Early life nutrition and genetic contributors to carotenoid status in children

Background. Carotenoids are potent antioxidants that are found in vegetables, fruits, eggs, and some seafood. Circulating carotenoids are associated with a reduced risk for cardiovascular disease and some types of cancers. Carotenoid accumulation in certain tissues, such as the retina, brain, and skin, benefits visual function and cognition in children and adults. Many factors contribute to the interindividual variability in carotenoid status, including dietary intake, sex, adiposity, and genetics. Although the impact of these factors on carotenoid status has been examined in adults, there is a paucity of knowledge of how these factors affect children’s carotenoid status. It is crucial to understand the inter-individual variability of macular pigment in children, as this is a critical time for visual and cognitive development Objectives. The objectives of the thesis were to: 1) investigate the association between early life nutrition (i.e. breastfeeding exclusivity and duration) and carotenoids in skin and retina in children aged 7-12 years; 2) to explore the potential mediating effect of body weight and adiposity on the relationship between breastfeeding and carotenoid status in children aged 7-12 years; and, 3) to examine the genetic determinants of macular pigment optical density (MPOD) in children aged 8- 9 years. Methods. Secondary data were analyzed from previous studies conducted among children between 7-12 years of age. Skin carotenoid reflection scores are obtained utilizing reflection spectroscopy using a Veggie Meter device. MPOD was assessed using customized heterochromatic flicker photometry. Habitual dietary intake was assessed via 7-day diet records, which were entered and analyzed using Nutrition Data Systems Research software. Height and weight were measured using a stadiometer and a digital scale, respectively. Dual-energy X-ray absorptiometry was used to assess whole-body fat percentage and visceral adiposity. A pediatric health history survey was administered to one parent of each participant to obtain information on early life nutrition retrospectively. DNA was extracted from saliva samples and genotyped for 26 SNPs in genes that are relevant to carotenoid metabolism as well as 75 ancestry information markers using the GeneAmp 7900 Real-Time PCR System. All statistical analyses were performed using SPSS Statistics version 24. A p-value of 0.05 was considered as statistically significant. LDmatrix with LDlink 1.1 was used to report linkage disequilibrium on SNPs included. Results. For aims 1 and 2, the mean age of the subjects was 9.4± 1.5 years (N=73, 35 females). Approximately 82% of the subjects were exclusively breastfed through 3 months and 72% of the subjects had a total breastfeeding duration over 6 months. Exclusive breastfeeding duration was correlated with skin carotenoids (r=0.23, p<0.05). There was a significant indirect effect of exclusive breastfeeding duration and skin carotenoids through BMI percentile (ab (effect size of the indirect effect) = 3.29, 95% CI [0.71, 8.04]) and VAT (ab = 2.91, 95% CI [0.70, 5.99]). After adjusting for dietary carotenoid intake, total energy intake, and weight-for-gestational age percentile at birth, the indirect effects through BMI-for-age percentile (ab=3.00, 95% CI [0.35, 7.53]) and VAT (ab=2.85, 95%CI [0.66, 6.38]) and VAT (ab=2.85, 95%CI [0.66, 6.38]) remained significant. A total of 134 subjects (79 females) were included for aim 3). The mean age was 8.64 ± 0.52 years old. Following adjustment for ancestry, age, sex, and visceral adiposity, lower MPOD was presented in children who carried at least one T, C and A alleles on BCO1-rs7501331 (P = 0.045) , CD36-rs3173798 (P < 0.01), and CD36-rs1527483 (P = 0.04), respectively. Only CD36-rs3173798 (P < 0.01) remained a significant predictor for MPOD after accounting for dietary lutein and zeaxanthin intake. Conclusions. The findings indicate that exclusive breastfeeding duration was positively correlated with skin carotenoids in children at 9 years of age. This relationship was mediated by child weight status and visceral fat mass. Longer exclusive breastfeeding duration was associated with lower BMI percentile and visceral adiposity, which, in turn, were associated with higher skin carotenoids. These findings might call for further investigation of the relationship between early life nutrition and carotenoid status with larger and more diverse samples. The results also showed that genetic variations play a role in the inter-individual variability in MPOD in children. These results may aid in the identification of individuals who are more at risk for low macular carotenoid accumulation, which in turn, may support the need for personalized nutrition interventions to target cognitive development during childhood.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste