Betainized metabolites as biomarkers of whole grain wheat, not oat: insights from controlled pharmacokinetic and dietary intervention studies

Authors: LI, YANHE - North Carolina A&t State University; Novotny Dura, Janet; Baer, David; HU, YANG - Harvard University; SUN, QI - Harvard University; ZHANG, SHUWEI - North Carolina A&t State University; SANG, SHENGMIN - North Carolina A&t State University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: The interest in precision health initiatives continues to grow in the medical, nutrition, and health care communities. Better understanding of dietary intake and its connection to health outcomes will support precision health. To that end, nutrition researchers are conducting studies to identify blood and urine biomarkers that reflect dietary intake, for a more accurate assessment of diet and health. We conducted two studies to find blood and urine biomarkers that would reflect short term and longer term whole grain oat and wheat intake. Whole grain oats and wheat are associated with a number of potential health benefits, including reduced risk for cardiovascular disease and diabetes. For one study, we fed a meal of whole grain wheat porridge or whole grain oatmeal to volunteers, then collected blood and urine at many time points over a 2-day period. For the other study, we fed whole grain wheat or oat products daily and collected blood and urine samples weekly. We analyzed the blood and urine with specialized instruments to find compounds specific to whole grain wheat or oats. We successfully identified a number of compounds that were specific to the different whole grains, and we tracked how fast they rose and fell in blood and urine. We also found different patterns for males vs. females, lean vs. obese, and young vs. old. The identification of these compounds and their time course pattern in blood and urine will be used by scientists to better predict dietary patterns in free-living adults and subsequently determine relationships between whole grain intake and health.

Technical Abstract: Betainized compounds are bioactive metabolites in one-carbon metabolism and cellular osmoprotection. Whole grains (WGs) are one of the major dietary sources of these compounds, but their postprandial and daily metabolic responses in humans remain understudied. We aimed to characterize the pharmacokinetic (PK) profiles and short-term accumulation patterns of 16 betainized metabolites following WG wheat and WG oat intake in healthy adults, to identify compounds that serve as specific biomarkers for WG wheat or oat consumption. Two randomized, controlled crossover trials were conducted in which subjects consumed WG treatments: (1) a 2-period acute PK study involving 12 healthy adults with serial plasma and urine collection up to 24 h and 48 h, respectively; and (2) a five-period controlled feeding study with 54 participants consuming WG oat or WG wheat daily, with weekly blood and urine collection. All samples were analyzed using LC-MS/MS. PK parameters (Cmax, Tmax, AUC, and cumulative urinary excretion) were calculated, and statistical analyses assessed interindividual variability, time-dependent trends, and grain-specific effects. Valine betaine, isoleucine betaine, and glutamine betaine exhibited distinct PK profiles with peak plasma concentrations at 5–6 hours post-consumption of WG wheat but not oat, coinciding with their major urinary excretion phase (4–6 h) as these compounds were 30- to 50-fold more abundant in WG wheat than oat. In the daily intake study, their plasma and urine concentrations increased significantly over time (p < 0.05), demonstrating clear dose- and time-dependent accumulation consistent with their kinetic behavior. Valine betaine, isoleucine betaine, and glutamine betaine are specific biomarkers of WG wheat intake, but not WG oat. Their distinct responses support use of dietary biomarkers for precision nutrition approaches when evaluating the health benefits of individual WGs.