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阿魏酸酰胺和燕麦糖苷作为燕麦摄入的生物标志物:单次和重复给药条件下固体和液体燕麦消费的药代动力学研究。

Avenanthramides and avenacosides as biomarkers of oat intake: a pharmacokinetic study of solid and liquid oat consumption under single and repeated dose conditions.

作者信息

Armeni Marina, Cardilin Tim, Fristedt Rikard, Karlsson Therese, Jenkins Caroline Orfila, Nordin Elise, Qin Panpan, Jirstrand Mats, Kristiansen Karsten, Savolainen Otto, Landberg Rikard

机构信息

Department of Life Sciences, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, 412 96, Sweden.

Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, 412 96, Sweden.

出版信息

Nutr J. 2025 Sep 9;24(1):136. doi: 10.1186/s12937-025-01204-7.

Abstract

BACKGROUND

Avenanthramides (AVAs) and Avenacosides (AVEs) are unique to oats (Avena Sativa) and may serve as biomarkers of oat intake. However, information regarding their validity as food intake biomarkers is missing. We aimed to investigate critical validation parameters such as half-lives, dose-response, matrix effects, relative bioavailability under single dose, and in relation to the abundance of Feacalibacterium prausnitzii, and under repeated dosing, to understand the potential applications of AVAs and AVEs as biomarkers of oat intake.

METHODS

Twenty-one healthy participants consumed two oat products (solid and liquid) in a non-blinded randomized crossover study for the pharmacokinetics (PK) assessment of multiple AVAs (2p, 2c,2f, 2fd and 2pd) and AVEs (A and B). At phase I, postprandial data were collected after a single dose of either product. At phase II, fasting sample was drawn after a 4-days repeated dose setup. The postprandial data were used in a compartmental PK model and the PK parameters were consequently utilized to predict individual plasma concentrations, which were compared with the data of the second phase of the study.

RESULTS

T values were shorter in liquid compared to solid form for AVAs (0.7-1.6 h and 1.1-2.3 h, respectively). In liquid, T were 1.3 h (AVA 2p and AVA 2fd), 3.2 h (AVA 2f, AVE A) and 2.5 h (AVA 2pd, AVE B). In solid form, T were shorter for AVAs (1.4-2.6 h) compared to AVEs (3.3-3.8 h). The normalized area under the curve (AUC) was greater for liquid than solid form for AVA2p, 2f and AVE-A [0.7-27 nM∙h (liquid), 0.4-20.1 (solid)] while for AVE-B AUC were comparable [1.8 ± 0.2 nM∙h (liquid),2.1 ± 0.3 nM∙h (solid)]. A pharmakcokinetic prediction model described 75% of the experimental plasma-concentration data from phase II, with good agreement (bias: -0.145 nM).

CONCLUSIONS

AVAs are promising candidates as compliance biomarkers of oat intake in intervention studies regardless of the tested food matrices. However, due to their short elimination half-lives, their applicability in nutritional epidemiology where long-term habitual intake is of main interest, seems restricted.

CLINICAL TRIAL NUMBER

This study was registered at clinicaltrials.gov with the clinical trial number: NCT05511077, on August 22nd, 2022.

摘要

背景

燕麦酰胺(AVAs)和燕麦糖苷(AVEs)是燕麦( Avena Sativa )所特有的,可作为燕麦摄入量的生物标志物。然而,关于它们作为食物摄入量生物标志物的有效性的信息尚缺。我们旨在研究关键的验证参数,如半衰期、剂量反应、基质效应、单剂量下的相对生物利用度,以及与普拉梭菌丰度的关系,以及重复给药后的情况,以了解 AVAs 和 AVEs 作为燕麦摄入量生物标志物的潜在应用。

方法

在一项非盲随机交叉研究中,21 名健康参与者食用了两种燕麦产品(固体和液体),用于对多种 AVAs(2p、2c、2f、2fd 和 2pd)和 AVEs(A 和 B)进行药代动力学(PK)评估。在第一阶段,单次服用任一产品后收集餐后数据。在第二阶段,在 4 天重复给药设置后采集空腹样本。餐后数据用于房室 PK 模型,PK 参数随后用于预测个体血浆浓度,并与研究的第二阶段数据进行比较。

结果

与固体形式相比,AVAs 在液体中的 T 值较短(分别为 0.7 - 1.6 小时和 1.1 - 2.3 小时)。在液体中,T 值分别为 1.3 小时(AVA 2p 和 AVA 2fd)、3.2 小时(AVA 2f、AVE A)和 2.5 小时(AVA 2pd、AVE B)。在固体形式中,AVAs 的 T 值(1.4 - 2.6 小时)比 AVEs(3.3 - 3.8 小时)短。对于 AVA2p、2f 和 AVE - A,液体形式的曲线下归一化面积(AUC)大于固体形式[0.7 - 27 nM∙h(液体),0.4 - 20.1(固体)],而 AVE - B 的 AUC 相当[1.8 ± 0.2 nM∙h(液体),2.1 ± 0.3 nM∙h(固体)]。一个药代动力学预测模型描述了来自第二阶段 75%的实验血浆浓度数据,一致性良好(偏差:-0.145 nM)。

结论

无论测试的食物基质如何,AVAs 都是干预研究中燕麦摄入量依从性生物标志物的有希望的候选者。然而,由于它们的消除半衰期较短,它们在主要关注长期习惯性摄入的营养流行病学中的适用性似乎受到限制。

临床试验编号

本研究于 2022 年 8 月 22 日在 clinicaltrials.gov 注册,临床试验编号:NCT05511077。

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