The Lutein and Zeaxanthin in Pregnancy (L-ZIP) study—carotenoid supplementation during pregnancy: ocular and systemic effects—study protocol for a randomized controlled trial

Abstract

Background Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), collectively called the macular pigment (MP), are dietary carotenoids that preferentially localize in the macula of the human eye. MP protects the macula from photo-oxidative damage and enhances visual function. Inadequate maternal intake of carotenoids, coupled with the placental transfer of maternal carotenoids to support fetal brain and retina development, potentially put mothers at risk of depletion systemically and in their ocular tissues. Presently, maternal carotenoid status throughout pregnancy remains poorly characterized, and no prospective randomized controlled trial of L and Z supplementation via prenatal vitamins has assessed maternal and infants’ systemic and ocular carotenoid status during pregnancy. We hypothesize that prenatal maternal carotenoid supplementation will counteract maternal carotenoid depletion during pregnancy and will improve biomarkers of carotenoid status of both mothers and infants. Methods Lutein and Zeaxanthin in Pregnancy (L-ZIP) is a phase 2, single-center, prospective, double-masked, randomized active-controlled clinical trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Participants consume a daily standard prenatal multivitamin with no added carotenoids and are randomized (1:1 allocation) to receive either a capsule containing 10 mg L and 2 mg Z in safflower oil (Carotenoid group) or a capsule containing only safflower oil with no added carotenoids (Control group) for a period of 6 to 8 months. Skin, serum, and ocular carotenoids are measured at every study visit (i.e., within the first trimester [baseline], second trimester, third trimester, and 0–2 weeks postpartum). Skin carotenoid assessment is by resonance Raman spectroscopy (RRS); serum carotenoid status is quantified using high-performance liquid chromatography (HPLC); and MP is measured with the dual-wavelength autofluorescence. Infants’ MP and foveal anatomy are assessed using RetCam retinal camera and Bioptigen SD-OCT, respectively. The primary outcomes are changes in maternal systemic and ocular carotenoid status during pregnancy. Discussion L-ZIP is the first prospective RCT to investigate maternal carotenoid status throughout pregnancy and to determine whether prenatal maternal carotenoid supplementation will offset maternal carotenoid depletion and improve biomarkers of maternal and infant’s carotenoid status. Findings from L-ZIP will strengthen recommendations regarding prenatal carotenoid supplementation and consequently inform policy decisions. Trial registration ClinicalTrials.gov NCT03750968. Registered on November 23, 2018

Lutein as a Modulator of Oxidative Stress-Mediated Inflammatory Diseases

“…A significant correlation was observed between macular pigment density and global cognitive function in healthy older adults [ 28 ]. Lutein, zeaxanthin, and meso-zeaxanthin are collectively called the macular pigment [ 29 ]. Adequate maternal intake of lutein couples with the placental transfer of maternal lutein to support fetal brain and retina development [ 29 ].…”

“…Lutein, zeaxanthin, and meso-zeaxanthin are collectively called the macular pigment [ 29 ]. Adequate maternal intake of lutein couples with the placental transfer of maternal lutein to support fetal brain and retina development [ 29 ]. Therefore, macular pigment is used as a biomarker of lutein in brain tissues.…”

“…Lutein, as a component of macular pigment, protects the macula from photo-oxidative damage and enhances visual function [ 29 ]. Lutein is an ocular antioxidant that can quench both singlet oxygen and lipid peroxy radicals [ 43 ].…”

Nourishing Better Vision: The ARVO 2021 Mildred Weisenfeld Award Lecture

“… 50 , 51 Based on these results, we are currently conducting a National Institutes of Health (NIH)-sponsored randomized, placebo-controlled, single-site clinical trial of 10 mg/day of lutein and 2 mg/day of zeaxanthin added to standard-of-care prenatal vitamins (the L-ZIP study) to determine if the active intervention can combat pregnancy-induced depletion of maternal carotenoids and enhance the infant's ocular and systemic carotenoid status and foveal structure at birth. 52 We recently completed enrollment of 47 subjects and expect to report our findings within a year.…”

Early Pediatric Benefit of Lutein for Maturing Eyes and Brain—An Overview

“…A prospective randomized controlled trial is currently being conducted to evaluate the effects of supplementation with 10 mg lutein + 2 mg zeaxanthin administered for 6 to 8 months during pregnancy (from the first trimester of pregnancy to 2 weeks postpartum). The study aims to assess wheter supplementation will counteract maternal carotenoid depletion during pregnancy and will improve biomarkers of carotenoid status (serum, MP and skin carotenoids) and ocular health of both mothers and infants [119].…”