Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive oxygen species (ROS). ROS can oxidize proteins, lipids, and DNA, and some of these oxidized products are excreted in urine, such as malondialdehyde (MDA), which is considered a biomarker for oxidative damage of lipids. To interpret changes of this biomarker as a measure of oxidative species overproduction in humans, a background range for urinary MDA concentration in the general population is needed. We sought to establish urinary MDA concentration ranges for healthy adult populations based on reported values in the available scientific literature. We conducted a systematic review and meta-analysis using the standardized protocol registered in PROSPERO (CRD42020146623). EMBASE, PubMed, Web of Science, and Cochrane library databases were searched from journal inception up to October 2020. We included 35 studies (divided into 47 subgroups for the quantitative analysis). Only studies that measured creatinine-corrected urinary MDA with high-performance liquid chromatography (HPLC) with mass spectrometry (MS), fluorescence detection, or UV photometry were included. The geometric mean (GM) of urinary MDA concentration was 0.10 mg/g creatinine and 95% percentile confidence interval (CI) 0.07–0.12. Age, geographical location but not sex, and smoking status had a significant effect on urinary MDA concentrations. There was a significant increasing trend of urinary MDA concentrations with age. These urinary MDA values should be considered preliminary, as they are based on mostly moderate to some low-quality evidence studies. Although urinary MDA can reliably reflect excessive oxidative stress in a population, the influence of physiological parameters that affect its meaning needs to be addressed as well as harmonizing the chemical analytical methods.

Many pathological conditions and certain airway exposures are associated with oxidative stress (OS). Malondialdehyde (MDA) is an end-product of the oxidation of lipids in our cells and is present in all biological matrices including exhaled breath condensate (EBC). To use MDA as a biomarker of OS in EBC, a reference interval should be defined. Thus, we sought to summarize reference values reported in healthy adult populations by performing a systematic review and meta-analysis using a standardized protocol registered in PROSPERO (CRD42020146623). Articles were retrieved from four major databases and 25 studies with 28 subgroups were included. Defining the distribution of MDA measured in reference populations with a detection combined with a separation technique still represents a challenge due to the low number of studies available, different analytical methods used, and questionable methodological qualities of many studies. The most salient methodological drawbacks have been in data collection and reporting of methods and study results by the researchers. The lack of compliance with the recommendations of the European Respiratory Society and American Thoracic Society was the major limitation in the current research involving EBC. Consequently, we were unable to establish a reference interval for MDA in EBC.