Safety of essential bee venom pharmacopuncture as assessed in a randomized controlled double-blind trial

J Ethnopharmacol. 2016 Dec 24;194:774-780. doi: 10.1016/j.jep.2016.11.012. Epub 2016 Nov 10.


Ethnopharmacological relevance: While bee venom (BV) pharmacopuncture use is common in Asia, frequent occurrence of allergic reactions during the treatment process is burdensome for both practitioner and patient.

Aim of the study: This study compared efficacy and safety in isolated and purified essential BV (eBV) pharmacopuncture filtered for phospholipase A2 (PLA2) and histamine sections, and original BV to the aim of promoting safe BV pharmacopuncture use.

Materials and methods: In in vitro, we examined the effect of BV and eBV on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and clinically, 20 healthy adults aged 20-40 years were randomly allocated and administered eBV 0.2mL and BV pharmacopuncture 0.2mL on left and right forearm, respectively, and physician, participant, and outcome assessor were blinded to treatment allocation. Local pain, swelling, itching, redness, wheals, and adverse reactions were recorded by timepoint.

Results: eBV and BV exhibited similar inhibitory effects on NO production. Also, in comparison between eBV and BV pharmacopuncture administration areas on each forearm, eBV displayed significantly lower local pain at 24h post-administration (P=0.0062), and less swelling at 30min (P=0.0198), 2 (P=0.0028), 24 (P=0.0068), and 48h post-administration (P=0.0253). eBV also showed significantly less itching at 24 (P=0.0119), 48 (P=0.0082), and 96h (P=0.0141), while redness was significantly less at 30min (P=0.0090), 6 (P=0.0005), and 24h (P<0.0001). Time-by-treatment interactions were statistically significant for itching and redness (P<0.001, and P<0.001, respectively), and all original BV pharmacopuncture administered regions showed a tendency toward more severe itching and redness in later measurements.

Conclusions: eBV and BV displayed comparable anti-inflammatory effects, and eBV pharmacopuncture presented less local allergic reactions.

Keywords: Anti-inflammatory agents; Bee venoms; Drug hypersensitivity; Drug-related side effects and adverse reactions; Safety; Toxicity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acupuncture / methods
  • Adult
  • Animals
  • Bee Venoms / administration & dosage*
  • Bee Venoms / immunology*
  • Cell Line
  • Double-Blind Method
  • Female
  • Forearm
  • Humans
  • Hypersensitivity / diet therapy*
  • Hypersensitivity / immunology
  • Insect Bites and Stings / drug therapy*
  • Insect Bites and Stings / immunology*
  • Lipopolysaccharides / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Nitric Oxide / immunology
  • Phospholipases A2 / immunology


  • Bee Venoms
  • Lipopolysaccharides
  • Nitric Oxide
  • Phospholipases A2