Research
Spermidine
49 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.
This 12-month randomized, double-masked, placebo-controlled trial investigated the effects of spermidine supplementation on memory performance and biomarkers in older adults with subjective cognitive decline. No significant changes were observed in mnemonic discrimination performance or secondary outcomes. Exploratory analyses suggested possible beneficial effects on verbal memory and inflammation.
Effects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study.
This pilot study examined the effects of spermidine from Miricell rice germ extract on biomarkers of autophagy, neuroprotection, and cardiometabolic health in 12 healthy adults over 56 days. The 3.3 mg dose increased Beclin-1, ULK-1, and BDNF levels, and decreased hs-CRP, VLDL, and triglycerides, indicating potential benefits for healthy aging.
Treatment of peri-implant mucositis using spermidine and calcium chloride as local adjunctive delivery to non-surgical mechanical debridement: a double-blind randomized controlled clinical trial.
Double-blind RCT evaluating the effects of non-surgical mechanical debridement with or without adjunctive application of spermidine and calcium chloride gel in treating peri-implant mucositis. Both groups showed significant improvement, but no statistically significant differences were found between them. However, the test group had fewer BOP-positive sites.
Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men.
This double-blind, randomized controlled trial investigated the safety of a high-purity spermidine trihydrochloride supplement (hpSPD) in 37 healthy older men. The study found that 40 mg/day of hpSPD for up to 28 days did not result in significant changes in clinical, lipids, chemistry, or hematological parameters compared to placebo, suggesting it is safe and well-tolerated.
Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men.
Pilot dose-escalation study in 5 healthy men evaluating a fasting mimetic formulation containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide. The supplements were bioavailable, increased plasma concentrations, and showed enhanced anti-inflammatory and antioxidant functions.
High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study
This randomized, placebo-controlled, triple-blinded crossover trial investigated the pharmacokinetics of oral spermidine supplementation in 12 healthy adults. The study found that while spermidine supplementation significantly increased spermine levels in plasma, it did not affect spermidine or putrescine levels in blood or saliva. The results suggest that dietary spermidine is converted into spermine, which enters systemic circulation.
Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.
The SmartAge trial is a randomized, double-blind, placebo-controlled phase IIb trial investigating the effects of 12 months of spermidine supplementation on memory performance and other neuropsychological, behavioral, and physiological parameters in 100 older adults with subjective cognitive decline. The primary outcome is the change in memory performance between baseline and post-intervention visits.
Higher spermidine intake is linked to lower mortality: a prospective population-based study.
This prospective cohort study examined the association between dietary spermidine intake and mortality in 829 participants aged 45-84 years. Higher spermidine intake was linked to lower all-cause mortality, with a significant reduction in mortality risk across increasing thirds of spermidine intake. The findings suggest that a diet rich in spermidine is associated with increased survival in humans.
Effect of oral polyamine supplementation pre-weaning on piglet growth and intestinal characteristics.
The study investigated the effects of oral spermine and spermidine supplementation on piglet growth and intestinal development pre-weaning. Spermine supplementation increased villus height and decreased crypt depth in the intestines, and both spermine and spermidine improved growth rates in piglets suckling first lactation sows.
A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.
The study investigates the role of spermidine in autophagy and longevity, showing that fasting-induced spermidine biosynthesis is crucial for autophagy and longevity in various organisms. Spermidine acts as a caloric restriction mimetic and is essential for the antiaging effects of fasting and rapamycin.
Spermidine is essential for fasting-mediated autophagy and longevity
The study investigates the role of spermidine in fasting-mediated autophagy and longevity across various species, including yeast, flies, mice, and humans. Spermidine levels increased with fasting or caloric restriction, enhancing autophagy and extending lifespan and healthspan. Blocking spermidine synthesis reduced these effects, highlighting its importance in the polyamine–hypusination axis for metabolic control.
Tumor cell–derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8+ T cell activation
The study reports that tumor cells release endogenous polyamine spermidine to suppress T cell activation in the tumor immune microenvironment (TIME). Spermidine down-regulates plasma membrane cholesterol levels, suppressing T cell antigen receptor clustering, suggesting a potential target for tumor immunotherapy.
Combined ability of salicylic acid and spermidine to mitigate the individual and interactive effects of drought and chromium stress in maize (Zea mays L.).
The study evaluated the effects of salicylic acid (SA) and spermidine (Spd) on maize under drought and chromium stress. SA and Spd treatments alleviated oxidative stress and improved growth metrics. Combined SA + Spd treatment was more effective in enhancing protein, water content, and photosynthetic pigments, and reducing chromium uptake.
Exogenous spermidine alleviates the adverse effects of aluminum toxicity on photosystem II through improved antioxidant system and endogenous polyamine contents.
The study investigates the role of exogenous spermidine in alleviating aluminum toxicity in rice chloroplasts. Spermidine reduced aluminum concentration, improved nutrient element levels, enhanced polyamine synthesis, and protected photosystem II by mitigating oxidative damage, thus improving photosynthetic performance under aluminum stress.
The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.
This randomized controlled trial evaluated the impact of spermidine supplementation on memory performance in older adults at risk for Alzheimer's disease. The study found that spermidine moderately enhanced memory performance and mnemonic discrimination ability compared to placebo, suggesting a positive impact on brain health.
Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.
The study assessed the safety and tolerability of spermidine supplementation using a wheat germ extract in mice and older adults with subjective cognitive decline. In mice, no morbidities or behavioral changes were observed during a 28-day tolerance study. In a 3-month RCT with 30 older adults, no significant differences in safety parameters were found between spermidine and placebo groups, indicating excellent tolerability.
Spermidine‐Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ
The study developed an injectable hydrogel functionalized with spermidine (DN-SPD) to reduce inflammation and enhance healing of acute and diabetic wounds. In vivo animal experiments showed that DN-SPD hydrogel reduced inflammation and promoted macrophage polarization towards a regenerative phenotype, leading to faster and more natural wound healing compared to a control hydrogel.
Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR/Nrf2 and AhR/STAT3 signaling pathways.
The study investigates the effects of spermidine on intestinal barrier function in murine models of colitis. Spermidine was found to significantly improve intestinal barrier integrity and modulate AhR/Nrf2 and AhR/STAT3 signaling pathways, suggesting its potential as a therapeutic agent for inflammatory bowel diseases.
Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins
Animal study where ICR mice were fed spermidine in drinking water for three months to explore its effects on ovarian function. Spermidine treatment reduced the number of atretic follicles, increased antioxidant enzyme activities, and altered the expression of autophagy-related proteins, suggesting protective effects on ovarian function.
Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.
The study identifies spermidine as a critical metabolite in ovaries that protects oocytes against aging. Spermidine supplementation in aged mice promoted follicle development, oocyte maturation, early embryonic development, and female fertility. The mechanism involves enhancement of mitophagy activity and mitochondrial function, suggesting potential therapeutic use for improving oocyte quality and reproductive outcomes.
Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis
The study investigates the role of spermidine, a metabolite of arginine, in kidney fibrosis. Spermidine activates Nrf2 and inhibits fibrotic signals in human proximal tubule cells and reduces fibrosis in Arg2 knockout mice with UUO-induced kidney fibrosis.
Spermidine alleviating oxidative stress and apoptosis by inducing autophagy of granulosa cells in Sichuan white geese
The study investigated the effects of spermidine on oxidative stress and apoptosis in granulosa cells of Sichuan white geese. Spermidine was found to alleviate oxidative stress and apoptosis by inducing autophagy, suggesting its potential to maintain proteostasis and sustain granulosa cell viability.
Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein
The study investigated the effects of spermidine on mitochondrial function in a cellular model of tauopathy using SH-SY5Y cells. Spermidine improved mitochondrial respiration, membrane potential, ATP production, decreased free radicals, increased autophagy, and restored mitophagy impairments induced by abnormal tau.
Spermidine Ameliorates Colitis via Induction of Anti-Inflammatory Macrophages and Prevention of Intestinal Dysbiosis
The study investigated the effects of oral spermidine administration on colitis severity in a mouse model. Spermidine protected mice from intestinal inflammation, promoted anti-inflammatory macrophages, and maintained a healthy gut microbiome. Its effects were dependent on PTPN2 in intestinal epithelial and myeloid cells.
Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression
The study investigates the role of spermidine in improving mitochondrial fatty acid oxidation and preventing the progression of non-alcoholic steatohepatitis (NASH) in mice. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function, and prevents NASH progression in vivo.
Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice
The study investigates the effects of spermidine supplementation on antitumor immunity in aged mice. Spermidine was found to enhance mitochondrial function and fatty acid oxidation in CD8+ T cells, improving the efficacy of PD-1 blockade cancer immunotherapy. The study suggests spermidine's potential in combating age-related immune pathologies and enhancing cancer treatment outcomes.
Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model
The study assessed the effects of spermidine, an autophagy activator, on amyloid beta pathology and neuroinflammation in an Alzheimer's disease mouse model. Spermidine treatment reduced neurotoxic soluble amyloid beta and decreased AD-associated neuroinflammation, highlighting its potential to enhance amyloid beta degradation and counteract glia-mediated neuroinflammation.
Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging.
The study investigates how dietary spermidine supplementation enhances eEF5/EIF5A hypusination, cerebral mitochondrial function, and cognition in aging mice. Spermidine supplementation is shown to prolong lifespan, activate autophagy, improve mitochondrial function, and refill polyamine pools that decline during aging.
Dietary spermidine improves cognitive function.
The study investigates the effects of dietary spermidine on cognitive function, showing that it crosses the blood-brain barrier in mice, enhances hippocampal function, and improves spatial learning. In Drosophila, spermidine boosts mitochondrial respiratory capacity, requiring autophagy and mitophagy mediators. Human data links higher spermidine intake with reduced cognitive impairment risk.
Spermidine inhibits neurodegeneration and delays aging via the PINK1-PDR1-dependent mitophagy pathway in C. elegans
The study investigates the effects of spermidine on neurodegeneration and aging in C. elegans models. Spermidine inhibits memory loss in Alzheimer's disease worms and improves locomotor capacity in Parkinson's disease worms via the PINK1-PDR1-dependent mitophagy pathway. It also delays aging and improves healthspan in a premature aging worm model.
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation
The study investigates the role of hypusinated EIF5A in colorectal cancer growth, showing that inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through knockdown reduces CRC cell growth. The mechanism involves regulation of MYC elongation, and the blockade of hypusination significantly reduces polyp size in APCMin/+ mice, a model of human familial adenomatous polyposis.
Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.
Study on diet-induced obese mice showing that spermidine supplementation leads to weight loss and improved insulin resistance. These effects are associated with enhanced intestinal barrier function and altered gut microbiota composition, suggesting spermidine may be a viable therapy for obesity.
Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway
The paper investigates the effects of spermidine on cardiac dysfunction following myocardial infarction, focusing on the AMPK/mTOR signalling pathway. Spermidine is suggested to enhance autophagic flux and improve heart health.
Exogenous spermidine enhances the photosynthetic and antioxidant capacity of rice under heat stress during early grain-filling period.
The study investigates the effect of exogenous spermidine on rice under heat stress during the early grain-filling period. Spermidine was found to enhance photosynthetic and antioxidant capacity, increase superoxide dismutase and peroxidase activities, reduce malondialdehyde accumulation, and improve photosynthetic and transpiration rates in rice varieties Wuyunjing 24 and Ningjing 3.
[Spermidine radioimmunoassay in monitor of precancerous lesions of esophagus].
Serum spermidine was measured by radioimmunoassay in different stages of esophageal carcinogenesis in a high-risk population. The study involved intervention treatments with Aminoretinoic Ester, Anticancer B, or placebo in patients with marked epithelial hyperplasia. Spermidine levels were used to monitor precancerous changes and could serve as an indicator for tumor-blocking drugs and early diagnosis of esophageal cancer.
Gut microbiota and anti-aging: Focusing on spermidine
This narrative review explores the role of spermidine, a natural polyamine, in anti-aging processes. It discusses how spermidine has anti-inflammatory and antioxidant properties, regulates protein expression, and improves mitochondrial metabolic activity. The review also examines the connection between polyamine metabolism and aging, and the potential of probiotics and prebiotics to increase spermidine levels.
Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms
This review discusses the anticancer properties of spermidine, a naturally occurring polyamine, highlighting its ability to interfere with tumor cell cycles, inhibit proliferation, and suppress tumor growth. It also explores spermidine's role in autophagy and its potential in diagnostic and therapeutic applications against cancer.
Spermidine - an old molecule with a new age-defying immune function.
This narrative review discusses the role of spermidine in immune cell regulation and anticancer responses. It highlights spermidine's potential in enhancing antitumor responses in aged animals and suggests its supplementation could improve the efficacy of anti-PD-1 treatment.
A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing.
This narrative review discusses the safety, health effects, absorption, and metabolism of spermidine, highlighting its potential benefits such as antitumor, antiaging, anti-inflammation, cardiovascular protection, and neuromodulation. It also covers advances in food processing and metabolic engineering strategies for spermidine biosynthesis.
Nutritional Aspects of Spermidine.
This narrative review discusses the nutritional aspects of polyamines, particularly spermidine and spermine, and their role in protecting against age-related diseases. It highlights the impact of dietary polyamine intake on health and longevity, summarizing preclinical, clinical, and epidemiological studies.
Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders.
This narrative review summarizes the neuroprotective effects of spermidine, an autophagy inducer, in neurological disorders. It discusses spermidine's role in promoting longevity, anti-aging, and anti-inflammatory properties, and its potential therapeutic action in age-related neurological disorders.
Cardioprotection and lifespan extension by the natural polyamine spermidine.
The study demonstrates that oral supplementation of spermidine extends lifespan and provides cardioprotective effects in mice, reducing cardiac hypertrophy and preserving diastolic function. Spermidine enhanced cardiac autophagy and improved cardiomyocyte properties. In Dahl salt-sensitive rats, spermidine reduced blood pressure and delayed heart failure progression. In humans, high dietary spermidine correlated with reduced blood pressure and lower cardiovascular disease incidence.
ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts
The study investigates the role of ATM in spermidine-induced mitophagy in human fibroblasts. Spermidine induces mitophagy by promoting mitochondrial depolarization and the accumulation of PINK1 and Parkin, leading to decreased mitochondrial mass. ATM is shown to be crucial for this process, as its absence or inhibition disrupts the mitophagic cascade.
Spermidine: A predictor for neurological outcome and infarct size in focal cerebral ischemia?
The study measured polyamine levels, specifically spermidine, in 16 patients with focal cerebral ischemia and 8 healthy controls. Spermidine levels were significantly elevated in patients and correlated positively with clinical outcomes and infarct volume, suggesting its potential as a predictor for prognosis in cerebral ischemia.
Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?
The paper discusses spermidine as a natural polyamine that induces autophagy and its potential role as an anti-aging agent. It highlights that spermidine supplementation extends lifespan and health span across various species and suggests a link between reduced spermidine levels and age-related deterioration in humans. Epidemiological data indicate that increased spermidine intake may reduce mortality associated with cardiovascular diseases and cancer.
Effect of polyamines on acidified ethanol-induced gastric lesions in rats.
The study investigated the role of polyamines and nonprotein sulfhydryls in gastric cytoprotection using a rat model with acidified ethanol-induced gastric lesions. Oral administration of cadaverine, spermidine, and spermine prevented lesion formation in a dose-dependent manner. The cytoprotective effect of spermine was not influenced by indomethacin or acetazolamide but was partially blocked by sulfhydryl blockers. Spermine and PGE2 partially prevented the decrease in nonprotein sulfhydryls caused by acidified ethanol.
Block of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by polyamines and polyamine toxins.
The study investigates the blocking effects of polyamines and polyamine toxins, such as spermine and spermidine, on AMPA receptors lacking the GluR2 subunit. The research demonstrates that these substances exert a use-dependent and weakly voltage-dependent block on recombinant AMPA receptors expressed in Xenopus oocytes and native AMPA receptors in rat hippocampal interneurons.
Characterization of the stimulatory and inhibitory effects of polyamines on [3H]N-(1-[thienyl]cyclohexyl) piperidine binding to the N-methyl-D-aspartate receptor ionophore complex.
The study tested spermidine, spermine, and related compounds in a binding assay to determine their effects on the N-methyl-D-aspartate receptor ion channel. Spermidine and spermine enhanced binding significantly, while putrescine and cadaverine showed inhibitory effects. Magnesium ions mimicked the inhibitory effects of putrescine.
Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site.
The study investigates the effects of polyamines, including spermidine and spermine, on the binding of [3H]MK-801 to NMDA receptors in rat brain membranes. It suggests the existence of a polyamine recognition site on the NMDA receptor complex, with spermidine increasing receptor affinity and other polyamines acting as selective antagonists.