Assessment of the Effects and Safety of Spermidine Supplementation on Blood Lipids and Body Weight in Overweight or Obese Individuals With Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial

Evaluate the effect of spermidine supplementation on lipid profile changes in individuals with overweight or obesity accompanied by hyperlipidemia. Analyze the impact of spermidine on metabolic parameters and assess the safety of spermidine supplementation, including liver and kidney function, gastrointestinal reactions, and other adverse effects.

Start Date01 Jan 2026

Sponsor / Collaborator

Shanghai No. 10 People's Hospital

ChiCTR2500115190

/ SuspendedEarly Phase 1IIT

Assessment of the Effects and Safety of Spermidine Supplementation on Blood Lipids and Body Weight in Overweight or Obese Individuals with Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial

Start Date25 Dec 2025

Sponsor / Collaborator

Shanghai No. 10 People's Hospital

100 Clinical Results associated with Spermidine

100 Translational Medicine associated with Spermidine

100 Patents (Medical) associated with Spermidine

11,612

Literatures (Medical) associated with Spermidine

01 Feb 2027·TISSUE & CELL

Spiraeoside prevents copper oxide nanoparticles-induced myocardial impairments via regulating Wnt/β-catenin, oxidative stress, and inflammation: An echocardiographic and histopathological investigation

Article

Author: Mehreen, Arifa ; Alzahrani, Khalid J ; Hassan, Hesham M ; Jamil, Salim ; Halawani, Ibrahim F ; Arshad, Rameesha ; Alsharif, Khalaf F

Copper oxide nanoparticles (CuONPs) are widely employed in industrial and biomedical applications; however, their long-term exposure induces severe cardiac impairments. Spiraeoside (SPD) is a naturally occurring flavonoid with diverse biological properties. The current study was designed to investigate the cardioprotective effects of SPD against CuONPs-induced cardiotoxicity. Thirty-two rats were randomly allocated into four groups: control, CuONPs (100 mg/ kg), CuONPs (100 mg/kg) + SPD (200 mg/ kg), and SPD (200 mg/kg) alone treated group. Our findings showed that CuONPs exposure substantially reduced the expression of ATP2A2, RYR2, CACNA1C, and GSK3B while upregulating CAMK2D, AXIN2, WNT3A, and CTNNB1. Moreover, CuONPs intoxication induced severe oxidative imbalance as evidenced by high levels of ROS and MDA while reducing the activities of GST, GSR, CAT, HO-1, SOD and GPx. Besides, CuONPs administration increased the levels of Troponin-I, LDH, Troponin-T, CRP, BNP, NT-proBNP, CPK, and CK-MB. Severe echocardiographic alterations were found after CuONPs exposure as indicated by significant reduction in heart rate, high EDV and ESV, as well as ventricular dilation. Similarly, CuONPs induced marked upregulation of pro-inflammatory markers including COX-2, IL-6, IL-1β and TNF-α. A significant upregulation of Bax, Caspase-3, and Caspase-9 while a marked reduction in the levels of Bcl-2 was found following the exposure of CuONPs. Histopathological analysis showed severe structural myocardial damage in response to CuONPs intoxication. Nonetheless, SPD notably protected cardiac tissues via regulating calcium-dependent signaling pathways, inflammatory and apoptotic responses, echocardiographic parameters, oxidative stress, and histopathological alterations. Collectively, these findings suggest that SPD is a promising natural bioactive molecule against cardiac injury caused by nanoparticles. All preclinical studies, such as pharmacokinetic, toxicological, and dose optimization investigation, are still needed to assess the potential clinical applicability.

01 Jan 2027·BIOMATERIALS

Injectable hydrogel-mediated spermidine delivery triggers tumor pyroptosis via oxidative metabolism for enhanced cancer therapy

Article

Author: Wu, Xirui ; Xiong, Zijian ; Huang, Tianhao ; Liu, Yuqian ; Deng, Zheng ; Liu, Zhuang ; Liu, Li ; Chen, Huiyuan ; Wu, Zhuochao ; Wang, Chunjie ; Yang, Guangbao

Intracellular polyamine metabolic homeostasis is closely linked to therapeutic outcomes in cancer. However, their intrinsic antitumor mechanisms have not been fully clarified. Herein, we demonstrate that the catabolism of spermine (Spm) and spermidine (Spd) mediated by polyamine oxidase directly generates two potent cytotoxic metabolites, namely acrolein and hydrogen peroxide. These metabolites act synergistically to trigger a marked elevation in intracellular reactive oxygen species (ROS), which in turn activate the caspase-1/GSDMD and caspase-3/GSDME signaling pathways, ultimately driving tumor cells into pyroptosis. Based on these findings, we develop a phenylboronic acid-functionalized sodium alginate-based hydrogel controlled-release system (Alg-PBA/Spd). This platform achieves sustained Spd release through coordination interactions and markedly inhibits tumor growth by inducing pyroptosis. Further studies demonstrate that the Alg-PBA/Spd hydrogel synergizes with radiotherapy (RT) to enhance radiosensitivity in an orthotopic breast cancer model and inhibit pulmonary metastasis. Moreover, this hydrogel enables co-delivery of αPD-L1 with sustained release, which significantly improves the response rate of immune checkpoint blockade therapy by inducing pyroptosis and remodeling the tumor immune microenvironment. Overall, this study not only elucidates a previously unrecognized mechanism underlying polyamine metabolism-driven pyroptosis but also offers a versatile platform to enhance the efficacy of RT and immunotherapy.

31 Dec 2026·RENAL FAILURE

AMD1-mediated polyamine metabolism governs tubular repair fate by restraining senescence after kidney injury

Article

Author: Pan, Miao ; Liu, Xiaohua ; Zheng, Zhihuang ; Fu, Wenxin ; Bao, Jinfang ; Wang, Lijun ; Mao, Baiwei ; Liu, Jun ; Zhan, Hongbin ; Cheng, Guozhe

Failure of adaptive repair after acute kidney injury (AKI) drives the transition to chronic kidney disease (CKD), yet the metabolic checkpoints governing tubular fate remain incompletely defined. Here, we investigated whether the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase 1 (AMD1) regulates tubular senescence and repair outcomes after AKI and elucidated the underlying mechanism. AMD1 dynamics were examined in an ischemia-reperfusion injury model using male C57BL/6J mice by immunofluorescence. AAV-mediated Ksp promoter-driven tubule-specific Amd1 conditional knockdown male mice (Amd1 ^cKD) were used to assess renal injury, cell-cycle status, senescence, and remodeling, and exogenous spermidine was administered for rescue. DNA damage signaling and p53/p21 activation were evaluated by immunostaining, Western blotting, and EdU incorporation assays. AMD1 was predominantly expressed in the tubular epithelium, with prominent dynamic induction in proximal tubules early after IRI, but declined to baseline levels during the late phase, representing a relative metabolic insufficiency that correlated inversely with fibrosis. Compared with wild-type controls, Amd1 ^cKD mice exhibited aggravated tubular injury, an over two-fold increase in SA-β-gal-positive areas, elevated p21, and reduced Ki67+ proliferation. Conversely, spermidine supplementation improved renal function, reduced fibrosis by 75.3%, and decreased senescent regions by 74%. Mechanistically, AMD1 deficiency increased γH2AX-marked DNA damage and activated the p53/p21 checkpoint, whereas spermidine attenuated this response and restored DNA synthesis capacity. Collectively, tubular AMD1 acts as a metabolic checkpoint that preserves polyamine homeostasis to restrain p53/p21-dependent senescence, promote adaptive repair after AKI, and spermidine supplementation represents a potential strategy to mitigate maladaptive AKI-to-CKD progression.

News (Medical) associated with Spermidine

29 Sep 2026

·www.biospace.com

Airway Therapeutics Awarded $1.9 Million NIH Grant to Advance Phase 2b/3 Study of Zelpultide Alfa for Prevention of Bronchopulmonary Dysplasia

NIH funding provides non-dilutive capital to advance late-stage U.S. clinical development of zelpultide alfa Program builds on favorable safety and tolerability results from a Phase 1b study and a strong start of the trial in Europe, Argentina, and Israel ATLANTA , Sept. 29, 2026 /PRNewswire/ -- Airway Therapeutics, Inc. , a late-stage clinical biopharmaceutical company developing novel biologic therapies for respiratory, inflammatory, and infectious diseases, today announced that it has been awarded a $1.9 million grant (R44HL186892) from the National Institutes of Health (NIH) to support its U.S. Phase 2b clinical study evaluating zelpultide alfa for the prevention of bronchopulmonary dysplasia (BPD) in very preterm infants. The award was made through the National Heart, Lung, and Blood Institute (NHLBI) of the NIH under the Small Business Innovation Research (SBIR) program and provides $1.9 million in non-dilutive funding. The funding will support Airway Therapeutics' late-stage clinical development program in BPD, a condition for which there are currently no approved preventive therapies. "This NIH award is an important recognition of the scientific rationale behind our program and the need for new preventive approaches in BPD," said Marc Salzberg, MD, Chairman and Chief Executive Officer of Airway Therapeutics. "It strengthens our ability to execute our late-stage development strategy and advance a differentiated biologic in an area of significant unmet need. We remain focused on advancing the clinical development of zelpultide alfa and evaluating its ability to improve outcomes for very preterm infants at risk of BPD." BPD is a serious chronic lung disease of prematurity associated with inflammation and injury to the developing lungs of very preterm infants. These infants are particularly vulnerable because important pulmonary defense mechanisms, including those mediated by surfactant protein D (SP-D), are not fully developed. SP-D plays an important role in regulating pulmonary inflammation, supporting innate immune defense and maintaining surfactant homeostasis. Zelpultide alfa is being developed as a recombinant human SP-D therapy designed to restore these protective functions in very preterm infants after birth, when the immature lung is particularly susceptible to inflammation, infection and injury that can contribute to BPD. The ongoing Phase 2b program in the U.S. builds on favorable safety and tolerability results from a Phase 1b study of zelpultide alfa, as well as a strong start to the trial in Europe, Argentina, and Israel. The late-stage study is designed to further evaluate the efficacy and safety of zelpultide alfa compared with standard of care in high-risk preterm neonates and to assess its potential to reduce the incidence and severity of BPD. About Zelpultide Alfa Zelpultide alfa is a recombinant human surfactant protein D (rhSP-D) precisely engineered to replicate the native protein's full quaternary structure and biological function, incorporating optimized glycosylation through advanced cell line technology. Its therapeutic activity is driven by three key mechanisms: modulation of immune responses to mitigate excessive inflammation, enhancement of pathogen recognition and clearance, and maintenance of surfactant homeostasis to support pulmonary function. As a versatile biologic platform, zelpultide alfa is being developed for patients across all age groups—from preventing bronchopulmonary dysplasia (BPD) in very preterm infants to treating acute and chronic respiratory, inflammatory and infectious conditions in adults. Zelpultide alfa's lead indication, BPD prevention, is currently progressing through a Phase 2b/3 clinical trial, following a Phase 1b study that demonstrated a favorable safety and tolerability profile. About Airway Therapeutics Airway Therapeutics is a late-stage clinical biopharmaceutical company developing a new class of biologic therapies to redefine the prevention and treatment of respiratory, inflammatory, and infectious diseases. Its lead candidate, zelpultide alfa, is currently in late-stage clinical development for the prevention of bronchopulmonary dysplasia (BPD) in very preterm infants, a condition with no approved preventive therapies. As a platform biologic, zelpultide alfa is also being advanced for broader application across age groups and disease settings, with the goal of improving outcomes for vulnerable patient populations. For more information, please visit NIH Funding Acknowledgment The clinical development program described in this press release is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R44HL186892. 4.3% of the total project costs, or $1,906,253, are financed with federal funds, and 95.7% of the total project costs, or $42,000,100, are financed by nongovernmental sources. The content is solely the responsibility of Airway Therapeutics and does not necessarily represent the official views of the National Institutes of Health. Company Contact: Libba Muzi Airway Therapeutics muzi@airwaytherapeutics.com 513-770-9630 View original content to download multimedia: SOURCE Airway Therapeutics

Phase 1Phase 2Clinical Result

17 Aug 2026

·allsci.com

Cell study uncovers polyamines as natural ferroptosis defense

Polyamines — small, positively charged metabolites long studied for roles in cell growth and translation — directly chelate labile intracellular iron and thereby suppress ferroptosis, the iron-dependent form of regulated cell death, according to a study published August 14 in Cell. The finding repositions a class of abundant endogenous molecules as constitutive guardians of cellular redox homeostasis, with potential implications for cancer therapy and neurodegeneration research. The work was led by Whitehead Institute and MIT researchers Pushkal Sharma, Whitney Henry, and Ankur Jain, with contributors from Koch Institute, Institut Curie, Broad Institute, and MIT's Department of Biology. The work identifies a non-enzymatic protective mechanism operating in parallel to the well-characterized glutathione peroxidase 4 (GPX4) pathway. Prior models of ferroptosis resistance have centered on enzymatic lipid repair; this study proposes that polyamines — principally spermine and spermidine — provide a chemical buffering layer by sequestering the labile iron pool (LIP), the redox-active Fe²⁺ fraction that drives Fenton chemistry and lipid peroxide generation. The researchers conducted a genome-wide CRISPR knockout screen to identify synthetic lethal interactions with GPX4 loss. Polyamine depletion emerged as a top hit: cells lacking polyamine biosynthetic capacity were dramatically sensitized to ferroptosis when GPX4 was also inhibited. To investigate the mechanism, the team developed a genetically encoded fluorescent reporter for redox-active iron, enabling real-time, single-cell visualization of the LIP — a technical advance the paper presents as a significant methodological contribution alongside the biological findings. Live-cell imaging with this reporter revealed a striking inverse correlation between intracellular polyamine levels and labile Fe²⁺ at single-cell resolution. Biochemical assays confirmed that spermine and spermidine directly coordinate Fe²⁺ through their multiple protonatable amine nitrogen atoms, forming stable chelate complexes analogous in principle to clinical iron chelators such as trientine. When polyamines were depleted, the LIP expanded; cells partially compensated by upregulating ferritin, the iron storage protein, but the paper reports this secondary response was insufficient to fully buffer the excess reactive iron. The study draws a direct line from polyamine abundance to ferroptosis susceptibility: high polyamine levels sequester Fe²⁺, reducing its availability to catalyze lipid peroxidation; depletion expands the LIP and, in the absence of GPX4 activity, produces synthetic lethality. The authors note this framework provides a mechanistic rationale for the ferroptosis-sensitizing effects of difluoromethylornithine (DFMO, eflornithine), an ornithine decarboxylase inhibitor already FDA-approved for neuroblastoma, suggesting that its clinical activity may partly reflect iron dyshomeostasis rather than effects on proliferation alone. The connection also extends to genetic diseases involving polyamine dysregulation. The connection also extends to genetic diseases involving polyamine dysregulation. The paper cites ATP13A2 mutations linked to early-onset Parkinson's disease, as well as Snyder-Robinson syndrome, as examples of conditions in which disrupted polyamine homeostasis may intersect with disease Ferroptosis has attracted substantial drug development interest across oncology, neurodegeneration, and ischemia-reperfusion injury. GPX4 inhibitors and system Xc⁻ (cystine-glutamate antiporter) blockers are the principal pharmacological tools used to induce ferroptosis in cancer models, while the same pathway is a therapeutic target for protection in degenerative disease. The polyamine-iron axis identified here represents a distinct, non-enzymatic entry point into ferroptosis regulation that has not previously been described at this mechanistic level, according to the paper. The work is entirely preclinical with experiments conducted primarily in mammalian cell lines and organoid models. The genetically encoded iron reporter developed for this study may itself be a broadly useful research tool, but its performance characteristics across diverse cell types and conditions are not detailed in the available data. Whether polyamine-iron buffering operates equivalently across the cell types most relevant to cancer or neurodegeneration, and whether it can be pharmacologically exploited with sufficient selectivity, remain open questions. No therapeutic candidate or clinical development program is described. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

Clinical ResultCell Therapy

20 Jul 2026

·www.sciencedaily.com

This food compound may help vaccines work better in older adults

A naturally occurring compound found in foods such as wheat germ, mushrooms, and aged cheese may help older adults build stronger protection after vaccination. In a small pilot trial, researchers gave spermidine supplements to adults over 65 following their third COVID-19 vaccine dose. The biggest improvements appeared among people whose immune systems initially responded poorly, with higher antibody levels and stronger activity against several variants.A naturally occurring compound called spermidine may help strengthen vaccine responses in some older adults by reducing biological signs of immune system aging, according to research published in Aging Cell. The immune system becomes less efficient as people grow older, making it harder for the body to fight infections and respond fully to vaccines. This gradual decline, known as immunosenescence, can increase vulnerability to age-related health problems and leave some older adults with weaker protection after vaccination. Spermidine May Support Aging Immunity The research was led by Dr. Katja Simon, Group Leader of the Cell Biology of Immunity lab at the Max Delbrück Center, and Dr. Ghada Alsaleh, Associate Professor at the Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences of University of Oxford (NDORMS). Their findings suggest that taking a daily spermidine supplement improved several measures of immune response following COVID-19 vaccination. Spermidine is produced naturally by human cells and is also present in foods including wheat germ, mushrooms, parmesan, and cheddar. Earlier research has indicated that the molecule may support cellular maintenance mechanisms that become less active with age. "Many older adults respond well to vaccines," Alsaleh explains. "But some do not develop strong protection, even after repeated vaccination. Biological aging of immune cells may be one reason why this happens. Our findings suggest that spermidine could help restore aspects of immune function in this group." The project also involved researchers from the Oxford Vaccine Group, including Drs. Paul Klenerman, Teresa Lambe, and Lucy Jones, along with Owen B. Spiller from Cardiff University. Why Vaccines Can Become Less Effective With Age The COVID-19 pandemic reinforced the importance of vaccination in preventing severe disease and death. However, older adults often develop fewer protective antibodies and T cells after receiving a vaccine. Similar patterns have also been observed with influenza vaccination. To investigate whether spermidine could improve this response, Simon and her colleagues enrolled 40 healthy adults aged 65 and older. After receiving their third COVID-19 vaccination, participants took either six milligrams of spermidine or a placebo each day for 13 weeks. About one quarter of the participants produced very weak antibody responses even after three vaccine doses. Their immune cells also showed distinct signs of biological aging, including greater DNA damage and molecular markers linked to cellular senescence. During cellular senescence, damaged or aging cells stop working normally but remain in the body and accumulate over time. Stronger Antibody Responses in Some Participants Among the vaccine nonresponders who received spermidine, several indicators of vaccine-related immunity improved substantially. These participants generally developed higher levels of antibodies against SARS-CoV-2 and showed stronger neutralizing activity against several viral variants. The researchers also found that spermidine lowered markers associated with immunosenescence and increased autophagy. Autophagy is a natural recycling process that allows cells to remove damaged material and maintain normal function. The supplement appeared to be safe and well tolerated. Researchers found no adverse effects associated with the treatment. Larger Trials Are Still Needed Because the study included only 40 participants, the researchers caution that the results should be viewed as early evidence rather than definitive proof that spermidine can improve vaccination outcomes. "This study was designed as a pilot trial and involved a relatively small number of participants," says Simon. "Larger studies will be needed to determine whether spermidine can consistently improve vaccine responses and whether similar effects are seen with other vaccines, such as those used against seasonal influenza."

VaccineClinical ResultImmunotherapyClinical Study

100 Deals associated with Spermidine

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	Austria	Medizinische Universität Graz	25 Feb 2020
Nasopharyngeal Carcinoma	Phase 2	China	West China Hospital	25 Jun 2025
Squamous Cell Carcinoma of Head and Neck	Phase 2	China	West China Hospital	25 Jun 2025
Xerostomia	Phase 2	China	West China Hospital	25 Jun 2025
Coronary Artery Disease	Phase 2	Denmark	-	01 Jan 2024
Diabetes Mellitus, Type 2	Phase 2	Denmark	-	01 Jan 2024
Metabolic Syndrome	Phase 2	Denmark	-	01 Jan 2024
Myocardial Infarction	Phase 2	Denmark	-	01 Jan 2024
Obesity	Phase 2	Denmark	-	01 Jan 2024
Amyotrophic Lateral Sclerosis	Preclinical	Belgium	VIB-KU Leuven Center for Brain & Disease Research	22 Dec 2025

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