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

• Published in: Food and chemical toxicology 2012-12, Vol.50 (12), p.4316-4324
• Main Authors: Frevel, Mathias A.E., Pipingas, Andrew, Grigsby, Warren J., Frampton, Chris M., Gilchrist, Nigel L.
• Format: Article
• Language: English
• Subjects: Aged; Animals; bark; Biological and medical sciences; blood chemistry; carbohydrates; clinical trials; diarrhea; dietary supplements; Dietary Supplements - toxicity; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; feed intake; Female; Flavonoids - toxicity; Food safety; hematology; histology; Humans; Hydroxybenzoates - toxicity; ingredients; Kidney - drug effects; Kidney - metabolism; liver; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Middle Aged; mutagenicity; Mutagens - toxicity; mutation; No-Observed-Adverse-Effect Level; Organ Size - drug effects; phenolic acids; Pine bark extract; Pinus - chemistry; Pinus radiata; Plant Bark - chemistry; Plant Extracts - toxicity; Proanthocyanidins; Proanthocyanidins - toxicity; Quercetin - analogs & derivatives; Quercetin - toxicity; Rats; Rats, Sprague-Dawley; renal function; taxifolin; tissue weight; Toxicity Tests - methods; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.08.051

► Enzogenol® polyphenolic pine bark extract is safe for foods and supplements. ► Presenting industrial production, chemical analyses and toxicity studies. ► Ames-test shows lack of mutagenic activity. ► MTD and NOAEL in rats and dogs: 2500 and 750mg/kg/day with no toxic effects found. ► Human clinical studies show excellent safety profile for Enzogenol®. 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 750mg/kg/day, respectively. Consumption of 480mg/day for 6months and 960mg/day for 5weeks 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.