Production, composition and toxicology studies of Enzogenol® Pinus radiata bark extract

Food Chem Toxicol. 2012 Dec;50(12):4316-24. doi: 10.1016/j.fct.2012.08.051. Epub 2012 Sep 12.


Enzogenol® pine bark extract is a dietary supplement and food ingredient produced by water extraction of Pinus radiata. We present production method, composition, and safety data from rat and dog toxicological and human clinical studies. The dry powder contains proanthocyanidins (>80%), taxifolin (1-2%), other flavonoids and phenolic acids (up to 8%), and carbohydrates (5-10%). Reverse mutation assays showed lack of mutagenic activity. Single and 14-day repeat dosing in rats and dogs had no influence on body weight, feed consumption, blood chemistry, and haematology at any dose level. There were no treatment related findings on gross and detailed necroscopy, organ weights, organ weight ratios and histology. The only adverse events were emesis and diarrhoea in dogs occurring mainly in un-fed condition and at the highest dose level in a total of 18% of applications. The MTD and NOAEL in the present rat and dog studies were 2500 and 750 mg/kg/day, respectively. Consumption of 480 mg/day for 6 months and 960 mg/day for 5 weeks in two human studies showed Enzogenol® had no adverse influence on liver and kidney function, haematology, and did not cause any adverse events. Our studies indicate lack of toxicity of Enzogenol® and support safe use as a food ingredient.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Animals
  • Dietary Supplements / toxicity*
  • Dogs
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Flavonoids / toxicity*
  • Humans
  • Hydroxybenzoates / toxicity
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Mutagens / toxicity
  • No-Observed-Adverse-Effect Level
  • Organ Size / drug effects
  • Pinus / chemistry*
  • Plant Bark / chemistry*
  • Plant Extracts / toxicity*
  • Proanthocyanidins / toxicity
  • Quercetin / analogs & derivatives*
  • Quercetin / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Toxicity Tests / methods


  • Flavonoids
  • Hydroxybenzoates
  • Mutagens
  • Plant Extracts
  • Proanthocyanidins
  • enzogenol
  • Quercetin
  • taxifolin
  • phenolic acid