4. Discussion
GUSTO, carotenemia
ADVERSE EVENTS, LATE PREGNANCY, SECONDARY, CAROTENEMIA
This is the first RCT to examine the effects of a pure encapsulated form of β-cryptoxanthin in healthy women. Multiple doses of β-cryptoxanthin of up to 6 mg/day for 8 weeks were well tolerated by the women in this study. No serious adverse events were observed, and none of the reported adverse events were determined to be related to β-cryptoxanthin except carotenemia, a benign yellowing of the skin [The mean β-cryptoxanthin concentration at baseline was 0.44 ± 1.2 µmol/L, which is similar to that observed in mothers at the time of delivery in the GUSTO cohort [Given the purity of the current β-cryptoxanthin and ingestion as a supplemental dose, this study was able to examine the subsequent impact on circulating concentrations of additional carotenoid species. β-cryptoxanthin supplementation at a dose of both 3 and 6 mg increased plasma β-cryptoxanthin concentration without any corresponding alterations in the plasma concentration of other carotenoids, including α-carotene, β-carotene, lycopene, lutein, and zeaxanthin. Our study extends these insights further to examine the effects of β-cryptoxanthin supplementation on the gene expression involved in retinol signaling in PBMCs. For this, we selected six candidate genes based on their gene expression level within human blood cells in the Genotype-Tissue Expression (GTEx) database (To our knowledge the current study is also the first study to examine the effects of β-cryptoxanthin supplementation on the gut microbiome. No significant differences in fecal microbial composition were observed after β-cryptoxanthin daily supplementation for 8 weeks, with a dose of 3 mg/day or 6 mg/day, compared to placebo. It has been reported that dietary and plasma carotenoids are positively associated with alpha diversity of fecal microbiota [Previous studies have reported a reduction in stress levels in female university students as measured by a reduction in salivary α-amylase activity on consuming β-cryptoxanthin in the form of concentrated Satsuma mandarin juice [In relation to health, higher plasma β-cryptoxanthin concentrations have previously been associated with lower blood pressure during late pregnancy [The strengths of this study were the use of a β-cryptoxanthin formulation with a very good bioavailability and the extensive amount of data collected. One limitation is the lack of follow-up after 8 weeks of β-cryptoxanthin supplementation to observe the long-term effects. Another limitation is that the study was underpowered such that secondary outcomes could not be adequately investigated. This study involved only healthy Asian women. It would be interesting to determine whether men and other ethnic groups would respond in the same way to β-cryptoxanthin supplementation. Overall, this pharmacokinetic human clinical trial in healthy women serves well for future clinical trials where the effects of β-cryptoxanthin supplementation on metabolic or mental health in women are investigated.