Unveiling the safe dose range of the conjugated linolenic acid cis9,trans11,cis15-CLNA from Bifidobacterium breve

Previous studies have demonstrated that cis9,trans11,cis15-CLNA (c9,t11,c15-CLNA), a metabolite of Bifidobacterium breve CCFM683, possesses anti-inflammatory properties in the intestine. However, its safety profile remains unexplored. This study establishes the safe dose range for c9,t11,c15-CLNA and investigates the potential damage pathways. The results indicate that the maximum safe dose for mice is lower than 625 mg/kg, primarily due to hepatocyte damage. In cellular experiments revealed that an overdose of c9,t11,c15-CLNA activates peroxisome proliferator-activated receptor gamma (PPAR-γ), leading to hepatic lipid accumulation. The addition of the PPAR-γ inhibitor partially mitigated this effect. In summary, this study established that the maximum tolerated dose of c9,t11,c15-CLNA in healthy adult C57BL/6N mice is 625 mg/kg. For human application, the estimated safe dose is below 50.62 mg/kg. Additionally, c9,t11,c15-CLNA was found to activate the PPAR-γ protein in the liver, leading to lipid accumulation within hepatic tissue.