**Background:** Lipid peroxidation (LPO) is an autocatalytic chain oxidation of polyunsaturated fatty acids that damages cellular membranes and contributes to diseases such as cancer, diabetes, and neurodegeneration. Vanadium, a first-row transition metal, can both induce and protect against LPO through direct ROS generation (via Fenton/Haber–Weiss chemistry) and indirect effects on cellular redox balance. The biological impact of vanadium depends critically on its speciation—particularly oxidation states IV and V—and the presence of ligands. This review synthesizes the mechanisms by which vanadium compounds affect ROS formation and LPO, emphasizing the role of decavanadate (V10) versus monomeric vanadate (V1).
**Methods:** The authors conducted a narrative review of the literature, covering in vitro, in vivo, and cell-based studies. They describe the chemical mechanisms of ROS generation by vanadium (e.g., reactions 1–12), the three-phase LPO process (initiation, propagation, termination), and biomarkers used to assess LPO (malondialdehyde [MDA], 4-hydroxynonenal [4-HNE], cis-parinaric acid, ascorbate, superoxide dismutase [SOD], catalase [CAT]). Key comparisons are made between V1 and V10 effects on mitochondria, plasma membranes, endomembrane systems, and DNA. The review also summarizes studies on vanadium compounds in cancer, diabetes, and neurodegenerative disease models.
**Key Results:** Vanadium induces ROS through Fenton-type reactions (VIV + H2O2 → VV + HO• + HO−), bioreduction of vanadate by glutathione or NADPH, and indirect mitochondrial interactions. V10 is 10–100 times more potent than V1 in depolarizing mitochondrial membranes (IC50 = 38.7 ± 10.2 nM for V10 vs. 5.4 ± 2.5 μM for V1 in rat liver mitochondria) and inhibiting oxygen consumption (IC50 = 98.5 ± 5.1 nM for V10 vs. 9.7 ± 1.4 μM for V1). In fish cardiac mitochondria, V10 inhibited superoxide production with IC50 = 610 nM (without NADH) and 15 nM (with NADH), while V1 required 237 nM for 50% inhibition. In vivo, V10 increased LPO in cardiac tissue by ~80% after 7 days (5 mM total vanadium), whereas V1 caused a ~60% increase. In diabetic animal models, vanadium compounds (e.g., sodium orthovanadate, vanadyl sulfate, metformin-decavanadate) restored altered antioxidant enzyme activities (SOD, CAT, GPx) and normalized elevated MDA levels. For example, metformin-decavanadate normalized MDA and 4-hydroxyalkenal levels in alloxan-diabetic rats. In cancer models, vanadium compounds showed both pro-oxidant (cytotoxic to osteosarcoma cells) and chemopreventive effects (reducing LPO in carcinogen-treated rats). Vanadium also affects DNA through direct intercalation and indirect ROS-mediated oxidation of guanine to 8-hydroxyguanine.
**Clinical Implications:** Vanadium compounds have potential therapeutic applications in diabetes (insulin-mimetic and antioxidant effects), cancer (selective cytotoxicity and chemoprevention), and neurodegenerative diseases (modulation of oxidative stress). However, the dual pro-oxidant/antioxidant nature of vanadium necessitates careful speciation analysis to predict biological outcomes. The review emphasizes that future studies must include vanadium speciation to distinguish direct from indirect effects on LPO and ROS. The development of novel vanadium-based therapeutics, such as V2C MXenzyme (a 2D vanadium carbide with multi-enzyme mimetic activity), may offer new strategies to combat oxidative stress-related diseases. Despite promising preclinical data, clinical translation remains limited, and further research is needed to establish safety and efficacy.