The relationship between cotinine levels in the blood with glutathione, and malondialdehyde levels of smokers: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]

Background: Smoking is associated with increased oxidative stress and inflammation, which can lead to the development of various diseases. Blood cotinine level is a reliable biomarker of nicotine exposure, and glutathione and malondialdehyde levels are biomarkers of oxidative stress and inflammation. Several studies have been conducted to investigate the relationship between blood cotinine levels, glutathione levels, and malondialdehyde levels in smokers. Therefore, we conducted this meta-analysis to investigate the association. Methods: All cross-sectional and case-control studies published in the last 20 years (2003-2023) were identified by searching electronic databases such as PubMed, Science Direct, DOAJ, ResearchGate, and Google Scholar. Inclusion criteria were studies that focused on the relationship between blood cotinine levels, glutathione levels, and malondialdehyde levels in smokers, while qualitative research type, non-human studies, and studies that included variable measurement parameters saliva, urine, and hair were excluded. Results: Six case-control and cross-sectional studies with 333 participants who were smokers and 267 participants who were non-smokers were included in the meta-analysis. There was a significant association between blood cotinine levels with malondialdehyde levels in smokers (MD = 115.37, p 0.0004, 95% CI = 51.92 to 178.82). The mean difference is positive indicating that the average blood levels of cotinine in smokers tend to be higher than malondialdehyde levels in smokers. Conclusions: Based on our meta-analysis, blood cotinine levels were significantly associated with malondialdehyde levels in smokers. Smoking can increase blood cotinine levels of smokers compared with that of non-smokers.