**Background:** Free radicals, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated during normal cellular metabolism and play beneficial roles in redox regulation, signaling, and immune function at low concentrations. However, when produced in excess, they cause oxidative stress, damaging lipids, proteins, and DNA, and contributing to the pathophysiology of numerous chronic diseases including cancer, cardiovascular disease, neurodegenerative disorders, rheumatoid arthritis, cataracts, and liver, renal, and lung diseases. The human body has endogenous antioxidant defenses (e.g., superoxide dismutase, catalase, glutathione peroxidase) and also relies on exogenous dietary antioxidants (e.g., vitamins C, E, A, selenium, polyphenols) to neutralize free radicals. This review aims to update current knowledge on free radical sources, types, and the mechanisms of action of both natural and synthetic antioxidants.
**Methods:** The authors conducted a narrative review by searching electronic databases (PubMed/Medline, Web of Science, Science Direct) using MeSH terms related to antioxidants, free radicals, oxidative stress, and human diseases. The taxonomy of plants mentioned was verified using 'The PlantList'. The review synthesizes information from a wide range of published studies, including in vitro, in vivo, and clinical investigations, but does not follow a systematic review methodology or meta-analysis.
**Key Results:** The review details the involvement of ROS in various cancers (lung, liver, colorectal, breast, prostate) through mechanisms such as DNA damage, chronic inflammation, metastasis, and angiogenesis. For example, in breast cancer, elevated levels of malondialdehyde (a marker of oxidative stress) are observed in advanced stages compared to early stages. In rheumatoid arthritis, a 5-fold increase in mitochondrial ROS in monocytes and whole blood of patients is reported compared to healthy individuals. The review also covers the role of ROS in liver diseases (e.g., alcohol-induced oxidative stress), renal diseases (e.g., ischemia-reperfusion injury), lung diseases (e.g., from cigarette smoke), neurological diseases (e.g., Parkinson's disease via iNOS and COX2), cardiovascular diseases (e.g., heart failure, ischemia-reperfusion injury), and cataracts (where oxidation is an initial step). The antioxidant section describes endogenous enzymes (SOD, CAT, GPx, G6PD) and exogenous agents including vitamins (E, C, A), selenium, and numerous natural compounds such as curcumin, resveratrol, flavonoids, phenolic acids (caffeic, gallic, ferulic), alkaloids, and terpenoids. Mechanisms of action include free radical scavenging, metal chelation, inhibition of pro-oxidant enzymes (e.g., xanthine oxidase, NADPH oxidase), and upregulation of antioxidant enzymes. The review also presents tables summarizing chemopreventive effects of dietary agents (e.g., soy, curcumin, epigallocatechin gallate) and clinical studies showing benefits of antioxidants like resveratrol, curcumin, quercetin, and vitamin E in conditions such as cardiovascular disease, diabetes, and inflammation.
**Clinical Implications:** The review emphasizes that oxidative stress is a common pathogenic mechanism in many chronic diseases, and antioxidants offer a promising therapeutic and preventive strategy. However, it notes significant limitations: high-dose antioxidant supplements can act as pro-oxidants and cause side effects; many antioxidants have poor bioavailability; and laboratory effects often do not translate to in vivo efficacy. The authors advocate for obtaining antioxidants from a diet rich in fruits, vegetables, nuts, and seeds rather than isolated supplements. They call for further research to understand the fine-tuning of oxidative stress in the body and to develop effective, non-toxic natural antioxidant therapies, especially for populations without access to costly drugs.