Kay Colin D, Tejera Noemi, Jennings Amy, Haldar Sumanto, Diment Bethany C, Bevan Damon, Crossman Lisa C, Li Sherly, Cassidy Aedin, Minihane Anne-Marie
Department of Paediatrics, Arkansas Children's Research Institute - Arkansas Children's Nutrition Center, Little Rock, AR, United States.
Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, United Kingdom.
Am J Clin Nutr. 2025 Jul;122(1):101-111. doi: 10.1016/j.ajcnut.2025.05.006. Epub 2025 May 12.
Nutrition intervention trials demonstrate that increased flavonoid intake can have clinically meaningful impacts on disease outcomes/biomarkers; however, high variability in absorption and metabolism and large heterogeneity in biochemical and physiological responses are observed. The etiology of this variability is poorly understood.
The objective of this study was to explore the relationships between sex, age, and microbiota speciation on mixed flavonoid elimination over 24 h.
Healthy males and females (n = 163) prospectively recruited on the basis of age (18-30 y or 65-77 y) and sex consumed a standardized flavonoid-rich test meal providing 640-mg cocoa/chocolate flavan-3-ols, 340-mg citrus flavanones, and 390-mg blackberry anthocyanins. Urinary samples collected at baseline (-24 to 0 h), 0 to 3.5 h, >3.5 h to 7 h, and >7 to 24 h were analyzed for flavonoids and their metabolites by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Stool microbiome speciation was determined via Illumina sequencing. Linear mixed-effect models were used to assess differences in cumulative excretion across age and sex with time-by-group interaction taken as the principal analysis of effect.
There were no group (older females, older males, younger females, and younger males) differences in total 24 h urinary metabolite recovery, but there was a trend toward a higher rate of cumulative recovery in older males versus younger males at 24 h (P-group at 24h = 0.06). Of 76 metabolites, 20 had significantly different times of maximum urine excretion (Tmax) by age and 9 by sex, with a later mean Tmax observed for older participants (92% of instances). Associations with age were not mediated by body mass index (BMI) or microbiome speciation. Significant differences in maximum urine excretion (Cmax) by sex were observed for only 6 metabolites and differences by age for 5 metabolites.
Total elimination recovery of (poly)phenols was relatively consistent across age and sex groups, whereas elimination kinetics (Tmax) differed substantially being much later in older indivudals, possibly resulting from differences in intestinal transit time or kidney clearance. Assuming (poly)phenol metabolites have varying biological activities, establishing dose-response relationships and defining metabolite profiles in population subgroups is required to inform the future development of dietary flavonoid/(poly)phenol recommendations. This trial was registered at clinicaltrials.gov as NCT01922869.
营养干预试验表明，增加类黄酮摄入量可对疾病结局/生物标志物产生具有临床意义的影响；然而，观察到吸收和代谢存在高度变异性，生化和生理反应存在很大异质性。这种变异性的病因尚不清楚。
本研究的目的是探讨性别、年龄和微生物群种类与24小时内混合类黄酮消除之间的关系。
根据年龄（18 - 30岁或65 - 77岁）和性别前瞻性招募的健康男性和女性（n = 163）食用标准化的富含类黄酮的试验餐，其中含有640毫克可可/巧克力黄烷 - 3 - 醇、340毫克柑橘类黄烷酮和390毫克黑莓花青素。在基线（-24至0小时）、0至3.5小时、>3.5小时至7小时以及>7至24小时收集的尿液样本通过超高效液相色谱 - 质谱联用仪（UPLC-MS/MS）分析类黄酮及其代谢物。通过Illumina测序确定粪便微生物群种类。使用线性混合效应模型评估不同年龄和性别的累积排泄差异，并将时间 - 组交互作用作为主要效应分析。
24小时尿代谢物总回收率在各年龄组（老年女性、老年男性、年轻女性和年轻男性）之间无差异，但老年男性在24小时时的累积回收率有高于年轻男性的趋势（24小时时P组 = 0.06）。在76种代谢物中，20种代谢物的最大尿排泄时间（Tmax）按年龄有显著差异，9种按性别有显著差异，老年参与者的平均Tmax较晚（92%的情况）。与年龄的关联不受体重指数（BMI）或微生物群种类的介导。仅6种代谢物的最大尿排泄量（Cmax）按性别有显著差异，5种代谢物按年龄有显著差异。
（多）酚类的总消除回收率在不同年龄和性别组中相对一致，而消除动力学（Tmax）差异很大，老年个体的消除时间要晚得多，这可能是由于肠道转运时间或肾脏清除率的差异所致。假设（多）酚类代谢物具有不同的生物活性，则需要在人群亚组中建立剂量反应关系并定义代谢物谱，以为未来膳食类黄酮/（多）酚类建议的制定提供依据。该试验已在clinicaltrials.gov上注册，注册号为NCT01922869。
