selenomethionine (SLM) / Holden Comprehensive Cancer Center, The University of Iowa - LARVOL DELTA

Methylseleninic acid enhances anti-FN14 CAR-T cell effector function and redirects cytotoxicity against TGF-β-rich kidney, prostate, and brain tumors (AACR 2026) - "MSA augments anti-FN14 CAR-T cytotoxicity, metabolic fitness, and sustained effector function by suppressing tumor-derived TGF-β1 and PD-L1 and directly enhancing CAR-T activity. As a clinically relevant TGF-β1 inhibitor and active seleno-L-methionine metabolite, MSA represents a readily translatable strategy to reduce CAR-T exhaustion and improve efficacy in TGF-β-rich solid tumors."

CAR T-Cell Therapy • Brain Cancer • Castration-Resistant Prostate Cancer • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Glioblastoma • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • IFNG • IL2 • TGFB1 • TNFSF12

L-Selenomethionine Alleviates Cryo-Induced Ferroptosis Through the NRF2-SLC7A11-GPX4 Pathway, Improving Post-Thaw In Vitro Quality of Dairy Goat Spermatozoa. (PubMed, Antioxidants (Basel)) - "Collectively, these findings demonstrate that L-SeMet protects spermatozoa from cryo-induced injury by stabilizing redox homeostasis, maintaining mitochondrial function, and inhibiting ferroptosis. The results highlight ferroptosis as a critical mechanism of sperm cryodamage and identify L-SeMet as a promising metabolic intervention to enhance post-thaw sperm quality and fertility."

Journal • Preclinical • GPX4 • SLC7A11 • VDAC3

Selenomethionine antagonizes sodium arsenite-induced reproductive toxicity in zebrafish. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "In addition, CYP17A1 protein expression in spermatogonia was markedly reduced by AsIII but showed a clear recovery tendency following Se-Met treatment. In conclusion, low-dose Se-Met supplementation partially alleviates AsIII-induced reproductive toxicity in zebrafish, supporting its potential role as a partially ameliorative agent against sodium arsenite exposure."

Journal • CYP17A1 • FSHB

Serum concentrations of selenium, selenium species and metals in children newly diagnosed with leukemia: a hospital-based case-control study. (PubMed, Environ Res) - "Two selenium species, selenoprotein P-bound selenium and selenomethionine, showed similar results to total selenium...These findings indicate the need for further investigation of the potential adverse role of some selenium species and copper in childhood leukemia. However, reverse causation bias and residual confounding could not be ruled out as possible explanations for our findings."

Journal • Hematological Malignancies • Leukemia • Oncology • SELENOP

Elucidating the Effects of Selenium Enrichment on the Structure and Antioxidant Properties of Selenium-Containing Proteins in Yeast Cells. (PubMed, Antioxidants (Basel)) - "Specifically, in selenium-enriched Saccharomyces cerevisiae, where Se was predominantly incorporated as selenomethionine (SeMet, 85.80%), a significant structural relaxation occurred...Consequently, Saccharomyces cerevisiae uniquely achieved highly significant (p < 0.001) antioxidant improvements, whereas other strains showed moderate or non-significant responses despite high Se yields. Our findings demonstrate that the antioxidant efficacy of selenoproteins is not solely determined by total Se content but is fundamentally driven by the targeted bioconversion of SeMet and its associated structural relaxation."

Journal

Selenotrisulfide delivery restores redox balance in myocardial infarction via a thiol-exchange reaction in situ. (PubMed, Bioact Mater) - "Compared to the traditional selenium sources such as sodium selenite (Na2SeO3), L-selenomethionine (SeMet) and L-selenocysteine ((Sec)2), STS exhibited superior antioxidative and therapeutic efficacy by augmenting selenium levels and oxidoreductase-like activities in vitro and in vivo. Proteomic analysis revealed that STS could better improve myocardial contraction and regulate glucolipid metabolism to enhance energy supply and cardiac repair. Furthermore, the core-shell nanofibrous ZPB@STS patch significantly contributed to lower inflammatory response, less cell death and collagen deposition, and stronger cardiac contraction through the cooperative interaction of selenium-regulation from STS and mechanical support from the elastomeric polyurethane fibrous patch."

Journal • Cardiovascular • Inflammation • Metabolic Disorders • Myocardial Infarction

Potential of Zinc-L-Selenomethionine to Improve the Health of Weaned Piglets and Its Antioxidant Stress Mechanism Through Modulation of PI3K/AKT and Nrf2/Keap1 Signaling Pathways. (PubMed, Int J Mol Sci) - "Furthermore, Zn-L-SeMet significantly increased the expression levels of Keap1, NQO1, HO-1, ARE, p-Nrf2, p-PI3K, and p-AKT, and protein ratio of p-Nrf2/Nrf2, PI3K/PI3K, and p-AKT/AKT compared to the H2O2 group (p < 0.05). In conclusion, Zn-L-SeMet improves health status with antioxidant potential in weaned piglets, and the mechanism is associated with activation of PI3K/AKT and Nrf2/Keap1 pathways."

Journal • NQO1

Anti-FN14 CAR-T cells overcome TGF-β-mediated suppression, and their synergy with methylseleninic acid enhances cytotoxicity and effector function in kidney, prostate, and brain tumors (AACR-IO 2026) - "MSA enhances anti-FN14 CAR-T cytotoxicity, metabolic fitness, and sustained effector activity by suppressing tumor-derived TGF-β1 and PD-L1 and by directly improving CAR-T functional capacity. Consistent with this mechanism, physiological TGF-β levels (0-5 ng/mL) did not significantly impair CAR-T proliferation or activation, demonstrating intrinsic resilience of FN14 CAR-T cells in TGF-β-rich environments. As a clinically relevant TGF-β1 inhibitor and active metabolite of seleno-L-methionine, MSA represents a readily translatable strategy to reduce CAR-T exhaustion and enhance efficacy in TGF-β-rich solid tumors including ccRCC, mCRPC, and GBM."

CAR T-Cell Therapy • IO biomarker • Brain Cancer • Castration-Resistant Prostate Cancer • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Glioblastoma • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CXCR3 • IFNG • IL2 • PD-1 • TGFB1 • TNFSF12

Species-specific effects and trophic transfer of selenium in a freshwater food chain. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "In this study, three microalgae species were exposed to selenite (Se(IV)) or seleno-L-methionine (Se-Met) (0-1000 μg/L) for 120 h, followed by dietary exposure of Daphnia magna to Se-contaminated C. pyrenoidosa (1-50 μg/L)...Moreover, Se-Met caused a 66% reduction in cumulative offspring production relative to Se(IV) treatment. This study provides a foundation for investigating Se trophic transfer mechanisms in freshwater food webs."

Journal

PVA/AgNP hydrogel SERS substrate combined with machine learning for highly sensitive detection of organic selenium species. (PubMed, Anal Methods) - "This substrate exhibited exceptional SERS performance for both L-selenomethionine (SeMet) and Se-(methyl) seleno-L-cysteine (SeMCys)...The support vector regression (SVR) model achieved a coefficient of determination (R2) greater than 0.991 on the prediction set, with root mean square error (RMSE) and mean absolute error (MAE) values of 35.884 µg L-1 and 8.663 µg L-1, respectively. The proposed method enabled accurate identification and precise quantification of organic selenium species in authentic water and soil samples, demonstrating potential for practical application."

Journal • Addiction (Opioid and Alcohol)

Integrating natural deep eutectic solvents and ionic liquids as green mobile phase additives for enhanced selenium speciation analysis in food samples by liquid chromatography-atomic fluorescence spectrometry. (PubMed, J Chromatogr A) - "The NADESs choline chloride:ethylene glycol and choline chloride:glycerol were applied as mobile phase additives for the separation of Se(IV), Se(VI), selenomethionine (SeMet) and Se-methylselenocysteine (SeMetSeCys)...The method achieved limits of detection of 1.59-2.78 µg L-1, with relative standard deviations of 0.53-1.86 % for retention times and 1.23-1.72 % for peak areas. Finally, the proposed analytical method was successfully applied to Se speciation analysis in complex food samples, including nuts and Se-enriched garlic, yielding recoveries of 93.4-106 %."

Journal

Targeting selenometabolites in the saliva of dairy cows: size-exclusion chromatography - inductively coupled plasma mass spectrometry-based characterization. (PubMed, Vet Anim Sci) - "A two-step feeding experiment was conducted with supplementing the selenite-containing daily ration with the hydroxy-analogue of selenomethionine (R,S-2-hydroxy-4-methylselenobutanoic acid, HMSeBA) at the highest authorized rate in the EU...The supplementation of HMSeBA did not significantly increase the blood selenium concentrations, and no correlation was found between the LMW selenium concentration and blood selenium concentrations. While the identification of LMW selenometabolites with electrospray ionization high-resolution mass spectrometry could not be achieved, a dedicated sample preparation protocol has been suggested for future experiments."

Journal • SELENOP

L-Se-methylselenocysteine alleviates iron deposit-induced anxiety- and depression-like behaviors in chronic renal failure rats receiving iron therapy via Nrf2/GPX4 activation. (PubMed, Free Radic Biol Med) - "L-SeMC alleviates iron overload-induced anxiety- and depression-like phenotypes in CRF rats by attenuating cerebral iron accumulation and activating the Nrf2/GPX4 pathway, thereby supporting its translational potential as an adjuvant therapy for CRF patients receiving iron supplements."

Journal • Preclinical • Chronic Kidney Disease • CNS Disorders • Depression • Hematological Disorders • Mood Disorders • Nephrology • Psychiatry • Renal Disease • GPX4 • TFRC

Personalized Antioxidant Supplementation Improves Muscle Strength, Physical Activity, and Quality of Life in Patients with FSHD1: A Real-World Longitudinal Study. (PubMed, Free Radic Biol Med) - "Patients (aged 15-76) at Montpellier Hospital received tailored antioxidant supplementation (vitamins C and E, zinc, copper, and selenomethionine) based on blood analyses during annual visits: 107 completed one year and 74 continued for two more years of supplementation...Baseline muscle strength and clinical scores, including the Brooke upper extremity scale score, allowed stratifying patients in responders and non-responders. These parameters underscore the importance of baseline assessments to predict outcomes and highlight the need of controlled studies to confirm these preliminary results."

HEOR • Journal • Observational data • Real-world evidence • Muscular Dystrophy • Myositis

Mechanism of Liver Injury Induced by Cr6+ in Zebrafish and Protective Effect of Selenomethionine. (PubMed, Animals (Basel)) - "Furthermore, transcriptomic profiling revealed that Se-Met exerts its protective effects primarily by modulating glycerolipid metabolism, thereby mitigating lipid accumulation. Collectively, our findings establish ferroptosis as a critical driver of Cr6+-induced hepatotoxicity and highlight Se-Met as a promising biochemical intervention to mitigate chromium-associated hepatic damage in aquaculture systems."

Journal • Hepatology • Liver Failure • Metabolic Disorders • GPX4

Selenomethionine Alleviates Zearalenone-Induced Liver Injury in Rabbits Through SIRT1-FOXO1/P53 Signaling Pathway. (PubMed, Antioxidants (Basel)) - "SeMet pretreatment activated SIRT1, reduced the acetylated FOXO1/P53 levels, and enhanced CAT and SOD2 expression, mitigating ZEA-induced oxidative stress, apoptosis, and mitophagy. Based on the above findings, SeMet's alleviating effect might be mediated via the SIRT1-FOXO1/P53 pathway, with 0.35 mg/kg of SeMet exerting the optimal efficacy, highlighting its therapeutic potential for mitigating ZEA-induced hepatotoxicity in rabbits."

Journal • Preclinical • Hepatology • Liver Failure • BAX • CASP3 • CASP9 • SOD2

Pharmacological activation of GPX4 by selenomethionine attenuates cisplatin-induced ototoxicity and hearing loss. (PubMed, Biochem Pharmacol) - "Inhibition of GPX4 using RSL3 or ML210 reversed the SeMet-induced reduction in ferroptosis and apoptosis, whereas inhibition of Nrf2 via siRNA or the inhibitor ML385 had no significant effect. Notably, SeMet did not compromise the ability of cisplatin to induce DNA damage and cell death in cancer cells. Collectively, these findings support SeMet as a promising protective agent for the prevention of CIHL and suggest that GPX4 may be a potential therapeutic target in managing CIHL."

Journal • Oncology • Otorhinolaryngology • GPX4

The content- and odor-advantaged volatile compounds and the visualized characteristic odor profile of n-3 PUFA-rich fried pork meat obtained from finishing pigs fed a diet enriched with linseed oil and selenomethionine. (PubMed, Food Chem) - "The visualized characteristic odor profiles were 1-octen-3-ol:hexanal:2,4-decadienal (13:5:1), 1-octen-3-ol:hexanal (3:1), and 1-octen-3-ol:hexanal:benzaldehyde (9:4:1) for fried meat from pigs fed traditional soybean oil, linseed oil, and linseed oil supplemented with Se-Met, respectively. The results of the electronic nose analysis and sensory evaluation confirmed significant differences in the characteristic odor profiles of fried meat from finishing pigs."

Journal

Selenomethionine as a dual-mechanism ferroptosis inhibitor: selenium-supply-driven GPX4 biosynthesis beyond transsulfuration and reductive-capacity-mediated ROS scavenging independent of GPX4 activity. (PubMed, Cell Death Dis) - "In the present study, we identified selenomethionine as a novel resister of ferroptosis induced by RSL3 through screening FDA drug library and natural product library. Significantly, selenomethionine administration effectively mitigated cisplatin-induced acute kidney injury in vivo by suppressing ferroptosis. This work establishes selenomethionine as a unique dual-mechanism ferroptosis suppressor that simultaneously modulates enzymatic antioxidant defense through GPX4 biosynthesis and non-enzymatic radical trapping via selenium-mediated redox cycling, providing new insights into therapeutic strategies for ferroptosis-related pathologies."

Journal • Acute Kidney Injury • Nephrology • Renal Disease • GPX4

Effects of L-selenomethionine supplementation on nutrient digestibility and metabolism, antioxidant capacity, hormone levels, and fecal microbiota diversity in pregnant Yili mares during mid- to late gestation. (PubMed, BMC Vet Res) - No abstract available

Journal

Harnessing the anti and pro-oxidants potential of selenium. (PubMed, J Trace Elem Med Biol) - "Once inside the plant, selenium undergoes complex speciation, transforming into organic compounds like selenomethionine and selenocysteine, which are then distributed throughout the plant tissues...Selenium-enriched crops are one of the key food sources of this vital trace element necessary for antioxidant defense and immune function in humans. Future research should focus on optimizing selenium biofortification protocols to maximize the antioxidant properties of selenium while minimizing the risk of pro-oxidant effects so as to promote sustainable agriculture and human nutrition."

Journal • Review

Efficient Biosynthesis of Selenium-Enriched Saccharomyces cerevisiae via Siderophore-Assisted selenite uptake and biotransformation. (PubMed, Bioresour Technol) - "X-ray Photoelectron Spectroscopy (XPS) and High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) analyses confirmed efficient biotransformation of Se (IV) to organic selenium, primarily selenomethionine (Se-Met), accounting for 97.85% of total selenoamino acids (1201.52 ng/g)...Transcriptomic analysis revealed that Siderophore-mediated selenium transport is not fully dependent on the high-affinity phosphate transporters and may involve the participation of Pho91p. This study offers a feasible strategy for producing selenium-enriched S. cerevisiae and a promising approach for bioavailable organic selenium supplements."

Journal

Exploring Interactive Effects of Arsenic and Selenium Exposure on Larval Zebrafish (Danio rerio). (PubMed, Environ Toxicol) - "To investigate this interplay, zebrafish embryos were exposed to As alone (as arsenite) or in combination with two different chemical forms of Se including As 120 μg/L alone (as arsenite), As 120 μg/L + Se 25 μg/L (as selenite), As 120 μg/L + Se 120 μg/L (as selenite), and As 120 μg/L + Se 2.5 μg/L (as selenomethionine, SeMet) until 4 days postfertilization...At the same time, co-treatment with As + Se 25 μg/L partially restored nrf2a expression (p < 0.05). These findings highlight the potential for naturally co-occurring Se to modulate As toxicity in aquatic environments, underscoring the importance of considering chemical interactions when assessing ecological risks."

Journal • NFE2L2

Toxicity of elemental selenium and selenium substances after pulmonary exposure; and environmental and occupational air concentrations: a review. (PubMed, Drug Chem Toxicol) - "Selenium distributes to blood and internal organs after pulmonary exposure. Animal inhalation studies indicate LOAECs of 1 and 33 mg Se/m3, while LOAELs of intratracheal instillation studies start at 0.06 mg Se/kg bw."

Journal • Review

The mechanism of selenomethionine alleviating fluoride-induced brain injury in carp by regulating mitochondrial dynamics, oxidative stress and neuroinflammation: Integrated analysis of transcriptomics and metabolomics. (PubMed, Aquat Toxicol) - "However, long-term exposure to Se-Met alone may also cause mild toxicity, indicating that its application requires strict control of dosage and exposure duration. This study elucidates the molecular mechanisms by which Se-Met mitigates F neurotoxicity and provides a theoretical basis for aquatic ecological risk assessment and selenium nutrition intervention strategies."

IO biomarker • Journal • Behavior Disorders • CNS Disorders • Inflammation • Mental Retardation • Metabolic Disorders • Psychiatry • Vascular Neurology • BAX • BCL2 • CASP3 • IL10 • IL1B • MFN1 • NLRP3 • TGFB1 • TNFA