Chee Wai Ku , Hiu Gwan Chan , Alexandrea Lishan Sia , Christine Huang , Jessica Quek , Yin Bun Cheung , Karen Mei Ling Tan , Jun Shi Lai , Keith M Godfrey , Jerry Kok Yen Chan , Fabian Yap , See Ling Loy
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引用次数: 0
Abstract
Background
One-carbon metabolism, which consists of the folate cycle, methionine cycle, and trans-sulphuration pathway, is associated with nucleotide synthesis. However, the association between one-carbon metabolites, metabolic status, and reproductive health remains poorly understood.
Objectives
We examined the association between the one-carbon cycle plasma metabolites and fecundability and determined whether it is modified by metabolic health status, as assessed by insulin resistance (IR).
Methods
This prospective cohort study utilized data from the Singapore PREconception Study of long-Term maternal and child Outcomes. Fasting blood samples were collected, and one-carbon cycle metabolites were measured. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrollment. We identified patterns in plasma one-carbon cycle metabolites using principal component (PC) analysis. We estimated fecundability ratios (FRs) and confidence intervals (CIs), with confounder adjustment using discrete-time proportional hazards models. IR was determined using the Homeostatic Model Assessment 2 Insulin Resistance score, classified into lower IR (<0.65) and higher IR (≥0.65). The role of IR was examined through interaction tests and stratification.
Results
We identified 3 one-carbon cycle PCs. PC1, characterized by higher folate and lower homocysteine concentrations; PC2, characterized by higher concentrations of dimethylglycine, choline, methionine, and betaine; and PC3, characterized by higher concentrations of vitamins B2, B12, and B6. Each z-score increase in PC1 was associated with a 17% increase in fecundability (FR: 1.17; 95% CI: 1.03, 1.33). The association between PC1 and fecundability was more evident in women with lower IR (FR: 1.30; 95% CI: 1.08, 1.57) but was attenuated in those with higher IR (FR: 1.09; 95% CI: 0.92, 1.30), with a P-for-interaction of 0.127. PC2 and PC3 were not associated with fecundability.
Conclusions
Our findings suggest that higher folate and lower homocysteine concentrations, which reflected the interlinked folate and methionine cycles, were associated with higher fecundability in preconception women with lower IR but less so in those with higher IR.
Clinical Trial Registration: This trial was registered at ClinicalTrials.gov as NCT03531658 (https://www.clinicaltrials.gov/study/NCT03531658).
期刊介绍:
American Journal of Clinical Nutrition is recognized as the most highly rated peer-reviewed, primary research journal in nutrition and dietetics.It focuses on publishing the latest research on various topics in nutrition, including but not limited to obesity, vitamins and minerals, nutrition and disease, and energy metabolism.
Purpose:
The purpose of AJCN is to:
Publish original research studies relevant to human and clinical nutrition.
Consider well-controlled clinical studies describing scientific mechanisms, efficacy, and safety of dietary interventions in the context of disease prevention or health benefits.
Encourage public health and epidemiologic studies relevant to human nutrition.
Promote innovative investigations of nutritional questions employing epigenetic, genomic, proteomic, and metabolomic approaches.
Include solicited editorials, book reviews, solicited or unsolicited review articles, invited controversy position papers, and letters to the Editor related to prior AJCN articles.
Peer Review Process:
All submitted material with scientific content undergoes peer review by the Editors or their designees before acceptance for publication.