Lipase inhibition is one of the directions to control obesity. In vitro assays have confirmed the inhibitory effect of selected xanthophylls, including astaxanthin, fucoxanthinol, fucoxanthin, and neoxanthin. Similarly, an in-silico study also demonstrated the successful inhibition of pancreatic lipase by astaxanthin. Unfortunately, the efficacy of these protocols in the emulsion state typical of lipid digestion remains untested. To address this issue, the current study employed the pH-stat test, which mimics lipid digestion in the gastrointestinal tract, to evaluate native and prepared sea buckthorn and rapeseed oils with varying xanthophyll contents from 0 to 1400 mg/kg oil. Furthermore, a molecular docking of zeaxanthin and violaxanthin (commonly found in plant-based foods), astaxanthin (widely distributed in foods of marine origin) and orlistat (approved as a drug) was performed. The in-silico studies revealed comparable inhibitory potential of all tested xanthophylls (variation from - 8.0 to - 9.3 kcal/mol), surpassing that of orlistat (- 6.5 kcal/mol). Nonetheless, when tested in an emulsified state, the results of pH-stat digestion failed to establish the inhibitory effect of xanthophylls in the digested oils. In fact, lipolysis of native xanthophyll-rich sea buckthorn oil was approximately 22% higher than that of the xanthophyll-low preparation. The key insight derived from this study is that the amphiphilic properties of xanthophylls during the digestion of xanthophyll-rich lipids/meals facilitate emulsion formation, which leads to enhanced fat lipolysis.
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