Traditional views of adverse health effects of macronutrient have largely centered around calories and the intake-expenditure balance. Recent advancements in the biomedical technology have allowed measurements of metabolic and physiologic responses to macronutrient from molecular, cellular to system levels. These scientific achievements have enabled a deeper understanding of the qualitative aspects of macronutrient, beyond simple calorie values, and their impact on health and disease on an individualized manner.

Cellular response to oxidative stress is difficult to measure as it is a transient reaction to external stimuli. The study team has previously developed a home-built, desktop-sized micro-NMR system that can measure the oxidative stress status of red blood cells^1,2. Red blood cells are ubiquitous in the human body and well homogenized through blood circulation. They may provide a view into the acute phase oxidative stress in the circulation following nutritional intake³. The NMR system was deployed in this clinical study involving fourteen healthy subjects to examine the acute oxidative stress response in red blood cells following different mixed-meal tolerance test. Additionally, urine F2-isoprostane was also measured using LC-MSMS as an orthogonal marker for oxidative stress status. 

Based on the homeostatic model of assessment insulin resistance (HOMA-IR) and body mass index, the subjects were divided into metabolically healthy and lean (MHL; HOMA-IR 0.83±0.10; 18.5 kg/m²≤ BMI≤ 23 kg/m²), and metabolically unhealthy and obese (MUO; HOMA-IR 4.34±0.41; BMI ≥27.5 kg/m²) subgroups, respectively.

The subjects were given standardized isocaloric mixed meal tolerance tests with three different dominant macronutrient compositions, namely, high fat (HF), high carbohydrate (HC), and high protein (HP). The meals were given in a randomized order with a 7-day washout period between each trial. Blood samples were collected at baseline and every 30 min for 3 hours following the meal challenge, along with urine samples. Details of the study can be found in the recent published article in npj Science of Food.³

Overall, oxidative stress measured in the red blood cells increased with all meal challenges with the MUO subgroup having higher values than the MHL subgroup. These findings were corroborated in the urine F2-isoprostane measurements, which were similarly elevated following the HF and HP mixed meal tests, but not the HC meal, which paradoxically decreased. The results of the red blood cells and urine oxidative stress markers as well as the red blood cell oxidative stress and blood glucose were further combined into newly proposed framework to provide an integrated view of different oxidative and metabolic response to a mixed meal. Another advantage of these integrated approaches is the ability to assess integrated responses of individual subjects that may not be apparent from information provided by a single biomarker.

The findings of the study demonstrated the oxidative responses of red blood cells using the micro-NMR system. The proposed oxidative-metabolic framework for interpreting integrated dual-biomarker information fits enhances current understanding of metabolic and inflammatory drivers of oxidative response following nutritional intake. The findings of this study should be considered preliminary and larger studies should be conducted to confirm them. Additionally, prospective clinical trials are needed to determine the association between the biomarkers (and the newly proposed interpretative framework) and the diagnostic and prognostic performance of diabetes and its complications.

 by WKPeng and TPLoh

1. Peng, W. K., Chen, L., Boehm, B. O., Han, J. & Loh, T. P. Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system. Npj Aging Mech. Dis. 6, 11 (2020).
2. Peng, W. K., Chen, L. & Han, J. Development of miniaturized, portable magnetic resonance relaxometry system for point-of-care medical diagnosis. Rev. Sci. Instrum. 83, 095115 (2012).
3. DOI 10.1038/s41538-024-00282-x