The Relative Bioavailability of Lutein and Zeaxanthin in the Presence of Omega-3 Supplements and Their Effect on Oxidative Stress Levels in Humans: A Pilot Study

Introduction: Lutein+Zeaxanthin (L+Z) are the major constituents of macular pigments of the retina. There is a lack of information on the bioavailability of the two compounds in the presence and absence of omega-3 fatty acids in L+Z supplements which are commonly prescribed to treat macular degeneration. Despite growing interest in L+Z supplementation, there remains a limited understanding of their short-term bioavailability dynamics and the potential added value of omega-3 co-supplementation. This pilot study reports on the bioavailability of serum responses to L+Z supplements in the presence of omega-3 fatty acids and evaluates time-resolved analytical approaches using Area Under the Curve. Subjects/Methods: A total of 10 men and six women with an average age of 31.38 ± 1.27 years participated in this randomised, non-blinded, controlled study for a total of 19 days (7-day wash-out period plus 12-day intervention period). The control group (n = 9) consumed the L+Z supplement (12 mg/d) only, while the intervention group (n = 7) consumed the L+Z supplement along with 900 mg/d of an omega-3 supplement (540 mg EPA + DHA 360 mg). Each group adhered to a comprehensive low-carotenoid and omega-3 diet list (LCOD) for the 7-day wash-out period and the 12-day intervention period. The participants reported the foods they consumed daily in their diet logbooks, online logs, and the ASA 24 diet assessment log over the study period. The body composition of each subject in the two groups was assessed before and after the study using a SECA body composition analyser, and the relative serum L+Z response in both groups was determined using Area Under the Curve (AUC and incremental AUC) by trapezoidal approximation. Results: The mean ± SEM baseline serum lutein+zeaxanthin (L+Z) concentrations measured at the end of the wash-out period (Day 7) were 2.23 ± 0.65 µg/mL in the control group and 1.20 ± 0.53 µg/mL in the intervention group. Following wash-out, serum L+Z concentrations increased in both groups, reaching 2.81 ± 0.90 µg/mL (control) and 2.63 ± 1.21 µg/mL (intervention) at Day 13, and 2.98 ± 0.69 µg/mL (control) and 3.02 µg/mL (intervention) at Day 19. Total exposure assessed by AUC₇–₁₃ and AUC₁₃–₁₉ did not differ significantly between the groups (p > 0.05). Incremental exposure analyses identified the post-wash-out period as the primary biologically responsive window, with higher mean incremental L+Z bioavailability in the intervention group (4.36 µg/day/mL) compared with the control group (3.00 µg/day/mL), although this difference was not statistically significant (p > 0.05). No significant effect of omega-3 co-supplementation on oxidative stress biomarkers was observed (p > 0.05). Conclusion: Omega-3 co-supplementation did not demonstrate a consistent additional benefit on L+Z bioavailability or oxidative stress markers. Day-resolved analyses using iAUC revealed temporal patterns not captured by conventional AUC measures. These exploratory findings should be interpreted with caution and confirmed in larger, longer-term studies.