Safety, Tolerability, and Pharmacokinetics of ß-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: ß-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. METHODS: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral ß-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of ß-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. RESULTS: ß-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma ß-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p < 0.03), and placebo (0.4 ± 0.1 µmol/L) (p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, ß-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. CONCLUSIONS: Oral ß-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of ß-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women.

Integrative multi-omics database (iMOMdb) of Asian pregnant women.

Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N = 1079), DNA methylation (N = 915) and transcriptome profiling (N = 238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (~480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.