, 71 and in
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animal models at treatment for bacterial infections,72 such as prostatitis,73 and chronic kidney
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disease.74 Future in vitro and in vivo testing should further establish more definitively the role of bee
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venom acupuncture in the treatment of disease.

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8. References
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1. Bogdanov S. Bee venom: composition, health, medicine: a review. www.bee-hexagon.net, 2017.

2. Cherniack EP. Bugs as drugs, Part 1: Insects: the "new" alternative medicine for the 21st century?

Altern Med Rev. 2010;15: 124-135.

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3. O'Connor R, Peck L. Bee sting: the chemistry of an insect venom. J Chem Educ. 1980;57: 206-209.

4. Zhang S, Liu Y, Ye Y, et al. Bee venom therapy: Potential mechanisms and therapeutic applications.

Toxicon. 2018;148: 64-73.

5. Vazquez-Revuelta P, Madrigal-Burgaleta R. Death due to Live Bee Acupuncture Apitherapy. Journal

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of Investigational Allergology and Clinical Immunology. 2018;28: 45-46.

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6. Chen HS, Qu F, He X, Liao D, Kang SM, Lu SJ. The anti-nociceptive effect and the possible mechanism

of acupoint stimulation caused by chemical irritants in the bee venom pain model. Brain Res.

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2010;1355: 61-69.

7. Roh DH, Kwon YB, Kim HW, et al. Acupoint stimulation with diluted bee venom (apipuncture)

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alleviates thermal hyperalgesia in a rodent neuropathic pain model: involvement of spinal alpha 2-
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adrenoceptors. J Pain. 2004;5: 297-303.

8. Yoon SY, Roh DH, Kwon YB, et al. Acupoint stimulation with diluted bee venom (apipuncture)
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potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a
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neuropathic pain model. J Pain. 2009;10: 253-263.

9. Choi J, Jeon C, Lee JH, et al. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced
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Neuropathic Pain in Rats: Mediation by Spinal alpha(2)-Adrenergic Receptor. Toxins (Basel). 2017;9.
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10. Yeo JH, Yoon SY, Kwon SK, et al. Repetitive Acupuncture Point Treatment with Diluted Bee Venom

Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced
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Neuropathic Mice. J Pain. 2016;17: 298-309.

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11. Lim BS, Moon HJ, Li DX, et al. Effect of bee venom acupuncture on oxaliplatin-induced cold

allodynia in rats. Evid Based Complement Alternat Med. 2013;2013: 369324.

12. Kim HW, Kwon YB, Han HJ, Yang IS, Beitz AJ, Lee JH. Antinociceptive mechanisms associated with

diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending

adrenergic and serotonergic pathways. Pharmacol Res. 2005;51: 183-188.

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13. Kwon YB, Han HJ, Beitz AJ, Lee JH. Bee venom acupoint stimulation increases Fos expression in

catecholaminergic neurons in the rat brain. Molecules and Cells. 2004;17: 329-333.

14. Lee JH, Li DX, Yoon H, et al. Serotonergic mechanism of the relieving effect of bee venom

acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats. BMC Complement Altern Med.

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2014;14: 471.

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15. Yoon H, Kim MJ, Yoon I, Li DX, Bae H, Kim SK. Nicotinic Acetylcholine Receptors Mediate the

Suppressive Effect of an Injection of Diluted Bee Venom into the GV3 Acupoint on Oxaliplatin-Induced

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Neuropathic Cold Allodynia in Rats. Biol Pharm Bull. 2015;38: 710-714.

16. Kim W, Kim MJ, Go D, Min BI, Na HS, Kim SK. Combined Effects of Bee Venom Acupuncture and

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Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. Toxins (Basel). 2016;8: 33.
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17. Huh JE, Seo BK, Lee JW, et al. Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by

delta-Opioid and alpha2-Adrenergic Receptors in Osteoarthritic Rats. Altern Ther Health Med. 2017.
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18. Nascimento de Souza R, Silva FK, Alves de Medeiros M. Bee Venom Acupuncture Reduces
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Interleukin-6, Increases Interleukin-10, and Induces Locomotor Recovery in a Model of Spinal Cord

Compression. J Acupunct Meridian Stud. 2017;10: 204-210.

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19. Kwon YB, Lee JD, Lee HJ, et al. Bee venom injection into an acupuncture point reduces arthritis
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associated edema and nociceptive responses. Pain. 2001;90: 271-280.

20. Lee MS, Pittler MH, Shin BC, Kong JC, Ernst E. Bee venom acupuncture for musculoskeletal pain: a
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review. J Pain. 2008;9: 289-297.

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21. Seo BK, Han K, Kwon O, Jo DJ, Lee JH. Efficacy of Bee Venom Acupuncture for Chronic Low Back

Pain: A Randomized, Double-Blinded, Sham-Controlled Trial. Toxins (Basel). 2017;9.

22. Tsai LC, Lin YW, Hsieh CL. Effects of Bee Venom Injections at Acupoints on Neurologic Dysfunction

Induced by Thoracolumbar Intervertebral Disc Disorders in Canines: A Randomized, Controlled

Prospective Study. Biomed Res Int. 2015;2015: 363801.

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23. Lee SH, Kwon GS, Kang MS, Yoon HM, Kim CH. Comparative study on the effects of bee venom

pharmacopuncture according to the treatment method for knee osteoarthritis. J Pharmacopuncture.

2012;15: 7-14.

24. Park YC, Koh PS, Seo BK, et al. Long-term effectiveness of bee venom acupuncture and

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physiotherapy in the treatment of adhesive capsulitis: a one-year follow-up analysis of a previous

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randomized controlled trial. J Altern Complement Med. 2014;20: 919-924.

25. Jung S, Lee C, Yeo I, et al. A case study of 20 patients with lateral epicondylitis of the elbow by

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using hwachim (burning acupuncture therapy) and sweet bee venom pharmacopuncture. J

Pharmacopuncture. 2014;17: 22-26.

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26. Kang SY, Roh DH, Choi JW, Ryu Y, Lee JH. Repetitive Treatment with Diluted Bee Venom
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Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury

Model. Toxins (Basel). 2015;7: 2571-2585.

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27. Yoon J, Jeon JH, Lee YW, et al. Sweet bee venom pharmacopuncture for chemotherapy-induced
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peripheral neuropathy. J Acupunct Meridian Stud. 2012;5: 156-165.

28. Park JW, Jeon JH, Yoon J, et al. Effects of sweet bee venom pharmacopuncture treatment for
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