Health Impacts of Micro- and Nanoplastics in Humans: Systematic Review of <i>In Vivo</i> Evidence

SUMMARY Background Microplastics and nanoplastics (MNPs; &lt;5 mm) are pervasive environmental contaminants with potential human health implications. Although laboratory models implicate MNPs in oxidative stress, inflammation, and endocrine disruption, a comprehensive synthesis of direct in vivo human evidence is lacking. We aimed to systematically review studies measuring MNPs in living human subjects and summarize associated health findings. Methods We systematically searched PubMed, Web of Science, Scopus, Cochrane and Embase through 26 December 2024. Two investigators independently screened and selected original research articles that quantified MNPs in biological samples from living humans (blood, tissues, or fluids). We excluded animal, in vitro , cell-line, and injection-based studies, as well as reports on non-plastic micro- and nanoparticles. Data extraction, performed in duplicate, included study design, participant characteristics, detection methods, polymer types, and reported health outcomes. Methodological quality was appraised using Risk Of Bias in Non-Randomized Studies - of Exposures (ROBINS-E). The primary outcome was the presence and burden of MNPs; secondary outcomes were clinical or biomarker associations. We did not perform meta-analysis due to heterogeneity. Findings From 5 522 records, 25 studies (n=1498 participants) met inclusion. Studies employed pyrolysis-gas chromatography/mass spectrometry (n=9), Raman (n=8), infrared spectroscopy (n=7), and Fourier-transform infrared spectroscopy (n=3), often combined with microscopy. Predominant polymers were polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, and polystyrene. In cardiovascular research (five studies; n=454), higher thrombus and plasma MNP burdens correlated with inflammatory markers and adverse cardiac events. Reproductive research (seven studies; n=327) linked semen and tissue MNP levels to reduced sperm quality and higher burdens in tumor and placental samples. Gastrointestinal research (nine studies; n=537) associated fecal MNPs with liver enzyme elevations and gut dysbiosis. Respiratory (three studies; n=171) and ocular (one study; n=49) research detected MNPs in airway fluids and vitreous humor, with suggestive links to inflammation and increased intraocular pressure. ROBINS-E assessments indicated moderate to high risk of confounding and exposure-measurement bias; consistency across detection modalities was limited. Interpretation Human in vivo evidence confirms that MNPs accumulate in multiple organ systems and are associated with inflammation and functional impairment. Methodological heterogeneity and bias constrain causal inference. Standardized, prospective cohort studies with rigorous exposure assessment and confounder control are needed to advance understanding and guide policy. Funding This study was funded by the SingHealth Duke-NUS Academic Medical Centre under the Nurturing Clinician Scientist Award scheme (15/FY2025/P1/17-A45) and the Clinician Investigator Advancement Programme (15/FY2022/CIVA/03-A03).