**Background:** Ionizing radiation generates reactive oxygen species (ROS) that cause cellular damage, including DNA single-strand and double-strand breaks, base damage, and DNA–protein cross-links, leading to gene alteration, cell death, and genomic instability. Radioprotective agents—including sulfhydryl compounds, antioxidants, adaptogens, and absorbents—work by suppressing reactive species formation and detoxifying radiation-induced species. Vitamins, as essential organic compounds with antioxidant properties, represent a potentially safe and accessible class of radioprotective agents. This review aimed to evaluate the radioprotective effect of vitamins in single use, combination form, or with other nutritional and non-nutritional compounds across ex vivo, in vitro, and in vivo studies.
**Methods:** The review was conducted following the PRISMA statement using PubMed and Embase databases. PubMed search used MeSH terms 'vitamin', 'radioprotective', and 'radiation'; Embase search used 'vitamin', 'radioprotector', 'radioprotective', and 'radiation'. Boolean operators AND/OR were applied. The search was limited to English-language publications from January 2001 to January 2023. Inclusion criteria were ex vivo, in vitro, and in vivo studies from original papers, review papers, theses, and experimental procedures. Exclusion criteria included abstracts only, unrelated abstracts, books, letters, conference literature, case reports, editorials, and pilot studies. Three paired reviewer teams independently screened titles, abstracts, and full texts, with disagreements resolved by a separate researcher.
**Key Results:** A total of 38 articles were included. Most research (n=27) was in vivo studies, followed by in vitro (n=9) and ex vivo (n=2). Only four of thirteen vitamins demonstrated radioprotective properties, ranked from highest to lowest: vitamin E, vitamin C, vitamin A, and vitamin D. Vitamin E, particularly γ- and δ-tocotrienol isoforms, showed superior radioprotective effects compared to α-tocopherol, though low bioavailability remains a limiting factor. Vitamin E protected the ileum and colon in rats, improved survival in irradiated mice, and reduced radiation-induced apoptosis in MOLT-4 cell lines. Vitamin C demonstrated antioxidant and pro-oxidative activity, reducing DNA damage by 30–50% in gamma-irradiated thymus cells, protecting mice from radiation lethality, decreasing chromosomal aberrations in bone marrow cells, and ameliorating serum oxidative stress in differentiated thyroid cancer patients ablated with radioiodine. Vitamin D showed anti-inflammatory, antioxidant, and radioprotective effects on lacrimal glands in rats. Vitamin A was used only in combination with other vitamins. Combined vitamin use with other compounds showed variable results; the highest protection factor value (4.3) was obtained with vitamin C and famotidine, reducing the frequency of micronucleous polychromatic erythrocytes after irradiation. Notably, 75 mg/kg of α-tocopherol caused negative effects or death in non-human primates, indicating potential toxicity at high doses.
**Clinical Implications:** The findings suggest that vitamins E, C, A, and D may serve as accessible radioprotective agents for individuals exposed to ionizing radiation, including patients undergoing diagnostic or therapeutic radiation, personnel handling nuclear emergencies, and space travelers. However, significant gaps remain: radiation injury mechanisms are not fully identified, in vivo toxicity of agents under development is a concern, the duration of radioprotective or radiomitigative effects after exposure is unclear, and the selective protection of normal versus cancer cells is not well understood. The review emphasizes that more cellular, molecular, and whole-animal or human-level research is needed to guarantee the security and efficiency of vitamins as radioprotective agents before clinical translation.