Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study

Abstract

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

Bioaccessibility of carotenoids from plant and animal foods

“…Some studies using this new standardized methodology have already surfaced . However, because this model has not been designed to specifically digest carotenoid‐rich foods, we consider that further advanced adjustments are required to improve the base model proposed by Minekus et al .…”

“…Carotenoids are considered to be normally present only in their free forms in human plasma. Although the accumulation of carotenoid esters has previously been reported in human skin, and most recently in human colostral milk, small amounts of carotenoid esters that might have been briefly present in human plasma TRL fractions . It has been hypothesized that the cleavage step takes place in the intestinal phase of digestion.…”

“…However, this might be highly complex because the in vitro cleavage as catalyzed by porcine cholesterol esterase has only been highly effective for β ‐cryptoxanthin esters . Esters of lutein, zeaxanthin, cryptocapsin and capsanthin have been showed to be only poorly cleaved . Breithaupt et al .…”

“…The term ‘bioavailability’ corresponds to the ‘fraction of an oral dose of a parent compound or active metabolite that reaches the systemic circulation’ . Therefore, most bioavailability assessment studies focus on carotenoid levels in plasma and plasma fractions, ideally, on the triacylglycerol‐rich lipoprotein (TRL) fraction containing mostly carotenoids newly absorbed after the consumption of a test meal …”

“…13 Therefore, most bioavailability assessment studies focus on carotenoid levels in plasma and plasma fractions, ideally, on the triacylglycerol-rich lipoprotein (TRL) fraction containing mostly carotenoids newly absorbed after the consumption of a test meal. [14][15][16][17] Because the release of a compound into an absorbable form is logically required for its transfer into the systemic circulation, it has been suggested that a high bioaccessibility is a prerequisite for a high bioavailability. Nevertheless, the ultimate determination of bioavailability clearly requires human clinical trials.…”