Impact of Microplastic Exposure on Human Health: A Systematic Review of Mechanisms, Biomarkers, and Clinical Outcomes.

Microplastics (≤5 mm) are increasingly recognized as pervasive environmental pollutants with potential implications for human health. Human exposure occurs primarily through ingestion and inhalation, with limited evidence also suggesting dermal contact. Microplastics have been detected in human blood, placental tissue, and gastrointestinal samples, indicating systemic exposure. Proposed biological pathways include oxidative stress, inflammation, endocrine disruption, and alterations in the gut microbiota; however, direct evidence linking these mechanisms to adverse health outcomes in humans remains limited. This systematic review synthesizes human-based evidence to evaluate health outcomes associated with microplastic exposure. The review includes primary human studies, specifically observational studies and clinical trials, as well as human-focused systematic reviews. Animal and in vitro studies were excluded from outcome synthesis because they do not directly reflect human clinical effects. Mechanistic insights derived from non-human experimental studies were included only to provide biological context and were clearly separated from human outcome data to avoid over-interpretation. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for articles published between January 2010 and May 2025. Primary human studies constituted the core evidence base for data extraction, qualitative synthesis, and certainty of evidence assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. Systematic reviews were evaluated at the review level only using AMSTAR-2 to assess methodological quality, examine consistency or discordance in reported associations, and identify evidence gaps. These reviews were not decomposed into their constituent primary studies to prevent duplication. In total, 30 articles were included, comprising 22 observational studies, five clinical trials, and three systematic reviews. Across included studies, inflammatory biomarkers (CRP (C-reactive protein), IL-6, TNF-α), endocrine markers (thyroid hormones, cortisol), and oxidative stress indicators (8-OHdG, MDA (malondialdehyde)) were frequently reported. These findings represent recurrent statistical associations and convergent qualitative trends identified through structured narrative synthesis, rather than evidence of biological causation. Evidence related to neurocognitive outcomes and chronic diseases, including diabetes and cardiovascular disease, was limited and inconsistent. Methodological heterogeneity across studies precluded meta-analysis, necessitating an organized qualitative synthesis. Overall, evidence certainty was moderate for inflammatory and endocrine biomarkers but low for neurocognitive and chronic disease outcomes. Overall, current human evidence suggests associative links between microplastic exposure and biological markers of inflammation, oxidative stress, and endocrine alteration. However, causal relationships with specific clinical diseases remain unestablished, underscoring the need for standardized biomarkers, longitudinal cohort studies, and interdisciplinary research to clarify long-term health implications.