| Summary: | Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and <i>Plasmodium</i> infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different <i>Plasmodium</i> species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls (<i>p</i> < 0.01, Cohen d: 2.51, 95% confidence interval (CI): 1.88–3.14, I<sup>2</sup>: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with <i>P. falciparum</i> malaria (<i>p</i> < 0.01, Cohen d: 2.50, 95% CI: 1.90–3.10, I<sup>2</sup>: 89.7%, 7 studies) and <i>P. vivax</i> malaria (<i>p</i> < 0.01, Cohen d: 3.70, 95% CI: 2.48–4.92, I<sup>2</sup>: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during <i>Plasmodium</i> infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria.
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