Moslehi Nazanin, Marzbani Rezvan, Rezadoost Hassan, Mirmiran Parvin, Ramezani Tehrani Fahimeh, Azizi Fereidoun
Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
Nutr Metab (Lond). 2021 Jun 27;18(1):66. doi: 10.1186/s12986-021-00591-y.
Dairy intake has been implicated in later ovarian aging but mechanism underlying the association is unknown. This study aimed to investigate (1) associations between dairy intake and metabolites previously shown related to anti-müllerian hormone (AMH) decline rate; (2) mediating roles of these metabolites in the prospective association of total dairy consumption with odds of AMH fast decline rate.
The participants comprised 186 reproductive-aged women randomly selected from the Tehran Lipid and Glucose Study. AMH was measured at baseline (1999-2001) and the 5th follow-up (2014-2017), and dietary data was collected at the second follow-up (2005-2008) using a food frequency questionnaire. Untargeted metabolomics was performed by gas chromatography-mass spectrometry using fasting-serum samples of the second follow-up. We analyzed dairy intake in association with the eight metabolites linked to the higher odds of AMH fast decline rate using linear regression with the Benjamini-Hochberg false discovery correction. Mediatory roles of the metabolites were assessed by bootstrapping.
Mean age and BMI of the participants at metabolomics assessment were 44.7 ± 5.87 years and 28.8 ± 4.88 kg/m, respectively. Phosphate, branched-chain amino acids (BCAAs), and proline decreased significantly from the first to the third tertile of total dairy intake. Total dairy as a continuous variable inversely associated with phosphate (beta = -0.166; p value = 0.018), valine (beta = -0.176; p value = 0.016), leucine (beta = -0.226; p value = 0.002), proline (beta = -0.219; p value = 0.003), and urea (beta = -0.156; p = 0.035) after accounting for all potential covariates and correction for multiplicity (q-value < 0.1). Fermented dairy showed similar results, but milk did not associate with any of the metabolites. Simple mediation showed significant indirect effects for phosphate, proline, and BCAAs but not urea. Entering the sum of phosphate, proline, and BCAAs as a mediator, the metabolites' total indirect effects were significant [β = -0.12 (95% CIs - 0.26, - 0.04)]. In contrast, the direct association of total dairy intake with the fast decline in AMH was non-significant [β = -0.28 (95% CIs - 0.67, 0.10)].
Total dairy was inversely associated with AMH decline rate-related metabolites. Inverse association of dairy intakes with the odds of AMH fast decline rate was indirectly mediated by lower phosphate, proline, and BCAAs.
乳制品摄入与后期卵巢衰老有关，但其潜在关联机制尚不清楚。本研究旨在调查：（1）乳制品摄入量与先前显示与抗苗勒管激素（AMH）下降率相关的代谢物之间的关联；（2）这些代谢物在总乳制品摄入量与AMH快速下降率几率的前瞻性关联中的中介作用。
研究对象包括从德黑兰脂质与葡萄糖研究中随机选取的186名育龄妇女。在基线期（1999 - 2001年）和第5次随访（2014 - 2017年）测量AMH，并在第2次随访（2005 - 2008年）使用食物频率问卷收集饮食数据。使用第2次随访的空腹血清样本，通过气相色谱 - 质谱法进行非靶向代谢组学分析。我们使用线性回归和Benjamini - Hochberg错误发现校正分析了乳制品摄入量与与AMH快速下降率较高几率相关的8种代谢物之间的关联。通过自抽样评估代谢物的中介作用。
代谢组学评估时参与者的平均年龄和体重指数分别为44.7±5.87岁和28.8±4.88kg/m²。从总乳制品摄入量的第一个三分位数到第三个三分位数，磷酸盐、支链氨基酸（BCAAs）和脯氨酸显著下降。在考虑所有潜在协变量并进行多重性校正（q值<0.1）后，总乳制品作为连续变量与磷酸盐（β = -0.166；p值 = 0.018）、缬氨酸（β = -0.176；p值 = 0.016）、亮氨酸（β = -0.226；p值 = 0.002）、脯氨酸（β = -0.219；p值 = 0.003）和尿素（β = -0.156；p = 0.035）呈负相关。发酵乳制品显示出类似结果，但牛奶与任何代谢物均无关联。简单中介分析显示磷酸盐、脯氨酸和BCAAs有显著间接效应，但尿素没有。将磷酸盐、脯氨酸和BCAAs的总和作为中介变量纳入分析，代谢物的总间接效应显著[β = -0.12（95%置信区间 - 0.26， - 0.04）]。相比之下，总乳制品摄入量与AMH快速下降的直接关联不显著[β = -0.28（95%置信区间 - 0.67，0.10）]。
总乳制品摄入量与AMH下降率相关代谢物呈负相关。乳制品摄入量与AMH快速下降率几率的负相关是由较低的磷酸盐、脯氨酸和BCAAs间接介导的。
