This study investigated the bioaccessibility of ten synthetic lutein diesters using the in vitro INFOGEST human digestion model, enabling comparative evaluation of their digestive behavior under controlled food-matrix conditions. We revealed that lutein ester chain length was the primary determinant of bioaccessibility, while branching influenced the extent of hydrolysis. Linear short-chain diesters demonstrated superior bioaccessibility (6.7–18.9%). Branched and bulky derivatives, surprisingly, achieved comparable bioaccessibility (6.6–8.3%) despite high hydrolytic resistance, suggesting mechanisms beyond simple ester cleavage. Conversely, long-chain lutein diesters (> C10), prevalent in commercial supplements, exhibited poor micellization, limited hydrolysis, and consequently very low bioaccessibility (<3%). Finally, two pharmaceutical formulations of the lead lutein diester, lutein di(2,2-dimethylpropanoate), were developed: a sunflower oil formulation and a liquisolid formulation utilizing a porous aluminometasilicate carrier. The sunflower oil formulation enabled significantly higher pigment stability and bioaccessibility, highlighting its superior potential for effective lutein delivery in novel food and pharmaceutical applications. • Lutein diester bioaccessibility is dictated by structure once matrix effects are contolled. • Bioaccessibility is governed by ester chain length and hydrolysis by branching. • Branched short-chain compounds provide optimal stability and bioaccessibility. • Effective and stable lutein supplement is provided by a sunflower oil formula.
Krstić et al. (Sun,) studied this question.