Table 1.

List of studies examining the bioavailability of carotenoid zeaxanthin in Fructus lycii.

Authors (year)	Type of Study	Subjects	F. lycii Formulation	Aim	Conclusion
HUMAN STUDIES (HEALTHY SUBJECTS)
Breithaupt et al. (2004) [21]	Single-blinded, crossover study (3-week of depletion period)	N = 12, Males = 6; Females = 6	A Z-standardized dose (5 mg) suspended in yoghurt, esterified (3R,3R’-Z dipalmitate from F. lycii) and non-esterified 3R,3R’-Z forms	Bioavailability of esterified Z versus non-esterified Z	Administration of both esterified and non-esterified Z increased plasma Z levels; however, levels were significantly higher with former suggesting an enhanced bioavailability of esterified form of Z.
Cheng et al. (2005) [19]	Single-blinded, placebo-controlled study	N = 27, supplementation group = 14; age and gender-matched controls = 13	Whole F. lycii (15g/d, equivalent to about 3mg Z) for 28 days	Change in fasting plasma Z levels	Following supplementation, there was 2.5-fold rise in plasma Z levels suggesting that Z in whole F. lycii was bioavailable and that modest daily intake will markedly increases fasting plasma Z levels.
Benzie et al. (2006) [22]	Double-blinded, crossover study (3-5 week wash out period)	N = 12, Males = 5, Females = 7	A Z-standardized dose (15 mg) from freeze dried powder of F. lycii homogenized in 3 forms: warm skimmed milk (40°); hot skimmed milk (80°); hot water (80°, control)	Bioavailability of different formulations of F. lycii	Homogenization of F. lycii in hot skimmed milk resulted in a formulation that has a 3-fold enhanced bioavailability of Z compared with both the ‘classical’ hot water and warm skimmed milk treatment of berries.
Bucheli et al. (2011) [20]	Randomized, double masked, placebo controlled study	N = 150, supplementation group = 75, placebo group = 75	Milk based formulation of F. lycii (equivalent to 10mg/d Z) for 90 days	Effect on plasma Z levels	Daily dietary supplementation of F. lycii increased plasma Z levels by 26% and plasma antioxidant capacity by 57% in elderly subjects aged 65–70 years.
Hempel et al. (2017) [14]	Randomized, single-blinded, two-way crossover study	N = 16, Males =8, Females = 8	Z extracted from F. lycii in two forms: H-aggregated Z and J-aggregated Z (equivalent to 10 mg Z)	Bioavailability of H aggregated versus J-aggregated Z in vivo (humans) and in-vitro (INFOGEST digestion protocol)	Overall, J-aggregated Z showed marginally higher bioavailability (23%) than H-aggregated Z in both humans and in-vitro models but bioaccessibility (micellization rate) were seen higher with H-aggregated Z. Combined effect of aggregation and esterification represents a small magnitude of effect on Z bioavailability in humans.
IN-VITRO STUDIES
Hempel et al. (2017) [13]	In-vitro study	In-vitro digestion model	Fresh (both unripe and fully ripe) and dried berry fruits of F. lycii	Ultrastructure of F. lycii during fruit ripening; carotenoid profiling of unripe and ripe berry fruits; in-vitro bioaccessibility of xanthophyll carotenoids in dried F. lycii versus fresh spinach	There was ripening induced modification in carotenoid profile (high amounts of xanthophyll esters, mainly Z dipalmitate) and deposition (tubular chromoplasts presumably containing liquid-crystalline state of Z). F. lycii might represent a more potent source of xanthophyll carotenoid than green leafy vegetable due to enhanced liberation and bioaccessibility of Z from these berries.
Sun et al. (2017) [23]	In-vitro study	F. lycii Infusion	5 g of F. lycii in 150 mL of F. lycii infusion in hot water at different temperatures (60 °C, 70 °C, 80 °C, 90 °C, 100 °C), for different lengths of time (15, 30, 60, 120, 150, 180 min), and for different infusion times (1, 2, 3, 4 times)	Assessment of bioactive compounds and antioxidant activity of F. lycii infusions	The bioactive compounds and antioxidant activity of F. lycii infusion increased with increased infusion temperature and time but were equivalent with preparation conditions of 100 °C for 1~3 h, 90 °C for 2~3 h and 80 °C for 2.5~3 h. The antioxidant activity was contributed by polyphenols followed by flavonoids, carotenoids and polysaccharides.