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Context Although the nutritional composition of organic food has been thoroughly researched, there is a dearth of published data relating to its impact on human health. Objective This systematic review aimed to examine the association between organic food intake and health effects, including changes in in vivo biomarkers, disease prevalence, and functional changes. Data Sources PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception through Nov 13, 2022. Data Extraction Both observational and interventional studies conducted in human populations were included, and association between level of organic food intake and each outcome was quantified as "no association," "inconsistent," "beneficial correlation/harmful correlation," or "insufficient". For outcomes with sufficient data reported by at least 3 studies, meta-analyses were conducted, using random-effects models to calculate standardized mean differences. Data Analysis Based on the included 23 observational and 27 interventional studies, the association between levels of organic food intake and (i) pesticide exposure biomarker was assessed as "beneficial correlation," (ii) toxic metals and carotenoids in the plasma was assessed as "no association," (iii) fatty acids in human milk was assessed as "insufficient," (iv) phenolics was assessed as "beneficial", and serum parameters and antioxidant status was assessed as "inconsistent". For diseases and functional changes, there was an overall "beneficial" association with organic food intake, and there were similar findings for obesity and body mass index. However, evidence for association of organic food intake with other single diseases was assessed as "insufficient" due to the limited number and extent of studies. Conclusion Organic food intake was found to have a beneficial impact in terms of reducing pesticide exposure, and the general effect on disease and functional changes (body mass index, male sperm quality) was appreciable. More long-term studies are required, especially for single diseases. Systematic Review Registration PROSPERO registration no. CRD42022350175. [ABSTRACT FROM AUTHOR]