High-Dose β-Carotene Suppresses Non-Alcoholic Steatohepatitis Progression in a Mouse Model

Abstract

ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. Anti-oxidative vitamins, such as vitamin C (VC) and vitamin E (VE), are used to treat NASH in humans. In addition, some carotenoids (e.g., astaxanthin, β-cryptoxanthin, fucoxanthin, lycopene, and zeaxanthin) could suppress the progression of NASH in a mouse model. However, it is unclear whether β-carotene is effective against NASH. Therefore, we examined the effects of β-carotene on diet-induced NASH in mice. C57BL/6J male mice (10 weeks of age) were fed a control diet or NASH diet containing various amounts of β-carotene (0.0005%–0.5% [w/w]). A 12-week feeding NASH diet induced NASH in a mouse model. This model presented increased liver weight, plasma levels of hepatic marker enzymes (aspartate transaminase; AST, alanine transaminase; ALT), hepatic triglycerides (TG) content, and NAFLD activity score. The physiological dose (0.0005%–0.005%) of β-carotene failed to suppress the progression of NASH. However, high-dose (0.5%) of β-carotene suppressed hepatic lipid accumulation and NASH progression, especially lobular inflammation, in the NAFLD activity score. In conclusion, a high-dose of β-carotene intake prevented hepatic lipid accumulation and the progression of NASH in a mouse model. In contrast, the physiological dose of β-carotene did not show any beneficial effects on NASH. However, β-carotene's presence in food is valuable and could be expanded to reflect real-world implications. Further studies, especially observational studies, are needed to clarify whether β-carotene can prevent the progression of NASH in humans. Practical Application: The physiological dose of β-carotene did not show any beneficial effects on NASH. However, a high-dose of β-carotene suppressed the progression of NASH, especially steatosis and lobular inflammation, in a mouse model. Further studies are needed to clarify whether β-carotene can prevent the progression of NASH in humans. β-Carotene is known to have various biological functions in addition to its role as provitamin A. So, active consumption of β-carotene via regular foods, but not dietary supplements, is recommended, even if the effect on NASH in humans is unclear.