13-week oral toxicity study with stanol esters in rats

Area of Science:

• Nutrition Science
• Toxicology
• Biochemistry

Background:

• Plant sterols and stanols effectively reduce serum cholesterol at ~2 g/day.
• Stanol fatty acid esters are a more fat-soluble form, potentially enhancing cholesterol-lowering efficacy.
• Dietary intake of stanol esters is typically below cholesterol-lowering levels.

Purpose of the Study:

• To assess the safety of subchronic ingestion of stanol esters.
• To evaluate stanol esters at dietary levels comparable to or exceeding cholesterol-lowering recommendations.

Main Methods:

• Two stanol ester preparations (wood-derived and vegetable oil-derived) were administered to Wistar rats (20 males, 20 females) for 13 weeks.
• Dietary concentrations ranged from 0 to 5% total stanols.
• Safety was evaluated through clinical observations, hematology, clinical chemistry, organ weights, and histopathology.

Main Results:

• Both stanol ester preparations were well-tolerated, showing no major adverse effects across various parameters.
• Plasma cholesterol and phospholipids decreased slightly in males; plasma sterols decreased while stanols increased.
• Fecal excretion of sterols and stanols significantly increased; some hepatic changes in males were attributed to nutritional status, not pathology.

Conclusions:

• Stanol esters are safe for subchronic ingestion at dietary levels up to 1% total stanols.
• The no-observed-adverse-effect level (NOAEL) was identified as 1% total stanols in the diet.
• Stanol esters demonstrate potential for cholesterol management without significant safety concerns at recommended intake levels.