How stable is oxidative stress level? An observational study of intra- and inter-individual variability in urinary oxidative stress biomarkers of DNA, proteins, and lipids in healthy individuals

Environ Int. 2019 Feb;123:382-389. doi: 10.1016/j.envint.2018.12.009. Epub 2018 Dec 17.


Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF [8-PGF], 11β-prostaglandinF [11-PGF], 15(R)-prostaglandinF [15-PGF], and 8-iso,15(R)-prostaglandinF [8,15-PGF]); proteins (o,o'-dityrosine [diY]); and DNA (8-hydroxy-2'-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.

Keywords: 8-hydroxy-2′-deoxyguanosine; Biomarker; ICC; Isoprostane; Oxidative stress; Urine; Variability.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Biomarkers / urine*
  • Creatinine / urine
  • DNA
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Female
  • Healthy Volunteers
  • Humans
  • Lipids
  • Male
  • Malondialdehyde / urine
  • Nutritional Status
  • Oxidation-Reduction
  • Oxidative Stress*
  • Reference Values
  • Tyrosine / analogs & derivatives
  • Tyrosine / urine


  • Biomarkers
  • Lipids
  • Tyrosine
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Creatinine
  • dityrosine
  • Deoxyguanosine